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Sample records for premalignant bronchial lesions

  1. Histochemical identification of malignant and premalignant lesions

    NASA Astrophysics Data System (ADS)

    Liebow, Charles; Maloney, M. J.

    1991-06-01

    Malignant and transforming cells can be identified by biochemical parameters which can be used to localize lesions in situ for laser surgery. These cells express unique proteins, proteins in unusual quantities, or other biochemical alterations which can be utilized to image lesions of such cells. Several methods have been identified, both in vitro and in vivo, to identify such lesions. Several antibodies were examined for their properties of tissue identification, including CEA, F36/22, and AE1/AE3. F36/22, an antibody developed by M. T. Chu against human breast cancer cells, associated with two lines of oral cancer (KB and HCPC), and against two naturally occurring human oral squamous cell cancers. CEA, an antibody developed against human colon cancer, also reacted against both cell lines and both pathological samples. AE1/AE3, developed against normal fibrous components, also reacted against the samples, but in a much less regular manner. F36/22 associated with the histologically identifiably most dedifferentiated cells at the leading edge of the invading cancer. CEA, on the other hand, associated with more quiescent, older, established cancer cells. This demonstrates that antibodies developed against cancers of different organs can be used to identify a wide variety of cancers, and may have prognostic value. F36/22 coupled to fluorescein was used to identify oral cancer cells. Other properties of cancers and developing cancers can also be exploited to identify cancers, including their over-expression of tyrosine kinase and tyrosine kinase stimulating hormones such as Epidermal Growth Factor (EGF). A model of premalignant lesion produced in the hamster buccal cheek pouch with 6 week application of DMBA over-expresses constitutive tyrosine kinase which can be demonstrated biochemically. This initiated lesion can be promoted to frank cancer by growth factors released in response to laser surgery. Preliminary results suggest that these lesions can be identified by

  2. Is endoscopic nodular gastritis associated with premalignant lesions?

    PubMed

    Niknam, R; Manafi, A; Maghbool, M; Kouhpayeh, A; Mahmoudi, L

    2015-06-01

    Nodularity on the gastric mucosa is occasionally seen in general practice. There is no consensus about the association of nodular gastritis and histological premalignant lesions. This study is designed to investigate the prevalence of histological premalignant lesions in dyspeptic patients with endoscopic nodular gastritis. Consecutive patients with endoscopic nodular gastritis were compared with an age- and sex-matched control group. Endoscopic nodular gastritis was defined as a miliary nodular appearance of the gastric mucosa on endoscopy. Biopsy samples of stomach tissue were examined for the presence of atrophic gastritis, intestinal metaplasia, and dysplasia. The presence of Helicobacter pylori infection was determined by histology. From 5366 evaluated patients, a total of 273 patients with endoscopic nodular gastritis and 1103 participants as control group were enrolled. H. pylori infection was detected in 87.5% of the patients with endoscopic nodular gastritis, whereas 73.8% of the control group were positive for H. pylori (p < 0.001). Prevalence of incomplete intestinal metaplasia (p = 0.016) and dysplasia (p < 0.001) in patients with endoscopic nodular gastritis were significantly higher than in the control group. Prevalence of atrophic gastritis and complete intestinal metaplasia were also more frequent in patients with endoscopic nodular gastritis than in the control group. Dysplasia, incomplete intestinal metaplasia and H. pylori infection are significantly more frequent in patients with endoscopic nodular gastritis. Although further studies are needed before a clear conclusion can be reached, we suggest that endoscopic nodular gastritis might serve as a premalignant lesion and could be biopsied in all patients for the possibility of histological premalignancy, in addition to H. pylori infection.

  3. Betel nut chewing, oral premalignant lesions, and the oral microbiome

    PubMed Central

    Hernandez, Brenda Y.; Zhu, Xuemei; Goodman, Marc T.; Gatewood, Robert; Mendiola, Paul; Quinata, Katrina; Paulino, Yvette C.

    2017-01-01

    Oral cancers are attributed to a number of causal agents including tobacco, alcohol, human papillomavirus (HPV), and areca (betel) nut. Although betel nut chewing has been established as an independent cause of oral cancer, the mechanisms of carcinogenesis are poorly understood. An investigation was undertaken to evaluate the influence of betel nut chewing on the oral microbiome and oral premalignant lesions. Study participants were recruited from a dental clinic in Guam. Structured interviews and oral examinations were performed. Oral swabbing and saliva samples were evaluated by 454 pyrosequencing of the V3- V5 region of the 16S rRNA bacterial gene and genotyped for HPV. One hundred twenty-two adults were enrolled including 64 current betel nut chewers, 37 former chewers, and 21 with no history of betel nut use. Oral premalignant lesions, including leukoplakia and submucous fibrosis, were observed in 10 chewers. Within-sample bacterial diversity was significantly lower in long-term (≥10 years) chewers vs. never chewers and in current chewers with oral lesions vs. individuals without lesions. Between-sample bacterial diversity based on Unifrac distances significantly differed by chewing status and oral lesion status. Current chewers had significantly elevated levels of Streptococcus infantis and higher and lower levels of distinct taxa of the Actinomyces and Streptococcus genera. Long-term chewers had reduced levels of Parascardovia and Streptococcus. Chewers with oral lesions had significantly elevated levels of Oribacterium, Actinomyces, and Streptococcus, including Streptococcus anginosus. In multivariate analyses, controlling for smoking, oral HPV, S.anginosus, and S. infantis levels, current betel nut chewing remained the only predictor of oral premalignant lesions. Our study provides evidence that betel nut chewing alters the oral bacterial microbiome including that of chewers who develop oral premalignant lesions. Nonetheless, whether microbial changes

  4. Betel nut chewing, oral premalignant lesions, and the oral microbiome.

    PubMed

    Hernandez, Brenda Y; Zhu, Xuemei; Goodman, Marc T; Gatewood, Robert; Mendiola, Paul; Quinata, Katrina; Paulino, Yvette C

    2017-01-01

    Oral cancers are attributed to a number of causal agents including tobacco, alcohol, human papillomavirus (HPV), and areca (betel) nut. Although betel nut chewing has been established as an independent cause of oral cancer, the mechanisms of carcinogenesis are poorly understood. An investigation was undertaken to evaluate the influence of betel nut chewing on the oral microbiome and oral premalignant lesions. Study participants were recruited from a dental clinic in Guam. Structured interviews and oral examinations were performed. Oral swabbing and saliva samples were evaluated by 454 pyrosequencing of the V3- V5 region of the 16S rRNA bacterial gene and genotyped for HPV. One hundred twenty-two adults were enrolled including 64 current betel nut chewers, 37 former chewers, and 21 with no history of betel nut use. Oral premalignant lesions, including leukoplakia and submucous fibrosis, were observed in 10 chewers. Within-sample bacterial diversity was significantly lower in long-term (≥10 years) chewers vs. never chewers and in current chewers with oral lesions vs. individuals without lesions. Between-sample bacterial diversity based on Unifrac distances significantly differed by chewing status and oral lesion status. Current chewers had significantly elevated levels of Streptococcus infantis and higher and lower levels of distinct taxa of the Actinomyces and Streptococcus genera. Long-term chewers had reduced levels of Parascardovia and Streptococcus. Chewers with oral lesions had significantly elevated levels of Oribacterium, Actinomyces, and Streptococcus, including Streptococcus anginosus. In multivariate analyses, controlling for smoking, oral HPV, S.anginosus, and S. infantis levels, current betel nut chewing remained the only predictor of oral premalignant lesions. Our study provides evidence that betel nut chewing alters the oral bacterial microbiome including that of chewers who develop oral premalignant lesions. Nonetheless, whether microbial changes

  5. Sialyl Lewis x expression in cervical scrapes of premalignant lesions.

    PubMed

    Velázquez-Márquez, Noé; Santos-López, Gerardo; Jiménez-Aranda, Lucio; Reyes-Leyva, Julio; Vallejo-Ruiz, Verónica

    2012-12-01

    Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumour progression and metastases. Altered expression of glycosidic antigens has been reported in cervical cancer. In cervix premalignant lesions, an increased expression of sialic acid has been reported. In the present study we determined the expression profiles of the glycosidic antigens Tn, sialyl Tn (sTn), Lewis a (Lea), sialyl Lewis a (sLea), Lewis x (Lex) and sialyl Lewis x (sLex) in cervical scrapes with cytological diagnoses of normal, low-grade squamous intraepithelial lesions (LGSIL) and highgrade squamous intraepithelial lesions (HGSIL). Cervical scrapings were collected to detect tumour antigens expressions by flow cytometry using monoclonal antibodies. Cytometry analysis of Tn, sTn, Lea and Lex did not reveal differences at the expression level among groups. The number of positive cells to sLea antigen increased in the HGSIL group with respect to the normal group (p=0.0495). The number of positive cells to sLex antigen in the samples increased with respect to the grade of squamous intraepithelial lesion (SIL) (p less than 0.001, Mann-Whitney U test). The intensity of expression of this antigen increased in the HGSIL samples with respect to normal samples (p less than 0.0068). sLex antigen could be a candidate to be used as biomarker for the early diagnosis of cervical cancer.

  6. Indomethacin Treatment of Mice with Premalignant Oral Lesions Sustains Cytokine Production and Slows Progression to Cancer

    PubMed Central

    Johnson, Sara D.; Young, M. Rita I.

    2016-01-01

    Current treatment options for head and neck squamous cell carcinoma (HNSCC) patients are often ineffective due to tumor-localized and systemic immunosuppression. Using the 4-NQO mouse model of oral carcinogenesis, this study showed that premalignant oral lesion cells produce higher levels of the immune modulator, PGE2, compared to HNSCC cells. Inhibiting prostaglandin production of premalignant lesion cells with the pan-cyclooxygenase inhibitor indomethacin stimulated their induction of spleen cell cytokine production. In contrast, inhibiting HNSCC prostaglandin production did not stimulate their induction of spleen cell cytokine production. Treatment of mice bearing premalignant oral lesions with indomethacin slowed progression of premalignant oral lesions to HNSCC. Flow cytometric analysis of T cells in the regional lymph nodes of lesion-bearing mice receiving indomethacin treatment showed an increase in lymph node cellularity and in the absolute number of CD8+ T cells expressing IFN-γ compared to levels in lesion-bearing mice receiving diluent control treatment. The cytokine-stimulatory effect of indomethacin treatment was not localized to regional lymph nodes but was also seen in the spleen of mice with premalignant oral lesions. Together, these data suggest that inhibiting prostaglandin production at the premalignant lesion stage boosts immune capability and improves clinical outcomes. PMID:27713748

  7. Proteomic patterns of preinvasive bronchial lesions.

    PubMed

    Rahman, S M Jamshedur; Shyr, Yu; Yildiz, Pinar B; Gonzalez, Adriana L; Li, Huiming; Zhang, Xueqiong; Chaurand, Pierre; Yanagisawa, Kiyoshi; Slovis, Bonnie S; Miller, Robert F; Ninan, Mathew; Miller, York E; Franklin, Wilbur A; Caprioli, Richard M; Carbone, David P; Massion, Pierre P

    2005-12-15

    A proteomics approach is warranted to further elucidate the molecular steps involved in lung tumor development. We asked whether we could classify preinvasive lesions of airway epithelium according to their proteomic profile. We obtained matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiles from 10-microm sections of fresh-frozen tissue samples: 25 normal lung, 29 normal bronchial epithelium, and 20 preinvasive and 36 invasive lung tumor tissue samples from 53 patients. Proteomic profiles were calibrated, binned, and normalized before analysis. We performed class comparison, class prediction, and supervised hierarchic cluster analysis. We tested a set of discriminatory features obtained in a previously published dataset to classify this independent set of normal, preinvasive, and invasive lung tissues. We found a specific proteomic profile that allows an overall predictive accuracy of over 90% of normal, preinvasive, and invasive lung tissues. The proteomic profiles of these tissues were distinct from each other within a disease continuum. We trained our prediction model in a previously published dataset and tested it in a new blinded test set to reach an overall 74% accuracy in classifying tumors from normal tissues. We found specific patterns of protein expression of the airway epithelium that accurately classify bronchial and alveolar tissue with normal histology from preinvasive bronchial lesions and from invasive lung cancer. Although further study is needed to validate this approach and to identify biomarkers of tumor development, this is a first step toward a new proteomic characterization of the human model of lung cancer tumorigenesis.

  8. Premalignant Oral Lesion Cells Elicit Increased Cytokine Production and Activation of T-cells

    PubMed Central

    JOHNSON, SARA D.; LEVINGSTON, CORINNE; YOUNG, M. RITA I.

    2016-01-01

    Background Head and neck squamous cell carcinomas (HNSCC) are known to evade the host immune response. How premalignant oral lesions modulate the immune response, however, has yet to be elucidated. Materials and Methods A mouse model of oral carcinogenesis was used to determine how mediators from premalignant oral lesion cells vs. HNSCC cells impact on immune cytokine production and activation. Results Media conditioned by premalignant lesion cells elicited an increased production of T cell-associated cytokines and proinflammatory mediators from cervical lymph node cells compared to media conditioned by HNSCC cells or media alone. In the presence of premalignant lesion cell-conditioned media, CD4+ T cell expression of the IL-2 receptor CD25 and CD8+ T cell expression of the activation marker CD69 was greater, compared to what was induced in HNSCC cell-conditioned media or media alone. Conclusion Premalignant lesion cells promote a proinflammatory environment and induce immune changes before HNSCC tumors are established. PMID:27354582

  9. Evaluation of Pre-Malignant and Malignant Lesions in Cervico Vaginal (PAP) Smears by Nuclear Morphometry

    PubMed Central

    Rani M.N, Divya; Kumar ML, Harendra; SR, Sheela

    2014-01-01

    Background: Cervical cancer is the second most common cancer occurring among women worldwide, with almost half a million new cases each year. Normal cells gradually transform to form cancer cells through several stages. So, the changes occurring during the transformational stages need to be assessed. Aim: Our aim was to study various nuclear parameters useful in evaluating pre-malignant and malignant cervico-vaginal pap smears. Materials and Methods: Bethesda System was used to categorize cervical pap smears into premalignant and malignant lesions. Nuclear parameters were calculated using J 1.44C morphometric software. Several nuclear size parameters were analysed. Results: The nuclear area, perimeter, diameter were found to be statistically significant (p<0.05) parameters in differentiating premalignant from malignant cervical smears. Conclusion: Nuclear morphometry was thus a useful objective tool in differentiating premalignant from malignant cervical smears. PMID:25584229

  10. Targeting Premalignant Lesions: Implications for Early Breast Cancer Detection and Intervention

    DTIC Science & Technology

    2016-04-01

    1 AWARD NUMBER: W81XWH-14-1-0032 TITLE: Targeting Premalignant Lesions: Implications for Early Breast Cancer Detection and Intervention...ABSTRACT Breast cancer progression constitutes a multistep process through a series of intermediate hyperplastic and neoplastic stages to invasive...Considerable numbers of CAFs are frequently observed within the tumor- associated stroma of various human cancers , including those of the breast

  11. Recurrent acute thermal lesion induces esophageal hyperproliferative premalignant lesions in mice esophagus.

    PubMed

    Rapozo, D C M; Blanco, T C M; Reis, B B; Gonzaga, I M; Valverde, P; Canetti, C; Barja-Fidalgo, C; Simao, T A; Albano, R M; Kruel, C D P; Pinto, L F Ribeiro

    2016-04-01

    Hot beverage consumption is a risk factor for esophageal squamous cell carcinoma, but the underlying mechanisms are still unknown. We developed an experimental mouse model to understand the mechanism of thermal lesion to esophageal carcinogenesis. Female BALB/c mice were treated by gavage with water at different temperatures three times a week and nitrosamines in the drinking water. Water at 70°C, but not at lower temperatures, initially induced an esophageal necrosis that healed and became resistant to necrosis after further administrations. However, when 70°C water was associated with N-nitrosodiethylamine at doses above 1 ppm, there was interference in epithelial regeneration, allowing recurrent thermal injury and inflammation. Recurrent thermal injury resulted in hyper proliferative premalignant lesions being induced earlier (at 4 weeks) and at a higher frequency (4-fold increase at 16 weeks) when compared to mice treated with NDEA only. Ki-67 immunostaining revealed that recurrent thermal injury induced basal cell proliferation resulting in the expansion of epithelial basal cells, confirmed by the increase in cytokeratin 14 positive cells with concomitant reduction of differentiated cytokeratin 5 positive cells. We conclude that recurrent thermal lesion may act as a tumor promoter though a strong proliferation stimulus of esophageal epithelial basal cells. Copyright © 2016. Published by Elsevier Inc.

  12. Premalignant and Malignant Skin Lesions in Two Recipients of Vascularized Composite Tissue Allografts (Face, Hands)

    PubMed Central

    Kanitakis, Jean; Petruzzo, Palmina; Gazarian, Aram; Testelin, Sylvie; Devauchelle, Bernard; Badet, Lionel; Dubernard, Jean-Michel; Morelon, Emmanuel

    2015-01-01

    Recipients of solid organ transplants (RSOT) have a highly increased risk for developing cutaneous premalignant and malignant lesions, favored by the lifelong immunosuppression. Vascularized composite tissue allografts (VCA) have been introduced recently, and relevant data are sparse. Two patients with skin cancers (one with basal cell carcinoma and one with squamous cell carcinomas) have been so far reported in this patient group. Since 2000 we have been following 9 recipients of VCA (3 face, 6 bilateral hands) for the development of rejection and complications of the immunosuppressive treatment. Among the 9 patients, one face-grafted recipient was diagnosed with nodular-pigmented basal cell carcinoma of her own facial skin 6 years after graft, and one patient with double hand allografts developed disseminated superficial actinic porokeratosis, a potentially premalignant dermatosis, on her skin of the arm and legs. Similar to RSOT, recipients of VCA are prone to develop cutaneous premalignant and malignant lesions. Prevention should be applied through sun-protective measures, regular skin examination, and early treatment of premalignant lesions. PMID:26550517

  13. Apoptotic Index and Proliferative Index in Premalignant and Malignant Squamous Cell Lesions of the Oral Cavity

    PubMed Central

    Viswanathan, Vidya; Juluri, Ravichandra; Goel, Seema; Madan, Jyotsna; Mitra, Subir K; Gopalakrishnan, Dharmarajan

    2015-01-01

    Background: Oral squamous cell lesions are most commonly diagnosed lesions in India. Both premalignant and malignant lesions are frequently encountered. In this study, we evaluated the role and significance of apoptotic indices (AI) and proliferative indices (PI) in premalignant and malignant squamous cell lesions of the oral cavity. Materials and Methods: A total of 62 histologically proven cases of premalignant and malignant oral squamous cell lesions were analyzed. The biopsies were stained with hematoxylin and eosin and also with monoclonal antibody Ki-67. AI and PI were assessed using a light microscope. Results: AI was found to increase gradually from normal to dysplasia to carcinoma. The highest AI was seen in well-differentiated squamous cell carcinomas (SCCs). PI also was found to increase significantly from normal to dysplasia to carcinoma. The highest PI was seen in poorly differentiated SCC. Conclusion: AI in conjunction with the PI offers an accurate idea as to the nature and course of the lesion and may help to plan timely surgical intervention that results in better clinical prognosis and outcome. PMID:25709366

  14. PCNA--a cell proliferation marker in vocal chord cancer. Part I: Premalignant laryngeal lesions.

    PubMed

    Pignataro, L D; Broich, G; Lavezzi, A M; Biondo, B; Ottaviani, F

    1995-01-01

    Laryngeal hyperkeratotic lesions can progress to fully developed malignant carcinoma in some cases. These premalignant lesions are proliferative disorders whose potential for further tumour progression is perhaps difficult to assess by mere histology. Immunostaining with PCNA, a protein correlated with cell proliferation, has been used to study tissue behavior in 30 cases of premalignant laryngeal vocal chord lesions treated by epithelial stripping in microlaryngoscopy, 15 of whom had no progression and 15 had recurrence and final development of full malignancy. The results showed a statistically significantly higher PCNA-index in the cases which underwent further tumour progression towards malignancy. PCNA testing may thus be suggested as a marker for tumour progression potential and help in determining clinical treatment choices.

  15. Surgical management of premalignant lesions of the oral cavity with the CO2 laser.

    PubMed

    Pinheiro, A L; Frame, J W

    1996-01-01

    The management of patients with premalignant and malignant lesions of the oral cavity can present problems. The potentially invasive nature of premalignant lesions together with their large extent influences the treatment. The common modalities of treatment of these lesions are surgical excision, cryotherapy, electrosurgery and radiotherapy. Recently, CO2 laser surgery has become available. Less pain, little bleeding, minimal post-operative edema, reduced risk of infection, and low recurrence rates were advantages observed following CO2 laser surgery in the mouth when compared to other modalities of treatment. Healing following CO2 laser surgery progressed well with little postoperative scarring and re-epithelialization was complete after 4-6 weeks. The newly formed epithelium appeared normal and was soft on palpation.

  16. Flow Cytometric Ploidy Determination of Oral Premalignant and Malignant Lesions

    DTIC Science & Technology

    1990-01-01

    aneuploid superficially invasive carcinoma from case 8B . . . . . . . . . 54 FIGURE 14 Light microscopic appearance of the aneuploid verrucous carcinoma...from case 15 . . . . . . . . . . . . . . . . . 54 FIGURE 15 Light microscopic appearance of the verrucous carcinoma exhibiting a high S phase...presence of erythroplakia as a component of the lesion, a clinical verrucous -papillary pattern, and long duration of the lesion. In other longitudinal

  17. Benign, Premalignant, and Malignant Lesions Encountered in Bariatric Surgery

    PubMed Central

    Kini

    2012-01-01

    Background: Obesity is associated with several comorbidities like diabetes, hypertension, hyperlipidemia, and obstructive sleep apnea. It is also well established that obese patients have an increased risk of several types of cancer like kidney, pancreas, endometrial, breast, and others. The bariatric surgeon needs to be aware of the problem of benign tumors and cancer in obese patients as well as the optimal management of these conditions that may be present at the time of evaluation for bariatric surgery, during the surgical procedure, and in the postoperative period. Database: A PubMed search for the words “cancer” and “bariatric surgery” and subsequent review of the abstracts identified 40 articles concerning cancerous, benign, and premalignant conditions in bariatric surgery patients. Data were then extracted from full-text articles. Conclusion: Bariatric surgery decreases cancer risk especially in women. RYGB can be an effective treatment for Barrett's esophagus. Patients having esophageal cancer should not undergo bariatric surgery, while those who develop the same postoperatively are usually managed by a combined abdominal and thoracic approach (Ivor Lewis technique). Gastric cancer of the remnant stomach is usually managed by a remnant gastrectomy. A remnant gastrectomy during RYGB would be necessary in conditions that require endoscopic surveillance of the stomach like gastric polyps, intestinal metaplasia, and carcinoid tumors. Sleeve gastrectomy is an excellent option in a patient with GIST or a carcinoid who needs a bariatric operation. Preoperative endoscopy usually does not detect malignant conditions. Postoperative evaluation of the bypassed stomach is possible using various percutaneous and novel endoscopic techniques. PMID:23318060

  18. Premalignant and malignant lesions in endometrial polyps in patients undergoing hysteroscopic polypectomy

    PubMed Central

    Lenci, Marco Antonio; do Nascimento, Vanessa Alessandra Lui; Grandini, Ana Beatriz; Fahmy, Walid Makin; Depes, Daniella de Batista; Baracat, Fausto Farah; Lopes, Reginaldo Guedes Coelho

    2014-01-01

    ABSTRACT Objective: To evaluate the incidence of premalignant lesions and cancer in endometrial polyps, in patients undergoing hysteroscopic polypectomy. Methods: The results of 1,020 pathological examinations of patients submitted to hysteroscopic polypectomy were analyzed, as well as their diagnostic and surgical hysteroscopy findings. As to their menstrual status, 295 (28.9%) patients were in menacme. Of the total, 193 (65.4%) presented abnormal uterine bleeding, and 102 (34.6%) were asymptomatic with altered endometrial echo on transvaginal ultrasound. Out of 725 (71.1%) postmenopausal patients, 171 (23.6%) were symptomatic (abnormal uterine bleeding), and 554 (76.4%) were asymptomatic with endometrial echo >5.0mm. Results: Twenty-one (2.0%) patients presented premalignant lesions in the polyps, 13 had simple glandular hyperplasia, of which 5 had no atypia, and eight presented atypia. Eight polyps presented focal area of complex hyperplasia: 4 with atypia and 4 without lesions. Cancer was diagnosed in 5 (0.5%) polyps. Of the 21 polyps that harbored premalignant lesions, 12 were interpreted as benign in diagnostic and surgical hysteroscopy. Of the polyps with cancer, 4 were also histeroscopically interpreted as normal. Conclusion: Symptomatic polyps in menacme and in all postmenopausal women should be resected and submitted to histopathological examination, since they may have a benign aspect, even when harboring areas of cellular atypia or cancer. PMID:24728240

  19. [Recommendations for the diagnosis, staging and treatment of pre-malignant lesions and pancreatic adenocarcinoma].

    PubMed

    Martin-Richard, Marta; Ginès, Angels; Ayuso, Juan Ramón; Sabater, Luis; Fabregat, Joan; Mendez, Ramiro; Fernández-Esparrach, Glòria; Molero, Xavier; Vaquero, Eva C; Cuatrecasas, Miriam; Ferrández, Antonio; Maurel, Joan

    2016-11-18

    Clinical management of adenocarcinoma of the pancreas is complex, and requires a multidisciplinary approach. The same applies for the premalignant lesions that are increasingly being diagnosed. The current document is an update on the diagnosis and management of premalignant lesions and adenocarcinoma of the pancreas. A conference to establish the basis of the literature review and manuscript redaction was organized by the Grupo Español Multidisciplinar en Cáncer Digestivo. Experts in the field from different specialties (Gastroenterology, Surgery, Radiology, Pathology, Medical Oncology and Radiation Oncology) met to prepare the present document. The current literature was reviewed and discussed, with subsequent deliberation on the evidence. Final recommendations were established in view of all the above. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  20. Anatomic Site Based Ploidy Analysis of Oral Premalignant Lesions

    PubMed Central

    Islam, M. N.; Kornberg, L.; Veenker, E.; Cohen, D. M.

    2009-01-01

    The location of oral leukoplakia correlates strongly with the probability of finding dysplastic or malignant alterations at biopsy. It is well established that early detection can dramatically improve the 5-year survival rates for oral squamous cell carcinomas. Since aneuploidy is predictive of future conversion to malignancy, we hypothesized that dysplastic lesions from high-risk sites (floor of mouth, tongue and lips) would exhibit greater aneuploidy than low-risk sites (palate, gingiva and buccal mucosa). Epithelial sections from 60 archival samples diagnosed as mild dysplasia (36 females, 20 males) from various high/low risk locations were stained with Blue Feulgen Stain for DNA Ploidy Analysis (Clarient, Aliso Viejo, CA) and ploidy was analyzed using a ChromaVision ACIS II (Clarient, ALiso Viejo, CA) Image cytometry system. A DNA histogram was generated using an image analyzing software that evaluated the amount of Feulgen stain which is proportional to the amount of nuclear DNA. An ANOVA analysis followed by the Student’s‘t’ test revealed significant differences between means (P ≤ 0.05). Lesions originating from lateral/ventral tongue (85%), floor of mouth (50%) and soft palate (44%) exhibited a higher frequency of aneuploidy than lesions from gingiva (22%) and lower lip (25%). This pilot study demonstrates that dysplastic lesions from high-risk sites such as the floor of the mouth and lateral/ventral tongue have higher frequency of aneuploidy. PMID:20237983

  1. Optical detection of (pre-)malignant lesions of the oral mucosa: autofluorescence characteristics of healthy mucosa

    NASA Astrophysics Data System (ADS)

    de Veld, Diana C. G.; Witjes, Max; Roodenburg, Jan L.; Star, Willem M.; Sterenborg, Hericus J. C. M.

    2001-10-01

    Previous clinical results demonstrate the potential of in vivo autofluorescence spectroscopy for early detection of (pre-)malignant lesions of the oral mucosa. For reliable diagnosis, it is necessary to study autofluorescence spectra of healthy mucosa first. We measured excitation-emission maps in healthy subjects and subjects with a history of cancer in the head -neck region. Our results show that different anatomical locations produce distinct autofluorescence spectra. Influences of, among others, smoking and drinking habits require further investigation.

  2. Chemoprevention of premalignant and malignant lesions of oral cavity: Recent trends

    PubMed Central

    Bodhade, Ashish S.; Dive, Alka M.

    2013-01-01

    The word chemoprevention includes prevention of initiation, promotion, and progression of carcinogenesis to cancer. This article is an attempt to review the dietary chemopreventive agents and their mode of action in chemoprevention of oral premalignant lesions and oral cancer using a systematic approach. Selected chemoprevention trials are discussed with a focus on strategies of trial design and clinical outcome. Future in the field of chemoprevention will be more promising than the recently available therapeutic alternatives. PMID:24883036

  3. Standard examination and adjunctive techniques for detection of oral premalignant and malignant lesions.

    PubMed

    Kerr, A Ross; Shah, Sonal S

    2013-05-01

    This article outlines how to perform a standard comprehensive extraoral and intraoral examination and the existing commercially available adjunctive techniques for the early detection of oral cancer and premalignant lesions. Visualization-based techniques (e.g., autofluorescence and chemiluminescence), toluidine blue vital staining, cytopathologic tests and high-risk human papillomavirus testing are discussed in detail, including the indications and protocols for use, their advantages and disadvantages and clinical cases.

  4. Facts and fiction: premalignant lesions of lung tissues.

    PubMed

    Klebe, S; Henderson, D W

    2013-04-01

    Lung cancer is now the leading cause of death from cancer in Australia. Most patients are diagnosed with late-stage disease. Although diagnosis at pre-invasive stages could theoretically improve outcomes, mooted precursor lesions are often asymptomatic and often undetectable by non-invasive investigations. Nonetheless, they merit study to identify early and essential molecular steps involved in lung carcinoma pathogenesis, with the aim of developing therapies targeted against one or more such steps. Some lung cancers appear to develop via a series of progressive morphological changes with correlating molecular alterations, but others seem to arise in histologically normal epithelium, and these differences may reflect anatomically and functionally distinct epithelial compartments of the respiratory tract. Pre-invasive precursor lesions recognised by the World Health Organization (WHO) include squamous metaplasia with dysplasia and carcinoma in situ, atypical adenomatous hyperplasia, and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Other lesions that likely represent pre-invasive lesions, but which are not currently WHO-listed, include human papillomavirus (HPV)-related respiratory papillomatosis and mesothelioma in situ. No single cancer stem cell marker has been identified. Field cancerisation plays an important role in lung cancer development, and includes the spread of pre-invasive clones along the respiratory epithelium or the occurrence of multiple separate foci of pre-invasive abnormalities such as squamous dysplasia and carcinoma in situ.In addition to well-characterised step-wise progression in squamous cell carcinomas and some adenocarcinomas, alternative pathways exist, and are currently being investigated. In addition, molecular techniques, including miRNA screening on blood samples or cytology samples--such as sputum samples--may become clinically relevant and more accurate in predicting lung cancer progression.

  5. The antigenic repertoire of premalignant and high-risk lesions.

    PubMed

    Marquez, Juan Pablo; Stanton, Sasha E; Disis, Mary L

    2015-04-01

    Prophylactic vaccines have been a major advance in preventing the development of infections after exposure to pathogens. When contemplating an effective approach to cancer prevention, vaccines offer unique advantages over other more standard approaches: First, once appropriately stimulated, antigen-specific T cells will travel to all sites of disease and eradicate cells bearing the proteins to which the T cells have been primed by vaccination. Second, successful immunization will further result in the development of immunologic memory, providing lifelong immunologic surveillance. There is evidence of an adaptive tumor immune infiltrate even at the earliest stages of breast and colon cancer development. Furthermore, there is measurable immunity to lesion-associated antigens present in patients who will eventually develop malignancy even before cancer is clinically evident. Recent studies are beginning to unmask the preinvasive antigenic repertoire for these two malignancies. Preliminary experiments in transgenic mouse models of mammary and intestinal tumors suggest that immunization against antigens expressed in preinvasive and high-risk lesions may be effective in preventing the development of invasive malignancy.

  6. Association of AS3MT polymorphisms and the risk of premalignant arsenic skin lesions

    SciTech Connect

    Valenzuela, Olga L.; Drobna, Zuzana; Hernandez-Castellanos, Erika; Sanchez-Pena, Luz C.; Garcia-Vargas, Gonzalo G.; Borja-Aburto, Victor H.; Styblo, Miroslav; Del Razo, Luz M.

    2009-09-01

    Exposure to naturally occurring inorganic arsenic (iAs), primarily from contaminated drinking water, is considered one of the top environmental health threats worldwide. Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the biotransformation pathway of iAs. AS3MT catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to trivalent arsenicals, resulting in the production of methylated (MAs) and dimethylated arsenicals (DMAs). MAs is a susceptibility factor for iAs-induced toxicity. In this study, we evaluated the association of the polymorphism in AS3MT gene with iAs metabolism and with the presence of arsenic (As) premalignant skin lesions. This is a case-control study of 71 cases with skin lesions and 51 controls without skin lesions recruited from a iAs endemic area in Mexico. We measured urinary As metabolites, differentiating the trivalent and pentavalent arsenical species, using the hydride generation atomic absorption spectrometry. In addition, the study subjects were genotyped to analyze three single nucleotide polymorphisms (SNPs), A-477G, T14458C (nonsynonymus SNP; Met287Thr), and T35587C, in the AS3MT gene. We compared the frequencies of the AS3MT alleles, genotypes, and haplotypes in individuals with and without skin lesions. Marginal differences in the frequencies of the Met287Thr genotype were identified between individuals with and without premalignant skin lesions (p = 0.055): individuals carrying the C (TC+CC) allele (Thr) were at risk [odds ratio = 4.28; 95% confidence interval (1.0-18.5)]. Also, individuals with C allele of Met287Thr displayed greater percentage of MAs in urine and decrease in the percentage of DMAs. These findings indicate that Met287Thr influences the susceptibility to premalignant As skin lesions and might be at increased risk for other adverse health effects of iAs exposure.

  7. Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD-1 antibodies.

    PubMed

    Levingston, Corinne A; Young, M Rita I

    2017-04-01

    A carcinogen-induced premalignant oral lesion model that progresses to oral cancer was used to examine the impact of blocking PD-1 on cytokine expression and on progression of lesions to cancer. The results of this study show increased production of IL-2 and the inflammatory cytokines IL-6, IL-17 and TNF-α by spleen cells of lesion-bearing mice that were treated with PD-1 antibody for 1 week compared to cytokine production by spleen cells of lesion-bearing mice treated with control antibody. Production of IFN-γ increased at 3 weeks of PD-1 antibody treatment, although production of the other Th1 and inflammatory mediators declined. By 5 weeks, levels of these cytokines declined for both control and PD-1 antibody-treated mice. Flow cytometric analysis for IFN-γ-expressing cells showed shifts in CD4(+) cells expressing IFN-γ consistent with the changes in cytokine secretion. Whether or not treatment generated reactivity to lesions or HNSCC was determined. Spleen cells from PD-1 antibody-treated mice were stimulated by lysates of premalignant lesion and HNSCC tongue tissues to produce increased levels of Th1 and select inflammatory cytokines early in the course of PD-1 antibody treatment. However, with continued treatment, reactivity to lesion and HNSCC lysates declined. Analysis of clinical response to treatment suggested an early delay in lesion progression but, with continued treatment, lesions in PD-1 antibody-treated mice progressed to the same degree as in control antibody-treated mice. Overall, these results show an early beneficial response to PD-1 antibody treatment, which then fails with continued treatment and lesion progression.

  8. Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD‐1 antibodies

    PubMed Central

    Levingston, Corinne A.

    2017-01-01

    A carcinogen‐induced premalignant oral lesion model that progresses to oral cancer was used to examine the impact of blocking PD‐1 on cytokine expression and on progression of lesions to cancer. The results of this study show increased production of IL‐2 and the inflammatory cytokines IL‐6, IL‐17 and TNF‐α by spleen cells of lesion‐bearing mice that were treated with PD‐1 antibody for 1 week compared to cytokine production by spleen cells of lesion‐bearing mice treated with control antibody. Production of IFN‐γ increased at 3 weeks of PD‐1 antibody treatment, although production of the other Th1 and inflammatory mediators declined. By 5 weeks, levels of these cytokines declined for both control and PD‐1 antibody‐treated mice. Flow cytometric analysis for IFN‐γ‐expressing cells showed shifts in CD4+ cells expressing IFN‐γ consistent with the changes in cytokine secretion. Whether or not treatment generated reactivity to lesions or HNSCC was determined. Spleen cells from PD‐1 antibody‐treated mice were stimulated by lysates of premalignant lesion and HNSCC tongue tissues to produce increased levels of Th1 and select inflammatory cytokines early in the course of PD‐1 antibody treatment. However, with continued treatment, reactivity to lesion and HNSCC lysates declined. Analysis of clinical response to treatment suggested an early delay in lesion progression but, with continued treatment, lesions in PD‐1 antibody‐treated mice progressed to the same degree as in control antibody‐treated mice. Overall, these results show an early beneficial response to PD‐1 antibody treatment, which then fails with continued treatment and lesion progression. PMID:27914100

  9. Vitamin D Repletion Reduces the Progression of Premalignant Squamous Lesions in the NTCU Lung Squamous Cell Carcinoma Mouse Model

    PubMed Central

    Mazzilli, Sarah A.; Hershberger, Pamela A.; Reid, Mary E.; Bogner, Paul N.; Atwood, Kristopher; Trump, Donald L.; Johnson, Candace S.

    2015-01-01

    The chemopreventive actions of vitamin D were examined in the N-nitroso-tris-chloroethylurea (NTCU) mouse model, a progressive model of lung squamous cell carcinoma (SCC). SWR/J mice were fed a deficient diet (D) containing no vitamin D3, a sufficient diet (S) containing 2000 IU/kg vitamin D3, or the same diets in combination with the active metabolite of vitamin D, calcitriol (C) (80 μg/kg, weekly). The percentage (%) of the mucosal surface of large airways occupied by dysplastic lesions was determined in mice after treatment with a total dose of 15 or 25 μmol NTCU (N). After treatment with 15 μmol NTCU, the % of the surface of large airways containing high-grade dysplastic (HGD) lesions were vitamin D-deficient +NTCU (DN), 22.7 % (p<0.05 compared to vitamin D-sufficient +NTCU (SN)); DN + C, 12.3%; SN, 8.7%; and SN + C, 6.6%. The extent of HGD increased with NTCU dose in the DN group. Proliferation, assessed by Ki-67 labeling, increased upon NTCU treatment. The highest Ki-67 labeling index was seen in the DN group. As compared to SN mice, DN mice exhibited a 3-fold increase (p <0.005) in circulating white blood cells (WBC), a 20% (p <0.05) increase in IL-6 levels, and a 4 -fold (p <0.005) increase in WBC in bronchial lavages. Thus, vitamin D repletion reduces the progression of premalignant lesions, proliferation, and inflammation, and may thereby suppress development of lung SCC. Further investigations of the chemopreventive effects of vitamin D in lung SCC are warranted. PMID:26276745

  10. Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice

    PubMed Central

    Fukuta, Kazufumi; Shirakami, Yohei; Maruta, Akinori; Obara, Koki; Iritani, Soichi; Nakamura, Nobuhiko; Kochi, Takahiro; Kubota, Masaya; Sakai, Hiroyasu; Tanaka, Takuji; Shimizu, Masahito

    2017-01-01

    Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks. At the time of sacrifice, PTX administration markedly suppressed the development of premalignant lesions in the colorectum. The levels of oxidative stress markers were significantly decreased in the PTX-treated group compared with those in the untreated control group. In PTX-administered mice, the mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-6, and TNF-α, and the number of proliferating cell nuclear antigen (PCNA)-positive cells in the colonic mucosa, were significantly reduced. These observations suggest that PTX attenuated chronic inflammation and oxidative stress, and prevented the development of colonic tumorigenesis in an obesity-related colon cancer model. PMID:28212276

  11. Progress and Opportunities in Molecular Pathological Epidemiology of Colorectal Premalignant Lesions

    PubMed Central

    Lochhead, Paul; Chan, Andrew T.; Giovannucci, Edward; Fuchs, Charles S.; Wu, Kana; Nishihara, Reiko; O’Brien, Michael; Ogino, Shuji

    2014-01-01

    Molecular pathological epidemiology (MPE) is integrative molecular and population health science to address molecular pathogenesis and heterogeneity of disease processes. MPE of colon and rectal premalignant lesions (including hyperplastic polyps, tubular adenomas, tubulovillous adenomas, villous adenomas, traditional serrated adenomas, sessile serrated adenomas / sessile serrated polyps, and hamartomatous polyps) can provide unique opportunities to examine the influence of diet, lifestyle and environmental exposures on specific pathways of carcinogenesis. Colorectal neoplasia can provide a practical model where both malignant epithelial tumor (carcinoma), and its precursor, are subjected to molecular pathology analyses. KRAS, BRAF, and PIK3CA oncogene mutations, microsatellite instability, CpG island methylator phenotype, and LINE-1 methylation are commonly-examined tumor biomarkers. Future opportunities include comprehensive interrogation of genomics, epigenomics and pan-omics, as well as in vivo pathology analyses of tissue microenvironment, molecular networks and interactome by endomicroscopy. Considering the colorectal continuum hypothesis and emerging roles of gut microbiota and host immunity in tumorigenesis, detailed tumor location is important information. There are unique strengths and caveats, especially with regard to case ascertainment by colonoscopy. MPE of colorectal premalignant lesions can identify etiologic exposures associated with neoplastic initiation and progression, help us better understand colorectal carcinogenesis, and facilitate personalized prevention, screening, and therapy. PMID:24935274

  12. Does uterine prolapse alter endometrial cyclooxygenase 2 expression and promote the development of premalignant lesions?

    PubMed

    Genc, Mine; Sivrikoz, Oya Nermin; Sahin, Nur; Celik, Esin; Turan, Guluzar Arzu; Guclu, Serkan

    2015-01-01

    The aim of this study was to evaluate the expression of cyclooxygenase 2 (COX-2) and its association with the development of premalignant lesions in gland structures of the endometrium in patients with uterine prolapse, a condition which exposes the uterus to mechanical and infectious stress. The study included 102 patients who underwent hysterectomy to correct grade 3-4 uterine prolapse and 105 patients who underwent hysterectomy for other causes. Endometrial gland structures underwent immunohistochemical staining and COX-2 expression was graded. Grades 0 and 1 represent low expression; grades 2 and 3 correspond to high levels of COX-2 expression. The prevalence of grade 2-3 COX-2 expression was significantly higher in the endometrial gland structures of patients with prolapse and hyperplasia compared to the remaining patients (p = 0.014). Grade 0-1 COX-2 expression was significantly more common in the endometrial gland structures of patients without uterine prolapse or hyperplasia (p = 0.004). Among the patients without endometrial hyperplasia, COX-2 expression was elevated in the endometrial gland structures of those with uterine prolapse compared to those without prolapse. Elevated COX-2 expression may explain the presence of unexpected premalignant lesions of the endometrium in patients with uterine prolapse. © 2015 S. Karger AG, Basel.

  13. Cyclooxygenase-2 Expression in Helicobacter pylori-Associated Premalignant and Malignant Gastric Lesions

    PubMed Central

    Sung, Joseph J. Y.; Leung, Wai K.; Go, Minnie Y. Y.; To, Ka F.; Cheng, Alfred S. L.; Ng, Enders K. W.; Chan, Francis K. L.

    2000-01-01

    Expression of cyclooxygenase-2 (COX-2) in various stages of the Helicobacter pylori-associated gastric carcinogenesis pathway has not been elucidated. We investigated the distribution and intensity of COX-2 expression in premalignant and malignant gastric lesions, and monitored the changes after H. pylori eradication. Gastric biopsies from H. pylori-infected patients with chronic active gastritis, gastric atrophy, intestinal metaplasia (IM), gastric adenocarcinoma, and noninfected controls were studied. Expression of COX-2 was evaluated by immunohistochemistry and in situ hybridization. Endoscopic biopsies were repeated 1 year after successful eradication of H. pylori in a group of IM patients for comparing COX-2 expression and progression of IM. In all H. pylori-infected patients, COX-2 expression was predominantly found in the foveolar and glandular epithelium and, to a lesser extent, in the lamina propria. In the noninfected group, only 35% of cases demonstrated weak COX-2 expression. Intensity of COX-2 was not significantly different between the chronic active gastritis, gastric atrophy, IM, and gastric adenocarcinoma groups. In 17 patients with IM, COX-2 expressions in the epithelial cells and stromal cells were reduced 1 year after H. pylori eradication. However, the changes in COX-2 expression did not correlate with progression/regression of IM. Both premalignant and malignant gastric lesions demonstrate strong COX-2 expression. Successful eradication of H. pylori leads to down-regulation of COX-2 expression but failed to reverse IM at 1 year. PMID:10980112

  14. Discrimination of premalignant lesions and cancer tissues from normal gastric tissues using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Luo, Shuwen; Chen, Changshui; Mao, Hua; Jin, Shaoqin

    2013-06-01

    The feasibility of early detection of gastric cancer using near-infrared (NIR) Raman spectroscopy (RS) by distinguishing premalignant lesions (adenomatous polyp, n=27) and cancer tissues (adenocarcinoma, n=33) from normal gastric tissues (n=45) is evaluated. Significant differences in Raman spectra are observed among the normal, adenomatous polyp, and adenocarcinoma gastric tissues at 936, 1003, 1032, 1174, 1208, 1323, 1335, 1450, and 1655 cm-1. Diverse statistical methods are employed to develop effective diagnostic algorithms for classifying the Raman spectra of different types of ex vivo gastric tissues, including principal component analysis (PCA), linear discriminant analysis (LDA), and naive Bayesian classifier (NBC) techniques. Compared with PCA-LDA algorithms, PCA-NBC techniques together with leave-one-out, cross-validation method provide better discriminative results of normal, adenomatous polyp, and adenocarcinoma gastric tissues, resulting in superior sensitivities of 96.3%, 96.9%, and 96.9%, and specificities of 93%, 100%, and 95.2%, respectively. Therefore, NIR RS associated with multivariate statistical algorithms has the potential for early diagnosis of gastric premalignant lesions and cancer tissues in molecular level.

  15. Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

    PubMed

    Arista-Nasr, J; Trolle-Silva, A; Aguilar-Ayala, E; Martínez-Benítez, B

    2016-01-01

    In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions

    PubMed Central

    Mehrotra, Ravi; Gupta, Anurag; Singh, Mamta; Ibrahim, Rahela

    2006-01-01

    Early detection of a premalignant or cancerous oral lesion promises to improve the survival and the morbidity of patients suffering from these conditions. Cytological study of oral cells is a non-aggressive technique that is well accepted by the patient, and is therefore an attractive option for the early diagnosis of oral cancer, including epithelial atypia and squamous cell carcinoma. However its usage has been limited so far due to poor sensitivity and specificity in diagnosing oral malignancies. Lately it has re-emerged due to improved methods and it's application in oral precancer and cancer as a diagnostic and predictive method as well as for monitoring patients. Newer diagnostic techniques such as "brush biopsy" and molecular studies have been developed. Recent advances in cytological techniques and novel aspects of applications of scraped or exfoliative cytology for detecting these lesions and predicting their progression or recurrence are reviewed here. PMID:16556320

  17. Application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions.

    PubMed

    Mehrotra, Ravi; Gupta, Anurag; Singh, Mamta; Ibrahim, Rahela

    2006-03-23

    Early detection of a premalignant or cancerous oral lesion promises to improve the survival and the morbidity of patients suffering from these conditions. Cytological study of oral cells is a non-aggressive technique that is well accepted by the patient, and is therefore an attractive option for the early diagnosis of oral cancer, including epithelial atypia and squamous cell carcinoma. However its usage has been limited so far due to poor sensitivity and specificity in diagnosing oral malignancies. Lately it has re-emerged due to improved methods and it's application in oral precancer and cancer as a diagnostic and predictive method as well as for monitoring patients. Newer diagnostic techniques such as "brush biopsy" and molecular studies have been developed. Recent advances in cytological techniques and novel aspects of applications of scraped or exfoliative cytology for detecting these lesions and predicting their progression or recurrence are reviewed here.

  18. Role of the Chinese Herbal Medicine Xianhuayin on the Reversal of Premalignant Mucosal Lesions in the Golden Hamster Buccal Pouch

    PubMed Central

    Xu, Yan-zhi; Qiu, Yong-le; An, Zhi-guang; Yang, Feng-ying

    2010-01-01

    Aim To investigate the role of the Chinese herbal medicine Xianhuayin on the reversal of 7,12-dimethylbenz[a]anthracene (DMBA)-induced premalignant mucosal lesions in the oral buccal pouch of golden hamsters. Methodology The animals were randomly divided into a non-diseased control group (n=5) and an experimental group including 50 animals in which the buccal mucosa had been painted with DMBA (0.5% in acetone) to generate an oral mucosa premalignant lesion. Animals in the experimental group were further divided into Xianhuayin-treated group (n=30), untreated premalignant lesion group (n=10) and normal saline (NS)-treated group (n=10). The cheek (buccal) pouch mucosa of the golden hamsters in each group was observed with light and electron microscopy eight weeks after intragastric administration with NS or Xianhuayin. Results In the non-diseased control group, the buccal mucosa was keratinized and stratified squamous epithelium under a light microscope. In the untreated premalignant lesion group, variable degrees of epithelial dysplasia was observed. The irregular epithelial mucosa gradually became distinct in the Xianhuayin-treated group. Scanning electronic microscopic (SEM) analysis showed that surface of the cells exhibited honeycomb structures in the hamster of untreated-group. The cells were morphologically irregular, overlapped and loosened in the untreated premalignant lesion group. Most of the cell surface exhibited honeycomb structure in the Xianhuayin-treated group. Transmission electronic microscopic (TEM) analysis showed that buccal mucosal epithelial cells were morphologically regular in the non-diseased control group. Desmosomes and tonofibrils were reduced and the nucleus was morphologically irregular in the untreated premalignant lesion group. In the Xianhuayin-treated group, the widening intercellular gap was gradually reduced, desmosomes and the cells becoming morphologically regular. No significant difference was observed between the hamsters in

  19. Photodynamic detection in visualisation of cutaneous and oral mucosa premalignant and malignant lesions: two clinical cases

    NASA Astrophysics Data System (ADS)

    Jurczyszyn, Kamil; Ziólkowski, Piotr; Osiecka, Beata; Gerber, Hanna; Dziedzic, Magdalena

    2008-11-01

    Photodynamic diagnosis (PDD) is promising method of visualisation of premalignant and malignant lesions. PDD is consisted of two main agents: special chemical compound which is called photosensitizer and light. Photosensitizer has affinity to fast proliferating cells such as pre- or malignant. During light irradiation (with proper wavelength - corresponding to absorption peak of photosensitizer) photosensitizer gains energy and passes into excited singlet state S1. Returning to basic singlet state Sn, leads to fluorescence. Due to difference between concentration of photosensitizer in lesion and normal tissue it is possible to obtain high contrast image of lesion. Case #1: 53 years old woman with basal cell carcinoma (BCC) in nasal region; 20% delta-aminolevulinic acid as a precursor of photosensitizer on eucerin base was used. Case #2: 57 years old woman with multifocal oral leukoplakia on cheek mucosa and tongue; 2% chlorophyll gel as photosesitizer was used. All photographs were taken in white light without any filter and in blue and UV light with orange filter: in both cases the total area of the lesions appeared to be larger than it has been clinically observed. Thus, the PDD might be helpful in evaluation of margins of surgical excision of such lesions.

  20. Reports: plasma and dietary phytoestrogens and risk of premalignant lesions of the cervix.

    PubMed

    Hernandez, Brenda Y; McDuffie, Katharine; Franke, Adrian A; Killeen, Jeffrey; Goodman, Marc T

    2004-01-01

    A number of epidemiological studies have observed an inverse association between phytoestrogens and risk of certain hormonally dependent cancers. We undertook an exploratory analysis of the relationship between specific phytoestrogens and premalignant cervical lesions. A case-control study of 122 women with histologically confirmed cervical squamous intraepithelial lesions (SILs) of the cervix and 183 cytologically normal controls was conducted from 1992 to 1996 in Honolulu, Hawaii. A cervical cell sample was obtained for human papillomavirus (HPV) testing. Dietary information was collected using a structured survey, and a fasting blood sample was taken for measurement of five isoflavonoids (genistein, glycitein, daidzein, O-desmethylangolensin, and equol), two flavonoids (hesperetin and naringenin), and two lignans (enterodiol and enterolactone). Plasma levels of equol and enterodiol were positively associated with cervical SIL risk: odds ratio, OR = 6.5; 95% confidence interval, CI = 1.4-29.2; P for trend = 0.02 and OR = 2.7; 95% CI = 1.1-6.3; P for trend = 0.01, respectively, for the highest relative to the lowest quartile level after adjustment for age, race/ethnicity, HPV infection, cigarette smoking, alcohol drinking, and lifetime number of sexual partners. A nonsignificant positive association with cervical SIL risk was observed for plasma enterolactone. Consistent with the relationships observed for the plasma lignans, dietary sources of lignans, including garlic and taro leaves/ong choy/marunggay, were positively associated with cervical SIL risk. A positive association was also suggested for other lignan sources such as seaweed, onions, grapefruit, and seeds. This is the first study to observe a positive association between specific phytoestrogens and premalignancies of the cervix. The results of this investigation should be considered preliminary and need to be verified in larger, prospective studies.

  1. Lectin-functionalized mesoporous silica nanoparticles for endoscopic detection of premalignant colonic lesions.

    PubMed

    Chen, Nai-Tzu; Souris, Jeffrey S; Cheng, Shih-Hsun; Chu, Chia-Hui; Wang, Yu-Chao; Konda, Vani; Dougherty, Urszula; Bissonnette, Marc; Mou, Chung-Yuan; Chen, Chin-Tu; Lo, Leu-Wei

    2017-08-01

    Colorectal cancer (CRC) is one of the leading causes of cancer-deaths worldwide. Methods for the early in situ detection of colorectal adenomatous polyps and their precursors - prior to their malignancy transformation into CRC - are urgently needed. Unfortunately at present, the primary diagnostic method, colonoscopy, can only detect polyps and carcinomas by shape/morphology; with sessile polyps more likely to go unnoticed than polypoid lesions. Here we describe our development of polyp-targeting, fluorescently-labeled mesoporous silica nanoparticles (MSNs) that serve as targeted endoscopic contrast agents for the early detection of colorectal polyps and cancer. In vitro cell studies, ex vivo histopathological analysis, and in vivo colonoscopy and endoscopy of murine colorectal cancer models, demonstrate significant binding specificity of our nanoconstructs to pathological lesions via targeting aberrant α-L-fucose expression. Our findings strongly suggest that lectin-functionalized fluorescent MSNs could serve as a promising endoscopic contrast agent for in situ diagnostic imaging of premalignant colonic lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. A Prospective Study of Blood Selenium Levels and the Risk of Arsenic-related Premalignant Skin Lesions

    PubMed Central

    Chen, Yu; Hall, Marni; Graziano, Joseph H.; Slavkovich, Vesna; van Geen, Alexander; Parvez, Faruque; Ahsan, Habibul

    2007-01-01

    Arsenic exposure from drinking water is considered to be a risk factor for skin and internal cancers. Animal studies suggest a potential antagonism between As and Se in the body. We performed a case-cohort analysis to prospectively evaluate the association between As-related premalignant skin lesions and prediagnostic blood Se levels in 303 cases of skin lesions newly-diagnosed from November 2002 to April 2004 and 849 subcohort members randomly-selected from the 8,092 participants in the Health Effects of As Longitudinal Study with available baseline blood and urine samples collected in 2000. Incidence rate ratios for skin lesions in increasing blood Se quintiles were 1.00 (ref), 0.68 (95% confidence interval (CI): 0.39, 1.18), 0.51 (95% CI: 0.29, 0.87), 0.52 (95% CI: 0.30, 0.91), and 0.53 (95% CI: 0.31, 0.90). Effect estimates remained similar with adjustments for age, sex, BMI, smoking status, excessive sunlight exposure (in men), well water As concentration at baseline, and nutritional intakes of folate, iron, protein, Vitamin E, and B Vitamins. At any given As exposure level, the risk of premalignant skin lesions was consistently greater among participants with blood Se lower than the average level. The findings support the hypothesis that dietary Se intake may reduce the incidence of As-related premalignant skin lesions among populations exposed to As exposure from drinking water. PMID:17301251

  3. Usefulness and Future Prospects of Confocal Laser Endomicroscopy for Gastric Premalignant and Malignant Lesions

    PubMed Central

    Lee, Sang Kil

    2015-01-01

    Confocal laser endomicroscopy (CLE) is a new technology enabling endoscopists to visualize tissue at the cellular level. CLE has the fundamental potential to provide a histologic diagnosis, and may theoretically replace or reduce the need for performing biopsy for histology. The clinical benefits of CLE are more obvious in esophageal disease, including Barrett’s esophagus. Currently, this technology has been adapted to the diagnosis and surveillance of Barrett’s esophagus and related neoplasia. Standard white light endoscopy is the primary tool for gastric cancer screening. Currently, the only method available to precisely diagnose these lesions is upper endoscopy with an appropriate biopsy. A recent study showed that CLE could characterize dysplasia or cancer and identify the risk factors for gastric cancer, such as intestinal metaplasia and the presence of Helicobacter pylori in vivo, although fewer studies on CLE were performed on the stomach than on Barrett’s esophagus and other esophageal diseases. However, the application of CLE to routine clinical endoscopy continues to be refined. This review focused on the usefulness and future prospects of CLE for gastric premalignant and malignant lesions. PMID:26668797

  4. Glucose transporter-1 (GLUT-1) immunoreactivity in benign, premalignant and malignant lesions of the gallbladder.

    PubMed

    Legan, Mateja; Tevžič, Spela; Tolar, Ana; Luzar, Boštjan; Marolt, Vera Ferlan

    2011-03-01

    GLUT-1 is a transmembrane glucose transport protein that allows the facilitated transport of glucose into cells, normally expressed in tissues which depend mainly on glucose metabolism. Enhanced expression of GLUT-1 can also be found in a large spectrum of carcinomas. This study aimed to investigate GLUT-1 expression in gallbladder tissue: from normal tissue samples, hyperplasias, low-grade and high-grade dysplasias to gallbladder carcinomas. In all, 115 archived samples of gallbladder tissue from 68 patients, presented after cholecystectomy, were immunohistochemically stained for GLUT-1. According to the intensity of GLUT-1 immunoreactivity, samples were divided into negative (stained 0-10% of cells stained), positive with weak to moderate (10-50%) and positive with strong (>50%) GLUT-1 expression. The GLUT-1 immunoreactivity of the samples showed a characteristic increase from premalignant lesions to carcinomas. Normal gallbladder tissue samples did not express GLUT-1 (100%). Weak expression was shown only focally in hyperplasias, but to a greater extent with low-grade dysplasias (20%), high-grade dysplasias (40%) and carcinomas (51.8%). Normal gallbladder tissue is GLUT-1 negative. GLUT-1 expression in carcinoma tissue is significantly higher than in dysplastic lesions. Strong GLUT-1 expression indicates 100% specificity for detecting gallbladder carcinomas. Therefore, GLUT-1 is a candidate as a diagnostic as well as a tissue prognostic marker in gallbladder carcinoma patients.

  5. Tumor-associated macrophages in oral premalignant lesions coexpress CD163 and STAT1 in a Th1-dominated microenvironment.

    PubMed

    Mori, Kazumasa; Haraguchi, Shigeki; Hiori, Miki; Shimada, Jun; Ohmori, Yoshihiro

    2015-08-05

    Tumor-associated macrophages (TAMs) are implicated in the growth, invasion and metastasis of various solid tumors. However, the phenotype of TAMs in premalignant lesions of solid tumors has not been clarified. In the present study, we identify the phenotype of TAMs in leukoplakia, an oral premalignant lesion, by immunohistochemical analysis and investigate the involvement of infiltrated T cells that participate in the polarization of TAMs. The subjects included 30 patients with oral leukoplakia and 10 individuals with normal mucosa. Hematoxylin and eosin slides were examined for the histological grades, and immunohistochemical analysis was carried out using antibodies against CD68 (pan-MΦ), CD80 (M1 MΦ), CD163 (M2 MΦ), CD4 (helper T cells: Th), CD8 (cytotoxic T cells), CXCR3, CCR5 (Th1), CCR4 (Th2), signal transducer and activator of transcription (STAT1), phosphorylated STAT1 (pSTAT1) and chemokine CXCL9. The differences in the numbers of positively stained cells among the different histological grades were tested for statistical significance using the Kruskal-Wallis test. Correlations between different types of immune cells were determined using Spearman's rank analysis. An increase in the rate of CD163(+) TAM infiltration was observed in mild and moderate epithelial dysplasia, which positively correlated with the rate of intraepithelial CD4(+) Th cell infiltration. Although CCR4(+) cells rarely infiltrated, CXCR3(+) and CCR5(+) cells were observed in these lesions. Cells positive for STAT1 and chemokine CXCL9, interferon- (IFN)-induced gene products, and pSTAT1 were also observed in the same lesions. Double immunofluorescence staining demonstrated that the cells that were positive for CD163 were also positive for STAT1. CD163(+) TAMs in oral premalignant lesions coexpress CD163 and STAT1, suggesting that the TAMs in oral premalignant lesions possess an M1 phenotype in a Th1-dominated micromilieu.

  6. Treatment to sustain a Th17-type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer.

    PubMed

    Young, M Rita I; Levingston, Corinne A; Johnson, Sara D

    2016-05-15

    While immune suppression is a hallmark of head and neck squamous cell carcinoma (HSNCC), the immunological impact of premalignant oral lesions, which often precedes development of HNSCC, is unknown. The present study assessed the changes in splenic and draining lymph node CD4(+) cell populations and their production of select cytokines that occur in mice with carcinogen-induced premalignant oral lesions and the changes that occur as lesions progress to oral cancer. These studies found skewing toward Th1 and Th17-type phenotypes in the spleen and lymph nodes of mice with premalignant oral lesions and a shift to Treg as lesions progress to cancer. Since the role of Th17 cells in the progression from premalignant lesions to cancer is not clear, studies determined the immunological and clinical effect of treating mice bearing premalignant oral lesions with a TGF-β type 1 receptor inhibitor plus IL-23 as an approach to sustain the Th17 phenotype. These studies showed that the treatment approach not only sustained the Th17 phenotype, but also increased distal spleen cell and regional lymph node cell production of other stimulatory/inflammatory mediators and slowed premalignant lesion progression to cancer. © 2016 UICC.

  7. HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction

    PubMed Central

    Zhang, Paul J.; Furth, Emma E.; Ginsberg, Gregory G.; McMillan, Matthew T.; Datta, Jashodeep; Czerniecki, Brian J.; Roses, Robert E.

    2016-01-01

    Overexpression of receptor tyrosine kinases (RTK), including members of the HER family, has prognostic and therapeutic significance in invasive esophagogastric carcinoma. RTK expression in premalignant gastroesophageal lesions has not been extensively explored. Formalin-fixed paraffin-embedded tissue samples of esophageal biopsy specimens from 73 patients with Barrett’s esophagus with either low-grade dysplasia (LGD) (n = 32) or high-grade dysplasia (HGD) (n = 59) were analyzed for HER1, HER2, HER3 and CMET expression by immunohistochemistry (IHC). Immunophenotype was correlated with histologic and clinical features. High-grade dysplasia (HGD) was associated with overexpression of HER1 (20.7% vs. 3.1%, p = 0.023), HER2 (5.3% vs. 0.0%, p = 0.187) and HER3 (47.4% vs. 9.4%, p<0.001) compared to low-grade dysplasia (LGD). There was a significant association of HER2 (20.0% vs. 2.1%, p = 0.022) and HER3 (80.0% vs. 40.4%, p = 0.023) overexpression in HGD lesions associated with foci of invasive carcinoma compared to those without invasive foci. Overexpression of CMET was observed in 42.9% of specimens, was increasingly observed with HGD compared to LGD (58.3% vs. 36.7%, p = 0.200), and was most often co-expressed with HER3 (62.5% of HER3-positive specimens vs. 38.2% of HER3-negative specimens, p = 0.212). In summary, HER3 is frequently overexpressed in high-grade dysplastic lesions of the gastroesophageal junction and may be a marker of invasive progression. These data provide rationale for targeting HER2 and HER3 pathways in an early disease setting to prevent disease progression. PMID:27559738

  8. Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions

    PubMed Central

    Vazquez-Martin, Alejandro; López-Bonetc, Eugeni; Cufí, Sílvia; Oliveras-Ferraros, Cristina; Del Barco, Sonia; Martin-Castillo, Begoña; Menendez, Javier A.

    2013-01-01

    Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therapeutic capacity to eliminate CSC traits in pre-invasive intraepithelial neoplasias. First, we describe a signalling network signature that overrides bioenergetics stress- and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions. Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin (“old drugs”) to their recently recognized CSC targets (“new uses”) within the network. By discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self-renewal of CSCs we finally underscore the expected translational impact of the “old drugs–new uses” repurposing strategy to open a new CSC-targeted chemoprevention era. PMID:21600837

  9. Aldose reductase inhibition suppresses azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice.

    PubMed

    Saxena, Ashish; Shoeb, Mohammad; Tammali, Ravinder; Ramana, Kota V; Srivastava, Satish K

    2014-12-01

    Type-2 diabetes and obesity-related metabolic abnormalities are major risk factors for the development of colon cancer. In the present study, we examined the effects of polyol pathway enzyme aldose reductase (AR) inhibitor, fidarestat, on the development of azoxymethane (AOM)-induced colonic premalignant lesions in C57BL/KsJ-db/db obese mice. Our results indicate that fidarestat given in the drinking water caused a significant reduction in the total number of colonic premalignant lesions in the AOM treated obese mice. Further, the expression levels of PKC-β2, AKT, COX-2 and iNOS in the colonic mucosa of AOM-treated mice were significantly decreased by fidarestat. The serum levels of IL-1α, IP-10, MIG, TNF-α and VEGF are significantly suppressed in AOM + fidarestat treated obese mice. Fidarestat also decreased the expression of COX-2, iNOS, XIAP, survivin, β-catenin and NF-κB in high glucose-treated HT29 colon cancer cells. In conclusion, our results indicate that fidarestat inhibits the development of colonic premalignant lesions in an obesity-related colon cancer and is chemopreventive to colorectal carcinogenesis in obese individuals. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Automated classification of oral premalignant lesions using image cytometry and Random Forests-based algorithms.

    PubMed

    Baik, Jonathan; Ye, Qian; Zhang, Lewei; Poh, Catherine; Rosin, Miriam; MacAulay, Calum; Guillaud, Martial

    2014-06-01

    A major challenge for the early diagnosis of oral cancer is the ability to differentiate oral premalignant lesions (OPL) at high risk of progressing into invasive squamous cell carcinoma (SCC) from those at low risk. Our group has previously used high-resolution image analysis algorithms to quantify the nuclear phenotypic changes occurring in OPLs. This approach, however, requires a manual selection of nuclei images. Here, we investigated a new, semi-automated algorithm to identify OPLs at high risk of progressing into invasive SCC from those at low risk using Random Forests, a tree-based ensemble classifier. We trained a sequence of classifiers using morphometric data calculated on nuclei from 29 normal, 5 carcinoma in situ (CIS) and 28 SCC specimens. After automated discrimination of nuclei from other objects (i.e., debris, clusters, etc.), a nuclei classifier was trained to discriminate abnormal nuclei (8,841) from normal nuclei (5,762). We extracted voting scores from this trained classifier and created an automated nuclear phenotypic score (aNPS) to identify OPLs at high risk of progression. The new algorithm showed a correct classification rate of 80% (80.6% sensitivity, 79.3% specificity) at the cellular level for the test set, and a correct classification rate of 75% (77.8% sensitivity, 71.4% specificity) at the tissue level with a negative predictive value of 76% and a positive predictive value of 74% for predicting progression among 71 OPLs, performed on par with the manual method in our previous study. We conclude that the newly developed aNPS algorithm serves as a crucial asset in the implementation of high-resolution image analysis in routine clinical pathology practice to identify lesions that require molecular evaluation or more frequent follow-up.

  11. Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells

    PubMed Central

    2012-01-01

    Background Abnormal expression of Rho-GTPases has been reported in several human cancers. However, the expression of these proteins in cervical cancer has been poorly investigated. In this study we analyzed the expression of the GTPases Rac1, RhoA, Cdc42, and the Rho-GEFs, Tiam1 and beta-Pix, in cervical pre-malignant lesions and cervical cancer cell lines. Methods Protein expression was analyzed by immunochemistry on 102 cervical paraffin-embedded biopsies: 20 without Squamous Intraepithelial Lesions (SIL), 51 Low- grade SIL, and 31 High-grade SIL; and in cervical cancer cell lines C33A and SiHa, and non-tumorigenic HaCat cells. Nuclear localization of Rac1 in HaCat, C33A and SiHa cells was assessed by cellular fractionation and Western blotting, in the presence or not of a chemical Rac1 inhibitor (NSC23766). Results Immunoreacivity for Rac1, RhoA, Tiam1 and beta-Pix was stronger in L-SIL and H-SIL, compared to samples without SIL, and it was significantly associated with the histological diagnosis. Nuclear expression of Rac1 was observed in 52.9% L-SIL and 48.4% H-SIL, but not in samples without SIL. Rac1 was found in the nucleus of C33A and SiHa cells but not in HaCat cells. Chemical inhibition of Rac1 resulted in reduced cell proliferation in HaCat, C33A and SiHa cells. Conclusion Rac1 is expressed in the nucleus of epithelial cells in SILs and cervical cancer cell lines, and chemical inhibition of Rac1 reduces cellular proliferation. Further studies are needed to better understand the role of Rho-GTPases in cervical cancer progression. PMID:22443139

  12. The Association Between Gastric Endoscopic Findings and Histologic Premalignant Lesions in the Iranian Rural Population

    PubMed Central

    Niknam, Ramin; Manafi, Alireza; Fattahi, Mohammad Reza; Mahmoudi, Laleh

    2015-01-01

    Abstract Atrophic gastritis, intestinal metaplasia, and gastric dysplasia are histologic premalignant lesions (PMLs). Correlation between the gastric endoscopic findings and histologic PMLs is not clear. This study was designed to determine the possible association of endoscopic findings and histologic PMLs. Over 28 months gastric endoscopic findings of consecutive rural patients with dyspepsia were categorized into 3 groups: 1—normal, 2—ulcerative with or without concurrent abnormality, 3—abnormal non-ulcerative. Biopsies of antrum and body were taken from all included patients and examined for the presence of histologic PMLs. Any mucosal abnormality was also biopsied. From 7340 evaluated patients, an overall of 1973 patients were included. 55.7% of patients were in group 1; 3.8% in group 2 and 40.5% in group 3. A within sex analysis showed that the majority of male patients were in PMLs subgroup (P < 0.001) likewise in groups 2 and 3 (P < 0.001). The prevalence of histologic PMLs in groups 2 and 3 was significantly higher than group 1 (P < 0:001) but the difference was not significant between groups 2 and 3 (P = 0.484). Mean (±SD) age of patient with PMLs was 50.25 ± 17.71 whereas in patients without PMLs was 41.16 ± 16.48 (P < 0.001). This study has showed that abnormal gastric endoscopic findings, male sex and increased age can be considered as risk factors of the formation of histologic PMLs. Until further investigations we propose that any abnormality on gastric mucosa (ulcerative or non-ulcerative) could be biopsied for the evaluation of probable histologic PMLs especially in old men. PMID:25929902

  13. The association between gastric endoscopic findings and histologic premalignant lesions in the Iranian rural population.

    PubMed

    Niknam, Ramin; Manafi, Alireza; Fattahi, Mohammad Reza; Mahmoudi, Laleh

    2015-05-01

    Atrophic gastritis, intestinal metaplasia, and gastric dysplasia are histologic premalignant lesions (PMLs). Correlation between the gastric endoscopic findings and histologic PMLs is not clear. This study was designed to determine the possible association of endoscopic findings and histologic PMLs.Over 28 months gastric endoscopic findings of consecutive rural patients with dyspepsia were categorized into 3 groups: 1-normal, 2-ulcerative with or without concurrent abnormality, 3-abnormal non-ulcerative. Biopsies of antrum and body were taken from all included patients and examined for the presence of histologic PMLs. Any mucosal abnormality was also biopsied.From 7340 evaluated patients, an overall of 1973 patients were included. 55.7% of patients were in group 1; 3.8% in group 2 and 40.5% in group 3. A within sex analysis showed that the majority of male patients were in PMLs subgroup (P < 0.001) likewise in groups 2 and 3 (P < 0.001). The prevalence of histologic PMLs in groups 2 and 3 was significantly higher than group 1 (P < 0:001) but the difference was not significant between groups 2 and 3 (P = 0.484). Mean (±SD) age of patient with PMLs was 50.25 ± 17.71 whereas in patients without PMLs was 41.16 ± 16.48 (P < 0.001).This study has showed that abnormal gastric endoscopic findings, male sex and increased age can be considered as risk factors of the formation of histologic PMLs. Until further investigations we propose that any abnormality on gastric mucosa (ulcerative or non-ulcerative) could be biopsied for the evaluation of probable histologic PMLs especially in old men.

  14. Immunohistochemical assessment of mitochondrial superoxide dismutase (MnSOD) in colorectal premalignant and malignant lesions

    PubMed Central

    Piecuch, Adam; Dziewit, Bartosz; Segiet, Oliwia; Kurek, Józef; Kowalczyk-Ziomek, Grażyna; Wojnicz, Romuald; Helewski, Krzysztof

    2016-01-01

    Introduction It is generally accepted that mitochondria are a primary source of intracellular reactive oxygen species (ROS). Under physiological circumstances they are permanently formed as by-products of aerobic metabolism in the mitochondria. To counter the harmful effect of ROS, cells possess an antioxidant defence system to detoxify ROS and avert them from accumulation at high concentrations. Mitochondria-located manganese superoxide dismutase (MnSOD, SOD2) successfully converts superoxide to the less reactive hydrogen peroxide (H2O2). To the best of our knowledge, there are no available data regarding immunohistochemical expression of MnSOD in colorectal neoplastic tissues. Aim To investigate the immunohistochemical expression status of MnSOD in colorectal premalignant and malignant lesions. Material and methods This study was performed on resected specimens obtained from 126 patients who had undergone surgical resection for primary sporadic colorectal cancer, and from 114 patients who had undergone colonoscopy at the Municipal Hospital in Jaworzno (Poland). Paraffin-embedded, 4-µm-thick tissue sections were stained for rabbit polyclonal anti SOD2 antibody obtained from GeneTex (clone TF9-10-H10 from America Diagnostica). Results Results of our study demonstrated that the development of colorectal cancer is connected with increased expression of MnSOD both in adenoma and adenocarcinoma stages. Samples of adenocarcinoma with G2 and G3 grade showed significantly higher levels of immunohistochemical expression of this antioxidant enzyme. Moreover, patients with the presence of lymphovascular invasion and higher degree of regional lymph node status have been also characterised by higher levels of MnSOD expression. The samples of adenoma have been characterised by higher levels of MnSOD expression in comparison to normal mucosa as well. Interestingly, there was no significant correlation between expression and histological type of adenoma. Conclusions Development

  15. Increased leukocyte mitochondrial DNA copy number is associated with oral premalignant lesions: an epidemiology study.

    PubMed

    He, Yonggang; Gong, Yilei; Gu, Jian; Lee, J Jack; Lippman, Scott M; Wu, Xifeng

    2014-08-01

    Although changes in the mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes (PBLs) have been linked to increased susceptibility to several cancers, the relationship between the mtDNA copy number in PBLs and the risk of cancer precursors has not been investigated. In this study, we measured the relative mtDNA copy number in PBLs of 143 patients with histologically confirmed oral premalignant lesions (OPLs) and of 357 healthy controls that were frequency-matched to patients according to age, sex and race. OPL patients had a significantly higher mtDNA copy number than the controls (1.36 ± 0.74 versus 1.11 ± 0.32; P < 0.001). In analyses stratified by sex, race, alcohol consumption and smoking status, the mtDNA copy number was higher in the OPL patients than in the controls in all the strata. Using the median mtDNA copy number in the control group as a cutoff, we found that individuals with a high mtDNA copy number had significantly higher risk of having OPLs than individuals with a low mtDNA copy number (adjusted odds ratio, 1.93; 95% confidence interval, 1.23-3.05, P = 0.004). Analysis of the joint effect of alcohol consumption and smoking revealed even greater risk for OPLs. Our results suggest that high mtDNA copy number in PBLs is significantly associated with having OPLs. To our knowledge, this is the first epidemiologic study to show that the mtDNA copy number may indicate the risk of cancer precursors.

  16. Optimized endoscopic autofluorescence spectroscopy for the identification of premalignant lesions in Barrett's oesophagus.

    PubMed

    Holz, Jasmin A; Boerwinkel, David F; Meijer, Sybren L; Visser, Mike; van Leeuwen, Ton G; Aalders, Maurice C G; Bergman, Jacques J G H M

    2013-12-01

    Fluorescence spectroscopy has the potential to detect early cellular changes in Barrett's oesophagus before these become visible. As the technique is based on varying concentrations of intrinsic fluorophores, each with its own optimal excitation wavelength, it is important to assess the optimal excitation wavelength(s) for identification of premalignant lesions in patients with Barrett's oesophagus. The endoscopic spectroscopy system used contained five (ultra)violet light sources (λexc=369-416 nm) to generate autofluorescence during routine endoscopic surveillance. Autofluorescence spectroscopy was followed by a biopsy for histological assessment and spectra correlation. Three intensity ratios (r1, r2, r3) were calculated by dividing the area, A, under the spectral curve of selected emission wavelength ranges for each spectrum generated by each excitation wavelength λexc as follows (Equation is included in full-text article.). Double intensity ratios were calculated using two excitation wavelengths. Fifty-eight tissue areas from 22 patients were used for autofluorescence spectra analysis. Excitation with 395, 405 or 410 nm showed a significant (P≤0.0006) differentiation between intestinal metaplasia and grouped high-grade dysplasia/early carcinoma for intensity ratios r2 and r3. A sensitivity of 80.0% and specificity of 89.5% with an area under the ROC curve of 0.85 was achieved using 395 nm excitation and intensity ratio r3. Double excitation showed no additional value over single excitation. The combination of 395 nm excitation and intensity ratio r3 showed optimal conditions to discriminate nondysplastic from early neoplasia in Barrett's oesophagus.

  17. The Interaction between GSTT1, GSTM1, and GSTP1 Ile105Val Gene Polymorphisms and Environmental Risk Factors in Premalignant Gastric Lesions Risk

    PubMed Central

    Moldovan, Valeriu; Mocan, Simona

    2017-01-01

    The study investigated the possible influence of GSTM1, GSTT1, and GSTP1 gene polymorphisms as predisposing factors for premalignant gastric lesions as well as their interaction with H. pylori infection, gastrotoxic drugs, smoking, and alcohol consumption. In this study, 270 patients with a complet set of gastric biopsies and successfully genotyped were finally included. The GSTM1 gene polymorphism had significant contribution in mild/severe endoscopic lesions (p = 0.01) as well as in premalignant lesions (p = 0.01). The GSTM1 null genotype increased the risk for mucosal defects in H. pylori-negative patients (OR = 2.27, 95% CI: 1.20–4.37) and the risk for premalignant lesions in patients with no alcohol consumption (OR = 2.13, 95% CI: 1.19–3.83). The GSTT1 deleted polymorphism did not significantly increase the risk for premalignant lesions in the absence of gastrotoxic drugs (OR = 1.82, 95% CI: 0.72–4.74). The combined GSTT1T1 and GSTM1 null polymorphisms were borderline correlated with an increased risk for premalignant lesions (OR = 1.72, 95% CI: 1.00–2.97). The wild-type GSTP1 Ile/Ile genotype versus the variant genotypes Ile/Val + Val/Val was significantly associated with a decreased risk of gastric atrophy/intestinal metaplasia (OR = 0.60, 95% CI: 0.37–0.98). In conclusion, the GSTM1 and GSTT1 null genotypes increased the risk for premalignant and endoscopic gastric lesions, modulated by H. pylori, alcohol, or gastrotoxic drug consumption, while the presence of the GSTP1Val allele seemed to reduce the risk for premalignant lesions. PMID:28182092

  18. (-)-Epigallocatechin gallate suppresses azoxymethane-induced colonic premalignant lesions in male C57BL/KsJ-db/db mice.

    PubMed

    Shimizu, Masahito; Shirakami, Yohei; Sakai, Hiroyasu; Adachi, Seiji; Hata, Kazuya; Hirose, Yoshinobu; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

    2008-09-01

    Obesity and diabetes mellitus are risk factors for colon cancer. The activation of the insulin-like growth factor (IGF)/IGF-IR axis plays a critical role in this carcinogenesis. (-)-Epigallocatechin gallate (EGCG), the major constituent of green tea, seems to have both antiobesity and antidiabetic effects. This study examined the effects of EGCG on the development of azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) mice, which are obese and develop diabetes mellitus. Male db/db mice were given four weekly s.c. injections of azoxymethane (15 mg/kg body weight) and then they received drinking water containing 0.01% or 0.1% EGCG for 7 weeks. At sacrifice, drinking water with EGCG caused a significant decrease in the number of total aberrant crypt foci, large aberrant crypt foci, and beta-catenin accumulated crypts in these mice, all of which are premalignant lesions of the colon. The colonic mucosa of db/db mice expressed high levels of the IGF-IR, phosphorylated form of IGF-IR (p-IGF-IR), p-GSK-3beta, beta-catenin, cyclooxygenase-2, and cyclin D1 proteins, and EGCG in drinking water caused a marked decrease in the expression of these proteins. Treating these mice with EGCG also caused an increase in the serum level of IGFBP-3 while conversely decreasing the serum levels of IGF-I, insulin, triglyceride, cholesterol, and leptin. EGCG overcomes the activation of the IGF/IGF-IR axis, thereby inhibiting the development of colonic premalignant lesions in an obesity-related colon cancer model, which was also associated with hyperlipidemia, hyperinsulinemia, and hyperleptinemia. EGCG may be, therefore, useful in the chemoprevention or treatment of obesity-related colorectal cancer.

  19. Associated factors with cervical pre-malignant lesions among the married fisher women community at Sadras, Tamil Nadu

    PubMed Central

    Ganesan, Sornam; Subbiah, Vasantha N.; Michael, Jothi Clara J.

    2015-01-01

    Objective: To identify the associated factors of cervical pre-malignant lesions among the married fisher women residing in the coastal areas of Sadras, Tamil Nadu. Methods: The study was conducted in five fishermen communities under Sadras, a coastal area in Tamil Nadu, India. Two hundred and fifty married fisher women residing in the area. Quantitative descriptive approach with a cross-sectional study design was used. Data were collected using a structured interview schedule for identifying the associated factors and Pap smear test was performed for identifying the pre-malignant cervical lesions among the married fisher women. Data were analyzed using descriptive and inferential statistics. Results: Among 250 women, about six (2.4%) of them presented with pre-cancerous lesions such as atypical squamous cell of undifferentiated significance (ASCUS) — five (2%) and mild dysplasia one (0.4%). Majority of the women, about 178 (71.2%) women, had abnormal cervical findings. Statistical analysis showed a significant association of risk factors such as advanced age, lack of education, low socioeconomic status, using tobacco, multiparity, premarital sex, extramarital relationship, using cloth as sanitary napkin, etc. Conclusion: The study findings clearly show the increased vulnerable state of the fisher women for acquiring cervical cancer as they had many risk factors contributing to the same. PMID:27981091

  20. Exploring type II microcalcifications in benign and premalignant breast lesions by shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS)

    NASA Astrophysics Data System (ADS)

    Liang, Lijia; Zheng, Chao; Zhang, Haipeng; Xu, Shuping; Zhang, Zhe; Hu, Chengxu; Bi, Lirong; Fan, Zhimin; Han, Bing; Xu, Weiqing

    2014-11-01

    The characteristics of type II microcalcifications in fibroadenoma (FB), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) breast tissues has been analyzed by the fingerprint features of Raman spectroscopy. Fresh breast tissues were first handled to frozen sections and then they were measured by normal Raman spectroscopy. Due to inherently low sensitivity of Raman scattering, Au@SiO2 shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique was utilized. A total number of 71 Raman spectra and 70 SHINERS spectra were obtained from the microcalcifications in benign and premalignant breast tissues. Principal component analysis (PCA) was used to distinguish the type II microcalcifications between these tissues. This is the first time to detect type II microcalcifications in premalignant (ADH and DCIS) breast tissue frozen sections, and also the first time SHINERS has been utilized for breast cancer detection. Conclusions demonstrated in this paper confirm that SHINERS has great potentials to be applied to the identification of breast lesions as an auxiliary method to mammography in the early diagnosis of breast cancer.

  1. Association between PD-L1 and HPV status and the prognostic value for HPV treatment in premalignant cervical lesion patients

    PubMed Central

    Yang-Chun, Feng; Zhen-Zhen, Cheng; Yan-Chun, Huang; Xiu-Min, Ma

    2017-01-01

    Abstract The difference of PD-L1 expression between only HPV-positive patients and premalignant cervical lesion patients did not be reported in present studies. And to test the PD-L1 expression in some cervical cell lesion studies using cervical exfoliated cells sample also was ignored. Meanwhile, the PD-L1 expression as a predictive biomarker still existed controversy. So in the study, first to compare the expression of PD-L1 between only HPV-positive patients and premalignant cervical lesion patients, then to research the association between PD-L1 and HPV status, lastly to explore the possible prognostic value for HPV treatment in premalignant cervical lesion patients. Cervical exfoliated cells samples of 54 premalignant cervical lesion patients with HPV16 infection were collected; meanwhile the cervical exfoliated cells samples from 20 healthy women without HPV infection and 20 patients with only HPV16 infection but cervical cytology normal were collected as 2 control groups. Flow-through hybridization and gene chip (FHGC) was used to detect the HPV type, the PD-L1 expression was tested by Flow cytometry analysis, the methylation-sensitive high-resolution melting (MS-HRM) was used to test the HPV16 L1 gene methylation. The 54 premalignant cervical lesion patients were followed up in 18 months to assess the prognostic value of PD-L1 for HPV treatment. The PD-L1 positive cell rate and mean fluorescence intensity of PD-L1 positive cell in premalignant cervical lesion patients with HPV16 infection were higher than 2 control groups. Mean fluorescence intensity of PD-L1 positive cell were increased in 54 cases when existing multiple HPV status and high HPV16-L1 gene methylation (L1 gene methylation more than 50%). High PD-L1 expression (PD-L1 positive cell rate more than 10%), high HPV16-L1 gene methylation, and multiple HPV infection status could prolong the time to clean HPV infection by Kaplan–Meier analysis. Multivariate Cox proportional hazards analysis also

  2. Improved diagnosis of oral premalignant lesions in submucous fibrosis patients with 5-aminolevulinic acid induced PpIX fluorescence

    NASA Astrophysics Data System (ADS)

    Wang, Chih-Yu; Tsai, Tsuimin; Chiang, Chung-Ping; Chen, Hsin-Ming; Chen, Chin-Tin

    2009-07-01

    We investigate the possibility of using ALA-derived PpIX fluorescence spectroscopy for the detection of epithelial hyperkeratosis (EH) or epithelial dysplasia (ED) lesions in oral submucous fibrosis (OSF) patients that could not be found by autofluorescence spectroscopy. Twenty percent of ALA solution gel was applied onto oral neoplasia and surrounding normal tissue [normal oral mucosa (NOM)] for 90 min. Fluorescence emission spectra were measured under 410 nm excitation. Generally, the most intense fluorescence emission peaks occurred at 460 and 630 nm. The ratios of the area under red peak (630+/-10 nm) to the area under blue peak (460+/-10 nm), denoted as R/B, were calculated. We found that OSF mucosa has the lowest R/B value, followed by NOM, EH on OSF, and ED on OSF. An ANOVA test showed significant differences between OSF, NOM, EH on OSF, and ED on OSF (p<0.05). However, measurements of autofluorescence (i.e., before ALA application) show no significant differences between OSF, NOM, EH on OSF, and ED on OSF (ANOVA test, p>0.05). These results indicate that ALA-induced PpIX fluorescence spectroscopy could be used to identify the premalignant lesions on oral fibrotic mucosa, which could not be found by autofluorescence.

  3. Transcriptional regulation of ataxia-telangiectasia and Rad3-related protein by activated p21-activated kinase-1 protects keratinocytes in UV-B-induced premalignant skin lesions.

    PubMed

    Beesetti, S; Mavuluri, J; Surabhi, R P; Oberyszyn, T M; Tober, K; Pitani, R S; Joseph, L D; Venkatraman, G; Rayala, S K

    2017-07-10

    Sun-induced skin lesions, in particular actinic keratosis, are generally considered as premalignant skin lesions that can progress into squamous cell carcinoma (SCC) and invasive SCC if left untreated. Therefore, understanding the molecular mechanisms by which the ultraviolet-B (UV-B)-exposed cells are being protected and the signaling pathways that promote the progression of certain premalignant skin lesions to malignant lesions will permit us to prevent or cure skin cancers. In the current study, we found that phospho-p21-activated kinase-1 (Pak1) and Pak1 expression was high in clinical samples of sunlight-induced premalignant skin lesions assessed by immunohistochemistry. Further, we observed that phospho-Pak1 and Pak1 levels are high in UV-B-exposed hairless SKH mouse model skin samples as compared with unexposed skin tissue. Our results from cell line and animal models showed that Pak1 is activated in response to UV-B radiation, and this activated Pak1 translocates from the cytoplasm to the nucleus. Inside the nucleus, Pak1 via C-Fos binds to a specific promoter region of DNA repair kinase ATR (ataxia-telangiectasia and Rad3-related protein) and acts as a transcriptional regulator of ATR. Results from our analysis showed that Pak1 overexpression, knockdown and Pak1 knockout cell line models showed that Pak1 confers protection to keratinocytes from UV-B-induced apoptosis and DNA damage via ATR. To our knowledge, this is the first study that evaluates the functional and clinical significance of a signaling molecule, Pak1, in sun-induced premalignant skin lesions and indicates that increased Pak1 activation and expression could serve as an early warning sign of progression toward non-melanoma skin cancer, if ignored.Oncogene advance online publication, 10 July 2017; doi:10.1038/onc.2017.218.

  4. Prevalence and implications of TERT promoter mutation in uveal and conjunctival melanoma and in benign and premalignant conjunctival melanocytic lesions.

    PubMed

    Koopmans, Anna E; Ober, Kimberley; Dubbink, Hendrikus J; Paridaens, Dion; Naus, Nicole C; Belunek, Stephan; Krist, Bart; Post, Edward; Zwarthoff, Ellen C; de Klein, Annelies; Verdijk, Robert M

    2014-08-26

    Hot-spot mutations in the promoter region of telomerase reverse transcriptase (TERT promoter mutations) occur frequently in cutaneous and conjunctival melanoma and are exceedingly rare in uveal melanoma. No information is available on the presence of these mutations in the conjunctival melanocytic precursor lesion primary acquired melanosis (PAM). We tested a cohort of uveal and conjunctival melanomas as well as conjunctival benign and premalignant melanocytic lesions for TERT promoter mutations in order to elucidate the role of these mutations in tumor progression. TERT promoter mutation analysis on fresh tumor DNA and DNA from formalin-fixed, paraffin-embedded specimens was performed by SNaPshot analysis in 102 uveal melanomas, 39 conjunctival melanomas, 26 PAM with atypia, 14 PAM without atypia, and 56 conjunctival nevi. Mutations of the TERT promoter were not identified in conjunctival nevi or PAM without atypia, but were detected in 2/25 (8%) of PAM with atypia and 16/39 (41%) of conjunctival melanomas. A single TERT promoter mutation was detected in 102 uveal melanomas (1%). We present the second documented case of TERT promoter mutation in uveal melanoma. In comparison with other types of melanoma, TERT promoter mutations occur at extremely low frequency in uveal melanoma. TERT promoter mutations are frequent in conjunctival melanoma and occur at lower frequency in PAM with atypia but were not detected in benign conjunctival melanocytic lesions. These findings favor a pathogenetic tumor progression role for TERT promoter mutations in conjunctival melanocytic lesions. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  5. Lymphoepithelial cysts of the pancreas. Can preoperative imaging distinguish this benign lesion from malignant or pre-malignant cystic pancreatic lesions?

    PubMed

    Kavuturu, Srinivas; Sarwani, Nabeel E; Ruggeiro, Fransesca M; Deshaies, Isabelle; Kimchi, Eric T; Kaifi, Jussuf T; Staveley-O'Carroll, Kevin F; Gusani, Niraj J

    2013-05-10

    Lymphoepithelial cysts of the pancreas are rare true benign cystic tumors of the pancreas of uncertain etiology. Cystic neoplasms of the pancreas present a significant diagnostic dilemma in differentiating benign from premalignant or malignant variants. Since the first description of lymphoepithelial cysts in 1985, 109 cases have been reported in the literature. We describe 6 cases of this rare tumor, the preoperative imaging results, and a review the literature. Five males and one female ranging in age from 47 to 76 years underwent resection for lymphoepithelial cysts. Five patients presented with abdominal pain related to the lesion and in one patient the lesion was discovered incidentally. Four patients had elevated serum CA 19-9 levels. Pre-operative imaging with a CT scan and MRI of the abdomen typically revealed a well defined hypodense mass with Hounsfield units (HU) in the range of 15 to 20. One patient had papillary projections into the lesion. The mean size was 3.3 cm (ranging from 1.8 cm to 4 cm). All lesions were exophytic off the pancreatic parenchyma (1 cyst was located in the head of the pancreas, 2 were in the body, and 3 were in the tail region). Pre-operative EUS-guided/CT-guided needle aspiration, when performed, was not diagnostic. All patients underwent resection (one pancreaticoduodenectomy, five left pancreatectomies) to remove these cystic neoplasms. Pathology revealed a cyst lined by non-dysplastic squamous cells surrounded by sheets of benign lymphocytes. No evidence of malignancy was found. Lymphoepithelial cysts of the pancreas are rare and are characteristically seen in men. While a hypodense mass (less than 20 HU) with papillary projections should be considered suspicious for lymphoepithelial cyst, a definitive diagnosis cannot be made solely based on preoperative imaging. EUS-guided biopsy coupled with biochemical/tumor marker studies are increasingly being used as a diagnostic tool to help differentiate between the various types of

  6. Targeting Premalignant Lesions: Implications for Early Breast Cancer Detection and Intervention

    DTIC Science & Technology

    2015-04-01

    characterized by distinct phenotypic changes that occur in the mammary gland . We proposed to utilize this animal model to probe early stage...of the matrix in the mammary glands containing the early cancer lesions. On further analysis, we determined that CSG peptide co-localizes with

  7. Optical biopsy of pre-malignant or degenerative lesions: the role of the inflammatory process

    NASA Astrophysics Data System (ADS)

    da Silva Martinho, Herculano

    2011-03-01

    Recent technological advances in fiber optics, light sources, detectors, and molecular biology have stimulated unprecedented development of optical methods to detect pathological changes in tissues. These methods, collectively termed "optical biopsy," are nondestructive in situ and real-time assays. Optical biopsy techniques as fluorescence spectroscopy, polarized light scattering spectroscopy, optical coherence tomography, confocal reflectance microscopy, and Raman spectroscopy had been extensively used to characterize several pathological tissues. In special, Raman spectroscopy technique had been able to probe several biochemical alterations due to pathology development as change in the DNA, glycogen, phospholipid, non-collagenous proteins. All studies claimed that the optical biopsy methods were able to discriminate normal and malignant tissues. However, few studies had been devoted to the discrimination of very common subtle or early pathological states as inflammatory process, which are always present on, e.g., cancer lesion border. In this work we present a systematic comparison of optical biopsy data on several kinds of lesions were inflammatory infiltrates play the role (breast, cervical, and oral lesion). It will be discussed the essential conditions for the optimization of discrimination among normal and alterated states based on statistical analysis.

  8. [Basal cell carcinoma, squamous cell carcinoma and premalignant skin lesions--how to treat?].

    PubMed

    Pitkänen, Sari; Jeskanen, Leila; Ylitalo, Leea

    2014-01-01

    Increasing exposure to UV radiation is considered the most important etiologic factor of nonmelanoma skin cancers. Consequently, exposed areas such as the scalp and face, are the primary areas for developing non-melanoma skin cancers. Once a patient has presented with one tumor, additional lesions are common. The diagnosis is based on typical clinical picture and biopsy or excision for histopathological analysis. Various non-surgical treatment options have been established. Superficial basal cell carcinoma, superficial carcinoma in situ and all actinic keratoses are preferentially treated non-surgically. Most other basal cell and squamous cell carcinomas should be surgically removed.

  9. Macrophages promote the progression of premalignant mammary lesions to invasive cancer.

    PubMed

    Carron, Emily C; Homra, Samuel; Rosenberg, Jillian; Coffelt, Seth B; Kittrell, Frances; Zhang, Yiqun; Creighton, Chad J; Fuqua, Suzanne A; Medina, Daniel; Machado, Heather L

    2017-01-31

    Breast cancer initiation, progression and metastasis rely on a complex interplay between tumor cells and their surrounding microenvironment. Infiltrating immune cells, including macrophages, promote mammary tumor progression and metastasis; however, less is known about the role of macrophages in early stage lesions. In this study, we utilized a transplantable p53-null model of early progression to characterize the immune cell components of early stage lesions. We show that macrophages are recruited to ductal hyperplasias with a high tumor-forming potential where they are differentiated and polarized toward a tumor-promoting phenotype. These macrophages are a unique subset of macrophages, characterized by pro-inflammatory, anti-inflammatory and immunosuppressive factors. Macrophage ablation studies showed that macrophages are required for both early stage progression and primary tumor formation. These studies suggest that therapeutic targeting of tumor-promoting macrophages may not only be an effective strategy to block tumor progression and metastasis, but may also have critical implications for breast cancer prevention.

  10. [Usefulness of systematic chromoendoscopy with a double dye staining technique for the detection of dysplasia in patients with premalignant gastric lesions].

    PubMed

    Yep-Gamarra, Víctor; Díaz-Vélez, Cristian; Araujo, Isis; Ginès, Àngels; Fernández-Esparrach, Gloria

    2016-02-01

    Premalignant gastric lesions have an increased risk to develop gastric cancer. To evaluate the usefulness of systematic endoscopy that includes chromoendoscopy with a double dye staining technique for the detection of dysplasia in patients with premalignant gastric lesions. This longitudinal, prospective study was performed in patients with gastric atrophy, intestinal metaplasia or dysplasia who were referred for endoscopy less than 6 months after the initial diagnosis. The second endoscopy was performed in three phases: phase 1, exhaustive and systematic review of the mucosa with photographic documentation and biopsies of suspicious areas; phase 2, chromoendoscopy with a double dye staining technique using acetic acid 1.2% and indigo carmine 0.5%; phase 3, topographic mapping and random biopsies. A total of 50 patients were included. Nine (18%) had atrophic gastritis, 38 (76%) had intestinal metaplasia, and 3 (6%) had low-grade dysplasia. Systematic endoscopy with chromoendoscopy using a double dye staining technique detected more patients with dysplasia (9 versus 3, p<.05), and a larger number of biopsies with the diagnosis of dysplasia were obtained. This occurred for visible (6 vs. 0, p<.05) and non-visible lesions (6 vs. 3, p=NS). In one patient, initial low-grade dysplasia was not detected again in the systematic endoscopy, giving a global endoscopic performance for the detection of lesions of 92%. Patients with premalignant gastric lesions have synchronous lesions with greater histological severity, which are detected when systematic endoscopy is conducted with indigo carmine dye added to acetic acid. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  11. Long-term proton pump inhibitor (PPI) use and the development of gastric pre-malignant lesions.

    PubMed

    Song, Huan; Zhu, Jianwei; Lu, DongHao

    2014-12-02

    Proton pump inhibitors (PPIs) are the most effective drugs to reduce gastric acid secretion. PPIs are one of the most commonly prescribed classes of medications worldwide. Apart from short-term application, maintenance therapy with PPIs is recommended and increasingly used in certain diseases, such as Zollinger-Ellison syndrome and gastro-oesophageal reflux disease, especially for people with erosive oesophagitis or Barrett's oesophagus. Although PPIs are generally safe, their efficacy and safety of long-term use remains unclear. The question of whether the long-term use of PPIs could promote the development of gastric pre-malignant lesions has been widely investigated, but results are inconsistent. Limited insight on this problem leads to a dilemma in decision making for long-term PPI prescription. To compare the development or progression of gastric pre-malignant lesions, such as atrophic gastritis, intestinal metaplasia, enterochromaffin-like (ECL) cell hyperplasia, and dysplasia, in people taking long-term (six months or greater) PPI maintenance therapy. We searched the following databases (from inception to 6 August 2013): the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL. In addition, we searched the reference lists of included trials and contacted experts in the field. We searched for randomised controlled trials (RCTs) in adults (aged 18 years or greater) concerning the effects of long-term (six months or greater) PPI use on gastric mucosa changes, confirmed by endoscopy or biopsy sampling (or both). Two review authors independently performed selection of eligible trials, assessment of trial quality, and data extraction. We calculated odds ratios (OR) for analysis of dichotomous data and mean differences for continuous data, with 95% confidence intervals (CI). We included seven trials (1789 participants). Four studies had high risk of bias and the risk of bias in the other three trials was unclear. In addition, it was

  12. Review of Atrophic Gastritis and Intestinal Metaplasia as a Premalignant Lesion of Gastric Cancer

    PubMed Central

    Park, Yo Han; Kim, Nayoung

    2015-01-01

    Atrophic gastritis (AG) and intestinal metaplasia (IM) are the main precursor lesions of gastric cancer as the incidence of gastric cancer increases in the gastric mucosa involved with AG and IM. The prevalence of AG and IM vary depending on countries, even it represents diverse results in the same nation. Usually AG is antecedent of IM but the etiologies of AG and IM are not always the same. The sensitivity and specificity of diagnostic methods to detect AG and IM are different. Furthermore, the management strategy of AG and IM has not been established, yet. Helicobacter pylori infection has been proved as the most important cause of AG and IM. Thus the eradication of H. pylori is very important to prevent the progression to gastric cancer which is still placed in the high rank in morbidity and mortality among cancers. However, the reversibility of AG and IM by eradication of H. pylori which was assumed to be certain by meta-analysis is; however, controversial now. Therefore, the understanding and early diagnosis of AG and IM are very important, especially, in high incidence area of gastric cancer such as Republic of Korea. PMID:25853101

  13. Prospects in the Application of Photodynamic Therapy in Oral Cancer and Premalignant Lesions

    PubMed Central

    Saini, Rajan; Lee, Nathan V.; Liu, Kelly Y. P.; Poh, Catherine F.

    2016-01-01

    Oral cancer is a global health burden with significantly poor survival, especially when the diagnosis is at its late stage. Despite advances in current treatment modalities, there has been minimal improvement in survival rates over the last five decades. The development of local recurrence, regional failure, and the formation of second primary tumors accounts for this poor outcome. For survivors, cosmetic and functional compromises resulting from treatment are often devastating. These statistics underscore the need for novel approaches in the management of this deadly disease. Photodynamic therapy (PDT) is a treatment modality that involves administration of a light-sensitive drug, known as a photosensitizer, followed by light irradiation of an appropriate wavelength that corresponds to an absorbance band of the sensitizer. In the presence of tissue oxygen, cytotoxic free radicals that are produced cause direct tumor cell death, damage to the microvasculature, and induction of inflammatory reactions at the target sites. PDT offers a prospective new approach in controlling this disease at its various stages either as a stand-alone therapy for early lesions or as an adjuvant therapy for advanced cases. In this review, we aim to explore the applications of PDT in oral cancer therapy and to present an overview of the recent advances in PDT that can potentially reposition its utility for oral cancer treatment. PMID:27598202

  14. Oral premalignant lesions: epidemiological and clinical analysis in the northern Polish population

    PubMed Central

    Pawłowska, Anita; Renkielska, Dorota; Michajłowski, Igor; Sobjanek, Michał; Błażewicz, Izabela

    2014-01-01

    Introduction Leukoplakia is the most common potentially malignant condition of the oral cavity. Aim Epidemiological and clinical analysis of patients with oral leukoplakia (OL) diagnosed and treated in the Department of Maxillofacial and Oral Surgery, Medical University of Gdansk. Material and methods The study was retrospective and prospective. Among 55 911 patients diagnosed and treated in the Department in 1999–2009, 204 people with OL were selected. The material includes 104 women and 100 men with an average age of 58.1. Most of the patients were in the age group of 50–70 years, average age was 58.1. Results The most common concomitant disease was diabetes. More than 88% of the patients declared occurrence of OL predisposing development factors (50.49% – cigarette smoking). Three hundred and twenty foci of OL were found among patients. Homogeneous OL dominated (72.05%). Multifocal OL was diagnosed in 58.3% of patients. The most common location of lesions was buccal mucosa (52.2%). Cancers developed on the basis of OL in 7 patients (3.43%). The percentage of malignant transformation was 12.19% for untreated patients and 1.41% for treated patients. The floor of the oral cavity was proven to be the location of the highest risk of oral squamous cell carcinoma. Patients with diabetes may be more likely to develop OL. The risk of malignant transformation is relatively high. In our material it was equal to 3.43%. Conclusions Cigarette smoking is the most important factor, which can influence the effectiveness of treatment. PMID:25610347

  15. Value of the ViziLite Plus System as a diagnostic aid in the early detection of oral cancer/premalignant epithelial lesions.

    PubMed

    Mojsa, Izabela; Kaczmarzyk, Tomasz; Zaleska, Malgorzata; Stypulkowska, Jadwiga; Zapala-Pospiech, Agnieszka; Sadecki, Daniel

    2012-03-01

    The aim of the study was to assess the value of the chemiluminescent light and 1% tolonium chloride as a diagnostic aid in the early detection of oral cancer/premalignant epithelial lesions. Thirty consecutive patients with 41 visually identified oral lesions suggestive of being premalignant underwent chemiluminescence and tolonium chloride examination followed by incisional biopsy with histopathologic evaluation. The biopsies of 34 lesions (82.92%) revealed no dysplasia, 3 lesions (7.32%) revealed mild dysplasia, 3 lesions (7.32%) demonstrated severe dysplasia, and 1 lesion (2.44%) was malignant (squamous cell carcinoma). The chemiluminescent examination improved the brightness (58.54% of the cases), sharpness (56.1% of the cases), texture (60.98% of the cases), and size of the lesion (53.66% of the cases). With references to serious pathologies, 7 cases (100.0%) were brighter, and size was more visualized in 6 cases (85.71%) when using chemiluminescence examination than under incandescent light. Twenty-five (73.53%) of nonserious pathology and 7 (100.0%) of serious pathology (6 dysplasias, 1 squamous cell carcinoma) were positively stained by toluidine blue. Three (8.82%) of nonserious pathology and 0 (0.0%) of serious pathology lesions were identified as true negatives when toluidine blue staining was used. The overall toluidine blue sensitivity and specificity were 81.8% and 37.5%, respectively. Chemiluminescent light demonstrates better visualization (brightness, size) of serious pathology lesions in comparison with conventional clinical oral examination under incandescent light. Toluidine blue demonstrates 100% sensitivity in staining serious pathology. The ViziLite Plus system may help the practitioner to visualize oral pathologies that are not readily detectable with conventional incandescent lighting.

  16. Effective detection of bronchial preinvasive lesions by a new autofluorescence imaging bronchovideoscope system.

    PubMed

    Chiyo, Masako; Shibuya, Kiyoshi; Hoshino, Hidehisa; Yasufuku, Kazuhiro; Sekine, Yasuo; Iizasa, Toshihiko; Hiroshima, Kenzo; Fujisawa, Takehiko

    2005-06-01

    Autofluorescence bronchoscopy is an important tool for the early detection of preinvasive bronchial lesions. However, autofluorescence bronchoscopy has difficulty distinguishing between preinvasive lesions and other benign epithelial changes. A new autofluorescence imaging bronchovideoscope system (AFI) comprises three signals, including an autofluorescence (460-690 nm) on excitation blue light (395-445 nm) and two different bands of reflected light: G' (550 nm) and R' (610 nm). We hypothesized that color analyses of these three wave lengths would improve our ability to differentiate between inflammation and preinvasive lesions. In order to prove this hypothesis and to evaluate the efficacy of AFI for detecting preinvasive lesions, we conducted a prospective study. A total of 32 patients with suspected or known lung cancer were entered into this study. Conventional white light bronchovideoscopy (WLB) and light induced fluorescence endoscopy (LIFE) were performed prior to using AFI. WLB and LIFE detected 62 lesions, including lung cancers (n=2), squamous dysplasias (n=30), and bronchitis (n=30). By utilizing AFI, 24 dysplasias and 2 cancer lesions were magenta in color, while 25 bronchitis lesions were blue. The sensitivities of detecting dysplasia by LIFE and AFI were 96.7% and 80%, respectively. The specificity of AFI (83.3%) was significantly higher than that of LIFE (36.6%) (p=0.0005). We conclude that AFI appears to represent a significant advance in distinguishing preinvasive and malignant lesions from bronchitis or hyperplasia under circumstances where LIFE would identify these all as abnormal lesions.

  17. Prevalence of human papillomavirus in archival samples obtained from patients with cervical pre-malignant and malignant lesions from Northeast Brazil

    PubMed Central

    2010-01-01

    Background Human Papillomavirus (HPV) is considered as a necessary, but not sufficient, cause of cervical cancer. In this study, we aimed to assess the prevalence of HPV in a series of pre-malignant and malignant cervical lesion cases, to identify the virus genotypes, and to assess their distribution pattern according to lesion type, age range, and other considered variables. The samples were submitted to histopathological revision examination and analysed by polymerase chain reaction (PCR) for the presence of HPV DNA, followed by HPV typing by dot blot hybridisation. Findings Of the analysed samples, 53.7% showed pre-malignant cervical lesions, and 46.3% presented with cervical cancer. Most cancer samples (84.1%) were classified as invasive carcinoma. The mean age of these cancer patients was 47.3 years. The overall HPV prevalence was 82.4% in patients with pre-malignant lesions and 92.0% in the cancer patients. HPV 16 was the most prevalent type, followed by HPV 18 and 58, including both single and double infections. Double infection was detected in 11.6% of the samples, and the most common combination was HPV 16+18. Conclusions Cervical cancer appears to occur in women in a lower age range in the studied area, compared to the situation in other Brazilian regions. Furthermore, among the patients with CIN 3 and those with cancer, we observed a higher proportion of married women, women with more than one sexual partner, smokers, and individuals with less than an elementary education, relative to their counterparts. Findings The overall HPV prevalence was 82.4% in patients with pre-malignant lesions and 92.0% in the cervical cancer patients from Northeast Brazil. HPV 16 was the most prevalent type, followed by HPV 18 and 58. The most common double infection was HPV 16+18. Cervical cancer appears to occur in women in a lower age range in the Northeast Brazil. Among the patients with CIN 3 and those with cancer, we observed a higher proportion of married women, women

  18. Matrix metalloproteinase 7 restrains Helicobacter pylori-induced gastric inflammation and premalignant lesions in the stomach by altering macrophage polarization.

    PubMed

    Krakowiak, M S; Noto, J M; Piazuelo, M B; Hardbower, D M; Romero-Gallo, J; Delgado, A; Chaturvedi, R; Correa, P; Wilson, K T; Peek, R M

    2015-04-02

    results suggest that MMP7 exerts a restrictive role on H. pylori-induced gastric injury and the development of premalignant lesions by suppressing M1 macrophage polarization.

  19. Expression of p53 in preneoplastic and early neoplastic bronchial lesions.

    PubMed

    Martin, B; Verdebout, J-M; Mascaux, C; Paesmans, M; Rouas, G; Verhest, A; Ninane, V; Sculier, J-P

    2002-01-01

    p53 alteration has been reported to be an early event in bronchial carcinogenesis. Our study purpose was to determine the rate of p53 expression in the various preneoplastic and early neoplastic bronchial lesions obtained by biopsy during fluorescence bronchoscopy and to analyse its association with patients characteristics. Various stages of preneoplastic lesions as well as radio-occult lung cancer were studied in biopsies obtained by fluorescence bronchoscopy. We assessed the expression of p53 by immunohistochemistry using monoclonal antibody clone DO7. The p53 expression was considered as positive if > or = 1% of cells were positive and the level of positivity was expressed in percentage of positive cells. Fourteen patients were included in each category of preneoplastic lesions. At the threshold of 1% of positive cells p53 expression was observed in 28.5% of the patients with a histologically normal epithelium. This number of positive patients increased with the severity of preneoplastic lesions and reached 100% in the mild dysplasia. The mean rates of p53 positive cells for normal epithelium, hyperplasia, metaplasia, mild and severe dysplasia, carcinoma in situ and invasive radio-occult carcinoma were respectively 0.9, 3.4, 9.1, 20.5, 50.2, 34.7 and 42.5%. There was no statistically significant correlation between p53 expression and patient characteristics such as sex, age, smoking habits and indication for fluorescence bronchoscopy. The alteration of p53 expression in patients with high risk of lung cancer was an early event: this abnormality increased with the severity of the lesions, without significant correlation with patient characteristics.

  20. Changes in Gene Expression Profiles in Response to Selenium Supplementation among Individuals with Arsenic-induced Pre-malignant Skin Lesions

    PubMed Central

    Kibriya, Muhammad G.; Jasmine, Farzana; Argos, Maria; Verret, Wendy J.; Rakibuz-Zaman, Muhammad; Ahmed, Alauddin; Parvez, Faruque; Ahsan, Habibul

    2007-01-01

    The molecular basis and downstream targets of oral selenium supplementation in individuals with elevated risk of cancer due to chronic exposure from environmental carcinogens has been largely unexplored. In this study, we investigated genome-wide differential gene expression in peripheral blood mononuclear cells (PBMC) from individuals with pre-malignant arsenic (As)-induced skin lesions before and after six months daily oral supplementation of 200 μg l-selenomethionine. The Affymetrix GeneChip Human 133A 2.0 array, containing probes for 22,277 gene transcripts, was used to assess gene expression. Three different normalization methods, RMA (Robust Multi-chip Analysis), GC-RMA and PLIER (Probe Logarithmic Intensity Error), were applied to explore differentially expressed genes. We identified a list of 28 biologically meaningful, significantly differentially expressed genes. Genes up-regulated by selenium supplementation included TNF, IL1B, IL8, SOD2, CXCL2 and several other immunological and oxidative stress-related genes. When mapped to a biological association network, many of the differentially expressed genes were found to regulate functional classes such as fibroblast growth factor, collagenase, matrix metalloproteinase and stromelysin-1, and thus, considered to affect cellular processes like apoptosis, proliferation and others. Many of the significantly up-regulated genes following selenium-supplementation were previously found by us to be down-regulated in a different set of individuals with As-induced skin lesions compared to those without. In conclusion, findings from this study may elucidate the biological effect of selenium supplementation in humans. Additionally, this study suggests that long-term selenium supplementation may revert some of the gene expression changes presumably induced by chronic As exposure in individuals with pre-malignant skin lesions. PMID:17293063

  1. Expression of cell-cycle proteins p53, p21 (WAF-1), PCNA and Ki-67 in benign, premalignant and malignant skin lesions with implicated HPV involvement.

    PubMed

    Lu, S; Tiekso, J; Hietanen, S; Syrjänen, K; Havu, V K; Syrjänen, S

    1999-07-01

    A series of 120 biopsies from benign (verruca vulgaris and keratoacanthoma), premalignant (actinic keratosis and extragenital Bowen's disease) and malignant (squamous cell carcinoma) skin lesions were studied immunohistochemically for the expression of cell-cycle proteins p53, p21 (WAF-1), PCNA and Ki-67. The presence of human papillomavirus (HPV) DNA in these samples had been analysed previously using in situ hybridization (ISH) and PCR. Moderate to intense expression of both PCNA and Ki-67 was present in most of the lesions studied. PCNA staining was extensive in the epidermis underneath the layers where abundant HPV DNA staining was shown in HPV DNA-positive verrucas. In keratoacanthomas, p21 and PCNA expression remained low, despite intense p53 expression. In actinic keratosis, only half of the specimens showed overexpression of p53 associated with moderate or intense expression of PCNA. In extragenital Bowen's lesions, all these cell-cycle markers were overexpressed, but in squamous cell carcinomas, they were heterogeneously expressed and showed no correlation with tumour differentiation. Our results suggest a mechanism by which HPV can reactivate the host genes (leading to cell proliferation) to support its own DNA replication. Also p21 might start keratinocyte differentiation in areas where HPV DNA replication starts. Cell proliferation remained active in actinic keratosis and Bowen's lesions, emphasizing the precancer character of these lesions in contrast with the benign nature of keratoacanthoma and verruca vulgaris.

  2. Analysis of Sensitivity, Specificity, and Positive and Negative Predictive Values of Smear and Colposcopy in Diagnosis of Premalignant and Malignant Cervical Lesions

    PubMed Central

    Barut, Mert Ulaş; Kale, Ahmet; Kuyumcuoğlu, Umur; Bozkurt, Murat; Ağaçayak, Elif; Özekinci, Server; Gul, Talip

    2015-01-01

    Background This study aimed to examine the positive and negative predictive value in the diagnosis of premalignant and malignant lesions of cervical colposcopy, the sensitivity and specificity of smear, and to evaluate the correlation with histopathology of abnormal cytology and colposcopy. Material/Methods The criteria for inclusion of patients with unhealthy cervix in the study were: Erosion, Chronic cervicitis, and Healed lacerations, Hypertrophied cervix, bleeding on touch, suspicious growth/ulcer/polyp on the cervix, and abnormal discharges from the cervix. Women with frank carcinoma cervix, pregnant females, patients with bleeding per vaginum at the time of examination, and those who had used vaginal medications, vaginal contraceptives or douches in the last 48 h of examination were excluded from the study. Demographic analysis was performed for 450 patients who were admitted to the clinic. Sensitivity, specificity, positive predictive value and negative predictive values of patients to identify cervical pathologies of smear and colposcopy were histopathologically calculated. The statistical software package SPSS 15.0 (SPSS Inc., Chicago, IL, USA) and Spearman‘s and Chi-Square tests were used for statistical analysis. Results Sensitivity, specificity, PPD and NDP of smear were 0.57%, 0.76%, 0.26%, 0.92% respectively. Sensitivity, specificity, PPD and NDP of colposcopy were 0.92%, 0.67%, 0.52%, 0.96% respectively. A statistically significant correlation was found between abnormal cytology and histopathology, and abnormal colposcopy finding and histopathology. Conclusions Women with clinical diagnosis of unhealthy cervix should be evaluated by cytology to detect any premalignant or malignant lesions. It was concluded that Pap smear, colposcopy and histopathology should be collectively evaluated to evaluate cervical findings in low socio-economic regions. PMID:26655816

  3. Analysis of Sensitivity, Specificity, and Positive and Negative Predictive Values of Smear and Colposcopy in Diagnosis of Premalignant and Malignant Cervical Lesions.

    PubMed

    Barut, Mert Ulaş; Kale, Ahmet; Kuyumcuoğlu, Umur; Bozkurt, Murat; Ağaçayak, Elif; Özekinci, Server; Gül, Talip

    2015-12-10

    BACKGROUND This study aimed to examine the positive and negative predictive value in the diagnosis of premalignant and malignant lesions of cervical colposcopy, the sensitivity and specificity of smear, and to evaluate the correlation with histopathology of abnormal cytology and colposcopy. MATERIAL AND METHODS The criteria for inclusion of patients with unhealthy cervix in the study were: Erosion, Chronic cervicitis, and Healed lacerations, Hypertrophied cervix, bleeding on touch, suspicious growth/ulcer/polyp on the cervix, and abnormal discharges from the cervix. Women with frank carcinoma cervix, pregnant females, patients with bleeding per vaginum at the time of examination, and those who had used vaginal medications, vaginal contraceptives or douches in the last 48 h of examination were excluded from the study. Demographic analysis was performed for 450 patients who were admitted to the clinic. Sensitivity, specificity, positive predictive value and negative predictive values of patients to identify cervical pathologies of smear and colposcopy were histopathologically calculated. The statistical software package SPSS 15.0 (SPSS Inc., Chicago, IL, USA) and Spearman's and Chi-Square tests were used for statistical analysis. RESULTS Sensitivity, specificity, PPD and NDP of smear were 0.57%, 0.76%, 0.26%, 0.92% respectively. Sensitivity, specificity, PPD and NDP of colposcopy were 0.92%, 0.67%, 0.52%, 0.96% respectively. A statistically significant correlation was found between abnormal cytology and histopathology, and abnormal colposcopy finding and histopathology. CONCLUSIONS Women with clinical diagnosis of unhealthy cervix should be evaluated by cytology to detect any premalignant or malignant lesions. It was concluded that Pap smear, colposcopy and histopathology should be collectively evaluated to evaluate cervical findings in low socio-economic regions.

  4. Comparison of spatula and cytobrush cytological techniques in early detection of oral malignant and premalignant lesions: a prospective and blinded study.

    PubMed

    Nanayakkara, P G C L; Dissanayaka, W L; Nanayakkara, B G; Amaratunga, E A P D; Tilakaratne, W M

    2016-04-01

    The use of oral cytology to diagnose malignant and premalignant lesions at an early stage is considered crucial. The aim of this study was to evaluate the diagnoses of the spatula and the cytobrush techniques compared with the gold standard histopathological findings, analysed according to different diagnostic criteria. Cytological smears were obtained from 76 suspicious oral malignant lesions and 116 oral leukoplakia lesions using two techniques: cytobrush plus cell collector and metal spatula. Subsequently, a surgical biopsy was performed on each lesion to achieve a histopathological diagnosis. Evaluation was conducted with respect to three different diagnostic criteria. The sensitivity for diagnosing carcinoma in clinically malignant cases was 89.58% and 60.42% for cytobrush and spatula techniques, respectively. Inclusion of severe dysplastic cases for 'high-risk' lesions increased the sensitivity up to 96.36% and 78.18% for two techniques, respectively. In leukoplakia lesions, malignant and severely dysplastic cells were diagnosed at a sensitivity of 88.89% in the cytobrush and 55.56% in the spatula techniques. Extending the criteria by defining malignant or any dysplastic findings as positive, sensitivity was increased to 98.02% and 89.11% for the spatula and the cytobrush techniques, respectively. Specificity for both techniques increased to 100%. The difference between the diagnoses of histopathology and the spatula cytology was statistically significant (P < 0.01), while no such difference was found with the cytobrush technique (P > 0.1). The cytobrush, unlike the spatula, is a useful screening instrument for early diagnosis of suspicious oral lesions and could therefore contribute to improved oral cancer prognosis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Chromosomal Aneusomy in Bronchial High-Grade Lesions Is Associated with Invasive Lung Cancer

    PubMed Central

    Jonsson, Steinn; Varella-Garcia, Marileila; Miller, York E.; Wolf, Holly J.; Byers, Tim; Braudrick, Sarah; Kiatsimkul, Porntip; Lewis, Marina; Kennedy, Timothy C.; Keith, Robert L.; Bjornsson, Johannes; McWilliams, Annette; Lam, Stephen; Hirsch, Fred R.; Franklin, Wilbur A.

    2008-01-01

    Rationale: The development of lung cancer (LC) is accompanied by field changes in the airway mucosa that may have prognostic importance. Objectives: To compare patients with prevalent LC to control subjects regarding their histologic dysplasia scores and chromosomal aneusomy as measured by fluorescence in situ hybridization (FISH). Methods: The most advanced bronchial histology lesion was assessed from each of 44 LC cases and 90 cancer-free control subjects using a four-color FISH probe set encompassing the chromosome 6 centromere, 5p15.2, 7p12 (epidermal growth factor receptor), and 8q24 v-myc myelocytomatosis viral oncogene homolog (MYC) sequences. Histology grades were coded as dysplasia (moderate or severe) or carcinoma in situ (CIS). Measurements and Main Results: CIS was the highest histologic grade for 32 subjects, and dysplasia was the highest grade for 102 subjects (54 moderate, 48 severe). Chromosomal aneusomy was seen in 64% of the LC cases, but in only 31% of the control subjects (odds ratio [OR], 4.68; 95% confidence interval [CI]. 1.97–11.04). Among those with any level of dysplasia, the OR for positive FISH and LC was 2.28 (95% CI, 0.75–6.86). Among those with CIS, the OR for positive FISH and LC was 5.84 (95% CI, 1.31–26.01). Conclusions: Chromosomal aneusomy is associated with LC. Prospective examination of aneusomy as a precursor lesion that predicts LC is needed. PMID:17989344

  6. BRONCHIAL LESIONS OF MOUSE MODEL OF ASTHMA ARE PRECEDED BY IMMUNE COMPLEX VASCULITIS AND INDUCED BRONCHIAL ASSOCIATED LYMPHOID TISSUE (iBALT)

    PubMed Central

    Guest, Ian; Sell, Stewart

    2015-01-01

    We systematically examined by immune-histology the lungs of some widely used mouse models of asthma. These models include sensitization by multiple intraperitoneal injections of soluble ovalbumin (OVA) or of OVA with alum, followed by three intranasal or aerosol challenges 3 days apart. Within 24 hours after a single challenge there is fibrinoid necrosis of arterial walls with deposition of immunoglobulin and OVA and infiltration of eosinophilic polymorphonuclear cells that lasts for about 3 days followed by peribronchial B-cell infiltration and slight reversible goblet cell hypertrophy. After 2 challenges, severe eosinophilic vasculitis is present at 6 hours, increases by 72 hours and then declines; B-cell proliferation and significant goblet cell hypertrophy and hyperplasia (GCHTH) and bronchial smooth muscle hypertrophy recur more prominently. After 3 challenges, there is significantly increased induced bronchus associated lymphoid tissue (iBALT) formation, GCHTH and smooth muscle hypertrophy. Elevated levels of Th2 cytokines: IL-4, IL-5 and IL-13, are present in bronchial lavage fluids. Sensitized mice have precipitating antibody and positive Arthus skin reactions but also develop significant levels IgE antibody to OVA but only 1 week after challenge. We conclude that the asthma like lung lesions induced in these models is preceded by immune complex mediated eosinophilic vasculitis and iBALT formation. There are elevations of Th2 cytokines that most likely produce bronchial lesions that resemble human asthma. However, it is unlikely that mast cell activated atopic mechanisms are responsible as we found only a few presumed mast cells by toluidine blue and metachromatic staining limited to the most proximal part of the main stem bronchus, and none in the remaining main stem bronchus or in the lung periphery. PMID:26006019

  7. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    NASA Astrophysics Data System (ADS)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  8. Comparsion of light dose on topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    NASA Astrophysics Data System (ADS)

    Yang, Deng-Fu; Tseng, Meng-Ke; Liu, Chung-Ji; Hsu, Yih-Chih

    2012-03-01

    Oral cancer has becomes the most prominent male cancer disease due to the local betel nut chewing habit combing with smoking and alcohol-drinking lifestyle. In order to minimize the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA -mediated PDT. We found that ALA reached its peak level in cancerous lesions about 2.5 hrs after topical application of ALA gel. The precancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 75 and 100 J/cm2 using LED 635 nm Wonderlight device. It is suggesting that optimization of the given light dose is critical to the success of PDT results.

  9. Oral-specific ablation of Klf4 disrupts epithelial terminal differentiation and increases premalignant lesions and carcinomas upon chemical carcinogenesis.

    PubMed

    Paparella, María L; Abrigo, Marianela; Bal de Kier Joffe, Elisa; Raimondi, Ana R

    2015-11-01

    Squamous cell carcinoma (SSC) of the head and neck is the sixth most common cancer and is rarely diagnosed in early stages. The transcription factor Krϋppel-like factor 4 (Klf4) suppresses cell proliferation and promotes differentiation. Inducible mice carrying an oral-specific ablation of Klf4 (K14-CreER(tam) /Klf4(flox/flox) ) develop mild dysplastic lesions and abnormal differentiation in the tongue. Aiming to analyze whether Klf4 cooperate in oral chemical carcinogenesis,we applied 4-nitroquinoline 1-oxide (4NQO), a tobacco surrogate, to this conditional Klf4 knockout mice. K14-CreER(tam) /Klf4(flox/flox) and control mice were treated with 4NQO for 16 weeks and monitored until week 30. Histopathological samples were used for diagnostic purposes and immunofluorescence detection of epithelial differentiation markers. 4NQO-treated K14-CreER(tam) /Klf4(flox/flox) mice (Klf4KO 4NQO) showed a significant weight loss and developed more severe dysplastic lesions than control mice with 4NQO (P < 0.005). The Klf4KO 4NQO showed a tendency to higher incidence of oral SCC and a marked keratinization pattern in dysplasias, in situ carcinomas and SCC. Also, tongues derived from Klf4KO 4NQO mice exhibited reduced terminal differentiation as judged by cytokeratin 1 staining when compared with 4NQO-treated controls. Klf4 ablation results in more severe dysplastic lesions in oral mucosa, with a tendency to higher incidence of SCC, after chemical carcinogenesis. We show here, in a context similar to the human carcinogenesis, that absence of Klf4 accelerates carcinogenesis and correlates with the absence of cytokeratin 1 expression. These results suggest a potential role for KLF4 as a tumor suppressor gene for the tongue epithelium. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota

    PubMed Central

    Whary, Mark T.; Muthupalani, Sureshkumar; Ge, Zhongming; Feng, Yan; Lofgren, Jennifer; Shi, Hai Ning; Taylor, Nancy S.; Correa, Pelayo; Versalovic, James; Wang, Timothy C.; Fox, James G.

    2014-01-01

    Higher prevalence of helminth infections in H. pylori infected children was suggested to potentially lower the life-time risk for gastric adenocarcinoma. In rodent models, helminth co-infection does not reduce Helicobacter-induced inflammation but delays progression of pre-malignant gastric lesions. Because gastric cancer in INS-GAS mice is promoted by intestinal microflora, the impact of Heligmosomoides polygyrus co-infection on H. pylori-associated gastric lesions and microflora were evaluated. Male INS-GAS mice co-infected with H. pylori and H. polygyrus for 5 months were assessed for gastrointestinal lesions, inflammation-related mRNA expression, FoxP3+ cells, epithelial proliferation, and gastric colonization with H. pylori and Altered Schaedler Flora. Despite similar gastric inflammation and high levels of proinflammatory mRNA, helminth co-infection increased FoxP3+ cells in the corpus and reduced H. pylori-associated gastric atrophy (p<0.04), dysplasia (p<0.02) and prevented H. pylori-induced changes in the gastric flora (p<0.05). This is the first evidence of helminth infection reducing H. pylori-induced gastric lesions while inhibiting changes in gastric flora, consistent with prior observations that gastric colonization with enteric microbiota accelerated gastric lesions in INS-GAS mice. Identifying how helminths reduce gastric premalignant lesions and impact bacterial colonization of the H. pylori infected stomach could lead to new treatment strategies to inhibit progression from chronic gastritis to cancer in humans. PMID:24513446

  11. Redirecting the focus of cancer immunotherapy to premalignant conditions.

    PubMed

    Young, M Rita I

    2017-04-10

    Much progress has been made in introducing immunological treatment approaches for cancer, with lessons learned from both the successes and failures of immunotherapy. Among the challenges of immunotherapeutic approaches for cancer are the multitudes of mechanisms by which cancers are known to subvert the immune defenses. This has led to the incorporation into the immunotherapeutic arsenal strategies by which to overcome the cancer's immunological blockades. What has been only superficially explored is the immunological milieu of premalignant lesions and the possibility of immunological approaches for the treatment of premalignant lesions so as to prevent secondary premalignant lesions and their progression to cancer. This review discusses the immunological environment associated with premalignant lesions, and the possible missed opportunity of utilizing immunological treatment strategies in the less hostile environment of premalignant lesions as compared to the immune subversive cancer environment.

  12. Exploring the molecular pathogenesis and biomarkers of high risk oral premalignant lesions on the basis of long noncoding RNA expression profiling by serial analysis of gene expression.

    PubMed

    Jia, Hongcheng; Wang, Xuan; Sun, Zheng

    2017-04-24

    Oral premalignant lesions (OPLs) have malignant transformation potential, with no reliable markers available. This study aimed to assess molecular events to identify biomarkers that can reflect high-risk lesions as predictive factors to tailor clinical decision for patients on the basis of long noncoding RNAs (lncRNA) expression profiling by serial analysis of gene expression. The GSE31021 and GSE8127 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and lncRNAs were identified using the LIMMA package in R language. The genes targeted by lncRNAs were predicted among screened DEGs using Pearson's correlation. Gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway analyses were carried out for genes targeted by lncRNAs using the Database for Annotation, Visualization, and Integrated Discovery online tool. A total of 674 DEGs and differentially expressed lncRNAs were screened. Thirty-two interactions of 10 lncRNAs and 524 target genes were predicted. The lncRNA NEAT1 was among the top 10 lncRNAs. The coregulated target genes RP4-684O24, RP11-283I3, and RP11-350G8 were significantly enriched in the immune response and mannosyl-oligosaccharide mannosidase activity. The target genes coregulated by LINC00665 and MIR378D2 were significantly enriched in the ubiquitin-dependent protein catabolic process, ubiquitin-protein ligase activity, and neurotrophin signaling. The lncRNA NEAT1 may play an important role in high-risk lesions. The novel lncRNAs and DEGs identified in OPLs may mediate the immune response and neurotrophin signaling and show ubiquitin ligase activity. These results improve our understanding of the molecular pathogenesis of OPLs and identify some potential targets for early diagnosis of high risk OPLs.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to

  13. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions.

    PubMed

    Cheng, A L; Hsu, C H; Lin, J K; Hsu, M M; Ho, Y F; Shen, T S; Ko, J Y; Lin, J T; Lin, B R; Ming-Shiang, W; Yu, H S; Jee, S H; Chen, G S; Chen, T M; Chen, C A; Lai, M K; Pu, Y S; Pan, M H; Wang, Y J; Tsai, C C; Hsieh, C Y

    2001-01-01

    Curcumin (diferuloylmethane), a yellow substance from the root of the plant Curcuma longa Linn., has been demonstrated to inhibit carcinogenesis of murine skin, stomach, intestine and liver. However, the toxicology, pharmacokinetics and biologically effective dose of curcumin in humans have not been reported. This prospective phase-I study evaluated these issues of curcumin in patients with one of the following five high-risk conditions: 1) recently resected urinary bladder cancer; 2) arsenic Bowen's disease of the skin; 3) uterine cervical intraepithelial neoplasm (CIN); 4) oral leucoplakia; and 5) intestinal metaplasia of the stomach. Curcumin was taken orally for 3 months. Biopsy of the lesion sites was done immediately before and 3 months after starting curcumin treament. The starting dose was 500 mg/day. If no toxicity > or = grade II was noted in at least 3 successive patients, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The concentration of curcumin in serum and urine was determined by high pressure liquid chromatography (HPLC). A total of 25 patients were enrolled in this study. There was no treatment-related toxicity up to 8,000 mg/day. Beyond 8,000 mg/day, the bulky volume of the drug was unacceptable to the patients. The serum concentration of curcumin usually peaked at 1 to 2 hours after oral intake of crucumin and gradually declined within 12 hours. The average peak serum concentrations after taking 4,000 mg, 6,000 mg and 8,000 mg of curcumin were 0.51 +/- 0.11 microM, 0.63 +/- 0.06 microM and 1.77 +/- 1.87 microM, respectively. Urinary excretion of curcumin was undetectable. One of 4 patients with CIN and 1 of 7 patients with oral leucoplakia proceeded to develop frank malignancies in spite of curcumin treatment. In contrast, histologic improvement of precancerous lesions was seen in 1 out of 2 patients with recently resected bladder cancer, 2 out of 7 patients of oral leucoplakia, 1 out

  14. DNA damage drives an activin a-dependent induction of cyclooxygenase-2 in premalignant cells and lesions.

    PubMed

    Fordyce, Colleen; Fessenden, Tim; Pickering, Curtis; Jung, Jason; Singla, Veena; Berman, Hal; Tlsty, Thea

    2010-02-01

    Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the synthesis of prostaglandins. Its overexpression induces numerous tumor-promoting phenotypes and is associated with cancer metastasis and poor clinical outcome. Although COX-2 inhibitors are promising chemotherapeutic and chemopreventative agents for cancer, the risk of significant cardiovascular and gastrointestinal complications currently outweighs their potential benefits. Systemic complications of COX-2 inhibition could be avoided by specifically decreasing COX-2 expression in epithelial cells. To that end, we have investigated the signal transduction pathway regulating the COX-2 expression in response to DNA damage in breast epithelial cells. In variant human mammary epithelial cells that have silenced p16 (vHMEC), double-strand DNA damage or telomere malfunction results in a p53- and activin A-dependent induction of COX-2 and continued proliferation. In contrast, telomere malfunction in HMEC with an intact p16/Rb pathway induces cell cycle arrest. Importantly, in ductal carcinoma in situ lesions, high COX-2 expression is associated with high gammaH2AX, TRF2, activin A, and telomere malfunction. These data show that DNA damage and telomere malfunction can have both cell-autonomous and cell-nonautonomous consequences and can provide a novel mechanism for the propagation of tumorigenesis.

  15. DNA Damage Drives an Activin A-Dependent Induction of COX-2 in Premalignant Cells and Lesions

    PubMed Central

    Fordyce, Colleen; Fessenden, Tim; Pickering, Curtis; Jung, Jason; Singla, Veena; Berman, Hal; Tlsty, Thea

    2010-01-01

    COX-2 catalyzes the rate-limiting step in the synthesis of prostaglandins. Its overexpression induces numerous tumor-promoting phenotypes and is associated with cancer metastasis and poor clinical outcome. Although COX-2 inhibitors are promising chemotherapeutic and chemopreventative agents for cancer, the risk of significant cardiovascular and gastrointestinal complications currently outweighs their potential benefits. Systemic complications of COX-2 inhibition could be avoided by specifically decreasing COX-2 expression in epithelial cells. To that end, we have investigated the signal transduction pathway regulating COX-2 expression in response to DNA damage in breast epithelial cells. In variant human mammary epithelial cells that have silenced p16 (vHMEC), double strand DNA damage or telomere malfunction results in a p53-and activin A-dependent induction of COX-2 and continued proliferation. In contrast, telomere malfunction in HMEC with an intact p16/Rb pathway induces cell cycle arrest. Importantly, in ductal carcinoma in situ (DCIS) lesions, high COX-2 expression is associated with high γH2AX, TRF2, activin A and telomere malfunction. These data demonstrate that DNA damage and telomere malfunction can have both cell autonomous and cell non-autonomous consequences and provides a novel mechanism for the propagation of tumorigenesis. PMID:20028875

  16. The variant of pri-mir-26a-1 polymorphism is associated with decreased risk of betel quid-related oral premalignant lesions and oral squamous cell carcinoma.

    PubMed

    Yang, Cheng-Mei; Chen, Chien-Chou; Tseng, Yu-Kai; Huang, Sin-Jhih; Liou, Huei-Han; Lee, Yi-Cheng; Lee, Jang-Hwa; Wang, Jyh-Seng; Chen, Hung-Chih; Chi, Chao-Chuan; Kang, Bor-Hwang; Lin, Yun-Chung; Tsai, Kuo-Wang; Ger, Luo-Ping

    2017-06-08

    This case-control study evaluated the association of the single nucleotide polymorphism rs7372209 (T>C) in pri-mir-26a-1 with the risk and progression of betel quid (BQ)-related oral premalignant lesions (OPLs) and oral squamous cell carcinoma (OSCC). In total, 597 BQ chewers were recruited: 196 healthy controls, 241 patients with OPLs, and 160 patients with OSCC. Genotypes were determined using the TaqMan real-time assay. The C/T + T/T genotypes and T allele in pri-mir-26a-1 were correlated with a decreased risk of BQ-related OPLs (P = .038 and .005, respectively), oral leukoplakia (P = .01 and .001, respectively), and advanced-stage OSCC (P = .021 and .004, respectively). The effects of the C/T + T/T genotypes and T allele on the decreased risk of OPLs were potent in the older age group (both Pinteraction < .001), heavy smokers (Pinteraction ≤ .003 and .006, respectively) and alcohol drinkers (Pinteraction ≤ .004 and .001, respectively). Furthermore, among patients with OSCC, the C/T + T/T genotypes and T allele were associated with a decreased risk of advanced pathologic stage (P = .032) and lymph node involvement (P = .017). BQ chewers carrying the T allele or C/T + T/T genotypes in pri-mir-26a-1 may have a decreased risk of oral leukoplakia, OPLs, and advanced-stage OSCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The A/G Allele of Rs16906252 Predicts for MGMT Methylation and Is Selectively Silenced in Premalignant Lesions from Smokers and in Lung Adenocarcinomas

    PubMed Central

    Leng, Shuguang; Bernauer, Amanda M.; Hong, Chibo; Do, Kieu C.; Yingling, Christin M.; Flores, Kristina G.; Tessema, Mathewos; Tellez, Carmen S.; Willink, Randall P.; Burki, Elizabeth A.; Picchi, Maria A.; Stidley, Christine A.; Prados, Michael D.; Costello, Joseph F.; Gilliland, Frank D.; Crowell, Richard E.; Belinsky, Steven A.

    2011-01-01

    Purpose To address the association between sequence variants within the MGMT promoter-enhancer region and methylation of MGMT in premalignant lesions from smokers and lung adenocarcinomas, their biological effects on gene regulation, and targeting MGMT for therapy. Experimental Design SNPs identified through sequencing a 1.9kb fragment 5' of MGMT were examined in relation to MGMT methylation in 169 lung adenocarcinomas and 1731 sputum samples from smokers. The effect of promoter haplotypes on MGMT expression was tested using a luciferase reporter assay and cDNA expression analysis along with allele-specific sequencing for methylation. The response of MGMT methylated lung cancer cell lines to the alkylating agent temozolomide was assessed. Results The A allele of rs16906252 and the haplotype containing this SNP were strongly associated with increased risk for MGMT methylation in adenocarcinomas (ORs ≥ 94). This association was observed to a lesser extent in sputum samples in both smoker cohorts. The A allele was selectively methylated in primary lung tumors and cell lines heterozygous for rs16906252. With the most common haplotype as the reference, a 20–41% reduction in promoter activity was seen for the haplotype carrying the A allele that correlated with lower MGMT expression. The sensitivity of lung cancer cell lines to temozolamide was strongly correlated with levels of MGMT methylation and expression. Conclusions These studies provide strong evidence that the A allele of a MGMT promoter-enhancer SNP is a key determinant for MGMT methylation in lung carcinogenesis. Moreover, temozolamide treatment may benefit a subset of lung cancer patients methylated for MGMT. PMID:21355081

  18. Detection of interleukins-6 and 8 in saliva as potential biomarkers of oral pre-malignant lesion and oral carcinoma: A breakthrough in salivary diagnostics in Pakistan.

    PubMed

    Khyani, Iqbal A Muhammad; Qureshi, Masood A; Mirza, Talat; Farooq, M Umar

    2017-05-01

    Oral cancer is at rise in our population due to increasing use of areca nut (Betel nut) with or without tobacco. It is the second frequent malignant tumour for both the gender in Pakistan. This non-interventional case control study was carried out with the aim to explore saliva as diagnostic medium for detecting interleukins (IL) 6 and 8 as biomarkers of pre-malignant lesions (PML) and oral carcinoma. Total 105 subjects were recruited and were divided into three groups "A", "B" and "C" each comprising of 35 subjects. Group "A" comprised of cases with strong clinical evidence of oral PML. Group "B" constitute clinical and histologically proven OSCC and group "C" include disease free subjects as controls. Saliva from all the recruited subjects was procured by drooling method and stored at-200C before further process. All the collected samples were centrifuged at 4500 rpm for 15 minutes at 4oC. Supernatant fluid was used in ELISA for detection and quantification of IL-6 & IL-8. Data was analysed by using Chi-square test and multivariate analysis was done by non-parametric test. P-value of 0.05 was taken as standard reference. Significant co-relation was found for qualitative salivary detection of IL-6 and IL-8 among the groups (P<0.001 and <0.0001 respectively). Regarding quantitative salivary concentration of leukotrienes, no significant co-relation was found in levels of IL-6 among the groups while there was significant association of IL-8 levels between the groups (P<0.0001).On post Hoc multiple comparison, significant co-relation was found among oral PML group and controls (P=0.001) and OSCC group and control (P=<0.0001). In conclusion salivary detection of IL-6 & IL-8 could be used as probable biomarker for early detection of oral PML & OSCC in etiologically distinct population of Pakistan.

  19. Exfoliative cytology as a tool for monitoring pre-malignant and malignant lesions based on combined stains and morphometry techniques.

    PubMed

    Gonzalez Segura, Ignacio; Secchi, Dante; Carrica, Andres; Barello, Rosario; Arbelo, Dario; Burgos, Adriana; Brunotto, Mabel; Zarate, Ana M

    2015-03-01

    Prevention and early diagnosis have the greatest potential for public health and are the most effective method in the long-term to control oral cancer. The aim was to apply PAP staining together with AgNOR staining and morphometric analysis in oral exfoliative cytology, to determine the sensitivity and specificity of these methods in the detection of malignant changes for the purposes of both initial population monitoring and follow-up. AgNOR, Papanicolau, and morphometric tests were conducted in samples of patients with oral cancer, oral potentially malignant disorders and controls (opposite side of lesions). Specificity and sensitivity values for each stain method and the curve under ROC area were estimated. The diagnostic variables which allowed greatest accuracy in identifying malignancy relative to the healthy control were cluster (76.92%), satellite (75.64%), and total (90%). The diagnosis was seen to be associated with PAP and total AgNOR, total AgNOR and PAP, total AgNOR and satellites and clusters, and total AgNOR nuclear area/cytoplasmic area ratio. The total number of AgNOR is a reliable marker for detecting neoplastic cells; this method increases sensitivity and specificity by decreasing the likelihood of false negatives or positives, as the accuracy obtained was 90%. It is also a low-cost, non-invasive, simple methodology that can be recommended to help the early detection of oral cancer and monitoring of patients with a first diagnosis of cancer. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. An in vitro diagnosis of oral premalignant lesion using time-resolved fluorescence spectroscopy under UV excitation-a pilot study.

    PubMed

    Kanniyappan, Udayakumar; Prakasarao, Aruna; Dornadula, Koteeswaran; Singaravelu, Ganesan

    2016-06-01

    In spite of rapid advancement in cancer treatment, early diagnosis of cancer and medicable precursors are still the finest approach towards the assurance of patient lives and enhancement in the quality of their life. In this regard, the present study deals with the time-resolved fluorescence spectroscopy of normal and premalignant oral tissues under UV excitations (280nm and 310nm). The decay kinetics at 350nm emission of normal tissues exhibit higher fluorescence lifetime than that of premalignant tissues and subsequent statistical analysis shows that the data were statistically significant. Further, the decay kinetics at 450nm emission for normal and premalignant oral tissues was obtained. Subsequently, statistical analysis revealed that except fast component, rest of the component lifetimes and fractional amplitudes were not statistically significant. An attempt has also been made to explore the better statistical tool to discriminate premalignant tissues from normal ones at 350nm emission. Among stepwise linear discriminant analysis (SLDA) and receiver operator characteristics (ROC), the former discriminates premalignant from normal tissues with 86.7% specificity and 93.3% sensitivity. Hence, fluorescence lifetime spectroscopy at 350nm emission opens a new avenue for early detection of oral cancer.

  1. [Quantitative image analysis in pulmonary pathology - digitalization of preneoplastic lesions in human bronchial epithelium (author's transl)].

    PubMed

    Steinbach, T; Müller, K M; Kämper, H

    1979-01-01

    The report concerns the first phase of a quantitative study of normal and abnormal bronchial epithelium with the objective of establishing the digitalization of histologic patterns. Preparative methods, data collecting and handling, and further mathematical analysis are described. In cluster and discriminatory analysis the digitalized histologic features can be used to separate and classify the individual cases into the respective diagnostic groups.

  2. Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota.

    PubMed

    Whary, Mark T; Muthupalani, Sureshkumar; Ge, Zhongming; Feng, Yan; Lofgren, Jennifer; Shi, Hai Ning; Taylor, Nancy S; Correa, Pelayo; Versalovic, James; Wang, Timothy C; Fox, James G

    2014-04-01

    Higher prevalence of helminth infections in Helicobacter pylori infected children was suggested to potentially lower the life-time risk for gastric adenocarcinoma. In rodent models, helminth co-infection does not reduce Helicobacter-induced inflammation but delays progression of pre-malignant gastric lesions. Because gastric cancer in INS-GAS mice is promoted by intestinal microflora, the impact of Heligmosomoides polygyrus co-infection on H. pylori-associated gastric lesions and microflora were evaluated. Male INS-GAS mice co-infected with H. pylori and H. polygyrus for 5 months were assessed for gastrointestinal lesions, inflammation-related mRNA expression, FoxP3(+) cells, epithelial proliferation, and gastric colonization with H. pylori and Altered Schaedler Flora. Despite similar gastric inflammation and high levels of proinflammatory mRNA, helminth co-infection increased FoxP3(+) cells in the corpus and reduced H. pylori-associated gastric atrophy (p < 0.04), dysplasia (p < 0.02) and prevented H. pylori-induced changes in the gastric flora (p < 0.05). This is the first evidence of helminth infection reducing H. pylori-induced gastric lesions while inhibiting changes in gastric flora, consistent with prior observations that gastric colonization with enteric microbiota accelerated gastric lesions in INS-GAS mice. Identifying how helminths reduce gastric premalignant lesions and impact bacterial colonization of the H. pylori infected stomach could lead to new treatment strategies to inhibit progression from chronic gastritis to cancer in humans. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  3. Biochemical basis of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation: a study in patients with (pre)malignant lesions of the oesophagus.

    PubMed Central

    Hinnen, P.; de Rooij, F. W.; van Velthuysen, M. L.; Edixhoven, A.; van Hillegersberg, R.; Tilanus, H. W.; Wilson, J. H.; Siersema, P. D.

    1998-01-01

    Administration of 5-aminolaevulinic acid (ALA) leads to porphyrin accumulation in malignant and premalignant tissues, and ALA is used as a prodrug in photodynamic therapy (PDT). To understand the mechanism of porphyrin accumulation after the administration of ALA and to investigate whether ALA-induced protoporphyrin IX might be a suitable photosensitizer in Barrett's oesophagus and adenocarcinoma, we determined the activities of porphobilinogen deaminase (PBG-D) and ferrochelatase (FC) in various malignant and premalignant as well as in normal tissues of the human oesophagus. A PDT power index for ALA-induced porphyrin accumulation, the ratio of PBG-D to FC normalized for the normal squamous epithelium of the oesophagus, was calculated to evaluate intertissue variation in the ability to accumulate porphyrins. In malignant and premalignant tissue a twofold increased PBG-D activity and a marginally increased FC activity was seen compared with normal squamous epithelium. A significantly increased PDT power index in Barrett's epithelium and adenocarcinoma was found. Our results suggest that, after the administration of ALA, porphyrins will accumulate in a greater amount in Barrett's epithelium and adenocarcinoma of the oesophagus because of an imbalance between PBG-D and FC activities. The PDT power index here defined might be a useful indicative parameter for predicting the susceptibility of these tissues to ALA-PDT. PMID:9744510

  4. Promoter region hypermethylation and mRNA expression of MGMT and p16 genes in tissue and blood samples of human premalignant oral lesions and oral squamous cell carcinoma.

    PubMed

    Bhatia, Vikram; Goel, Madhu Mati; Makker, Annu; Tewari, Shikha; Yadu, Alka; Shilpi, Priyanka; Kumar, Sandeep; Agarwal, S P; Goel, Sudhir K

    2014-01-01

    Promoter methylation and relative gene expression of O(6)-methyguanine-DNA-methyltransferase (MGMT) and p16 genes were examined in tissue and blood samples of patients with premalignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC). Methylation-specific PCR and reverse transcriptase PCR were performed in 146 tissue and blood samples from controls and patients with PMOLs and OSCC. In PMOL group, significant promoter methylation of MGMT and p16 genes was observed in 59% (P = 0.0010) and 57% (P = 0.0016) of tissue samples, respectively, and 39% (P = 0.0135) and 33% (P = 0.0074) of blood samples, respectively. Promoter methylation of both genes was more frequent in patients with OSCC, that is, 76% (P = 0.0001) and 82% (P = 0.0001) in tissue and 57% (P = 0.0002) and 70% (P = 0.0001) in blood, respectively. Significant downregulation of MGMT and p16 mRNA expression was observed in both tissue and blood samples from patients with PMOLs and OSCC. Hypermethylation-induced transcriptional silencing of MGMT and p16 genes in both precancer and cancer suggests important role of these changes in progression of premalignant state to malignancy. Results support use of blood as potential surrogate to tissue samples for screening or diagnosing PMOLs and early OSCC.

  5. Promoter Region Hypermethylation and mRNA Expression of MGMT and p16 Genes in Tissue and Blood Samples of Human Premalignant Oral Lesions and Oral Squamous Cell Carcinoma

    PubMed Central

    Bhatia, Vikram; Makker, Annu; Tewari, Shikha; Yadu, Alka; Shilpi, Priyanka; Kumar, Sandeep; Agarwal, S. P.; Goel, Sudhir K.

    2014-01-01

    Promoter methylation and relative gene expression of O6-methyguanine-DNA-methyltransferase (MGMT) and p16 genes were examined in tissue and blood samples of patients with premalignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC). Methylation-specific PCR and reverse transcriptase PCR were performed in 146 tissue and blood samples from controls and patients with PMOLs and OSCC. In PMOL group, significant promoter methylation of MGMT and p16 genes was observed in 59% (P = 0.0010) and 57% (P = 0.0016) of tissue samples, respectively, and 39% (P = 0.0135) and 33% (P = 0.0074) of blood samples, respectively. Promoter methylation of both genes was more frequent in patients with OSCC, that is, 76% (P = 0.0001) and 82% (P = 0.0001) in tissue and 57% (P = 0.0002) and 70% (P = 0.0001) in blood, respectively. Significant downregulation of MGMT and p16 mRNA expression was observed in both tissue and blood samples from patients with PMOLs and OSCC. Hypermethylation-induced transcriptional silencing of MGMT and p16 genes in both precancer and cancer suggests important role of these changes in progression of premalignant state to malignancy. Results support use of blood as potential surrogate to tissue samples for screening or diagnosing PMOLs and early OSCC. PMID:24991542

  6. Leveraging premalignant biology for immune-based cancer prevention

    PubMed Central

    Spira, Avrum; Disis, Mary L.; Schiller, John T.; Vilar, Eduardo; Rebbeck, Timothy R.; Bejar, Rafael; Ideker, Trey; Arts, Janine; Yurgelun, Matthew B.; Mesirov, Jill P.; Rao, Anjana; Garber, Judy; Jaffee, Elizabeth M.; Lippman, Scott M.

    2016-01-01

    Prevention is an essential component of cancer eradication. Next-generation sequencing of cancer genomes and epigenomes has defined large numbers of driver mutations and molecular subgroups, leading to therapeutic advances. By comparison, there is a relative paucity of such knowledge in premalignant neoplasia, which inherently limits the potential to develop precision prevention strategies. Studies on the interplay between germ-line and somatic events have elucidated genetic processes underlying premalignant progression and preventive targets. Emerging data hint at the immune system’s ability to intercept premalignancy and prevent cancer. Genetically engineered mouse models have identified mechanisms by which genetic drivers and other somatic alterations recruit inflammatory cells and induce changes in normal cells to create and interact with the premalignant tumor microenvironment to promote oncogenesis and immune evasion. These studies are currently limited to only a few lesion types and patients. In this Perspective, we advocate a large-scale collaborative effort to systematically map the biology of premalignancy and the surrounding cellular response. By bringing together scientists from diverse disciplines (e.g., biochemistry, omics, and computational biology; microbiology, immunology, and medical genetics; engineering, imaging, and synthetic chemistry; and implementation science), we can drive a concerted effort focused on cancer vaccines to reprogram the immune response to prevent, detect, and reject premalignancy. Lynch syndrome, clonal hematopoiesis, and cervical intraepithelial neoplasia which also serve as models for inherited syndromes, blood, and viral premalignancies, are ideal scenarios in which to launch this initiative. PMID:27638202

  7. HPV prevalence and type-distribution in cervical cancer and premalignant lesions of the cervix: A population-based study from Northern Ireland.

    PubMed

    Anderson, Lesley A; O'Rorke, Michael A; Wilson, Robbie; Jamison, Jackie; Gavin, Anna T

    2016-07-01

    Assessment of Human papillomavirus (HPV) prevalence and genotype distribution is important for monitoring the impact of prophylactic HPV vaccination. This study aimed to demonstrate the HPV genotypes predominating in pre-malignant and cervical cancers in Northern Ireland (NI) before the vaccination campaign has effect. Formalin fixed paraffin embedded tissue blocks from 2,303 women aged 16-93 years throughout NI were collated between April 2011 and February 2013. HPV DNA was amplified by PCR and HPV genotyping undertaken using the Roche(®) linear array detection kit. In total, 1,241 out of 1,830 eligible samples (68.0%) tested positive for HPV, with the majority of these [1,181/1,830 (64.5%)] having high-risk (HR) HPV infection; 37.4% were positive for HPV-16 (n = 684) and 5.1% for HPV-18 (n = 93). HPV type-specific prevalence was 48.1%, 65.9%, 81.3%, 92.2%, and 64.3% among cervical intraepithelial neoplasias (CIN) Grades I-III, squamous cell carcinomas (SCC) and adenocarcinoma (AC) cases, respectively. Most SCC cases (81.3%) had only one HPV genotype detected and almost a third (32.0%) of all cervical pathologies were HPV negative including 51.9% of CIN I (n = 283), 34.1% CIN II (n = 145), 18.7% of CIN III (n = 146), 7.8% of SCC (n = 5), and 35.7% of AC (n = 5) cases. This study provides important baseline data for monitoring the effect of HPV vaccination in NI and for comparison with other UK regions. The coverage of other HR-HPV genotypes apart from 16 and 18, including HPV-45, 31, 39, and 52, and the potential for cross protection, should be considered when considering future polyvalent vaccines. © 2015 Wiley Periodicals, Inc.

  8. Hyaluronidases and hyaluronan synthases expression is inversely correlated with malignancy in lung/bronchial pre-neoplastic and neoplastic lesions, affecting prognosis

    PubMed Central

    de Sá, V.K.; Rocha, T.P.; Moreira, AL.; Soares, F.A.; Takagaki, T.; Carvalho, L.; Nicholson, A.G.; Capelozzi, V.L.

    2015-01-01

    We collected a series of 136 lung/bronchial and 56 matched lung parenchyma tissue samples from patients who underwent lung/bronchial biopsies and presented invasive carcinoma after lung surgery. The lung/bronchial samples included basal cell hyperplasia, squamous metaplasia, moderate dysplasia, adenomatous hyperplasia, severe dysplasia, squamous cell carcinoma and adenocarcinoma. Matched lung parenchyma tissue samples included 25 squamous cell carcinomas and 31 adenocarcinomas. Immunohistochemistry was performed to analyze for the distribution of hyaluronidase (Hyal)-1 and −3, and hyaluronan synthases (HAS)-1, −2, and −3. Hyal-1 showed significantly higher expression in basal cell hyperplasia than in moderate dysplasia (P=0.01), atypical adenomatous hyperplasia (P=0.0001), or severe dysplasia (P=0.03). Lower expression of Hyal-3 was found in atypical adenomatous hyperplasia than in basal cell hyperplasia (P=0.01) or moderate dysplasia (P=0.02). HAS-2 was significantly higher in severe dysplasia (P=0.002) and in squamous metaplasia (P=0.04) compared with basal cell hyperplasia. HAS-3 was significantly expressed in basal cell hyperplasia compared with atypical adenomatous hyperplasia (P=0.05) and severe dysplasia (P=0.02). Lower expression of HAS-3 was found in severe dysplasia compared with squamous metaplasia (P=0.01) and moderate dysplasia (P=0.01). Epithelial Hyal-1 and −3 and HAS-1, −2, and −3 expressions were significantly higher in pre-neoplastic lesions than in neoplastic lesions. Comparative Cox multivariate analysis controlled by N stage and histologic tumor type showed that patients with high HAS-3 expression in pre-neoplastic cells obtained by lung/bronchial biopsy presented a significantly higher risk of death (HR=1.19; P=0.04). We concluded that localization of Hyal and HAS in lung/bronchial pre-neoplastic and neoplastic lesions was inversely related to malignancy, which implied that visualizing these factors could be a useful diagnostic

  9. Salivary detection of human Papilloma virus 16 & 18 in pre-malignant and malignant lesions of oral cavity: Is it feasible in Pakistani context of Socio-Cultural Taboos?

    PubMed Central

    Khyani, Iqbal A. Muhammad; Qureshi, Masood A.; Mirza, Talat; Farooq, M. Umar

    2015-01-01

    Objective: To evaluate salivary detection of HPV-16 & 18 would be feasible and informative biomarker for oral pre-malignant and malignant lesion in our population. Methods: This non-interventional, case control study was carried out at department of E.N.T, Head and Neck Surgery, Dow University of Health Sciences, Dow Medical College and Civil Hospital Karachi, Pakistan between July 2011 to December 2012. Total of 105 cases were recruited. These were divided in three groups ‘A’, ‘B’ & ‘C’ having 35 subjects each. Group‘A’ constitutes patients having strong clinical evidence of oral pre-malignant lesions (PML). Group ‘B’ includes histologically proven oral squamous cell carcinoma (OSCC) and Group ‘C’ comprised disease free subjects as controls. After taking informed consent, relevant clinical history was recorded on institutional approved performa. Saliva from all subjects was procured by standard ‘drooling method’. Samples were stored at +4°C and later transferred to Laboratory to store at-20°C before further process. Samples were centrifuged at 4500 rpm for 15 minutes at 4°C. Cell pellets sediments were used for identification of HPV-16 & 18 by real-time PCR method. Data was entered and analysed using SPSS version 16. P-value of 0.05 was taken as standard. Results: In group ‘A’, HPV-16 was detected in 3 (8.6%) cases while HPV-18 was not detected in any of the subject. In group ‘B’, HPV-16 was detected in 07 (20%) while HPV-18 was found in 06 (17.1%) cases. Mixed HPV-16 and HPV-18 were found in 02 (5.7%) cases. In group ‘C’, HPV-16 was detected in 03(8.6%) while HPV-18 was not detected in any of the subjects. Significant relationship was observed between the groups for HPV-18 detection (P= 0.002) while for HPV-16, no significant association was found (P= 0.245). Conclusion: HPV infection for the causation of oral cancer cannot be fully established possibly due to small sample size. More over differences in genetic makeup

  10. Evaluation of the p16 and Ki-67 Biomarkers as Predictors of the Recurrence of Premalignant Cervical Cancer Lesions after LEEP Conization.

    PubMed

    Leite, Paulo Macêdo de Oliveira; Tafuri, Luciene; Costa, Maria Zélia de Oliveira; Lima, Maria Inês de Miranda; Simões, Renata Toscano

    2017-06-01

    Objective To evaluate the expressions of biomarkers p16 and Ki-67 in low-grade (LG) or high-grade (HG) lesions, and to relate them to risk factors and the recurrence of these lesions. Methods A retrospective case-control study of 86 patients with LG and HG lesions who underwent a loop electrosurgical excision procedure (LEEP) between 1999 and 2004. The control group was composed of 69 women with no recurrence, and the study group, of 17 patients with recurrence. All patients were followed-up over a two-year period after surgery, and screened every six months, including cytology and colposcopy. Biopsy samples collected from LEEP were submitted to immunohistochemical analysis for p16 and Ki-67. The statistical analysis was performed using the Statistical Package for the Social Sciences software (SPSS, IBM-SPSS, Inc., Chicago, IL, US), with a significant p ​​< 0.05. Results The biomarkers p16 and Ki-67, separately or combined, showed no relation to recurrence on the total analysis. However, evaluating specifically HG lesions, the positive expression (2+ and 3+) of p16/Ki-67 was associated with recurrence (0.010). In addition, p16 isolated was also more expressive in HG lesions (2+ and 3 + , p = 0.018), but it was unrelated to recurrence. Conclusion Proteins p16 and Ki-67, both isolated and combined, are not reliable primary markers for the recurrence of cervical lesions in the majority of LG lesions. However, analyzing only the group with prior diagnosis of HG lesions, the expressions of p16 and of p16/Ki-67 were associated with recurrence, and they may be useful in monitoring these cases. Thieme-Revinter Publicações Ltda Rio de Janeiro, Brazil.

  11. Premalignant and neoplastic skin lesions associated with occupational exposure to “tarry” byproducts during manufacture of 4,4'-bipyridyl

    PubMed Central

    Bowra, G T; Duffield, D P; Osborn, A J; Purchase, I F H

    1982-01-01

    ABSTRACT Skin lesions have been identified in 20 workers manufacturing 4,4'-bipyridyl. The lesions were on the face, neck, and backs of the hands and arms. Larger localised lesions were removed surgically and examined histopathologically, but other lesions have been treated topically with fluorouracil cream. Histological diagnosis showed a progression from keratosis to Bowen's disease and, in six cases, to squamous cell carcinoma. Over 550 individuals associated with 4,4'-bipyridyl processes between 1961 and 1980 have been examined or questioned. All 20 patients identified worked in now obsolete production plants; 15 of whom were found among the 147 shift process operators. The time taken for the lesions to appear from first working on a 4,4'-bipyridyl plant was 6-19 years (average 12 years). Starting in the early 1960s three processes have been successively used to convert pyridine into 4,4'-bipyridyl. These differ in the reaction conditions used and in the efficiency of the conversion. In the two earlier plants a substantial quantity of pyridine was converted into polypyridyls and “tarry” byproducts, which caused operating difficulties and increased the risk of worker exposure. The exposure and occupational histories of the cases, including the fact that two had worked only on the obsolete production plants, indicates that the causative agent was present in these earlier processes. In-vitro tests for potential carcinogenicity on materials from the present plant and from an earlier process gave positive tests on the tarry byproducts from the earlier process, suggesting that they were the cause of the lesions. Tar impurity production on the present plant is minimal, and worker exposure to chemicals is low. No similar skin lesions have been seen in those who have worked only on the present plant. This observation supports the view that the causative agent was present only on the earlier plants but is not conclusive because of the shorter time that has elapsed

  12. A Prospective Study of the Synergistic Effects of Arsenic Exposure and Smoking, Sun Exposure, Fertilizer Use, and Pesticide Use on Risk of Premalignant Skin Lesions in Bangladeshi Men

    PubMed Central

    Melkonian, Stephanie; Argos, Maria; Pierce, Brandon L.; Chen, Yu; Islam, Tariqul; Ahmed, Alauddin; Syed, Emdadul H.; Parvez, Faruque; Graziano, Joseph; Rathouz, Paul J.; Ahsan, Habibul

    2011-01-01

    Skin lesions are classic clinical signs of toxicity due to long-term exposure to arsenic, and they are considered precursors to arsenic-related skin cancer. The authors prospectively evaluated synergisms between effects of arsenic exposure and those of tobacco use, sun exposure, and pesticide and fertilizer use on incident skin lesions using risk factor data from 5,042 men from the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, which recruited participants from October 2000 to May 2002. Discrete time hazard models were used to estimate measures of synergistic interactions on the additive scale. The authors observed significant synergistic effects between various measures of arsenic exposure and smoking and fertilizer use. The relative excess risks for the interactions between smoking status and arsenic exposure were 0.12 (95% confidence interval: 0.06, 0.19) for water arsenic and 0.11 (95% confidence interval: 0.05, 0.15) for urinary arsenic measures, respectively. Significant synergistic effects were also observed between fertilizer use and water arsenic (relative excess risk for the interaction = 0.06, 95% confidence interval: 0.01, 0.12). This is the first prospective study based on individual-level data that supports a role for smoking and certain occupational risk factors in modification of the effect of long-term arsenic exposure on skin lesions. Understanding differential arsenic susceptibility allows researchers to develop interventions to prevent the health consequences of this massive problem in the Bangladeshi population and beyond. PMID:21098630

  13. PRAME expression in head and neck cancer correlates with markers of poor prognosis and might help in selecting candidates for retinoid chemoprevention in pre-malignant lesions

    PubMed Central

    Szczepanski, Miroslaw J.; DeLeo, Albert B.; Łuczak, Michał; Molinska-Glura, Marta; Misiak, Jan; Szarzynska, Bronislawa; Dworacki, Grzegorz; Zagor, Mariola; Rozwadowska, Natalia; Kurpisz, Maciej; Krzeski, Antoni; Kruk-Zagajewska, Aleksandra; Kopec, Tomasz; Banaszewski, Jacek; Whiteside, Theresa L.

    2012-01-01

    Objectives PRAME (Preferentially Expressed Antigen in Melanoma) is a tumor-associated antigen recognized by immunocytes, and it induces cytotoxic T cell-mediated responses in melanoma. PRAME expression in tumors interferes with retinoic acid receptor (RAR) signaling thus promoting tumor progression. Here, we study PRAME expression in head and neck squamous cell carcinoma (HNSCC) to determine its potential clinical significance. Materials and Methods PRAME expression in HNSCC was evaluated by immunohistochemistry in tissue microarrays of primary tumors (n=53), metastatic lymph nodes (n=8) and normal oral mucosa (n=11). Biopsies of dysplastic oral lesions (n=12) were also examined. PRAME expression levels in tissues were correlated with markers of poor prognosis in HNSCC. PRAME mRNA in HNSCC cell lines and in normal immortalized human keratinocytes (HaCaT cell line) was measured by qRT-PCR, and the protein expression by flow cytometry and western blots. Results PRAME was expressed in HNSCC cell lines and HNSCC lesions. PRAME expression in dysplastic mucosa was variable. No or only weak expression was found in normal cells or tissues. PRAME expression levels significantly correlated with the tumor grade, size, nodal involvement and the clinical status of HNSCC patients. Conclusions Elevated PRAME expression associates with clinicopathologic markers of poor outcome in HNSCC and might identify potential candidates with pre-cancerous lesions for chemoprevention with retinoids. PMID:22944049

  14. A prospective study of the synergistic effects of arsenic exposure and smoking, sun exposure, fertilizer use, and pesticide use on risk of premalignant skin lesions in Bangladeshi men.

    PubMed

    Melkonian, Stephanie; Argos, Maria; Pierce, Brandon L; Chen, Yu; Islam, Tariqul; Ahmed, Alauddin; Syed, Emdadul H; Parvez, Faruque; Graziano, Joseph; Rathouz, Paul J; Ahsan, Habibul

    2011-01-15

    Skin lesions are classic clinical signs of toxicity due to long-term exposure to arsenic, and they are considered precursors to arsenic-related skin cancer. The authors prospectively evaluated synergisms between effects of arsenic exposure and those of tobacco use, sun exposure, and pesticide and fertilizer use on incident skin lesions using risk factor data from 5,042 men from the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, which recruited participants from October 2000 to May 2002. Discrete time hazard models were used to estimate measures of synergistic interactions on the additive scale. The authors observed significant synergistic effects between various measures of arsenic exposure and smoking and fertilizer use. The relative excess risks for the interactions between smoking status and arsenic exposure were 0.12 (95% confidence interval: 0.06, 0.19) for water arsenic and 0.11 (95% confidence interval: 0.05, 0.15) for urinary arsenic measures, respectively. Significant synergistic effects were also observed between fertilizer use and water arsenic (relative excess risk for the interaction = 0.06, 95% confidence interval: 0.01, 0.12). This is the first prospective study based on individual-level data that supports a role for smoking and certain occupational risk factors in modification of the effect of long-term arsenic exposure on skin lesions. Understanding differential arsenic susceptibility allows researchers to develop interventions to prevent the health consequences of this massive problem in the Bangladeshi population and beyond.

  15. Quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (gardasil(®)): a review of its use in the prevention of premalignant anogenital lesions, cervical and anal cancers, and genital warts.

    PubMed

    McCormack, Paul L

    2014-07-01

    Quadrivalent human papillomavirus (HPV) [types 6, 11, 16, 18] recombinant vaccine (Gardasil(®); Silgard(®)) is composed of virus-like particles formed by self-assembly of recombinant L1 capsid protein from each of HPV types 6, 11, 16 and 18. It is indicated for use from the age of 9 years as a two- or three-dose vaccination course over 6 months for the prevention of premalignant anogenital lesions, cervical and anal cancers, and genital warts caused by the vaccine HPV types. In placebo-controlled trials, quadrivalent HPV vaccine provided high-level protection against infection or disease caused by the vaccine HPV types over 2-4 years in females aged 15-45 years who were negative for the vaccine HPV types, and provided a degree of cross-protection against certain non-vaccine HPV types. The vaccine also provided high-level protection against persistent infection, anogenital precancerous lesions and genital warts caused by the vaccine HPV types over 3 years in susceptible males aged 16-26 years. Protection has been demonstrated for up to 8 years. In subjects who were negative for the vaccine HPV types, high seroconversion rates and high levels of anti-HPV antibodies were observed in females of all age ranges from 9 to 45 years and in males aged 9-26 years. The vaccine was generally well tolerated and was usually predicted to be cost effective in girls and young women. Therefore, quadrivalent HPV vaccine offers an effective means to substantially reduce the burden of HPV-related anogenital disease in females and males, particularly cervical cancer and genital warts.

  16. Genetic driver events in premalignancy: LOH validated for marking the risk of oral cancer.

    PubMed

    Cavenee, Webster K

    2012-09-01

    In this issue of the journal (beginning on page 1081), Zhang and colleagues extend the 30-year-old discovery of LOH profiles to provide validated markers of oral premalignant lesion risk for cancer. They prospectively show a dramatic difference in cancer progression between high-risk lesions (LOH) and low-risk (non-LOH) lesions (P = 0.002). This work has important implications for oral cancer prevention and risk modeling and for understanding genetic driver events in premalignancy.

  17. Outcomes of oral squamous cell carcinoma arising from oral epithelial dysplasia: rationale for monitoring premalignant oral lesions in a multidisciplinary clinic.

    PubMed

    Ho, M W; Field, E A; Field, J K; Risk, J M; Rajlawat, B P; Rogers, S N; Steele, J C; Triantafyllou, A; Woolgar, J A; Lowe, D; Shaw, R J

    2013-10-01

    Surveillance of oral epithelial dysplasia results in a number of newly diagnosed cases of oral squamous cell carcinoma (SCC). The clinical stage of oral SCC at diagnosis influences the magnitude of treatment required and the prognosis. We aimed to document the stage, treatment, and outcome of oral SCC that arose in patients who were being monitored for oral epithelial dysplasia in a dedicated multidisciplinary clinic. Those with histologically diagnosed lesions were enrolled on an ethically approved protocol and molecular biomarker study. Details of clinical and pathological TNM, operation, radiotherapy, recurrence, second primary tumour, and prognosis, were recorded in patients whose lesions underwent malignant transformation. Of the 91 patients reviewed (median follow-up 48 months, IQR 18-96), 23 (25%) had malignant transformation. All were presented to the multidisciplinary team with stage 1 disease (cT1N0M0). Of these, 21 were initially treated by wide local excision, 2 required resection of tumour and reconstruction, and 2 required adjuvant radiotherapy. At follow-up 3 had local recurrence, one had regional recurrence, one had metachronous lung cancer, and 5 had second primary oral SCC. There were further diagnoses of oral dysplasia in 5 during follow-up, and it is estimated that 76% of patients will have one or other event in 5 years. Disease-specific survival was 100% and overall survival was 96% (22/23). Median follow-up after diagnosis of oral SCC was 24 months (IQR 11-58). Specialist monitoring of oral epithelial dysplasia by a multidisciplinary team allows oral SCC to be detected at an early stage, and enables largely curative treatment with simple and usually minor surgical intervention. The high incidence of second primary oral SCC in high-risk patients with oral epithelial dysplasia further supports intensive targeted surveillance in this group.

  18. Keratin 17 in premalignant and malignant squamous lesions of the cervix: proteomic discovery and immunohistochemical validation as a diagnostic and prognostic biomarker

    PubMed Central

    Escobar-Hoyos, Luisa F; Yang, Jie; Zhu, Jiawen; Cavallo, Julie-Ann; Zhai, Haiyan; Burke, Stephanie; Koller, Antonius; Chen, Emily I; Shroyer, Kenneth R

    2014-01-01

    Most previously described immunohistochemical markers of cervical high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma may help to improve diagnostic accuracy but have a minimal prognostic value. The goals of the current study were to identify and validate novel candidate biomarkers that could potentially improve diagnostic and prognostic accuracy for cervical HSIL and squamous cell carcinoma. Microdissected tissue sections from formalin-fixed paraffin-embedded normal ectocervical squamous mucosa, low-grade squamous intraepithelial lesion (LSIL), HSIL and squamous cell carcinoma sections were analyzed by mass spectrometry-based shotgun proteomics for biomarker discovery. The diagnostic specificity of candidate biomarkers was subsequently evaluated by immunohistochemical analysis of tissue microarrays. Among 1750 proteins identified by proteomic analyses, keratin 4 (KRT4) and keratin 17 (KRT17) showed reciprocal patterns of expression in the spectrum of cases ranging from normal ectocervical squamous mucosa to squamous cell carcinoma. Immunohistochemical studies confirmed that KRT4 expression was significantly decreased in squamous cell carcinoma compared with the other diagnostic categories. By contrast, KRT17 expression was significantly increased in HSIL and squamous cell carcinoma compared with normal ectocervical squamous mucosa and LSIL. KRT17 was also highly expressed in immature squamous metaplasia and in endocervical reserve cells but was generally not detected in mature squamous metaplasia. Furthermore, high levels of KRT17 expression were significantly associated with poor survival of squamous cell carcinoma patients (Hazard ratio = 14.76, P = 0.01). In summary, both KRT4 and KRT17 expressions are related to the histopathology of the cervical squamous mucosa; KRT17 is highly overexpressed in immature squamous metaplasia, in HSIL, and in squamous cell carcinoma and the level of KRT17 in squamous cell carcinoma may help to identify

  19. Differential expression of CD66a (BGP), a cell adhesion molecule of the carcinoembryonic antigen family, in benign, premalignant, and malignant lesions of the human mammary gland.

    PubMed

    Riethdorf, L; Lisboa, B W; Henkel, U; Naumann, M; Wagener, C; Löning, T

    1997-07-01

    CD66a, also known as biliary glycoprotein (BGP), is a member of the carcinoembryonic antigen (CEA) family and the human homologue of the rat cell-CAM. There is evidence that aberrant expression or loss of CD66a in tumor tissue is of biological significance. No data about its expression in breast carcinoma cells and only sparse information about the expression of CD66a in normal breast are available thus far. In this study we used monoclonal antibodies to analyze the expression of CD66a and CEA in normal tissue, benign lesions, and in noninvasive and invasive carcinomas of the mammary gland. In normal tissue and benign lesions, CD66a was consistently expressed at the apical sites of epithelial cells and in myoepithelia, whereas CEA was absent or was restricted only to some apical membranes within the ductal tree. The specific staining of myoepithelia was most evident in pseudoinfiltrative radial scars and sclerosing adenosis. However, the apical expression of CD66a disappeared with the development of the malignant phenotype in noninvasive and invasive carcinomas, and changed gradually from low- to high-grade noninvasive carcinomas into a predominant uniform membrane staining all around the atypical cells. CEA expression was irregular in intensity and distribution. The native apical CD66a staining was partially preserved in some highly differentiated invasive carcinomas with a better prognosis, such as tubular and papillary carcinomas. These findings indicate that loss of CD66a expression rather than a change in staining patterns coincides with the development of the malignant phenotype.

  20. Germ-line p53-targeted disruption inhibits helicobacter-induced premalignant lesions and invasive gastric carcinoma through down-regulation of Th1 proinflammatory responses.

    PubMed

    Fox, James G; Sheppard, Barbara J; Dangler, Charles A; Whary, Mark T; Ihrig, Melanie; Wang, Timothy C

    2002-02-01

    p53 is a tumor suppressor gene that is mutated in many human malignancies, including gastric cancer. It remains unclear why patients with germ-line p53 mutations (i.e., Li-Fraumeni syndrome) are not at increased risk for gastric adenocarcinoma, despite the fact that they show a high rate of many other tumors. Furthermore, the precise relationship between germ-line p53 mutations and the response to chronic bacterial infections (such as Helicobacter spp.) has not been investigated. To assess the role of germ-line p53 deletions in modulating the progression to gastric cancer, p53(+/-) and wild-type (WT) C57BL/6 mice were infected with H. felis. The gastric pathology and immune response in these two groups of mice were analyzed for up to 15 months postinfection. The gastric fundus and antrum were evaluated independently using a 0-4 scale to score inflammation, parietal and chief cell loss, mucus metaplasia, and helicobacter colonization. Nonparametric statistical analysis was performed to determine the effects of p53(+/-), infection status, and postinoculation (p.i.) time on inflammation, preneoplastic changes, invasive lesions, and helicobacter colonization. mRNA expression for gammaIFN, interleukin (IL)-1, IL-10, and IL-4 was quantified by PCR. Sera were also evaluated for H. felis antibody by ELISA. Antral inflammation increased significantly with time in infected mice. There was a significant, protective effect on the development of preneoplastic fundic lesions and invasive carcinoma attributable to the deletion of one p53 allele (P < 0.05). Submucosal invasive foci were observed in 9 of 11 WT-infected mice ranging from 13 to 15 months p.i.; invasion of adjacent submucosal blood vessels by glandular epithelia also was present in 5 of these mice. None of these lesions were observed in 33 p53(+/-) mice, infected or not, at any time p.i. p53(+/-) mice had significantly higher helicobacter colonization consistent with a Th2 host response. In sera from WT mice, IgG2a

  1. Histomorphometric Analysis of Angiogenesis using CD31 Immunomarker and Mast Cell Density in Oral Premalignant and Malignant Lesions: A Pilot Study

    PubMed Central

    Jyothsna, M; Rammanohar, M

    2017-01-01

    Introduction Mast cells have been implicated in promoting angiogenesis in malignant tumors of lung, oesophagus and breast, but there are few studies on Oral Squamous Cell Carcinomas (OSCC). Most oral squamous cell carcinomas arise from pre-existing precancerous lesions exhibiting epithelial dysplasia. Aim The present pilot study attempts to compare Mast Cell Density (MCD), Microvessel Density (MVD), Microvessel Area (MVA) histomorphometrically between normal buccal mucosa, severe epithelial dysplasia and OSCC and to correlate the role of mast cells and angiogenesis in tumor progression. Material and Methods The retrospective study was conducted on eight cases of OSCC, eight cases of severe epithelial dysplasia and five cases of normal buccal mucosa. Immunohistochemical staining with anti CD–31, to demonstrate angiogenesis and toluidine blue staining for mast cells were employed. MVA, MVD and MCD were calculated using the measurement tools of the image analysis software and compared between the groups. One way ANOVA (Analysis of Variance) was used for comparing the parameter for multiple groups followed by Games Howell test. To assess the relationship between micro vessel density and mast cell density, Karl Pearson’s correlation was used. Results MCD and MVD increased with disease progression and were statistically higher in OSCC than in severe epithelial dysplasia and normal buccal mucosa (p<0.001). MVA increased from normal to severe dysplasia and decreased from dysplasia to OSCC, may be due to revascularization of tumor tissue. A positive correlation was observed between MCD and MVD in OSCC and dysplasia, though were not statistically significant. Conclusion These findings suggest that mast cells may up regulate angiogenesis in OSCC. MCD and MVD may be used as indicators for disease progression. PMID:28274041

  2. Bronchial malignant melanoma.

    PubMed

    Weshler, Z; Sulkes, A; Kopolovitch, J; Leviatan, A; Shifrin, E

    1980-01-01

    We describe a case of malignant melanoma presenting initially as an endobronchial lesion located in the left main bronchus causing total atelectasis. This resolved with radiation therapy. Widespread metastases developed shortly thereafter. The differential diagnosis of primary and metastatic bronchial malignant melanoma is discussed. Other isolated case reports are reviewed.

  3. The p53 status of cultured human premalignant oral keratinocytes.

    PubMed Central

    Burns, J. E.; Clark, L. J.; Yeudall, W. A.; Mitchell, R.; Mackenzie, K.; Chang, S. E.; Parkinson, E. K.

    1994-01-01

    Around 60% of oral squamous cell carcinomas (SCCs) have been shown to harbour p53 mutations, and other studies have demonstrated mutant p53 genes in normal and dysplastic squamous epithelium adjacent to these SCCs. In line with these earlier studies we show here that DOK, a keratinocyte cell line derived from a dysplasia, displays elevated levels of p53 protein and harbours a 12 bp in-frame deletion of the p53 gene spanning codons 188-191. In contrast, the coding region of the p53 gene was normal in a series of six benign recurrent laryngeal papillomas and a series of four premalignant oral erythroplakia biopsies and their cell cultures. All but one of these lesions were free of malignancy at the time of biopsy, in contrast to the premalignant lesions studied by previous investigators, but keratinocytes cultured from these lesions all displayed a partially transformed phenotype that was less pronounced than that of DOK. Since three out of four of the erythroplakia patients developed SCC within 1 year of biopsy, these lesions were by definition premalignant. The availability of strains of partially transformed keratinocytes from premalignant erythroplakias which possess normal p53 genes should enable us to test the role of mutant p53 in the progression of erythroplakia to SCC. The premalignant tissues and cultures were also tested for the presence of human papillomavirus (HPV), which is known to inactivate p53 function in some cases. Only the benign papillomas were shown to contain high levels of either HPV 6 or HPV 11 E6 DNA, but not both, and none of the samples contained detectable levels of HPV 16, HPV 18 or HPV 33 E6 DNA or L1 DNA of several other HPV types. There was therefore no evidence to suggest that p53 was being inactivated by a highly oncogenic HPV in these samples. Images Figure 1 Figure 2 Figure 3 PMID:7917902

  4. Immunotherapy for gastric premalignant lesions and cancer.

    PubMed

    Zorzetto, Valerio; Maddalo, Gemma; Basso, Daniela; Farinati, Fabio

    2012-06-01

    Chronic atrophic gastritis, a precancerous change for gastric cancer, shows a loss of appropriate glands, Helicobacter pylori infection and autoimmune gastritis being the two main etiologic factors. While H. pylori eradication is the mandatory treatment for the former, no etiologic treatment is available for the latter, in which a Th1-type response, modulated by Tregs and Th17 cells, is involved. H. pylori-related atrophic gastritis is a risk factor for gastric adenocarcinoma, while autoimmune atrophic gastritis is also linked to a substantial risk of gastric type I carcinoid, related to the chronic stimulus exerted by hypergastrinemia on enterochromaffin-like cells. Several studies have been published on gastric cancer treatment through an active specific immunotherapy, aimed at improving the immunoregulatory response and increasing the circulating tumor-specific T cells. No study on immunotherapy of carcinoids is available but, in our experience, the administration of an antigastrin 17 vaccine induced carcinoid regression in two out of three patients treated.

  5. Recurrence of squamous cell lung carcinoma is associated with the co-presence of reactive lesions in tumor-adjacent bronchial epithelium.

    PubMed

    Pankova, Olga V; Denisov, Evgeny V; Ponomaryova, Anastasia A; Gerashchenko, Tatiana S; Tuzikov, Sergey A; Perelmuter, Vladimir M

    2016-03-01

    Recurrences occur in 30 % of lung cancer patients after radical therapy; however, known prognostic factors are not always effective. In this study, we investigated whether the frequency of squamous non-small cell lung cancer (NSCLC) recurrence depends on the presence of reactive lesions in tumor-adjacent bronchial epithelium. Specimens of adjacent lung tissue from 104 patients with squamous NSCLC were used for the determination of basal cell hyperplasia (BCH) and squamous metaplasia (SM) and for the analysis of the expression of Ki-67, p53, Bcl-2, and CD138. We found that recurrence was observed in 36.7 % of patients with BCH combined with SM (BCH + SM+) in the same bronchus, compared with 1.8 % in patients with isolated BCH (BCH + SM-; odds ratio (OR) 31.26, 95 % confidence interval (CI) 3.77-258.60; p = 0.00002). The percentage of Ki-67-positive cells was significantly higher in BCH + SM+ than in BCH + SM- (34.9 vs. 18.3 %; effect size 2.86, 95 % CI 2.23-3.47; p = 0.003). P53 expression was also more significant in BCH + SM+ than in BCH + SM- (14.4 vs. 9.6 %; effect size 1.22, 95 % CI 0.69-1.76; p = 0.0008). In contrast, CD138 expression was lower in BCH + SM+ than in BCH + SM- (21.8 vs. 38.5 %; effect size -6.26, 95 % CI -7.31 to -5.22; p = 0.003). Based on our results, we concluded that the co-presence of reactive bronchial lesions is associated with the development of recurrent squamous NSCLC and may be a negative prognostic indicator. In addition, significant differences in Ki-67, p53, and CD138 expression exist between isolated BCH and BCH combined with SM that probably reflect part of biological differences, which could relate to the mechanism of lung cancer recurrence.

  6. Identification of Genes Expressed in Premalignant Breast Disease by Microscopy-Directed Cloning

    NASA Astrophysics Data System (ADS)

    Jensen, Roy A.; Page, David L.; Holt, Jeffrey T.

    1994-09-01

    Histopathologic study of human breast biopsy samples has identified specific lesions which are associated with a high risk of development of invasive breast cancer. Presumably, these lesions (collectively termed premalignant breast disease) represent the earliest recognizable morphologic expression of fundamental molecular events that lead to the development of invasive breast cancer. To study molecular events underlying premalignant breast disease, we have developed a method for isolating RNA from histologically identified lesions from frozen human breast tissue. This method specifically obtains mRNA from breast epithelial cells and has identified three genes which are differentially expressed in premalignant breast epithelial lesions. One gene identified by this method is overexpressed in four of five noncomedo ductal carcinoma in situ lesions and appears to be the human homologue of the gene encoding the M2 subunit of ribonucleotide reductase, an enzyme involved in DNA synthesis.

  7. Senescence and pre-malignancy: how do tumors progress?

    PubMed

    Saab, Raya

    2011-12-01

    Cellular senescence is a tumor suppressor response that has been observed both in vitro and in vivo, and features of senescence have been documented in various human premalignant lesions, including melanoma, colon and lung adenoma, prostatic intraepithelial neoplasia, and others. The fact that a subset of these lesions eventually progress to malignant invasive tumors suggests that premalignant cells can either bypass or escape the senescent response. Much work has been done to understand the mechanisms underlying such progression, but it remains unclear whether tumors progress by evasion of senescence induction, or by disruption of senescence maintenance, or whether both mechanisms can occur in human cancer development. This review presents the current evidence for mechanisms of senescence evasion and reversion, and discusses what has been learnt about this process using in vitro and in vivo experimental systems. As we learn more about the key signaling effectors of senescence, the hope is that appropriate targets will be identified for preservation and/or re-induction of senescence in human tumors. Such knowledge may also find application in better estimation of risks of cancer progression in individual premalignant lesions, which will lead to more accurate allocation of appropriate treatment options for such patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Bronchial haemangioma: exceptionally rare cause of haemoptysis.

    PubMed

    Jennings, Scott; Tharion, John; Jones, Peter; Brown, Michael

    2013-12-01

    Bronchial haemangioma is an exceptionally rare cause of haemoptysis in the adult. There are currently less than 10 recorded cases in the literature. Airway haemangiomas are generally seen in infants with coexistent cutaneous haemangiomas. The incidence of bronchial haemangioma in adults remains unknown. This case reports the diagnosis and treatment of a bronchial haemangioma in a 56 year-old male presenting with a one-month history of haemoptysis. Bronchial haemangioma diagnosis was confirmed and excision performed by bronchoscopy without complication. Bronchial haemangioma should be a considered differential diagnosis in the presence of meaningful haemoptysis when an endoluminal lesion is visualised on computed tomography scan. This case also demonstrates that bronchial haemangiomas can be successfully removed via bronchoscopy with minimal risk and discomfort to the patient.

  9. The hallmarks of premalignant conditions: a molecular basis for cancer prevention

    PubMed Central

    Ryan, Bríd M.; Faupel-Badger, Jessica M.

    2016-01-01

    The hallmarks of premalignant lesions were first described in the 1970s, a time when relatively little was known about the molecular underpinnings of cancer. Yet it was clear there must be opportunities to intervene early in carcinogenesis. A vast array of molecular information has since been uncovered, with much of this stemming from studies of existing cancer or cancer models. Here, examples of how an understanding of cancer biology has informed cancer prevention studies are highlighted and emerging areas that may have implications for the field of cancer prevention research are described. A note of caution accompanies these examples, in that while there are similarities, there are also fundamental differences between the biology of premalignant lesions or premalignant conditions and invasive cancer. These differences must be kept in mind, and indeed leveraged, when exploring potential cancer prevention measures. PMID:26970122

  10. The hallmarks of premalignant conditions: a molecular basis for cancer prevention.

    PubMed

    Ryan, Bríd M; Faupel-Badger, Jessica M

    2016-02-01

    The hallmarks of premalignant lesions were first described in the 1970s, a time when relatively little was known about the molecular underpinnings of cancer. Yet it was clear there must be opportunities to intervene early in carcinogenesis. A vast array of molecular information has since been uncovered, with much of this stemming from studies of existing cancer or cancer models. Here, examples of how an understanding of cancer biology has informed cancer prevention studies are highlighted and emerging areas that may have implications for the field of cancer prevention research are described. A note of caution accompanies these examples, in that while there are similarities, there are also fundamental differences between the biology of premalignant lesions or premalignant conditions and invasive cancer. These differences must be kept in mind, and indeed leveraged, when exploring potential cancer prevention measures.

  11. Bronchial thermoplasty.

    PubMed

    Cox, Gerard

    2010-03-01

    Asthma, by definition is a variable disease. When there is more than normal natural variation in airflow, asthma can be provoked by a wide range of stimuli that include infectious, allergic, and environmental agents. Bronchoconstriction determines much of the short-term variability in airflow that characterizes asthma. Current treatments do not redress the excess smooth muscle mass that is present in the remodeled airway in chronic asthma. Thus, it is intriguing to consider the potential contribution of bronchial thermoplasty (a procedure that involves controlled heat treatment to reduce the mass of the airway smooth muscle) as an effective therapy for poorly controlled asthma.

  12. Bronchial hygiene therapy.

    PubMed

    Peruzzi, W T; Smith, B

    1995-01-01

    Bronchial hygiene therapy is useful and effective in the presence of careful patient evaluation, clear definition of therapeutic goals, and application of appropriate modalities. This article defines the variable bronchial hygiene modalities and discusses their indications, contraindications, and applications. Prophylactic and therapeutic bronchial hygiene modalities, diagnostic methods associated with bronchial hygiene therapy, inhaled antibiotic therapy, and therapist driven protocols are also addressed.

  13. Correlation of P16 (Ink4a) and CK17 to HPV (16E6+18E6) in Premalignant and Malignant Lesions of Uterine Cervix: A Clinicopathologic Study

    PubMed Central

    Chaloob, Mohammed K.; Hussein, Alaa G.; Qasim, Ban J.

    2016-01-01

    Background: This research was accomplished to evaluate the IHC expression of p16 (ink4a) and CK17 in low grade cervical intraepithelial lesions (LSIL), high grade cervical intraepithelial lesions (HSIL) and invasive cervical carcinomas and to assess their correlation to HPV (16E6+18E6). Methods: The study included (127) formalin-fixed paraffin-embedded cervical biopsies; of which 22 cases were chronic cervicitis, 24 cases were LSIL, 28 cases were HSIL and 53 cases were invasive cervical carcinomas. Sections were immunohistochemically stained for p16 (ink4a), CK17 and HPV (16E6+18E6). Results: The study established a highly significant increase in IHC of expression of p16 (ink4a), CK17 and HPV (16E6+18E6) from LSIL through HSIL to invasive carcinomas (P-value˂0.001). There was non-significant association between IHC expression of all makers with age of patients; types, grade and stage of cervical carcinomas (P-value˃0.05). HPV (16E6+18E6) revealed a significantly positive correlation with p16 (ink4a) (P-value˂0.05) and a non- significant correlation with CK17 (P-value˃0.05); in LSIL, HSIL and invasive carcinoma cases. Conclusion: p16 (ink4a) expression directly reflects infection with high risk HPV in cervical lesions and can add a significant diagnostic accuracy in the evaluation of CIN. CK 17 is a good marker of malignant transformation, with increasing in its expression according to the severity of cervical lesions; however, it is not related to HPV infection. Both markers are not related to prognostic variables of patients with cervical carcinoma. PMID:28855930

  14. A Comparison of 3 Ways of Conventional Pap Smear, Liquid-Based Cytology and Colposcopy vs Cervical Biopsy for Early Diagnosis of Premalignant Lesions or Cervical Cancer in Women with Abnormal Conventional Pap Test.

    PubMed

    Karimi-Zarchi, Mojgan; Peighmbari, Fateme; Karimi, Neda; Rohi, Mitra; Chiti, Zohre

    2013-12-01

    The most cost effective method of prevention and detection of cervical cancer is the Pap smear. In abnormal Pap smear, colposcopy, endocervical curettage and biopsy will be done. Gold standard method in detecting cervical lesion is biopsy. Now in two ways conventional Pap smear and liquid base are routine diagnostic technique in Iran and given easily and cost-effectiveness of this method in the detection of cervical lesions to determine the sensitivity the objective of this study was compare three methods of Pap smear and colposcopy in detection of any lesion to gold standard biopsy in the positive ASC cases who referred to gynecologic Oncology Clinic of shahid Sadoughi University of Medical Science. This study is a descriptive analytic in 2009-2010 years on 150 cases of patients with Atypical Squamose Cell (ASC) results in previous pap smear ,conventional pap smear, liquid based pap smear, colposcopy and cervical biopsy had been done for all patient and finally data were analyzed with chi-square statistical test on spss ver 16 saftware. Average age of patients in this study was, 42 ± 9.9 year and reason for referring patients in 35.4% of cases was due to follow-up of abnormal results of previous Pap smear, in 30% bleeding, 12% Pain and 2.6% percent of cases was checking-up. In final results of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy any of the methods conventional and liquid based Pap smear and colposcopy were compared with cervical biopsy as a gold standard. The conventional Pap smear method had a sensitivity 51%, specificity 66.6%, PPV 96%, NPV was 8% and accuracy was 92%, about the liquid base Pap smear method, sensitivity was 55.3%, specificity was 77.7%, PPV was 97.5%, NPV was 10% and accuracy was 56/6%. About the colposcopy, sensitivity was70/9 % specificity 44/4%, PPV was 95.2%, NPV was 8/8% and accuracy was 69.3%. The relationship between sensitivity results of conventional Pap smear and

  15. Estimation of salivary sialic acid in oral premalignancy and oral squamous cell carcinoma

    PubMed Central

    Chaudhari, Vishakha; Pradeep, G. L.; Prakash, Nilima; Mahajan, Aarti M.

    2016-01-01

    Aims: Oral cancer is the most life-threatening disease of oral tissues. In societies where the incidence of oral cancer is high, clinically recognizable premalignant lesions are particularly common. Diagnosing oral cancers at an early stage is critical in improving the survival rate and reducing the morbidity associated with the disease. Alterations in the sialic acid levels in cancer patients have stimulated interest in this sugar residue as a possible tumor marker. Settings and Design: The purpose of this study was to estimate the salivary sialic acid levels in patients with oral premalignancy and squamous cell carcinoma and to correlate it with their grades to develop a cost-effective and noninvasive diagnostic parameter. Materials and Methods: Unstimulated whole saliva was collected from the groups under study and subjected to biochemical analysis for determination of sialic acid levels. Statistical Analysis Used: The salivary sialic acid levels were correlated with the clinical stage and histological grade by one-way ANOVA (SPSS software version 15). Results: Salivary sialic acid was elevated in oral squamous cell carcinoma (OSCC) compared to oral premalignancy and control group. A statistically significant correlation was observed between the grades of squamous cell carcinoma, grades of dysplasia in premalignancy, and sialic acid level. Conclusion and Clinical Significance: Evaluation of salivary sialic acid levels in premalignant and malignant lesions can serve as a screening tool. The mortality and morbidity of OSCC can be reduced if the lesions are diagnosed in early precancerous states using such noninvasive diagnostic methods for screening and monitoring of the population. PMID:27994410

  16. Noninvasive imaging of oral premalignancy and malignancy

    NASA Astrophysics Data System (ADS)

    Wilder-Smith, Petra; Krasieva, T.; Jung, W.; You, J. S.; Chen, Z.; Osann, K.; Tromberg, B.

    2005-04-01

    Objectives: Early detection of cancer and its curable precursors remains the best way to ensure patient survival and quality of life. Despite significant advances in treatment, oral cancer still results in 10,000 U.S. deaths annually, mainly due to the late detection of most oral lesions. Specific aim was to use a combination of non-invasive optical in vivo technologies to test a multi-modality approach to non-invasive diagnostics of oral premalignancy and malignancy. Methods: In the hamster cheek pouch model (120 hamsters), in vivo optical coherence tomography (OCT) and optical Doppler tomography (ODT) mapped epithelial, subepithelial and vascular change throughout carcinogenesis in specific, marked sites. In vivo multi-wavelength multi-photon (MPM) and second harmonic generated (SHG) fluorescence techniques provided parallel data on surface and subsurface tissue structure, specifically collagen presence and structure, cellular presence, and vasculature. Images were diagnosed by 2 blinded, pre-standardized investigators using a standardized scale from 0-6 for all modalities. After sacrifice, histopathological sections were prepared and pathology evaluated on a scale of 0-6. ANOVA techniques compared imaging diagnostics with histopathology. 95% confidence limits of the sensitivity and specificity were established for the diagnostic capability of OCT/ODT+ MPM/SHG using ROC curves and kappa statistics. Results: Imaging data were reproducibly obtained with good accuracy. Carcinogenesis-related structural and vascular changes were clearly visible to tissue depths of 2mm. Sensitivity (OCT/ODT alone: 71-88%; OCT+MPM/SHG: 79-91%) and specificity (OCT alone: 62-83%;OCT+MPM/SHG: 67-90%) compared well with conventional techniques. Conclusions: OCT/ODT and MPM/SHG are promising non-invasive in vivo diagnostic modalities for oral dysplasia and malignancy. Supported by CRFA 30003, CCRP 00-01391V-20235, NIH (LAMMP) RR01192, DOE DE903-91ER 61227, NIH EB-00293 CA91717, NSF BES

  17. Challenges in detecting pre-malignant pancreatic lesions during acute pancreatitis using a serum microRNA assay: a study based on KrasG12D transgenic mice

    PubMed Central

    Hong, Xiafei; Zhang, Jie; Wu, Qiao; Wang, Wenze; Ye, Adam Yongxin; Song, Wei; Dai, Hongmei; Wang, Xianze; Wu, Fan; You, Lei; Wu, Wenming; Zhao, Yupei

    2016-01-01

    Caerulein-induced acute pancreatitis accelerates the progression of pancreatic intraepithelial neoplasia (PanIN) lesions in a pancreas-specific KrasG12D mouse model. The purpose of this study was to explore whether serum microRNAs (miRNAs) can serve as sensitive biomarkers to detect occult PanIN in the setting of acute pancreatitis. Serum miRNA profiles were quantified by an array-based method and normalized by both Variance Stabilization Normalization (VSN) and invariant methods. Individual miRNAs were validated by TaqMan real-time PCR with synthetic spike-in C. elegans miRNAs as external controls. Serum miRNA profiles distinguished KrasG12D mice with pancreatitis from wild-type mice without pancreatitis, but failed to differentiate KrasG12D mice with pancreatitis from wild-type mice with pancreatitis. Most individual miRNAs that increased in KrasG12D mice with pancreatitis were not significantly different between KrasG12D mice without pancreatitis and wild-type mice without pancreatitis. Mechanistically, Gene Set Enrichment Analysis (GSEA) of the mRNA array data and immunohistochemical assays showed that caerulein-induced acute pancreatitis involved acinar cell loss and immune cell infiltration, which might contribute to serum miRNA profile changes. This study highlighted the challenges in using sensitive serum miRNA biomarker screening for the early detection of pancreatic malignancies during acute pancreatitis. PMID:27009811

  18. Anogenital malignancies and premalignancies: facts and controversies.

    PubMed

    Kutlubay, Zekayi; Engin, Burhan; Zara, Tuba; Tüzün, Yalçın

    2013-01-01

    Anogenital malignancies and premalignancies are an important personal/public health problem due to their effects on individuals' physical, mental, and sexual health. Also, due to their etiological association with human papillomavirus (HPV) infection, anogenital malignancies and premalignancies constitute an immense public health burden. In addition to HPV infection, immunosuppression, HIV infection, chronic dermatoses, such as lichen sclerosis, previous radiotherapy and chemotherapy treatments, and smoking, are the other important etiopathologic factors in the development of anogenital malignancies and premalignancies. The incidence of anal squamous cell carcinoma (SCC) has increased considerably in the past decade, mainly due to the growing number of cases in high-risk groups, such as men who have sex with men, immunosuppressed individuals, and patients with HIV infection. Also, an increase in vulvar intraepithelial neoplasia (VIN) and VIN-related invasive vulvar cancer has been noted in women younger than age 50 years due to its association with HPV infections over the past decade. SCC of the scrotum seems to be the first cancer linked to occupational exposure. Bowen's disease, Bowenoid papulosis, and erythroplasia of Queyrat are the most widely seen premalignancies of anogenital region and are all forms of squamous intraepithelial neoplasia. Histopathologically, these conditions share identical histologic features of SCC in situ, but their clinical features differ. Early diagnosis is vital to improve prognosis, especially in anogenital malignancies. Also, if a delay occurs in diagnosis, treatment options used will be associated with significant negative effects on the patient's psychological well-being and quality of life; hence, management of anogenital malignancies and premalignancies should be organized in a multidisciplinary fashion. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Discrimination of premalignant conditions of oral cancer using Raman spectroscopy of urinary metabolites

    NASA Astrophysics Data System (ADS)

    Elumalai, Brindha; Rajasekaran, Ramu; Aruna, Prakasarao; Koteeswaran, Dornadula; Ganesan, Singaravelu

    2015-03-01

    Oral cancers are considered to be one of the most commonly occurring malignancy worldwide. Over 70% of the cases report to the doctor only in advanced stages of the disease, resulting in poor survival rates. Hence it is necessary to detect the disease at the earliest which may increase the five year survival rate up to 90%. Among various optical spectroscopic techniques, Raman spectroscopy has been emerged as a tool in identifying several diseased conditions, including oral cancers. Around 30 - 80% of the malignancies of the oral cavity arise from premalignant lesions. Hence, understanding the molecular/spectral differences at the premalignant stage may help in identifying the cancer at the earliest and increase patient's survival rate. Among various bio-fluids such as blood, urine and saliva, urine is considered as one of the diagnostically potential bio-fluids, as it has many metabolites. The distribution and the physiochemical properties of the urinary metabolites may vary due to the changes associated with the pathologic conditions. The present study is aimed to characterize the urine of 70 healthy subjects and 51 pre-malignant patients using Raman spectroscopy under 785nm excitation, to know the molecular/spectral differences between healthy subjects and premalignant conditions of oral malignancy. Principal component analysis based Linear discriminant analysis were also made to find the statistical significance and the present technique yields the sensitivity and specificity of 86.3% and 92.9% with an overall accuracy of 90.9% in the discrimination of premalignant conditions from healthy subjects urine.

  20. Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B/sub 12/: report of a preliminary randomized, double-blind intervention trial

    SciTech Connect

    Heimburger, D.C.; Alexander, C.B.; Birch, R.; Butterworth, C.E. Jr.; Bailey, W.C.; Krumdieck, C.L.

    1988-03-11

    To test whether changes in folate and vitamin B/sub 12/ nutrition modify the severity of potentially premalignant lesions identified by cytology in sputum samples of smokers, the authors conducted a randomized, controlled prospective intervention trial in smokers with bronchial squamous metaplasia. Seventy-three men with a history of 20 or more pack-years of cigarette smoking who had metaplasia on one or more sputum samples were stratified according to smoking level and randomly assigned to four months' treatment with either placebo or 10 mg of folate plus 500 ..mu..g of hydroxocobalamin. Direct cytological comparison of the two groups after four months showed significantly greater reduction of atypia in the supplemented group. This provides preliminary evidence that atypical bronchial squamous metaplasia may be reduced by supplementation with folate and vitamin B/sub 12/. However, the significance of these findings is tempered by substantial spontaneous variation in sputum cytologies, the small study population, the short duration of the trial, and the supraphysiological doses of folate and B/sub 12/ used. The results should not be construed as pointing to a potential way of preventing lung cancer in individuals who continue to smoke or as supporting self-medication with large doses of folate or B/sub 12/ by smokers.

  1. Surgery in (pre)malignant celiac disease

    PubMed Central

    van de Water, Jolanda MW; Nijeboer, Petula; de Baaij, Laura R; Zegers, Jessy; Bouma, Gerd; Visser, Otto J; van der Peet, Donald L; Mulder, Chris JJ; Meijerink, Wilhelmus JHJ

    2015-01-01

    AIM: To report the outcome of surgery in patients with (pre)malignant conditions of celiac disease (CD) and the impact on survival. METHODS: A total of 40 patients with (pre)malignant conditions of CD, ulcerative jejunitis (n = 5) and enteropathy associated T-cell lymphoma (EATL) (n = 35), who underwent surgery between 2002 and 2013 were retrospectively evaluated. Data on indications, operative procedure, post-operative morbidity and mortality, adjuvant therapy and overall survival (OS) were collected. Eleven patients with EATL who underwent chemotherapy without resection were included as a control group for survival analysis. Patients were followed-up every three months during the first year and at 6-mo intervals thereafter. RESULTS: Mean age at resection was 62 years. The majority of patients (63%) underwent elective laparotomy. Functional stenosis (n = 13) and perforation (n = 12) were the major indications for surgery. In 70% of patients radical resection was performed. Early postoperative complications, mainly due to leakage or sepsis, occurred in 14/40 (35%) of patients. Eight patients required reoperation. More patients who underwent resection in the acute setting (n = 3, 20%) died compared to patients treated in the elective setting. With a median follow-up of 20 mo, seven patients (18%) required reoperation due to long-term complications. Significantly more patients who underwent acute surgery could not be treated with adjuvant chemotherapy. Patients who first underwent surgical resection showed significantly better OS than patients who received chemotherapy without resection. CONCLUSION: Although the complication rate is high, the preferred first step of treatment in (pre)malignant CD consists of local resection as early as possible to improve survival. PMID:26604647

  2. [Metastatic bronchial carcinoid tumors].

    PubMed

    Bouledrak, K; Walter, T; Souquet, P J; Lombard-Bohas, C

    2016-02-01

    Bronchial carcinoids are uncommon pulmonary neoplasms and represent 1 to 2 % of all lung tumors. In early stage of disease, the mainstay and only curative treatment is surgery. Bronchial carcinoids are generally regarded as low-grade carcinomas and metastatic dissemination is unusual. The management of the metastatic stage is not currently standardized due to a lack of relevant studies. As bronchial carcinoids and in particular their metastatic forms are rare, we apply treatment strategies that have been evaluated in gastrointestinal and pancreatic neuroendocrine tumors. However, bronchial carcinoids have their own characteristic. A specific therapeutic feature of these metastatic tumors is that they require a dual approach: both anti-secretory for the carcinoid syndrome, and anti-tumoral.

  3. [The premalignant disease of the endometrium: endometrial intraepithelial neoplasia].

    PubMed

    Francz, Mónika

    2008-03-01

    The WHO 1994 classification for endometrial hyperplasias is based on the morphologic features of the lesions. This system characterizes the nuclear cytologic morphology as typical or atypical and describes the glandular architectural pattern as simple or complex. The main problem of this classification is the poor reproducibility. Although the predictive value of the atypical category is high, there are many typical hyperplasia cases with cancer progression. Modern molecular data related to endometrial tumorigenesis and precise computerized morphometric analysis have identified the lesion that may be considered as a precursor of endometrioid adenocarcinoma. By definition, this endometrial intraepithelial neoplasia (EIN) is a clonal proliferation of architecturally and cytologically altered endometrial glands which are prone to malignant transformation to endometrioid (type I) endometrial adenocarcinoma. The morphometric basis of EIN diagnosis is the D-score (DS), which is a logical combination of three morphometric features that represent the glandular complexity, glandular volume and cytological alterations. PTEN inactivation and K-ras mutation are the earliest genetic changes that can be revealed in these lesions. Hyperplasia cases that do not fit into the EIN categories are considered as benign or hormonal endometrial hyperplasia. This is the theoretical basis of a new classification system in premalignant endometrial diseases. Retrospective clinical data proved the high predictive value of the EIN scheme, so the decision on therapy can be more established. The reproducibility is excellent with application of precise definitions and PTEN immunohistochemistry. In the "Blue book" published in 2003 the WHO introduces the new morphometric- and molecular-based EIN system, and recommends it as an alternative classification method.

  4. Role of oral exfoliative cytology in predicting premalignant potential of oral submucous fibrosis: A short study.

    PubMed

    Jaitley, Shweta; Agarwal, Pankaj; Upadhyay, Ramballabh

    2015-01-01

    The present study was undertaken with an aim of determining the cytological features observed in mucosal smears of oral submucous fibrosis (OSF) patients and comparing them with that of features of normal mucosal cells. The observed features were than analyzed for their reliability in detecting malignant changes in this premalignant condition. Objective of the study was to conduct an oral exfoliative cytology (OEC) study on 30 clinically diagnosed cases of OSF and 30 cases of clinically normal mucosa with no other systemic disease. We observed that all the smears from clinically normal buccal mucosa showed Class I cytology. The exfoliated cells were of normal size and shape with normal staining intensity and normal nuclear characteristics. All the 30 cases of our study group showed features suggestive of benign atypical cytological changes (Class II cytology). In the present study, despite the small number of cases, cytological features consistently observed in all the cases, were indicative of a premalignant change and emphasized a regular follow-up of patients. Early detection of a premalignant oral lesion promises to improve the survival rate of patients suffering from these conditions.

  5. Analytical performance of a bronchial genomic classifier.

    PubMed

    Hu, Zhanzhi; Whitney, Duncan; Anderson, Jessica R; Cao, Manqiu; Ho, Christine; Choi, Yoonha; Huang, Jing; Frink, Robert; Smith, Kate Porta; Monroe, Robert; Kennedy, Giulia C; Walsh, P Sean

    2016-02-26

    The current standard practice of lung lesion diagnosis often leads to inconclusive results, requiring additional diagnostic follow up procedures that are invasive and often unnecessary due to the high benign rate in such lesions (Chest 143:e78S-e92, 2013). The Percepta bronchial genomic classifier was developed and clinically validated to provide more accurate classification of lung nodules and lesions that are inconclusive by bronchoscopy, using bronchial brushing specimens (N Engl J Med 373:243-51, 2015, BMC Med Genomics 8:18, 2015). The analytical performance of the Percepta test is reported here. Analytical performance studies were designed to characterize the stability of RNA in bronchial brushing specimens during collection and shipment; analytical sensitivity defined as input RNA mass; analytical specificity (i.e. potentially interfering substances) as tested on blood and genomic DNA; and assay performance studies including intra-run, inter-run, and inter-laboratory reproducibility. RNA content within bronchial brushing specimens preserved in RNAprotect is stable for up to 20 days at 4 °C with no changes in RNA yield or integrity. Analytical sensitivity studies demonstrated tolerance to variation in RNA input (157 ng to 243 ng). Analytical specificity studies utilizing cancer positive and cancer negative samples mixed with either blood (up to 10 % input mass) or genomic DNA (up to 10 % input mass) demonstrated no assay interference. The test is reproducible from RNA extraction through to Percepta test result, including variation across operators, runs, reagent lots, and laboratories (standard deviation of 0.26 for scores on > 6 unit scale). Analytical sensitivity, analytical specificity and robustness of the Percepta test were successfully verified, supporting its suitability for clinical use.

  6. Paeonol attenuates aging MRC-5 cells and inhibits epithelial-mesenchymal transition of premalignant HaCaT cells induced by aging MRC-5 cell-conditioned medium.

    PubMed

    Yang, Lihua; Xing, Shangping; Wang, Kun; Yi, Hua; Du, Biaoyan

    2017-08-12

    Senescence-associated secretory phenotype (SASP) factors, such as IL-6 and IL-8, are extremely critical in tissue microenvironment. Senescent human fibroblasts facilitate epithelial-mesenchymal transition (EMT) in premalignant epithelial cells mainly through the secretion of SASP factors. Meanwhile, premalignant human HaCaT Keratinocyte (HaCaT) cells as immortal epithelial cells are susceptible to malignant transformation. Paeonol, an herbal phenolic component found in peonies, exerts anti-aging and anti-tumor efficacies, while the molecular mechanisms of paeonol on EMT in premalignant HaCaT cells induced by SASP factors are unclear. In this study, we first established a senescent human fetal lung fibroblast MRC-5 cell model using hydrogen peroxide evaluated by senescence-associated β-galactosidase assay. Upon paeonol treatment, intracellular reactive oxygen species levels in aging MRC-5 cells were significantly decreased via regulation of nuclear translocation of Nrf2. Then we curiously studied whether the aging MRC-5 cell-conditioned medium could induce EMT in premalignant HaCaT cells, and the results showed that paeonol significantly reduced the clonogenic, migratory, and invasive capacities of premalignant HaCaT cells potentially induced by IL-6 and IL-8. Moreover, we found that paeonol notably altered pluripotency of EMT-associated markers via the modulation of ERK and TGF-β1/Smad pathway in premalignant HaCaT cells. These findings suggest that paeonol may be used as an adjuvant therapy for SASP factor-mediated EMT in premalignant lesion.

  7. Endothelin receptor type B gene promoter hypermethylation in salivary rinses independently associates with risk of oral cavity cancer and premalignancy

    PubMed Central

    Pattani, Kavita Malhotra; Zhang, Zhe; Demokan, Semra; Glazer, Chad; Loyo, Myriam; Goodman, Steven; Sidransky, David; Bermudez, Francisco; Jean-Charles, Germain; McCaffrey, Thomas; Padhya, Tapan; Phelan, Joan; Spivakovsky, Silvia; Bowne, Helen Yoo; Goldberg, Judith D.; Rolnitzky, Linda; Robbins, Miriam; Kerr, A. Ross; Sirois, David; Califano, Joseph A.

    2010-01-01

    Endothelin receptor type B (EDNRB) and kinesin family member 1A(KIF1A) are candidate tumor suppressor genes that are inactivated in cancers. In this study we evaluated promoter hypermethylation of EDNRB and KIF1A and their potential use for risk classification in prospectively collected salivary rinses from patients with premalignant/malignant oral cavity lesions. Quantitative methylation-specific PCR(Q-MSP) was performed analyzing methylation status of EDNRB and KIF1A in salivary rinses of 191 patients. We proceeded to determine the association of methylation status with histologic diagnosis and estimate classification accuracy. On univariate analysis, diagnosis of dysplasia/cancer was associated with age and KIF1A or EDNRB methylation. Methylation of EDNRB highly correlated with that of KIF1A(p<0.0001). On multivariable modeling, histologic diagnosis independently associated with EDNRB(p=0.0003) or KIF1A(p=0.027) methylation). A subset of patients analyzed (n=161) without prior biopsy proven malignancy received clinical risk classification based on examination. On univariate analysis, EDNRB and risk classification were associated with diagnosis of dysplasia/cancer, and remained significant on multivariate analysis (EDNRB:p=0.047, risk classification:p=0.008). Clinical risk classification identified dysplasia/cancer with a sensitivity of 71% and specificity of 58%. The sensitivity of clinical risk classification combined with EDNRB methylation improved to 75%. EDNRB methylation in salivary rinses was independently associated with histologic diagnosis of premalignancy and malignancy and may have potential in classifying patients at risk for oral premalignant and malignant lesions in settings without access to a skilled dental practitioner. This may also potentially identify patients with premalignant and malignant lesions that do not meet criteria for high clinical risk based on skilled dental examination. PMID:20798208

  8. miR-196b Is Epigenetically Silenced during the Premalignant Stage of Lung Carcinogenesis.

    PubMed

    Tellez, Carmen S; Juri, Daniel E; Do, Kieu; Picchi, Maria A; Wang, Teresa; Liu, Gang; Spira, Avrum; Belinsky, Steven A

    2016-08-15

    miRNA silencing by promoter hypermethylation may represent a mechanism by which lung cancer develops and progresses, but the miRNAs involved during malignant transformation are unknown. We previously established a model of premalignant lung cancer wherein we treated human bronchial epithelial cells (HBEC) with low doses of tobacco carcinogens. Here, we demonstrate that next-generation sequencing of carcinogen-transformed HBECs treated with the demethylating agent 5-aza-2'deoxycytidine revealed miR-196b and miR-34c-5p to be epigenetic targets. Bisulfite sequencing confirmed dense promoter hypermethylation indicative of silencing in multiple malignant cell lines and primary tumors. Chromatin immunoprecipitation studies further demonstrated an enrichment in repressive histone marks on the miR-196b promoter during HBEC transformation. Restoration of miR-196b expression by transfecting transformed HBECs with specific mimics led to cell-cycle arrest mediated in part through transcriptional regulation of the FOS oncogene, and miR-196b reexpression also significantly reduced the growth of tumor xenografts. Luciferase assays demonstrated that forced expression of miR-196b inhibited the FOS promoter and AP-1 reporter activity. Finally, a case-control study revealed that methylation of miR-196b in sputum was strongly associated with lung cancer (OR = 4.7, P < 0.001). Collectively, these studies highlight miR-196b as a tumor suppressor whose silencing early in lung carcinogenesis may provide a selective growth advantage to premalignant cells. Targeted delivery of miR-196b could therefore serve as a preventive or therapeutic strategy for the management of lung cancer. Cancer Res; 76(16); 4741-51. ©2016 AACR.

  9. Gastro-bronchial fistula

    PubMed Central

    Missen, Anthony J. B.; Pemberton, James; Boon, Andrew

    1974-01-01

    1. Gastro-bronchial fistula is a rare condition occurring most commonly as a complication of a subphrenic abscess. 2. Other causes include trauma and necrosis within an infiltrating neoplasm. 3. The treatment of those fistulae which are secondary to a subphrenic abscess should be by drainage of the abscess, jejunal tube feeding and continuous gastric aspiration. ImagesFig. 1 PMID:4464513

  10. Use of a frameless LNG-IUS as conservative treatment for a pre-malignant uterine polyp in a premenopausal woman - a case report.

    PubMed

    Janssens, D; Verbeeck, G; Wildemeersch, D

    2015-12-28

    Prevention of progression to invasive carcinoma in patients with a premalignant endometrial lesion using longterm treatment with levonorgestrel (LNG) releasing intrauterine systems (IUS) remains controversial, especially when manifest cellular atypia has been found in the endometrial biopsy specimen. We present a case of a 44-year old premenopausal woman with a premalignant uterine polyp who declined hysterectomy and was followed-up for more than 12 years after the first LNG-IUS was inserted. Endometrial atrophy installed, no pathology was detected and hysterectomy was thereby successfully avoided. The positive experience in this case should encourage further studies as literature data indicate that conservative treatment of premalignant endometrial pathology is a real option with a high success rate for women who have a contra-indication for surgery, refuse the classical approach for personal reasons or want to preserve their fertility.

  11. Increased polysomy of chromosome 7 in bronchial epithelium from patients at high risk for lung cancer

    SciTech Connect

    Belinsky, S.A.; Neft, R.E.; Lechner, J.F.

    1995-12-01

    Current models of carcinogenesis suggest that tissues progress through multiple genetic and epigenetic changes which ultimately lead to development of invasive cancer. Epidemiologic studies of Peto, R.R. and J.A. Doll indicate that the accumulation of these genetic changes over time, rather than any single unique genetic change, is probably responsible for development of the malignant phenotype. The bronchial epithelium of cigarette smokers is diffusely exposed to a broad spectrum of carcinogens, toxicants, and tumor promoters contained in tobacco smoke. This exposure increases the risk of developing multiple, independent premalignant foci throughout the lower respiratory tract that may contain independent gene aberrations. This {open_quotes}field cancerization{close_quotes} theory is supported by studies that have demonstrated progressive histologic changes distributed throughout the lower respiratory tract of smokers. A series of autopsy studies demonstrated that cigarette smokers exhibit premalignant histologic changes ranging from hyperplasia and metaplasia to severe dysplasia and carcinoma in situ diffusely throughout the bronchial mucosa. The proximal bronchi appear to exhibit the greatest number of changes, particularly at bifurcations. The results described are the first to quantitate the frequency for a chromosome aberration in {open_quotes}normal{close_quotes} bronchial epithelial cells.

  12. Involvement of oxidative stress in the pre-malignant and malignant states of cervical cancer in women.

    PubMed

    Gonçalves, Thissiane L; Erthal, Fernando; Corte, Cristiane L D; Müller, Liz G; Piovezan, Clarice M; Nogueira, Cristina W; Rocha, João B T

    2005-12-01

    To evaluate the potential role of oxidative stress in the evolution of cervical cancer, including its pre-malignant states. Erythrocytes thiobarbituric acid reactive substances (TBARS) levels, plasma vitamin C and thiol content and total blood delta-ALA-D levels were estimated in 46 untreated cervical cancer and pre-malignant patients and in 46 age-sex-matched controls. Erythrocytes from patients, regardless of disease state, pre-malignant (low squamous intraepithelial lesion--LSIL and high squamous intraepithelial lesion--HSIL) or cancer, showed a significant 2-3 times increase in TBARS levels (P<0.01). Plasma vitamin C was lower in the carcinoma group (P<0.01). The reactivation index of delta-aminolevulinate dehydratase (delta-ALA-D) was higher in the patient group, when compared to control (P<0.01). LSIL, HSIL or cervical cancer can be associated with changes in 3 indicators of oxidative stress: increase in erythrocyte TBARS, ALA-D reactivation index and a decrease in vitamin C content, that may play an important role in carcinogenesis.

  13. Quantitative architectural analysis of bronchial intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Guillaud, Martial; MacAulay, Calum E.; Le Riche, Jean C.; Dawe, Chris; Korbelik, Jagoda; Lam, Stephen

    2000-04-01

    Considerable variation exists among pathologist in the interpretation of intraepithelial neoplasia making it difficult to determine the natural history of these lesion and to establish management guidelines for chemoprevention. The aim of the study is to evaluate architectural features of pre-neoplastic progression in lung cancer, and to search for a correlation between architectural index and conventional pathology. Quantitative architectural analysis was performed on a series of normal lung biopsies and Carcinoma In Situ (CIS). Centers of gravity of the nuclei within a pre-defined region of interest were used as seeds to generate a Voronoi Diagram. About 30 features derived from the Voronoi diagram, its dual the Delaunay tessellation, and the Minimum Spanning Tree were extracted. A discriminant analysis was performed to separate between the two groups. The architectural Index was calculated for each of the bronchial biopsies that were interpreted as hyperplasia, metaplasia, mild, moderate or severe dysplasia by conventional histopathology criteria. As a group, lesions classified as CIS by conventional histopathology criteria could be distinguished from dysplasia using the architectural Index. Metaplasia was distinct from hyperplasia and hyperplasia from normal. There was overlap between severe and moderate dysplasia but mild dysplasia could be distinguished form moderate dysplasia. Bronchial intraepithelial neoplastic lesions can be degraded objectively by architectural features. Combination of architectural features and nuclear morphometric features may improve the quantitation of the changes occurring during the intra-epithelial neoplastic process.

  14. Insertion mutation of the int-1 and int-2 loci by mouse mammary tumor virus in premalignant and malignant neoplasms from the GR mouse strain.

    PubMed Central

    Morris, D W; Barry, P A; Bradshaw, H D; Cardiff, R D

    1990-01-01

    Mouse mammary tumor virus (MMTV)-induced mammary adenocarcinomas can develop from several different premalignant precursors common in GR mice. Insertion mutagenesis of the mammary protooncogenes int-1 and int-2 was studied in this multistep system by analyzing samples from various stages of neoplastic development for novel int-1 and int-2 restriction fragments generated by MMTV provirus integration. int-1 and int-2 insertion mutations were observed in both premalignant lesions and malignant tumors. Some of the tumors with insertion mutations were experimentally derived from insertion mutation-free premalignant precursors. Each class of neoplasm examined had a characteristic frequency of int-1 and int-2 insertion mutations; however, no correspondence was observed between neoplasm morphology and mutation of either gene. These results indicate that insertion mutation of the int-1 and int-2 loci by MMTV provirus can be involved in the earliest identifiable stages of neoplastic development as well as during progression of premalignant lesions to tumors. Insertion mutation of int-1 and int-2 is therefore not stage specific in this system. Images PMID:2157060

  15. Diagnostic accuracy of diffuse reflectance imaging for early detection of pre-malignant and malignant changes in the oral cavity: a feasibility study

    PubMed Central

    2013-01-01

    Background Diffusely reflected light is influenced by cytologic and morphologic changes that take place during tissue transformation, such as, nuclear changes, extracellular matrix structure and composition as well as blood flow. Albeit with varying degree of sensitivity and specificity, the properties of diffusely reflected light in discriminating a variety of oral lesions have been demonstrated by our group in multiple studies using point monitoring systems. However, the point monitoring system could not identify the region with the most malignant potential in a single sitting. Methods In order to scan the entire lesion, we developed a multi-spectral imaging camera system that records diffuse reflectance (DR) images of the oral lesion at 545 and 575 nm with white light illumination. The diagnostic accuracy of the system for 2-dimensional DR imaging of pre-malignant and malignant changes in the oral cavity was evaluated through a clinical study in 55 patients and 23 healthy volunteers. The DR imaging data were compared with gold standard tissue biopsy and histopathology results. Results In total 106- normal/clinically healthy sites, 20- pre-malignant and 29- malignant (SCC) sites were compared. While the median pixel value of the R545/R575 image ratio for normal/clinically healthy tissue was 0.87 (IQR = 0.82-0.94), they were 1.35 (IQR = 1.13-1.67) and 2.44 (IQR = 1.78-3.80) for pre-malignant and malignant lesions, respectively. Area under the ROC curve to differentiate malignant from normal/clinically healthy [AUC = 0.99 (95% CI: 0.99-1.00)], pre-malignant from normal/clinically healthy [AUC = 0.94 (95% CI: 0.86-1.00)], malignant from pre-malignant [AUC = 0.84 (95% CI: 0.73-0.95)] and pre-malignant and malignant from normal/clinically healthy [AUC = 0.97 (95% CI: 0.94-1.00)] lesions were desirable. Conclusion We find DR imaging to be very effective as a screening tool in locating the potentially malignant areas of oral lesions with

  16. Detection of Bronchial Neoplasia in Uranium Miners by Autofluorescence Endoscopy (SAFE-1000)

    PubMed Central

    Horvathova, M.; Salajka, F.; Habanec, B.; Foretova, L.; Kana, J.; Koukalova, H.; Pafko, P.; Wurst, F.; Novotna, E.; Pecina, J.; Vagunda, V.; Vrbacky, R.; Talac, R.; Coupková, H.; Pacovsky, Z.

    1999-01-01

    The increase in the detection rate for premalignant changes of bronchial epithelium was studied in 56 symptom-free volunteers from the risk group of Czech uranium miners (mean age 50.69 years, mean WLM 21.06 (1 Working Level Month is equal to the absorption of latent energy of 2.08 × 10–5 J/m3 in one month, i.e. 170 working hours)) by the additional employment of the System of Autofluorescence Endoscopy (SAFE-1000 Pentax) to conventional white-light bronchoscopy, comparing results with those of bronchial biopsy histopathology examination. Histopathology using hematoxylin and eosin staining confirmed intraepithelial neoplasias in 15 areas in 10 persons. White-light bronchoscopy sensitivity was 21.05%, and specificity 93.7% which an autofluorescence bronchoscopy sensitivity was 78.95% and specificity 81.89%. PMID:18493487

  17. [Bronchial mucoepidermoid carcinoma].

    PubMed

    Bregante, J I; Rituerto, B; Font de Mora, F; Alonso, F; Andreu, M J; Figuerola, J; Mulet, J F

    1998-07-01

    We submit the case of a child afflicted with a mucoepidermoid bronchial tumor. The patient is a boy, aged seven, who after undergoing antibiotic treatment for six weeks because of a fever and atelectasia-condensation in the right lower lobe showed no signs of clinical improvement and was sent to our department to undergo further study and treatment. A bronchoscopy performed shows a polypoid mass that partially blocks the main bronchial tube a few milimiters under the access to the right upper lobe. A biopsy is carried out and the anatomopathological test shows there is a low degree epidermoid carcinoma. We decide to perform a lobectomy which for the tumor location and the lung condition has to be medium and lower right. We proceed to remove the adenopaty of hilium not affected by the tumor. The postoperative period develops without incidents. A check-up bronchoscopy performed three months later shows two polypoid masses in the right bronchial tube which, once a biopsy is performed, proved to be granulation tissue. Twelve months after undergoing surgery, the patient's condition is good, there is no evidence of tumor relapse and the breathing capacity is adequate, though there is an obstructive restrictive pattern in the espirometry. Even taking into consideration that lung tumors are extremely unusual, the epidermoid carcinoma is the one which most frequently occurs. The tumor's low malignancy is a sign that points to a good prognosis. Performing conservative surgery by means of bronchoplasty should be taken into account so as to keep the sequelae on the lung condition to a minimum, even though in this case the tumor location made it impossible.

  18. [The history of bronchial asthma].

    PubMed

    Carlo-Stella, N

    1998-01-01

    The history of bronchial asthma from ancient times is traced. The first accounts of asthma in the ancient Greeks and Romans with clinical descriptions by Aretus of Cappadocia and Aulus Celsus Cornelius are recounted. These are followed by the medieval habits of the Middle East as described by Moises Maimonides. The Renaissance is witness to a new scientific fervor in postulating theories on the pathogenesis of bronchial asthma by van Helmont, Willis and Floyer. The seventeenth and eighteenth centuries will see the discovery of the anatomical foundation of bronchial asthma thanks largely to the technical advances in the diagnostic field by Auerbrugge and Laennec. The allergic nature of bronchial asthma is studied by Salter. S Meltzer's hypothesis of histamine release as the pathogenesis of bronchial asthma leads the way for the twentieth century's leading discoveries.

  19. Monitoring the premalignant potential of Barrett's oesophagus'

    PubMed Central

    Graham, David; Lipman, Gideon; Sehgal, Vinay; Lovat, Laurence B

    2016-01-01

    The landscape for patients with Barrett's oesophagus (BE) has changed significantly in the last decade. Research and new guidelines have helped gastroenterologists to better identify those patients with BE who are particularly at risk of developing oesophageal adenocarcinoma. In parallel, developments in endoscopic image enhancement technology and optical biopsy techniques have improved our ability to detect high-risk lesions. Once these lesions have been identified, the improvements in minimally invasive endoscopic therapies has meant that these patients can potentially be cured of early cancer and high-risk dysplastic lesions without the need for surgery, which still has a significant morbidity and mortality. The importance of reaching an accurate diagnosis of BE remains of paramount importance. More work is needed, however. The vast majority of those undergoing surveillance for their BE do not progress towards cancer and thus undergo a regular invasive procedure, which may impact on their psychological and physical well-being while incurring significant cost to the health service. New work that explores cheaper endoscopic or non-invasive ways to identify the at-risk individual provides exciting avenues for research. In future, the diagnosis and monitoring of patients with BE could move away from hospitals and into primary care. PMID:27761232

  20. Visualization of bronchial circulation at bronchial anastomotic site using bronchial fluorescein angiography technique.

    PubMed

    Iga, Norichika; Miyoshi, Kentaroh; Takata, Katsuyoshi; Hirano, Yutaka; Konishi, Yusuke; Otani, Shinji; Sugimoto, Seiichiro; Yamane, Masaomi; Miyoshi, Shinichiro; Oto, Takahiro

    2016-11-01

    Successful bronchial healing after a bronchoplastic procedure mainly depends on bronchial circulation at the anastomostic site. We developed a bronchial fluorescein angiography (B-FAG) technique for visualizing circulation on the bronchial surface. The technique was evaluated in animals. Fluorescein was used as a contrast agent and an autofluorescence imaging (AFI) bronchoscope as a detector. The left main pulmonary artery (PA) and main bronchus of 10 pigs were isolated. After transection of the left main bronchus and bronchial arteries and re-anastomosis of the bronchus, the pigs were randomly divided into two groups: the PA- group (n = 5), in which the pulmonary artery was transected; and the PA+ group (n = 5), in which the pulmonary artery was preserved. Following intravenous injection of fluorescein, the distal anastomotic site was observed for 30 min with autofluorescence imaging bronchoscopy. Bronchial specimens sampled 2 days after the surgical intervention were histologically evaluated. In the PA- group, there was no fluorescein enhancement in the distal bronchus throughout the observation time. However, enhancement, which turned the bronchial surface from magenta to bright green, was clearly observed in less than 207 ± 102.5 s in the PA+ group. The enhancement status detected by bronchial fluorescein angiography was related to the extent of tissue damage, as was proven histologically in the acute healing stage. Bronchial fluorescein angiography clearly visualized the circulatory status promptly after the anastomosis procedure at the central bronchus. This technique is a potentially practical approach to predict ischaemic airway complications following bronchial anastomosis. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  1. Gastro-duodenal fluid induced nuclear factor-κappaB activation and early pre-malignant alterations in murine hypopharyngeal mucosa

    PubMed Central

    Vageli, Dimitra P.; Prasad, Manju L.; Sasaki, Clarence T.

    2016-01-01

    We recently described the role of gastro-duodenal fluids (GDFs) in generating changes consistent with hypopharyngeal neoplasia through activation of NF-κB pathway, using an in vitro model of human hypopharyngeal normal keratinocytes. Here, we further provide evidence that gastro-duodenal reflux is a risk factor for early pre-malignant alterations in hypopharyngeal mucosa (HM) related to an activated NF-κB oncogenic pathway, using both an in vitro and a novel in vivo model of C57Bl/6J mice. Histological, immunohistochemical and automated quantitative analysis documents significant NF-κB activation and early pre-malignant alterations in HM topically exposed to GDFs, compared to acid alone and other controls. Early pre-malignant histologic lesions exhibited increased Ki67, CK14 and ΔNp63, cell proliferation markers, changes of cell adhesion molecules, E-Cadherin and β-catenin, and STAT3 activation. The in vivo effect of NF-κB activation is positively correlated with p-STAT3, Ki67, CK14 or β-catenin expression, while GDFs induce significant transcriptional activation of RELA(p65), bcl-2, TNF-α, STAT3, EGFR and wnt5A, in vivo. Our in vivo model demonstrates selectively activated NF-κB in response to topically administrated GDFs, leading to early pre-malignant events in HM. PMID:26745676

  2. [Bronchial hyperreactivity in athletes].

    PubMed

    Carlsen, K H

    1994-01-01

    Elite athletics, particularly endurance sports, are characterised by a high prevalence of bronchial hyperresponsiveness (BHR) and exercise-induced asthma (EIA). Findings in several studies suggest short-term high intensity physical activity to cause a transient increase in BHR. Recent studies in Oslo have shown that regular physical endurance training over several years, particularly when combined with such climatic factors as low air temperatures, may result in an increased risk of BHR and EIA among elite athletes--e.g., cross-country skiers. Inhalation beta 2-agonists and steroids have been used by many athletes in endurance sports, particularly skiers. Athletes with symptoms of BHR or EIA should be examined with lung function tests and exercise testing, and the effect of antiasthmatic drugs should be ascertained. Inhaled beta 2-agonists have no beneficial effect upon physical performance in nonasthmatic athletes, and may have a slight limiting effect upon physical endurance.

  3. MicroRNA from pancreatic duct aspirate differentiates cystic lesions of the pancreas.

    PubMed

    Henry, Jon C; Bassi, Claudio; Giovinazzo, Francesco; Bloomston, Mark

    2013-12-01

    Prognostication for cystic neoplasms of the pancreas continues to evolve. Beyond simple size and cystic fluid CEA determination, microRNA (miRNA) detection holds great promise as molecular diagnostics for cancer risk. In this study, we sought to identify miRNAs that could predict malignant potential of pancreatic cystic lesions. RNA was harvested from the pancreatic duct aspirate of 72 cystic neoplasms of the pancreas. Samples with adequate RNA concentration (≥ 3 ng/μL) were selected for qRTPCR profiling using assays to 379 of the most common miRNAs. miRNA profiles were correlated with histopathology from resected specimens and grouped by benign (serous cystadenomas), premalignant (intraductal papillary mucinous neoplasms and mucinous cystadenomas), or malignant lesions (adenocarcinoma). Adequate RNA for analysis was obtained from 42 (58.3 %) of the samples. Malignant lesions were more likely to have adequate RNA (n = 17, 81 %) than either benign (n = 6, 33 %) or premalignant lesions (n = 19, 59 %; p = 0.011). Nine miRNA were identified as differentially expressed between benign and premalignant/malignant lesions (p < 0.05). A significant correlation was found between the number of differentially expressed miRNA and the likelihood of a premalignant/malignant lesion. All premalignant or malignant lesions expressed at least one miRNA surpassing the threshold of mean miRNA expression, whereas no benign lesions had more than one miRNA surpassing the threshold. The presence of RNA in the duct aspirate from patients with pancreatic cystic neoplasms may be a predictor of premalignancy or malignancy. miRNA may be utilized to further differentiate between benign, premalignant, and malignant cystic lesions of the pancreas.

  4. Disseminated typical bronchial carcinoid tumor.

    PubMed

    Novković, Dobrivoje; Skuletić, Vesna; Vuković, Jelena; Cerović, Snezana; Tomić, Ilija; Karlicić, Vukojica; Stojisavljević, Marko

    2013-05-01

    Bronchial carcinoids belong to a rare type of lung tumors. If they do not expose outstanding neuroendocrine activity, they develop without clearly visible symptoms. They are often detected during a routine examination. According to their clinical pathological features, they are divided into typical and atypical tumors. Typical bronchial carcinoids metastasize to distant organs very rarely. Localized forms are effectively treated by surgery. The methods of conservative treatment should be applied in other cases. We presented a 65-year-old patient with carcinoid lung tumor detected by a routine examination. Additional analysis (chest X-ray, computed tomography of the chest, ultrasound of the abdomen, skeletal scintigraphy, bronhoscopy, histopathological analysis of the bioptate of bronchial tumor, as well as bronchial brushing cytology and immunohistochemical staining performed with markers specific for neuroendocrine tumor) proved a morphologically typical lung carcinoid with dissemination to the liver and skeletal system, which is very rarely found in typical carcinoids. The presented case with carcinoid used to be showed morphological and pathohistological characteristics of typical bronchial carcinoid. With its metastasis to the liver and skeletal system it demonstrated unusual clinical course that used to be considered as rare phenomenon. Due to its frequent asymptomatic course and varied manifestation, bronchial carcinoid could be considered as a diagnostic challenge requiring a multidisciplinary approach.

  5. Obscure pulmonary masses: bronchial impaction revealed by CT

    SciTech Connect

    Pugatch, R.D.; Gale, M.E.

    1983-11-01

    Dilated bronchi impacted with mucus or tumor are recognized on standard chest radiographs because they are surrounded by aerated pulmonary parenchyma. When imaged in different projections, these lesions produce a variety of appearances that are generally familiar. This report characterizes less familiar computed tomographic (CT) findings in eight patients with pathologic bronchial distension of congenital, neoplastic, or infectious etiologies and correlates them with chest films. In seven patients, CT readily revealed dilated bronchi and/or regional lung hypodensity. In four of these cases, CT led to the initial suspicion of dilated bronchi. CT should be used early in the evaluation of atypical pulmonary mass lesions or to confirm suspected bronchial impaction because of the high probability it will reveal diagnostic features.

  6. Bronchial carcinoid tumors: clinical and radiological correlation.

    PubMed

    Squerzanti, Antonella; Basteri, Vittoria; Antinolfi, Gabriele; D'agostino, Fulvio; Scutellari, Pier Nuccio; Ravenna, Franco; Ghirardi, Redenta; Cavallesco, Giorgio

    2002-10-01

    To evaluate the incidence of bronchial carcinoid tumor (BCT) in population affected by various lung tumors, retrospectively reviewed between 1986-2001, and to emphasize the radiographic patterns if they are characteristic. In the above mentioned period, chest x-ray and CT were performed in 1110 patients, both male and female, affected by lung neoplasms. 20 patients were affected by BCT (16 males, and 13 females), aged between 26 and 75 years (mean age 57.5), with histopathologic diagnosis of typical (9 cases, 31%) and atypical (20 cases, 69%) bronchial carcinoid tumors. Localized right lung lesion were as follows: 7 cases in superior, 9 in middle and 4 in inferior lobes; in the left lung, 5 cases in superior, and 4 in inferior lobes. Size of the lesions was as average 2.4 cm in diameter (with a range of 0.5-12 cm). On x-ray and CT images, BCT appeared as a well marginated nodule, of which 9 were peripheral and 20 central. BCT are classified as neuroendocrine carcinomas,and are divided in typical and atypical forms, with variable grade of malignancy. Central neoplasms are symptomatic due to bronchial obstruction (i.e., pneumonia, atelectasis, bronchiectasis, emphysema and/or lung abscess); if airway obstruction is partial, then cough, wheezing and recurrent pulmonary infections occur. Peripheral tumors are generally asymptomatic and they are discovered occasionally, when chest x-ray is made for other reasons. Radiographic features are similar in typical and atypical BCT. In central tumors a rounded well circumscribed hilar mass is noted, with lobulated or bumpy margins. Central cavitation is not referred to. Peripheral BCT appear as a solitary nodule, inferioer then 3 cm in size, marginated, surrounded by normal pulmonary tissue. Signs and symptoms of BCT are evasive and vague. No current clinical or laboratory procedures are useful in confirming the diagnosis; particularly, no imaging modalities are able to differentiate between BCT and other pulmonary tumors. For

  7. Bronchial glomus tumor with right upper lobe atelectasis.

    PubMed

    Azevedo-Pereira, Artur Eugênio de; Rigueiro, Moacyr Pezati; Abrão, Fernando Conrado

    2010-01-01

    Glomus tumors are uncommon benign soft tissue neoplasms. We report the case of a 32-year-old male who presented with right upper lobe atelectasis due to an endobronchial tumor. The patient underwent right upper lobectomy and wedge bronchoplasty. The pathological diagnosis was bronchial glomus tumor. To our knowledge, this presentation (with right upper lobe atelectasis) has never before been reported. Glomus tumor should be considered in the differential diagnosis of endobronchial lesions causing lobar atelectasis.

  8. [Rhino-bronchial syndrome].

    PubMed

    Gani, F; Vallese, G; Piglia, P; Senna, G; Mezzelani, P; Pozzi, E

    2000-12-01

    A close anatomical and functional relationship between superior and inferior airways is well documented. A typical example is offered by the close relationship between allergic rhinitis and asthma whose close connection is documented by epidemiological and pathological data. The mechanisms which can explain this phenomenon are not fully known but naso-bronchial reflexes, mouth-breathing due to nasal obstruction and aspiration of nasal secretions seem all to be important. Moreover it has been recently proved that the treatment of rhinitis can improve the concomitant asthma thus confirming their relationship. Another less frequent association is between sinusitis and asthma. Such a connection seems to be frequent in patients suffering of atopic rhinitis but also in patients presenting a nasal obstruction of different nature such as deviations of the nasal septum, adenoid hypertrophy etc. Also in this case a correct medical or surgical treatment of sinusitis can improve asthma symptomathology. Finally a classic example of involvement of superior and inferior airways is represented by the syndrome of ASA intolerance. These patients in fact initially complain of rhinitis which afterwards is complicated by the onset of nasal polyposis and asthma which can prove clinically very severe. Nowadays, anyway, there is no evidence that the treatment of rhinitis or polypectomy can improve the clinical course of asthma. In conclusion, diseases of superior and inferior airways must be considered in strict connection and need the same global treatment.

  9. To Study the Prevalence of Premalignancies in Teenagers having Betel, Gutkha, Khaini, Tobacco Chewing, Beedi and Ganja Smoking Habit and Their Association with Social Class and Education Status.

    PubMed

    Kumar Srivastava, Vinay

    2014-05-01

    Premalignant oral lesions are usually associated with noxious oral addiction habits. These habits are common in both, high as well as low socioeconomic status but education status of parent and patients significantly affects the development of noxious oral addictions. A total of 872 patients (cases and controls) were included in the study. Social class was determined as per modified Prasad's classification (1970) with price index correction of 2004. Prevalence of lichen planus, to be only 0.4 and 2.6% present in groups III and IV of cases, and submucous fibrosis (SMF) - stromal one lanocytic foci - was 2.4% in male (group III) whereas it was not found in female cases (group IV). Teenagers having higher frequency and longer duration of noxious habits were more prone for development of premalignant lesions. 0.6% of leukoplakia, 0.3% erythroplakia, 0.7% lichen planus and 0.7% submucous fibrosis were present in 872 observed patients of control and cases. How to cite this article: Srivastava VK. To Study the Prevalence of Premalignancies in Teenagers having Betel, Gutkha, Khaini, Tobacco Chewing, Beedi and Ganja Smoking Habit and Their Association with Social Class and Education Status. Int J Clin Pediatr Dent 2014;7(2):86-92.

  10. [Bronchial mucoepidermoid carcinoma in childhood. Case report].

    PubMed

    Cuestas, Giselle; Rodríguez, Verónica; Doormann, Flavia; Bellia Munzón, Patricio; Bellia Munzón, Gastón

    2017-08-01

    Bronchial tumors are rare in children. Most of them are malignant, being the carcinoid tumor the most common. Less frequently the mucoepidermoid carcinoma is found in the tracheobronchial tree. Mucoepidermoid carcinoma accounts for 0.1 to 0.2% of all malignant bronchopulmonary tumors. It manifests with symptoms of airway obstruction and/or recurrent pneumonias. Early diagnosis and appropriate treatment are of great importance in the prognosis. Bronchoscopy with biopsy of the endobronchial mass is the method of choice to confirm the diagnosis. Treatment consists of surgical resection of the lesion. We present an 11-year-old girl with dyspnea on exertion and cough due to a low malignant mucoepidermoid arcinoma of the ronchi. We describe the clinical manifestations, the diagnostic methods and the treatment of this rare neoplasia in pediatrics. Sociedad Argentina de Pediatría.

  11. 21 CFR 868.5720 - Bronchial tube.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bronchial tube. 868.5720 Section 868.5720 Food and... ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5720 Bronchial tube. (a) Identification. A bronchial tube is a... leading directly to the lung) in order to isolate a portion of lung distal to the tube. (b)...

  12. 21 CFR 868.5720 - Bronchial tube.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Bronchial tube. 868.5720 Section 868.5720 Food and... ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5720 Bronchial tube. (a) Identification. A bronchial tube is a... leading directly to the lung) in order to isolate a portion of lung distal to the tube. (b)...

  13. 21 CFR 868.5720 - Bronchial tube.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Bronchial tube. 868.5720 Section 868.5720 Food and... ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5720 Bronchial tube. (a) Identification. A bronchial tube is a... leading directly to the lung) in order to isolate a portion of lung distal to the tube. (b)...

  14. 21 CFR 868.5720 - Bronchial tube.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Bronchial tube. 868.5720 Section 868.5720 Food and... ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5720 Bronchial tube. (a) Identification. A bronchial tube is a... leading directly to the lung) in order to isolate a portion of lung distal to the tube. (b)...

  15. 21 CFR 868.5720 - Bronchial tube.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Bronchial tube. 868.5720 Section 868.5720 Food and... ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5720 Bronchial tube. (a) Identification. A bronchial tube is a... leading directly to the lung) in order to isolate a portion of lung distal to the tube. (b)...

  16. The Significance of Bronchial Atrophy

    PubMed Central

    Maisel, John C.; Silvers, G. Wayne; George, Marlyce S.; Dart, Gladys A.; Petty, Thomas L.; Mitchell, Roger S.

    1972-01-01

    In a 4-year period, 196 lungs from patients with and without chronic obstructive pulmonary disease were examined postmortem for the presence of atrophy in segmental and subsegmental bronchi. As a result of simultaneous postmortem spirometry, cinefluorobronchography and partitioning of airways resistance, plus later assessment of anatomic emphysema, bronchial atrophy emerges as only one of at least three factors usually cooperating in production of abnormal expiratory airway collapse. In selected cases, bronchial atrophy appears to be an important contributor to expiratory airways obstruction. ImagesFig 1 PMID:5021107

  17. [The history of bronchial asthma].

    PubMed

    Glück, U

    1992-10-01

    'Panta rhei': everything flows. The significance of bronchial asthma is currently changing to no less a degree than medicine itself. In order to know where we are, we must know where we have come from. The historical course of bronchial asthma to some extent reflects the history of medicine itself: the Hellenic systems were followed by Byzantine, Galenic teaching methods, while Humanism and the Renaissance were followed by the considerable fireworks of early modern medicine. This continued with Magendie's experimental revolution in the 19th century and, finally, analytic medical research up to today.

  18. Premalignant Genetic and Epigenetic Alterations in Tubal Epithelium from Women with BRCA1 Mutations

    DTIC Science & Technology

    2009-10-08

    from ovarian, breast and prostate tissue. The HOXA gene cluster is a family of homeotic genes that encode transcription factors which are frequently...unique premalignant gene expression profile and to identify causal epigenetic relationships. As outlined in the statement of work, our analyses have...identified a premalignant expression signature which potentially reflects early steps in ovarian carcinogenesis. While genes differentially expressed in

  19. New developments in endocervical glandular lesions.

    PubMed

    McCluggage, W Glenn

    2013-01-01

    McCluggage W G (2012) Histopathology New developments in endocervical glandular lesions There is evidence that the prevalence of premalignant and malignant endocervical glandular lesions is increasing in real as well as in apparent terms. In this review, new developments and selected controversial aspects of endocervical glandular lesions are covered, concentrating mainly on premalignant and malignant lesions. The terminology of premalignant endocervical glandular lesions is discussed with a comparison of the World Health Organization classification and the cervical glandular intraepithelial neoplasia (CGIN) system, which is in widespread use in the United Kingdom. Primary cervical adenocarcinomas comprise a heterogeneous group of different morphological types, and while it is known that the majority of these are associated with high-risk human papillomavirus (HPV), it has become clear in recent years that most of the more uncommon morphological types are unassociated with HPV, although they may sometimes be p16-positive. A spectrum of benign, premalignant and malignant cervical glandular lesions exhibiting gastric differentiation is now recognized; these include type A tunnel clusters, typical and atypical lobular endocervical glandular hyperplasia, adenoma malignum and gastric-type adenocarcinoma. The latter is a recently described variant of primary cervical adenocarcinoma which has a different morphological appearance to the usual endocervical type and which is probably associated with different patterns of spread and a worse prognosis. There is accumulating evidence that 'early invasive' cervical adenocarcinomas have an excellent prognosis and are suitable for conservative management. Immunohistochemical markers of value in the distinction between a primary cervical and endometrial adenocarcinoma are discussed. While it is well known that a panel of markers comprising oestrogen receptor (ER), vimentin, p16 and monoclonal carcinoembryonic antigen (CEA) is

  20. p53 Restoration in Induction and Maintenance of Senescence: Differential Effects in Premalignant and Malignant Tumor Cells

    PubMed Central

    Harajly, Mohamad; Zalzali, Hasan; Nawaz, Zafar; Ghayad, Sandra E.; Ghamloush, Farah; Basma, Hussein; Zainedin, Samiha; Rabeh, Wissam; Jabbour, Mark; Tawil, Ayman; Badro, Danielle A.; Evan, Gerard I.

    2015-01-01

    The restoration of p53 has been suggested as a therapeutic approach in tumors. However, the timing of p53 restoration in relation to its efficacy during tumor progression still is unclear. We now show that the restoration of p53 in murine premalignant proliferating pineal lesions resulted in cellular senescence, while p53 restoration in invasive pineal tumors did not. The effectiveness of p53 restoration was not dependent on p19Arf expression but showed an inverse correlation with Mdm2 expression. In tumor cells, p53 restoration became effective when paired with either DNA-damaging therapy or with nutlin, an inhibitor of p53-Mdm2 interaction. Interestingly, the inactivation of p53 after senescence resulted in reentry into the cell cycle and rapid tumor progression. The evaluation of a panel of human supratentorial primitive neuroectodermal tumors (sPNET) showed low activity of the p53 pathway. Together, these data suggest that the restoration of the p53 pathway has different effects in premalignant versus invasive pineal tumors, and that p53 activation needs to be continually sustained, as reversion from senescence occurs rapidly with aggressive tumor growth when p53 is lost again. Finally, p53 restoration approaches may be worth exploring in sPNET, where the p53 gene is intact but the pathway is inactive in the majority of examined tumors. PMID:26598601

  1. Management of occult adrenocorticotropin-secreting bronchial carcinoids: limits of endocrine testing and imaging techniques.

    PubMed

    Loli, P; Vignati, F; Grossrubatscher, E; Dalino, P; Possa, M; Zurleni, F; Lomuscio, G; Rossetti, O; Ravini, M; Vanzulli, A; Bacchetta, C; Galli, C; Valente, D

    2003-03-01

    The differential diagnosis and the identification of the source of ACTH in occult ectopic Cushing's syndrome due to a bronchial carcinoid still represents a challenge for the endocrinologist. We report our experience in six patients with occult bronchial carcinoid in whom extensive hormonal, imaging, and scintigraphic evaluation was performed. All patients presented with hypercortisolism associated with high plasma ACTH values. The CRH test and high dose dexamethasone suppression test suggested an ectopic source of ACTH in three of six patients. During bilateral inferior petrosal sinus sampling, none of the patients showed a central to peripheral ACTH gradient. At the time of diagnosis, none of the patients had radiological evidence of the ectopic source of ACTH, whereas pentetreotide scintigraphy identified the lesion in two of four patients. Finally, a chest computed tomography scan revealed the presence of a bronchial lesion in all patients, and pentetreotide scintigraphy identified four of six lesions. In all patients a bronchial carcinoid was found and removed. In one patient with scintigraphic evidence of residual disease after two operations, radioguided surgery, using a hand-held gamma probe after iv administration of radiolabeled pentetreotide, was performed; this allowed detection and removal of residual multiple mediastinal lymph node metastases. In conclusion, our data show that there is not a single endocrine test or imaging procedure accurate enough to diagnose and localize occult ectopic ACTH-secreting bronchial carcinoids. Radioguided surgery appears to be promising in the presence of multiple tumor foci and previous incomplete removal of the tumor.

  2. Human papillomavirus in oral lesions.

    PubMed

    González, Joaquín V; Gutiérrez, Rafael A; Keszler, Alicia; Colacino, Maria del Carmen; Alonio, Lidia V; Teyssie, Angelica R; Picconi, Maria Alejandra

    2007-01-01

    Growing evidence suggests a role for human papillomavirus (HPV) in oral cancer; however its involvement is still controversial. This study evaluates the frequency of HPV DNA in a variety of oral lesions in patients from Argentina. A total of 77 oral tissue samples from 66 patients were selected (cases); the clinical-histopathological diagnoses corresponded to: 11 HPV- associated benign lesions, 8 non-HPV associated benign lesions, 33 premalignant lesions and 25 cancers. Sixty exfoliated cell samples from normal oral mucosa were used as controls. HPV detection and typing were performed by polymerase chain reaction (PCR) using primers MY09, 11, combined with RFLP or alternatively PCR using primers GP5+, 6+ combined with dot blot hybridization. HPV was detected in 91.0% of HPV- associated benign lesions, 14.3% of non-HPV associated benign lesions, 51.5% of preneoplasias and 60.0% of cancers. No control sample tested HPV positive. In benign HPV- associated lesions, 30.0% of HPV positive samples harbored high-risk types, while in preneoplastic lesions the value rose to 59.9%. In cancer lesions, HPV detection in verrucous carcinoma was 88.9% and in squamous cell carcinoma 43.8%, with high-risk type rates of 75.5% and 85.6%, respectively. The high HPV frequency detected in preneoplastic and neoplastic lesions supports an HPV etiological role in at least a subset of oral cancers.

  3. Thrombospondin-1 mediates oncogenic Ras–induced senescence in premalignant lung tumors

    PubMed Central

    Baek, Kwan-Hyuck; Bhang, Dongha; Zaslavsky, Alexander; Wang, Liang-Chuan; Vachani, Anil; Kim, Carla F.; Albelda, Steven M.; Evan, Gerard I.; Ryeom, Sandra

    2013-01-01

    Progression of premalignant lesions is restrained by oncogene-induced senescence. Oncogenic Ras triggers senescence in many organs, including the lung, which exhibits high levels of the angiogenesis inhibitor thrombospondin-1 (TSP-1). The contribution of TSP-1 upregulation to the modulation of tumorigenesis in the lung is unclear. Using a mouse model of lung cancer, we have shown that TSP-1 plays a critical and cell-autonomous role in suppressing Kras-induced lung tumorigenesis independent of its antiangiogenic function. Overall survival was decreased in a Kras-driven mouse model of lung cancer on a Tsp-1–/– background. We found that oncogenic Kras–induced TSP-1 upregulation in a p53-dependent manner. TSP-1 functioned in a positive feedback loop to stabilize p53 by interacting directly with activated ERK. TSP-1 tethering of ERK in the cytoplasm promoted a level of MAPK signaling that was sufficient to sustain p53 expression and a senescence response. Our data identify TSP-1 as a p53 target that contributes to maintaining Ras-induced senescence in the lung. PMID:24018559

  4. Adjunctive aids for the detection of oral premalignancy

    PubMed Central

    Charanya, D.; Raghupathy, L. P.; Farzana, Amjad Fazeela; Murugan, R.; Krishnaraj, R.; Kalarani, G.

    2016-01-01

    Early detection of cancer greatly decreases the morbidity and mortality rates and thereby increases the 5-year survival rates. In developing countries like India where the disease is highly prevalent focus is mainly on decreasing the mortality rates which can be easily achieved by detection at an asymptomatic stage. Visual examination has been the standard screening method for screening oral cancer through several decades, and it is well known that conventional visual examination is limited to subjective interpretation and cannot be easily achieved in certain anatomical sites. As a solution to all these adjunctive techniques have emerged, and it has been widely used. An effort is made through this paper to review the most commonly used adjunctive aids for the detection of premalignancy and cancer. PMID:27829738

  5. A solitary bronchial papilloma with unusual endoscopic presentation: case study and literature review

    PubMed Central

    Paganin, Fabrice; Prevot, Martine; Noel, Jean Baptiste; Frejeville, Marie; Arvin-Berod, Claude; Bourdin, Arnaud

    2009-01-01

    Background Solitary endobronchial papillomas (SEP) are rare tumors and most of them are described by case report. A misdiagnosis is common with viral related papillomas. A histopathological classification has recently permitted a major advancement in the understanding of the disease. Case Presentation We report a case of a mixed bronchial papilloma with an unusual endoscopic presentation. The literature was extensively reviewed to ascertain the unusual characteristics of the current case. A 39-year of age male was referred to our institution for the investigation of a slight hemoptysis. Routine examination was normal. A fibroscopy revealed an unusual feature of the right main bronchus. The lesion was a plane, non-bleeding, non-glistering sub-mucosal proliferation. No enhanced coloration was noticed. Biopsies revealed a mixed solitary bronchial papilloma. In situ HPV hybridization was negative. Endoscopic treatment (electrocautery) was effective with no relapse. Conclusion This lesion contrasts with the data of the literature where papilloma were described as wart-like lesions or cauliflower tumors, with symptoms generally related to bronchial obstruction. We advise chest physicians to be cautious with unusually small swollen lesions of the bronchi that may reveal a solitary bronchial papilloma. Endoscopic imaging can significantly contribute to the difficult diagnosis of SEP by pulmonary physicians and endoscopists. PMID:19689808

  6. Premalignant Genetic and Epigenetic Alterations in Tubal Epithelium from Women with BRCA1 Mutations

    DTIC Science & Technology

    2010-10-14

    Premalignant Genetic and Epigenetic Alterations in Tubal Epithelium from Women with BRCA1 Mutations PRINCIPAL INVESTIGATOR: Anton Krumm, Ph.D...REPORT TYPE 3. DATES COVERED (From - To) 15 Sept 2009 – 14 Sept 2010 4. TITLE AND SUBTITLE Premalignant Genetic and Epigenetic Alterations in Tubal 5a...Appendices…………………………………………………………………………… 8-33 10/14/2010 Anton Krumm 1 Premalignant Genetic and Epigenetic Alterations in Tubal Epithelium from Women

  7. Bronchial responsiveness in active steelworkers.

    PubMed

    Corhay, J L; Bury, T; Louis, R; Delavignette, J P; Kayembe, J M; Weber, G; Albert, A; Radermecker, M F

    1998-02-01

    Coke-oven workers are exposed to dust and irritant gases. Therefore they are at risk of developing lung diseases including chronic bronchitis. Nonspecific bronchial hyperresponsiveness (BHR) has been advocated as a potential risk factor predisposing to the development of chronic bronchitis. In a previous study, we showed that prevalence of BHR was higher in retired coke-oven workers than in retired blast furnace workers. The present study was carried out to determine the prevalence of BHR in active steelworkers. Thus, 137 coke-oven workers and 150 blast furnace workers underwent clinical examination, a standardized questionnaire for the study of respiratory symptoms, pulmonary function testing and methacholine aerosol challenge. The study demonstrates a higher prevalence and degree of BHR [provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) < or = 8 mg x mL(-1)] in coke-oven workers than in blast furnace workers (31.4 versus 6.7%; p<0.001). Moreover, the frequency of respiratory symptoms and basal bronchial obstruction were greater among coke-oven workers with BHR in nonresponders. The basal maximum expiratory flow from 25-75% of forced vital capacity and the respiratory symptoms were correlated with bronchial responsiveness. The lack of correlation observed between BHR and the intensity of smoking or years spent in coke-oven environment may be explained by the high proportion of smokers, the worker turnover in the steel plant, and the "healthy worker effect". In conclusion, the higher prevalence and degree of bronchial hyperresponsiveness in coke-oven workers suggests that coke-oven pollutants are more intense irritants than those that escape from blast furnaces.

  8. Social networks and bronchial asthma.

    PubMed

    D'Amato, Gennaro; Cecchi, Lorenzo; Liccardi, Gennaro; D'Amato, Maria; Stanghellini, Giovanni

    2013-02-01

    To focus on both positive and negative aspects of the interaction between asthmatic patients and the social networks, and to highlight the need of a psychological approach in some individuals to integrate pharmacological treatment is the purpose of review. There is evidence that in some asthmatic patients, the excessive use of social networks can induce depression and stress triggering bronchial obstruction, whereas in others their rational use can induce beneficial effects in terms of asthma management. The increasing asthma prevalence in developed countries seen at the end of last century has raised concern for the considerable burden of this disease on society as well as individuals. Bronchial asthma is a disease in which psychological implications play a role in increasing or in reducing the severity of bronchial obstruction. Internet and, in particular, social media are increasingly a part of daily life of both young and adult people, thus allowing virtual relationships with peers sharing similar interests and goals. Although social network users often disclose more about themselves online than they do in person, there might be a risk for adolescents and for sensitive individuals, who can be negatively influenced by an incorrect use. However, although some studies show an increased risk of depression, other observations suggest beneficial effects of social networks by enhancing communication, social connection and self-esteem.

  9. Increased accumulation of N-isopropyl-(I-123)p-iodoamphetamine in bronchial carcinoid tumor

    SciTech Connect

    Nishizawa, S.; Higa, T.; Kuroda, Y.; Sano, A.; Murakami, M.; Takahashi, Y. )

    1990-02-01

    Radionuclide imaging with N-isopropyl-(I-123)p-iodoamphetamine (({sup 123}I)IMP) was performed in a patient with recurrent bronchial carcinoid tumor. Increased accumulation of ({sup 123}I)IMP was observed in the known lesions of the brain and neck on both tomographic and planar images. Scintigraphy also revealed unknown metastatic lesions of the paraaortic lymph nodes, which were later confirmed on x-ray CT. Iodine-123-IMP may have a potential role in evaluating carcinoid tumors.

  10. [Synopsis of computed tomography, scintigraphy and bronchoscopy in the diagnosis of bronchial carcinoma].

    PubMed

    Beyer-Enke, S A; Clorius, J; Becker, H; Goerich, J; Probst, G; van Kaick, G

    1988-08-01

    In 87 patients with histologically proven bronchogenic carcinoma, computerised tomography (CT) and bronchoscopy were performed to assess the accuracy of CT in detecting bronchial stenosis. Whereas patent airways and mainstem stenosis were recognised in 85% of the cases, the overall accuracy was only 57%. Furthermore, the results of both methods were compared to scintigraphy (ventilation, perfusion) to evaluate the functional impairment due to altered lung morphology and bronchial stenosis. With an increasing number of CT-diagnosed atelectatic or infiltrated segments an almost linear decrease in ventilation and perfusion values was observed. In comparison, bronchoscopy-diagnosed tumour stenosis resulted in decreased ventilation and perfusion data only if the lesion was centrally located.

  11. [Bronchial carcinoid tumor: study of 60 patients].

    PubMed

    Madrid-Carbajal, Claudia; García-Clemente, Marta; Pando-Sandoval, Ana; Cubillas Martín, Hugo; González-Budiño, Teresa; Casan-Clarà, Pere

    2013-07-21

    To describe the casuistry of bronchial carcinoid tumor in the last 20 years in our hospital and determine survival after surgical treatment. We retrospectively reviewed the medical records from January 1992 to June 2012 of patients diagnosed with carcinoid tumor by the pulmonary service. Fifty-two patients (87%) had typical carcinoid and 8 (13%) atypical carcinoid. The mean age at diagnosis was 60 years (SD: 14.4). There was no relationship between consumption of tobacco and carcinoid tumor. Twenty-two per cent were asymptomatic radiographic finding (incidental finding) Three patients showed carcinoid syndrome and one patient had Cushing syndrome. There was a right dominance and the mean lesion size was between 2.1 and 5 cm. Nine per cent had lymph node involvement, predominantly in atypical carcinoid. Overall survival at 3.5 and 10 years was 94%, 86% and 82%. Survival at 5 years was 90% for typical and 86% for atypical and survival at 10 years was 85% for typical and 57% for atypical carcinoids. Carcinoid tumors are malignant tumors by their ability to metastasize. In our study, both histological type and staging were predictors of survival. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  12. Non-infectious inflammatory genital lesions.

    PubMed

    Andreassi, Lucio; Bilenchi, Roberta

    2014-01-01

    The genitalia may be the site of non-infectious inflammatory lesions that are generally manifested as balanoposthitis and vulvovaginitis. In men, these forms constitute 50% of all balanoposthitis forms, and in women, vulvovaginitis frequency is even higher. They consist of genital locations of general skin diseases, such as psoriasis, lichen planus, lichen sclerosus, and other clinical entities with their own physiognomy, such as Zoon's balanitis-vulvitis. Diagnosis of genital non-infectious inflammatory lesions is usually made on clinical criteria. A biopsy is only necessary for the identification of clinical conditions that may simulate inflammatory form but are actually premalignant processes.

  13. Premalignant Lesions of the Anal Canal and Squamous Cell Carcinoma of the Anal Canal

    PubMed Central

    Poggio, Juan Lucas

    2011-01-01

    Squamous cell carcinoma of the anus (SCCA) is a rare tumor. However, its incidence has been increasing in men and women over the past 25 years worldwide. Risk factors associated with this cancer are those behaviors that predispose individuals to human papillomavirus (HPV) infection and immunosuppression. Anal cancer is generally preceded by high-grade anal intraepithelial neoplasia (HGAIN), which is most prevalent in human immunodeficiency virus-positive men who have sex with men. High-risk patients may benefit from screening. The most common presentation is rectal bleeding, which is present in nearly 50% of patients. Twenty percent of patients have no symptoms at the time of presentation. Clinical staging of anal cancer requires a digital rectal exam and a positron emission tomography/computed tomography scan of the chest, abdomen, and pelvis. Endorectal/endoanal ultrasound appears to add more-specific staging information when compared with digital rectal examination alone. Treatment of anal cancer prior to the 1970s involved an abdominoperineal resection. However, the current standard of care for localized anal cancer is concurrent chemoradiation therapy, primarily because of its sphincter-saving and colostomy-sparing potential. Studies have addressed alternative chemoradiation regimens to improve the standard protocol of fluorouracil, misogynic, and radiation, but no alternative regimen has proven superior. Surgery is reserved for those patients with residual disease or recurrence. PMID:22942800

  14. [Thoracic actinomycosis versus bronchial cancer].

    PubMed

    Brombacher-Frey, I; Wöckel, W; Kreusser, T

    1992-01-01

    We report on 4 thoracic actinomycoses; in three of these four cases a bronchial carcinoma was suspected, and in case No. 2 this carcinoma had been considered to be in a very advanced and inoperable stage. A man of 51 years of age was in a generally run-down condition. He also noticed that his sputum was tinged with blood. The x-ray film showed a large space-occupying growth at the right lung hilus. Repeated perbronchial biopsies of the focus did not yield any diagnosis. Actinomycosis was identified histologically only in the tissue samples obtained via thoracotomy. After a three-month penicillin course the hilar shadow receded. A 61-year old male patient was transferred to our Pneumological Hospital, being strongly suspected of suffering from an extensive bronchial carcinoma, and having multiple intrathoracic space-occupying growths as well as pleural effusions, a pericardial effusion, and an infiltration of the left thoracic wall with fistula formation; however, histological examination of skin biopsies revealed that he was suffering from actinomycosis. Antibiotic therapy cured him completely in a six-month course. In a man of 32 years of age who had been indulging for many years in a severe abuse of nicotin, we suspected a central bronchial carcinoma on the basis of his x-ray, but histology of the tissue taken from the space-occupying growth via diagnostic thoracotomy revealed that this patient, too, suffered from actinomycosis. Complete recession occurred after several months of antibiotic treatment. A woman of 82 years had been an inpatient for several months in another hospital because of relapsing pleuropneumonias on the right side. She was transferred to us as an outpatient after a renewed relapse. We conducted a transcutaneous fine-needle biopsy of the right indurating pleural effusion. A few actinomyces filaments were seen on histological examination of the purulent exudate. Hence, actinomycosis was confirmed. After antibiotic therapy the finding receded

  15. Use of high kilovoltage filtered beam radiographs for detection of bronchial situs in infants and young children.

    PubMed Central

    Deanfield, J E; Leanage, R; Stroobant, J; Chrispin, A R; Taylor, J F; Macartney, F J

    1980-01-01

    Determination of atrial situs is of cardinal importance in the analysis of complex congenital heart lesions, and is best predicted from bronchial situs. Previous methods for assessing bronchial morphology, however, are unsuited to the very young patient. To assess bronchial morphology, 100 consecutive patients under 18 months of age (medium 57.5 days) with suspected congenital heart disease were studied by high kilovoltage filtered beam radiographs, before cardiac catheterisation. This low radiation dose technique clearly defined bronchial anatomy in 95 patients. The lengths of the left and right main bronchi were compared and 10 cases (10%) had a ratio less than 1.5 suggesting bronchial isomerism. Discriminant function analysis based on tracheal width and bronchial length enabled clear distinction of right from left bronchi. Four patients had bilateral right and six had bilateral left bronchi. Four of these 10 cases died and had necropsy confirmation of the radiological diagnosis. Practical prediction about cardiac anatomy, particularly the systemic and pulmonary venous return, may be made when bronchial morphology is known. Images PMID:7437200

  16. [Pharmacotherapeutical management of bronchial asthma].

    PubMed

    Leont'ev, S L; Mikhaĭlov, V G; Nevzorova, V P; Sadovnikova, R V; Shabashov, A F; Lugovkina, T K; Leshchenko, I V; Bel'tiukov, E K; Lebedeva, M K

    1998-01-01

    The analysis of the prescriptions for bronchial asthma (BA) patients in outpatient practice was made using data base created at the Regional Fund of Obligatory Health Insurance in the Sverdlovsk region with consideration of GINA principles of BA stepped care. The real structure of prescriptions was compared with the pattern drug official list for asthma care. The cost of each BA care step was calculated on the base of the computer programs. The analysis showed low quality of BA care in outpatient practice. The created computer programs are very useful for the prescriptions structure monitoring, cost-effect analysis and pharmacotherapeutical management of the diseases.

  17. [Epidural emphysema complicating bronchial asthma].

    PubMed

    Rouetbi, N; Ben Saad, A; Joobeur, S; Skhiri, N; Cheikh Mhamed, S; Mribah, H; El Kamel, A

    2012-12-01

    Epidural emphysema is an exceptional complication of bronchial asthma, revealed by an incidental finding in chest tomography. We report a case of a 21-year-old man admitted with asthma attack complicated by subcutaneous and mediastinal emphysema. Chest tomography confirmed the mediastinal emphysema and also revealed the epidural emphysema within the vertebral canal. Neurological examination was negative. The patient showed complete recovery 10days after the onset of symptoms. The epidural emphysema is a rare complication during asthma attacks. The benignity of this complication should not require a systematic chest tomography.

  18. Bronchial provocation tests in clinical practice.

    PubMed

    Borges, Marcos de Carvalho; Ferraz, Erica; Vianna, Elcio Oliveira

    2011-01-01

    Bronchial hyperresponsiveness, which consists of an exaggerated response of the airways to bronchoconstrictor stimuli, is one of the main characteristics of asthma, presented in nearly all asthmatic patients. Bronchial hyperresponsiveness may also be present in other diseases, such as allergic rhinitis, chronic obstructive pulmonary disease, cystic fibrosis, heart failure and respiratory infection, and with some medications, such as β-blockers. Bronchial provocation tests (also known as bronchial challenges) are used to evaluate bronchial responsiveness. These tests have become increasingly used over the last 20 years, with the development and validation of accurate, safe and reproducible tests, and with the publication of well-detailed protocols. Several stimuli can be used in a bronchial challenge, and they are classified as direct and indirect stimuli. There are many indications for a bronchial challenge. In this review, we discuss the main differences between direct and indirect stimuli, and the use of bronchial challenges in clinical practice, especially for confirming diagnoses of asthma, exercise-induced bronchoconstriction and cough-variant asthma, and for use among elite-level athletes.

  19. Ornithine decarboxylase as a marker for premalignancy in the stomach.

    PubMed Central

    Patchett, S E; Alstead, E M; Butruk, L; Przytulski, K; Farthing, M J

    1995-01-01

    Assessment of mucosal ornithine decarboxylase (ODC) activity in the human large bowel may be of value as a marker of potential malignant risk. Its value as a marker of premalignancy in the upper gastrointestinal tract is less clear. Using a [14C]-ornithine bioassay, gastric mucosal ODC activity was measured in 32 normal subjects and 22 patients with confirmed gastric cancer. These results were compared with 47 patients at increased risk of upper gastrointestinal malignancy, (32 patients with partial gastric resection, 15 patients with familial adenomatous polyposis). Median ODC activity in normal subjects was 371 pmol/mg protein/h, (interquartile range (IQR), 230-617). There was no variation with age or sex and no relation to Helicobacter pylori status. Normal subjects had significantly lower ODC activity than patients with a gastric resection or confirmed gastric cancer, but similar to patients with familial adenomatous polyposis. Furthermore, no difference in activity was identified between patients with a gastric resection and established gastric cancer. ODC activity was, however, significantly increased in areas of gastric atrophy or intestinal metaplasia, regardless of the clinical group from which the samples were obtained. It is concluded that measurement of mucosal ODC activity does not provide additional predictive information of malignant risk in the stomach and investigation of other potential biomarkers of malignancy is warranted. PMID:7672662

  20. [Applications for bronchial blockers in thoracic surgery].

    PubMed

    García-Guasch, R; Campos, J H; Granell, M; Peña, J J

    2007-11-01

    One-lung ventilation is commonly used to facilitate visualization of the field during thoracic surgery. New devices for performing this technique that have become available over the past 2 decades include the Univent bronchial blocker incorporated in a single-lumen tube, the Arndt endobronchial blocker, and the Cohen endobronchial blocker. Although insertion of a double-lumen tube is still the method used most often to isolate the lung, bronchial blockade is an increasingly common technique and, in certain clinical settings, provides advantages over the double-lumen tube. This review provides an update on new concepts in the use of bronchial blockers as a technique for lung isolation and one-lung ventilation. The literature search was performed on MEDLINE through PubMed using the keywords bronchial blockers and thoracic surgery. The search span started with 1982-the year the first modern bronchial blocker was described - and ended with February 2006.

  1. Misdiagnosed Case of Bronchial Carcinoid Presenting with Refractory Dyspnoea and Wheeze: A Rare Case Report and Review of Literature

    PubMed Central

    Santra, Avradip; Dutta, Pravati; Pothal, Sudarsan; Manjhi, Rekha

    2013-01-01

    A 59-year-old male smoker presented with persistent wheezing and occasional coughing that had been ongoing for two years and had been unsuccessfully treated with an inhalational β2 agonist, an anticholinergic and an inhalational steroid in the last year. On clinical examination, a left-sided wheeze was detected. The initial chest X-ray was normal. A computed tomography (CT) scan of thorax demonstrated a mass lesion in the left main bronchus. On subsequent bronchoscopy, an endobronchial polypoid mass was detected in the left main bronchus, completely occluding the bronchial lumen. A biopsy taken from the mass revealed features of bronchial carcinoid. Bronchial carcinoid can present uncommonly with wheezes, resulting in misdiagnosis as bronchial asthma or chronic obstructive pulmonary disease (COPD). If an asthma or COPD patient does not respond to conventional therapy, a CT scan and subsequent bronchoscopy is warranted. PMID:23966830

  2. Esophageal and Bronchial Perforations After Thoracic Aortic Aneurysm Replacement: Successful Repair with Covered Metallic Stents

    SciTech Connect

    Sueyoshi, Eijun; Imada, Tatsuya; Sakamoto, Ichiro; Uetani, Masataka; Hayashi, Kuniaki

    2003-09-15

    Esophageal and bronchial perforations are rare but potentially fatal complications of descending thoracic aortic aneurysm replacement. This report presents a 67-year-old man with both esophageal and bronchial perforations that occurred after descending thoracic aortic aneurysm replacement. Surgical repair was performed, but the lesions perforated again. Two covered metallic stent prostheses introduced into both the esophagus and left main bronchus led to the improvement of mediastinitis by sealing the perforations. To our knowledge, this is the first report describing successful treatment for esophageal and bronchial perforations using covered metallic stents. Placement of covered metallic stents can be an option for the treatment of patients with esophagorespiratory tract perforations, especially those who are in critical condition.

  3. [Congenital heart defects with tracheal and bronchial stenoses: surgical treatment with extracorporeal circulation].

    PubMed

    Cordovilla Zurdo, G; Cabo Salvador, J; Sanz Galeote, E; Lassaleta Garbayo, L; Benito Bartolomé, F; Alvarez Díaz, F

    1999-08-01

    We present our experience with the surgical management of congenital cardiac defects when tracheal or bronchial stenosis is present. Concerning pulmonary artery sling, we think that it is necessary to correct the cardiac malformation and trachea-bronchial stenosis at the same time. After surgical correction, if the patient cannot be weaned from mechanical ventilation (10-15 days), it is mandatory to rule out the presence of tracheo-bronchial tree lesions in order to perform surgery without delay. The operation should be performed under cardiopulmonary by-pass at the same time as the surgical correction of the cardiac malformation. We believe that the best technique for localized obstruction is resection of the stenotic area, followed by termino-terminal anastomosis (one case in our patient group). However, when the length of the obstruction is longer, our election is to enlarge the stenotic area with pre-molded cartilage (four cases).

  4. [Analysis of clinical manifestations and diagnosis of 102 children with bronchial tuberculosis].

    PubMed

    He, Ru-xuan; Zhao, Shun-ying

    2012-10-01

    Most of Endobronchial tuberculosis (EBTB) of children is caused by the bronchial erosion from the scrofula close to the bronchus. Due to its complicated mechanism, pediatricians have limited knowledge on the endobronchial tuberculosis, which makes the misdiagnosis rate high. This work explored the clinical features and diagnostic methods of endobronchial tuberculosis (EBTB), to improve the understanding of this disease. A total of 102 cases with endobronchial tuberculosis (EBTB) were investigated by analyzing clinical and bronchoscopic features, imaging manifestation, PPD results and etiological examination; 71 cases were male, 33 were female, the youngest was 4 months old, and the oldest was 10 years old. The patients were treated in the fourth ward of the Department of Internal Medicine, Beijing Children's Hospital, Capital Medical University. Of the 102 cases, 71 (69.6 percent) were infants and young children. (1) Age and clinical presentation: Infants and young children were more common, the main clinical manifestations were fever and cough, physical examination may find decreased breath sounds, wet and dry rale and wheezing. (2) In 81 cases who received CT there was bronchial obstruction, in 43 cases there were simultaneous manifestations of primary pulmonary tuberculosis (mediastinal and hilar lymph node enlargement and/or pulmonary consolidation), 21 cases had only manifestations of primary tuberculo. (3) The results of PPD: the positive rate was 95%. (4) Bronchoscopic feature: presence of mucosal swelling, caseous necrosis, bronchial stenosis/extrabronchial compression, granulomatous lesions and lymph node bronchial fistula. (5) Bacteriologic results: 21 patients were bacteriologically positive. Bronchial tuberculosis was more common in infants and young children, their major clinical manifestations were fever, cough, common findings on lung imaging was mediastinal and hilar lymph node enlargement and/or pulmonary consolidation, bronchial obstruction should

  5. Cortactin and focal adhesion kinase as predictors of cancer risk in patients with laryngeal premalignancy.

    PubMed

    Rodrigo, Juan P; Álvarez-Alija, Gustavo; Menéndez, Sofía Tirados; Mancebo, Gonzalo; Allonca, Eva; García-Carracedo, Darío; Fresno, Manuel Florentino; Suárez, Carlos; García-Pedrero, Juana María

    2011-08-01

    Novel markers are needed to accurately predict the risk of malignant transformation in laryngeal premalignancies. We therefore investigated the clinical significance of cortactin (CTTN) and focal adhesion kinase (FAK) during laryngeal tumorigenesis and their potential utility as cancer risk markers. CTTN and FAK protein expression and gene amplification were assessed in 82 patients with laryngeal dysplasia and correlated with clinicopathologic parameters and laryngeal cancer risk. Increased CTTN and FAK expression was found respectively in 41 (50%) and 40 (49%) of 82 laryngeal dysplasias; protein expression was maintained or further augmented in the corresponding patient-matched invasive tumors subsequently developed. CTTN and FAK/PTK2 gene amplifications were respectively detected in 10 (12%) and 26 (32%) laryngeal dysplasias. Both CTTN and FAK protein expression increased with the grade of dysplasia; however, CTTN and FAK expression but not histology correlated significantly with increased laryngeal cancer risk (P = 0.009 and P = 0.002, respectively). Patients carrying strong CTTN- or FAK-expressing dysplastic lesions experienced a significantly higher cancer incidence (P = 0.006 and P = 0.001, respectively; log-rank test). Furthermore, FAK expression was an independent predictor of laryngeal cancer development (HR = 3.706, 95% CI: 1.735-7.916; P = 0.001) and the combination of FAK and CTTN showed superior predictive value (HR = 5.042, 95% CI: 2.255-11.274; P < 0.001). Taken together, our findings support the involvement of CTTN and FAK in malignant transformation and provide original evidence for their potential clinical utility as biomarkers for the risk of developing laryngeal cancer.

  6. Impact of bronchial circulation on bronchial exudation following combined burn and smoke inhalation injury in sheep

    PubMed Central

    Morita, Naoki; Enkhbaatar, Perenlei; Maybauer, Dirk M.; Maybauer, Marc O.; Westphal, Martin; Murakami, Kazunori; Hawkins, Hal K.; Cox, Robert A.; Traber, Lillian. D.; Traber, Daniel L.

    2011-01-01

    We previously reported bronchial circulation contributes to pulmonary edema and increases shunt fraction following smoke inhalation, and bronchial blood flow significantly increases in inhalation injury. We hypothesized reduction of bronchial blood flow reduces exudation to the airway and ameliorates lung injury from combined burn and smoke insults (B & S injury). Method Merino ewes (n=28) randomly divided into three groups (1: bronchial artery ligated and injured (Injury + ligation group); 2: bronchial artery left intact and injured (Injury + no ligation group); 3: bronchial artery ligated but not injured (No injury + ligation group) were subjected to a flame burn and inhalation injury under halothane anesthesia. Parameters were analyzed using Scheffe’s post hoc test (P<0.05). All Groups were resuscitated with Ringer lactate solution and placed on a ventilator for 48 hours. Results Pulmonary gas exchange (PaO2/FiO2) improved in injury + ligation group. Further, obstruction score, an index of airway cast formation, significantly changed between injury + no ligation group compared to both ligation groups. Conclusion Bronchial circulation plays a significant role in lung injury after B & S injury, and reduction of bronchial blood flow by bronchial artery ligation reduces bronchial exudation, resulting in improved gas exchange. PMID:21195551

  7. Complete video-assisted thoracoscopic surgery (VATS) bronchial sleeve lobectomy

    PubMed Central

    Huang, Jun; Li, Shuben; Hao, Zhexue; Chen, Hanzhang; He, Jiaxi; Xu, Xin; Qiu, Yuan; Dong, Qinglong; Liang, Lixia; Pan, Hui

    2016-01-01

    Background To explore the effectiveness of video-assisted thoracoscopic surgery (VATS) bronchial sleeve resection and reconstruction. Methods The clinical data of patients who had received VATS bronchial sleeve lobectomy in our center from January 2008 to February 2015 were retrospectively analyzed. Results Totally 118 patients (105 men and 13 women) received the VATS bronchial sleeve lobectomy. The procedures included sleeve resection of right upper lobe (n=59), right middle lobe (n=7), right lower lobe (n=8), left upper lobe (n=34), and left lower lobe (n=10). The lesions were confirmed to be squamous cell carcinoma (n=68), adenocarcinoma (n=16), mucoepidermoid carcinoma (n=8), adenosquamous carcinoma (n=7), large cell carcinoma (n=1), carcinoids (n=5), and others (n=13; including small cell carcinoma, pleomorphic carcinoma, and inflammatory myofibroblastic tumor). Operations lasted 118–223 min [mean ± standard deviations (SD): 124.00±31.75 min]. The length of removed bronchus was 1.50–2.00 cm (mean ± SD: 1.75±0.26 cm). The duration of bronchial anastomosis (from the first puncture to the completion of knotting) was 15–42 min (mean ± SD: 30.20±7.97 min). The number of dissected lymph node stations (at least three mediastinal lymph node stations, including station 7) was 5–9 stations (mean ± SD: 6.50±1.18 min). The number of dissected lymph nodes was 10–46 (mean ± SD: 26.00±10.48). The intraoperative blood loss was 20–400 mL (mean ± SD: 71.00±43.95 mL), and no blood transfusion was performed. All patients were observed in intensive care unit (ICU) for 1 day. Postoperative drainage was performed for 3–8 days (mean ± SD: 5.00±1.49 days). Postoperative hospital stay was 3–8 days (mean ± SD: 5.10±2.07 days). Conclusions VATS bronchial sleeve resection and reconstruction is a safe and feasible technique. PMID:27076954

  8. Blue-violet excited autofluorescence spectroscopy and imaging of normal and cancerous human bronchial tissue after formalin fixation.

    PubMed

    Gabrecht, Tanja; Andrejevic-Blant, Snezana; Wagnières, Georges

    2007-01-01

    Autofluorescence (AF) imaging is a powerful tool for the detection of (pre-)neoplastic lesions in the bronchi. Several endoscopic imaging systems exploit the spectral and intensity contrast of AF between healthy and (pre-)neoplastic bronchial tissues, yet, the mechanisms underlying these contrasts are poorly understood. In this report, the effect of formalin fixation on the human bronchi AF, hence on the contrast, was studied by spectrofluorometric point measurements and DAFE (Diagnostic AutoFluorescence Endoscopy) broad field imaging. Generally, formalin-fixed samples have higher AF intensity than in vivo, whereas the emission spectral shape is similar. Additionally, the spectrofluorometric data showed a moderate decrease of the AF intensity on (pre-)neoplastic lesions relative to the healthy bronchial samples. However, this decrease was lower than that reported from in vivo measurements. Neither spectral measurements nor imaging revealed spectral contrast between healthy bronchial tissue and (pre-)neoplastic lesions in formalin. These results indicate that epithelial thickening and blood supply in the adjacent lamina propria are likely to play a key role in the generation of the AF contrast in bronchial tissues. Our results show that the AF contrast in bronchial tissues was significantly affected by standard, 10% buffered, formalin fixation. Therefore, these samples are not suited to AF contrast studies.

  9. Detection of early bronchial carcinoma by imaging of the tissue autofluorescence

    NASA Astrophysics Data System (ADS)

    Goujon, Didier; Glanzmann, Thomas M.; Gabrecht, Tanja; Zellweger, Matthieu; Radu, Alexandre; van den Bergh, Hubert; Monnier, Philippe; Wagnieres, Georges A.

    2001-10-01

    Early detection and localisation of bronchial cancer remains a challenging task. One approach is to exploit the changes in the autofluorescence characteristics of the bronchial tissue as a diagnostic tool with improved sensitivity. Evidence exists that this native fluorescence or autofluorescence of bronchial tissues changes when they turn dysplastic and to carcinoma in situ. There is an agreement in the literature that the lesions display a decrease of autofluorescence in the green region of the spectrum under illumination with violet light and a relative increase in the red region of the spectrum is often reported. Imaging devices rely on this principle to detect early cancerous lesions in the bronchi. Based on a previous spectroscopic study, an industrial imaging prototype has been developed to detect early cancerous lesions in collaboration with the firm 'Richard Wolf Endoskope GmbH'. A preliminary clinical trial involving 20 patients with this spectrally optimised system proved that autofluorescence can detect lesions that would otherwise have remained invisible even to an experienced endoscopist under white light illumination. A systematic analysis of the autofluorescence images pointed out that real-time decisional functions can be defined in order to reduce the number of false positive results. Using this method, a Positive Predictive Value (PPV) of 75% was achieved using autofluorescence only. A PPV of even 100% were obtained when white light mode and autofluorescence mode were combined under the applied conditions. Furthermore, the sensitivity was estimated to be twice as high in AF mode than in WL mode.

  10. Cellular events during hepatocarcinogenesis in rats and the question of premalignancy.

    PubMed

    Sell, S; Hunt, J M; Knoll, B J; Dunsford, H A

    1987-01-01

    The cellular, biochemical, and genetic changes that occur in the liver of rats exposed to chemical hepatocarcinogens are reviewed. Multiple new cell types appear in the liver of carcinogen-treated rats including foci, nodules, ducts, oval cells, and atypical hyperplastic areas. The application of phenotypic markers for these cell types suggests that hepatocellular carcinomas may arise from more than one cell type, including a putative liver stem cell that proliferates following carcinogen exposure. Study of DNA, RNA, and proteins produced by hepatocellular carcinomas and putative premalignant cells has so far failed to identify a gene or gene product clearly associated with the malignant or premalignant phenotype. Understanding the cellular lineage from normal cell through putative premalignant cell to cancer is critical to understanding the process of carcinogenesis. Application of new immunological (monoclonal antibody, transplantation) and molecular biological (gene cloning, oncogene identification) approaches to this problem holds promise that the process of hepatocarcinogenesis will be better known in the near future.

  11. Permanent Cortical Blindness After Bronchial Artery Embolization

    SciTech Connect

    Doorn, Colette S. van De Boo, Diederick W.; Weersink, Els J. M.; Delden, Otto M. van Reekers, Jim A. Lienden, Krijn P. van

    2013-12-15

    A 35-year-old female with a known medical history of cystic fibrosis was admitted to our institution for massive hemoptysis. CTA depicted a hypertrophied bronchial artery to the right upper lobe and showed signs of recent bleeding at that location. Bronchial artery embolization (BAE) was performed with gelfoam slurry, because pronounced shunting to the pulmonary artery was present. Immediately after BAE, the patient developed bilateral cortical blindness. Control angiography showed an initially not opacified anastomosis between the embolized bronchial artery and the right subclavian artery, near to the origin of the right vertebral artery. Cessation of outflow in the bronchial circulation reversed the flow through the anastomosis and allowed for spill of embolization material into the posterior circulation. Unfortunately the cortical blindness presented was permanent.

  12. Penetration of pefloxacin into bronchial secretions.

    PubMed Central

    Bonmarchand, G; Grès, J J; Lerebours, G; Massari, P; Mayoux, J J; Montay, A; Leroy, J

    1989-01-01

    Twelve patients, intubated for acute exacerbation of chronic obstructive pulmonary disease, received six intravenous doses of 400 mg of pefloxacin at 12-h intervals. Samples of blood and bronchial secretions were taken simultaneously, before the injection and at 0.5, 3, 6, 9, and 12 h after the end of the sixth infusion. There was a large variation in pefloxacin levels in both serum and bronchial secretions. The mean concentrations of pefloxacin in bronchial secretions ranged from 6.51 to 11.1 micrograms/ml and were higher than the corresponding concentrations in serum at all times. Of 61 bronchial specimens, 48 (79%) contained more than 8 micrograms of the antibiotic per ml. PMID:2729932

  13. Precancerous lesions of the cervix uteri in infertile women.

    PubMed Central

    Holst, N; Abyholm, T

    1983-01-01

    A study of 318 patients with tubal infertility and a control group of 200 unselected infertile women yielded 14 (4.4%) and 1 (0.5%), respectively, with precancerous lesions of the cervix uteri. The one patient in the control group with severe dysplasia was later shown to have tubal infertility. The overall incidence of premalignant lesions of the cervix uteri as reported to the National Cancer Registry of Norway was 0.1% for the age group and period studied. Women with tubal infertility represent a small but comparatively high risk group for the development of precancerous lesions of the cervix uteri. PMID:6412931

  14. Physiological perspectives of therapy in bronchial hyperreactivity.

    PubMed

    Pinto Pereira, L M; Orrett, F A; Balbirsingh, M

    1996-07-01

    This paper reviews the literature on the aetiology and therapy of bronchial hyperreactivity to describe the underlying pathophysiology, identify patients at risk and update knowledge on new and existing therapies. Information was obtained from monograms on New Drugs for Asthma, Respiratory Medicine: recent advances, Agents and Actions Supplements, Pulmonary Pharmacology, Anesth Analg, the European Journal of Respiration and a Medline literature search. Reduced airway calibre, increased bronchial contractility, altered permeability of the bronchial mucosa, humoral and cellular mediators, and dysfunctional neural regulation are critical factors for bronchial hyperreactivity, a characteristic feature of hyperreactive airways which results in bronchoconstriction after exposure to varied stimuli. Preoperative anaesthetic considerations in these patients include FEV1 and PEFR testing to assess the severity and for optimal control of the condition. Bronchospasm causing hypoxaemia is the major intraoperative problem anticipated in these patients. Current therapeutic management of bronchoconstriction focuses on the beta 2 agonists, theophylline and steroids. Besides relaxing the airway smooth muscle these agents are all capable of altering bronchial inflammatory responses. Future developments of therapy are directed towards the inflammatory components of the disease. This review has presented background information on physiological mechanisms of smooth muscle contractility, pathophysiological alterations of bronchial contractility and the pharmacological basis of therapy in bronchoconstrictive disease. Information is presented to enable the prompt arrest and reversal of airway constriction, and to maintain prophylactic treatment during the perioperative period. Intraoperative bronchospasm is managed by adequate oxygenation and reversal of bronchoconstriction.

  15. Anatomical modeling of the bronchial tree

    NASA Astrophysics Data System (ADS)

    Hentschel, Gerrit; Klinder, Tobias; Blaffert, Thomas; Bülow, Thomas; Wiemker, Rafael; Lorenz, Cristian

    2010-02-01

    The bronchial tree is of direct clinical importance in the context of respective diseases, such as chronic obstructive pulmonary disease (COPD). It furthermore constitutes a reference structure for object localization in the lungs and it finally provides access to lung tissue in, e.g., bronchoscope based procedures for diagnosis and therapy. This paper presents a comprehensive anatomical model for the bronchial tree, including statistics of position, relative and absolute orientation, length, and radius of 34 bronchial segments, going beyond previously published results. The model has been built from 16 manually annotated CT scans, covering several branching variants. The model is represented as a centerline/tree structure but can also be converted in a surface representation. Possible model applications are either to anatomically label extracted bronchial trees or to improve the tree extraction itself by identifying missing segments or sub-trees, e.g., if located beyond a bronchial stenosis. Bronchial tree labeling is achieved using a naïve Bayesian classifier based on the segment properties contained in the model in combination with tree matching. The tree matching step makes use of branching variations covered by the model. An evaluation of the model has been performed in a leaveone- out manner. In total, 87% of the branches resulting from preceding airway tree segmentation could be correctly labeled. The individualized model enables the detection of missing branches, allowing a targeted search, e.g., a local rerun of the tree-segmentation segmentation.

  16. Pendelluft in the bronchial tree

    PubMed Central

    Greenblatt, Elliot E.; Butler, James P.; Venegas, Jose G.

    2014-01-01

    Inhomogeneous inflation or deflation of the lungs can cause dynamic pressure differences between regions and lead to interregional airflows known as pendelluft. This work first uses analytical tools to clarify the theoretical limits of pendelluft at a single bifurcation. It then explores the global and regional pendelluft that may occur throughout the bronchial tree in a realistic example using an in silico model of bronchoconstriction. The theoretical limits of pendelluft volume exchanged at a local bifurcation driven by sinusoidal breathing range from 15.5% to 41.4% depending on the relative stiffness of the subtended regions. When nonsinusoidal flows are considered, pendelluft can be as high as 200% inlet tidal volume (Vin). At frequencies greater than 10 Hz, the inertia of the air in the airways becomes important, and the maximal local pendelluft is theoretically unbounded, even with sinusoidal breathing. In a single illustrative numerical simulation of bronchoconstriction with homogenous compliances, the overall magnitude of global pendelluft volume was <2% of the tidal volume. Despite the small overall magnitude, pendelluft volume exchange was concentrated in poorly ventilated regions of the lung, including local pendelluft at bifurcations of up to 13% Vin. This example suggests that pendelluft may be an important phenomena contributing to regional gas exchange, irreversible mixing, and aerosol deposition patterns inside poorly ventilated regions of the lung. The analytical results support the concept that pendelluft may be more prominent in diseases with significant heterogeneity in both resistance and compliance. PMID:25170072

  17. PERK Activation Promotes Medulloblastoma Tumorigenesis by Attenuating Premalignant Granule Cell Precursor Apoptosis.

    PubMed

    Ho, Yeung; Li, Xiting; Jamison, Stephanie; Harding, Heather P; McKinnon, Peter J; Ron, David; Lin, Wensheng

    2016-07-01

    Evidence suggests that activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum stress negatively or positively influences cell transformation by regulating apoptosis. Patched1 heterozygous deficient (Ptch1(+/-)) mice reproduce human Gorlin's syndrome and are regarded as the best animal model to study tumorigenesis of the sonic hedgehog subgroup of medulloblastomas. It is believed that medulloblastomas in Ptch1(+/-) mice results from the transformation of granule cell precursors (GCPs) in the developing cerebellum. Here, we determined the role of PERK signaling on medulloblastoma tumorigenesis by assessing its effects on premalignant GCPs and tumor cells. We found that PERK signaling was activated in both premalignant GCPs in young Ptch1(+/-) mice and medulloblastoma cells in adult mice. We demonstrated that PERK haploinsufficiency reduced the incidence of medulloblastomas in Ptch1(+/-) mice. Interestingly, PERK haploinsufficiency enhanced apoptosis of premalignant GCPs in young Ptch1(+/-) mice but had no significant effect on medulloblastoma cells in adult mice. Moreover, we showed that the PERK pathway was activated in medulloblastomas in humans. These results suggest that PERK signaling promotes medulloblastoma tumorigenesis by attenuating apoptosis of premalignant GCPs during the course of malignant transformation.

  18. An optimal bronchial treemay be dangerous

    NASA Astrophysics Data System (ADS)

    Mauroy, B.; Filoche, M.; Weibel, E. R.; Sapoval, B.

    2004-02-01

    The geometry and dimensions of branched structures such as blood vessels or airways are important factors in determining the efficiency of physiological processes. It has been shown that fractal trees can be space filling and can ensure minimal dissipation. The bronchial tree of most mammalian lungs is a good example of an efficient distribution system with an approximate fractal structure. Here we present a study of the compatibility between physical optimization and physiological robustness in the design of the human bronchial tree. We show that this physical optimization is critical in the sense that small variations in the geometry can induce very large variations in the net air flux. Maximum physical efficiency therefore cannot be a sufficient criterion for the physiological design of bronchial trees. Rather, the design of bronchial trees must be provided with a safety factor and the capacity for regulating airway calibre. Paradoxically, our results suggest that bronchial malfunction related to asthma is a necessary consequence of the optimized efficiency of the tree structure.

  19. The Bronchial Challenge Test: A New Direction in Asthmatic Management

    PubMed Central

    Dixon, Calvin

    1983-01-01

    Bronchial asthma can be diagnosed when a patient develops the clinical manifestations of bronchial reactivity: wheezing, cough, tachypnea, and dyspnea. Occasionally, despite immunotherapy, bronchodilator therapy, and avoidance of the provocative factors, some asthmatic patients do not respond to treatment. Bronchial inhalation challenge, a method to test airway reactivity after inhalation of a nonspecific drug, can be used to plan and assess different modes of treatment, as well as screen for bronchial hyperreactivity in an occupational setting. PMID:6827612

  20. Affinity of bronchial secretion glycoproteins and cells of human bronchial mucosa for Ricinus communis lectins.

    PubMed

    Lhermitte, M; Lamblin, G; Degand, P; Roussel, P; Mazzuca, M

    1977-01-01

    The coupling of Ricinus communis lectins to Sephadex G 25 was used in order to study mucins and other glycoproteins from human bronchial secretion. The major part of human bronchial mucins and other glycoproteins such as immunoglobulins A, bronchotransferrin and alpha1-antichymotrypsin were isolated by this procedure. A parallel study of human bronchial mucosa was achieved with peroxidase labeled Ricinus communis lectins; this study characterized goblet cells and mucous cells which contain mucins, and serous cells which are involved in the synthesis or the secretion of the other glycoproteins.

  1. CO2 laser in malignant lesions of the larynx.

    PubMed

    Annyas, A A; Van Overbeek, J J; Escajadillo, J R; Hoeksema, P E

    1984-06-01

    The CO2 laser is being used in several otolaryngology departments around the world. Clinical experience has shown that it is a unique surgical tool in the management of benign and in some malignant lesions of the larynx. Until now, little has been written about its indications in patients with carcinomas of the larynx. The purpose of this paper is to present our experience with 58 patients with various premalignant and malignant lesions of the larynx in which the CO2 laser was employed as a curative or palliative debulking procedure.

  2. Spectral Karyotyping Detects Chromosome Damage in Bronchial Cells of Smokers and Patients with Cancer

    PubMed Central

    Varella-Garcia, Marileila; Chen, Lin; Powell, Roger L.; Hirsch, Fred R.; Kennedy, Timothy C.; Keith, Robert; Miller, York E.; Mitchell, John D.; Franklin, Wilbur A.

    2007-01-01

    Rationale: Lung cancer is a multistep process that is preceded and often accompanied by molecular cytogenetic lesions in benign bronchial epithelium, the precise character, extent and timing of which are not well defined. Objectives: In this study we comprehensively defined molecular cytogenetic changes in bronchial cells that may precede lung carcinoma using spectral karyotyping (SKY). Methods: SKY was applied to cultured benign bronchial cells from 43 high-risk smokers without carcinoma, 14 patients with concurrent lung carcinoma, and 14 never-smoker healthy volunteers. Measurements and Main Results: The proportion of cells displaying numeric or structural anomalies/total number of metaphase cells was calculated for each case and was referred to as the chromosomal abnormality index. Mean chromosomal abnormality indices were 15.8, 10.1, and 0.7% for patients with cancer, high-risk smokers, and never-smokers, respectively. Clonal abnormalities were found in 17 (40%) of the high-risk smokers without carcinoma and 7 (50%) of the patients with carcinoma, but in none of 14 (0%) never-smokers. Chromosomal gains observed by SKY were confirmed in interphase cultured cells or paraffin sections of biopsy specimens by fluorescence in situ hybridization in 11 of 13 cases for which appropriate probes were available. In 6 of 57 high-risk patients or those with carcinoma, identical clonal abnormalities were dispersed at multiple bronchial sites and were admixed with nonclonal cells. Conclusions: Clonal and single-cell chromosomal abnormalities are frequent in benign bronchial epithelium during lung carcinogenesis, indicating that chromosomal missegregation and other chromosomal rearrangements occur before overt malignancy. PMID:17600274

  3. The role of laparoscopy and laparoscopic ultrasound in the diagnosis of cystic lesions of the pancreas.

    PubMed

    Schachter, Pinhas P; Shimonov, Mordechai; Czerniak, Abraham

    2002-10-01

    With the widespread use of advanced imaging techniques, cystic lesions of the pancreas are now diagnosed relatively frequently. The nature of these lesions vary from benign cysts (serous cvstadenoma) or an inflammatory process (pseudocyst), to premalignant (mucinous cystadenoma) or frankly malignant lesions (cystadenocarcinoma). Differentiation of various types of pancreatic cysts presents a diagnostic and therapeutic challenge, as clinical presentation may be vague. Laparoscopic ultrasonography (LAPUS), the biopsy of the cystic wall, and analysis of the cystic aspirate, although expensive and rather invasive procedures, significantly contribute to the differential diagnosis of pancreatic cystic lesions.

  4. Clinical practice trends in cryosurgery: a retrospective study of cutaneous lesions

    PubMed Central

    Erkan, Ceren Dagar; Karaca, Semsettin

    2015-01-01

    Introduction Cryosurgery is an alternative treatment for many benign, premalignant, and malignant lesions of the skin. Aim To review the indications of cryosurgery for cutaneous lesions. Material and methods The retrospective study was based on the assessment of medical records of 1031 dermatology patients who had cryosurgery. Results One thousand two hundred and forty-four sessions of cryosurgery were applied to the total of 1031 patients. Of the 1031 patients, the most frequent indication for cryosurgery was common warts which were present in 535 (61.59%) patients, followed by anogenital warts in 119 (11.54%) patients, callosity in 81 (7.85%) patients, actinic keratosis in 77 (7.46%) patients, molluscum contagiosum in 35 (3.39%) patients, and other benign or malignant skin lesions. Conclusions Cryosurgery is still a valuable treatment of choice in various benign, premalignant, and malignant skin diseases but seems to be underused for indications other than viral warts. PMID:26015777

  5. Detection and Localization of Pre-Cancerous Lesions and Early Lung Cancer Using Tissue Autofluorescence.

    NASA Astrophysics Data System (ADS)

    Hung, Jaclyn Yip-Chan

    fluorescence system to detect early lung cancer and dysplasia during standard bronchoscopy, therefore confirming the initial hypotheses even in a clinical setting. The major source of the autofluorescence in the normal bronchial tissue was determined to come from the sub-epithelial layers. The mechanism for the decrease in the autofluorescence in pre-malignant and malignant tissues was explored but not yet completely elucidated. (Abstract shortened by UMI.).

  6. Lung function and bronchial reactivity in farmers.

    PubMed Central

    Iversen, M; Dahl, R; Jensen, E J; Korsgaard, J; Hallas, T

    1989-01-01

    The purpose of this study was to evaluate the prevalence and type of lung function disorders in Danish farmers. Three samples of farmers were drawn from a group of unselected farmers who had participated in an epidemiological study. Group I (47 persons) was a sample of the 8% of all farmers who had reported that they had asthma; group II (63 persons) was a sample of the 28% of farmers who had had wheezing, shortness of breath, or cough without phlegm; and group III (34 persons) a sample of the farmers (64% of the total) who had no asthma and no respiratory symptoms. The farmers with symptoms (groups I and II) had low mean levels of FEV1 and high values for residual volume, whereas the symptomless farmers had normal lung function and no airways obstruction. The proportion of farmers with an FEV1 below the 95% confidence limit for predicted values was 43% in group I and 23% in group II; there were none in group III. Bronchial hyperreactivity to histamine occurred in 96% of asthmatic farmers, 67% of farmers with wheezing or shortness of breath, and 59% of symptomless farmers. A low level of FEV1 was associated with the number of years in pig farming and bronchial hyperreactivity in group II but not group I or III. Most of the bronchial hyperreactivity was explained in the multiple regression analysis by a low FEV1, though this was significant only for farmers in group II. Thus farmers who reported asthma, wheezing, shortness of breath, or a dry cough in general had airways obstruction with an increased residual volume, whereas symptomless farmers had normal lung function. Severe bronchial hyperreactivity was mostly explained by a diagnosis of asthma and poor lung function, though some farmers with normal lung function and no respiratory symptoms had increased bronchial reactivity. PMID:2799744

  7. Quantification of bronchial circulation perfusion in rats

    NASA Astrophysics Data System (ADS)

    Wietholt, Christian; Molthen, Robert C.; Haworth, Steven T.; Roerig, David L.; Dawson, Christopher A.; Clough, Anne V.

    2004-04-01

    The bronchial circulation is thought to be the primary blood supply for pulmonary carcinomas. Thus, we have developed a method for imaging and quantifying changes in perfusion in the rat lung due to development of the bronchial circulation. A dual-modality micro-CT/SPECT system was used to detect change in perfusion in two groups of rats: controls and those with a surgically occluded left pulmonary artery. Both groups were imaged following injections on separate days i) 2mCi of Tc99m labeled macroaggregated albumin (MAA) into the left carotid artery (IA) and ii) a similar injection into the femoral vein (IV). The IA injection resulted in Tc99m accumulation in capillaries of the systemic circulation including the bronchial circulation, whereas the IV resulted in Tc99m accumulation in the pulmonary capillaries. Ordered subset expectation maximization (OSEM) was used to reconstruct the SPECT image volumes and a Feldkamp algorithm was used to reconstruct the micro-CT image volumes. The micro-CT and SPECT volumes were registered, the SPECT image volume was segmented using the right and left lung boundaries defined from the micro-CT volume, and the ratio of IA radioactivity accumulation in the left lung to IV radioactivity accumulation in both lungs was used as a measure of left lung flow via the bronchial circulation. This ratio was ~0.02 for the untreated rats compared to the treated animals that had an increased flow ratio of ~0.21 40 days after left pulmonary artery occlusion. This increase in flow to the occluded left lung via the bronchial circulation suggests this will be a useful model for further investigating antiangiogenic treatments.

  8. Advanced endoscopic ultrasound management techniques for preneoplastic pancreatic cystic lesions

    PubMed Central

    Arshad, Hafiz Muhammad Sharjeel; Bharmal, Sheila; Duman, Deniz Guney; Liangpunsakul, Suthat; Turner, Brian G

    2017-01-01

    Pancreatic cystic lesions can be benign, premalignant or malignant. The recent increase in detection and tremendous clinical variability of pancreatic cysts has presented a significant therapeutic challenge to physicians. Mucinous cystic neoplasms are of particular interest given their known malignant potential. This review article provides a brief but comprehensive review of premalignant pancreatic cystic lesions with advanced endoscopic ultrasound (EUS) management approaches. A comprehensive literature search was performed using PubMed, Cochrane, OVID and EMBASE databases. Preneoplastic pancreatic cystic lesions include mucinous cystadenoma and intraductal papillary mucinous neoplasm. The 2012 International Sendai Guidelines guide physicians in their management of pancreatic cystic lesions. Some of the advanced EUS management techniques include ethanol ablation, chemotherapeutic (paclitaxel) ablation, radiofrequency ablation and cryotherapy. In future, EUS-guided injections of drug-eluting beads and neodymium:yttrium aluminum agent laser ablation is predicted to be an integral part of EUS-guided management techniques. In summary, International Sendai Consensus Guidelines should be used to make a decision regarding management of pancreatic cystic lesions. Advanced EUS techniques are proving extremely beneficial in management, especially in those patients who are at high surgical risk. PMID:27574295

  9. The configuration of clinics and the use of biopsy and photography in oral premalignancy: a survey of consultants of the British Association of Oral and Maxillofacial Surgeons.

    PubMed

    Kanatas, A N; Fisher, S E; Lowe, D; Ong, T K; Mitchell, D A; Rogers, S N

    2011-03-01

    Oral dysplastic lesions may have an increased chance of becoming oral squamous cell carcinoma, but to date their management remains controversial. The aim of this survey was to explore the current practical aspects of the management of patients with dysplasia by oral and maxillofacial consultants in the UK. In the survey we asked consultants about the numbers of patients they see with oral premalignant lesions, the frequency and specialty of designated hospital clinics, their use of photographs and biopsy, factors that influence their decision whether to biopsy a lesion at the first appointment, the procedure for treatment and follow-up and their use (if any) of chemopreventive agents. We found a wide variation in the practical aspects of managing patients with dysplasia, and the lack of consistency among clinicians supports the idea of an initiative to establish more robust national guidelines to use as a gold standard in the future. Copyright © 2010 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. Ectopic vestigial lesions of the neck and shoulders

    PubMed Central

    Shareef, DS; Salm, R

    1981-01-01

    A series of five vestigial lesions of the shoulder and back is reported. Their derivation is discussed and in four cases a branchial rather than a bronchial origin is favoured. The fifth case is held to represent skin involvement by thyroglossal duct elements. Images PMID:7309896

  11. [Serum and bronchial concentrations of amoxicillin administered with a bronchial fluidizer].

    PubMed

    Concia, E; Dos Santos, C; Marone, P; Sardi, C; Cremaschi, P

    1982-03-01

    The authors compared the serum and bronchial concentration of amoxycillin administered alone and in association with carboxymethylcysteine. The determinations were carried out in 10 patients affected with exacerbated acute and chronic bronchopneumopathies, treated first with amoxycillin alone (15 g/day in 3 administrations) and then with amoxycillin at the same dosage and carboxymethylcysteine (450 mg/day in 3 administrations). The bronchial secretions were collected during bronchoscopy performed 2 hours after the last administration of antibiotic. The bronchial secretion values of amoxycillin administered alone varied from 0.92 mcg/ml to 1.88 mcg/ml with a mean value of 1.44 mcg/ml. The percentage ratio between levels in bronchial secretion and levels in the serum varied from 12.7 to 36.1 with a mean value of 23.2. The administration of the amoxycillin-fluidizing agent association determined a statistically significant increase of the antibiotic levels in the bronchial secretions, varying from 1.26 mcg/ml to 6.39 mcg/ml, with a percentage ratio from 19.6 to 103.0.

  12. Photodynamic Therapy – A Non-invasive Treatment Modality for Precancerous Lesions

    PubMed Central

    Maloth, Kotya Naik; Velpula, Nagalaxmi; Kodangal, Srikanth; Sangmesh, Mithare; Vellamchetla, Kiran; Ugrappa, Sridevi; Meka, Nagajyothi

    2016-01-01

    Introduction: Oral premalignant lesions are conditions having high potential tendency for transformation into malignancy. The use of a conservative and effective treatment modality is one of the best strategies for cancer prevention. Photodynamic therapy (PDT) is a non-invasive method for topical and selective treatment of oral precancerous lesions. The present study was taken up to determine the efficacy of PDT in oral precancerous lesions. Methods: The study consisted 13 patients with 24 oral leukoplakia (OL) lesions and 8 with 20 oral lichen planus (OLP) lesions, divided into control and study groups. These lesions were affecting various intraoral sites, the buccal mucosa being the most common site followed by tongue and gingiva. The treatment regimen of PDT included 98% 5–aminolevulinic acid (5-ALA) which is topical applied and irradiated with light emitting diode (LED) of 420 nm wavelengths at several sessions. Results: In OL 16.6% of cases showed complete response, 66.6% partial response and 16.6% no response of the lesions to the treatment. In OLP 80% and 20% of the lesions showed partial and no response respectively. The differences with control groups for OL + OLP were found to be significant (P < 0.001). Conclusion: Based on the results of the present study, we can conclude that PDT appears to be a feasible alternative to conventional therapy for oral premalignant lesions. PMID:27330695

  13. Bronchial artery aneurysm as a cause of atelectasis.

    PubMed

    Oka, M; Fukuda, M; Terashi, K; Takatani, H; Narasaki, F; Nakano, R; Tsurutani, J; Nakamura, Y; Kasai, T; Nagashima, S; Noguchi, Y; Soda, H; Kohno, S

    1997-12-01

    A 54-year-old nonsmoker female developed atelectasis of the anterior basal segment of the right lower lobe. A non-pulsating endobronchial tumor was observed bronchoscopically obstructing the right basal bronchus. The tumor was confirmed on arteriography to be a saccular aneurysm of the right bronchial artery. The aneurysm was treated with bronchial artery embolization. Bronchial artery aneurysm, without a predisposing disease, is quite rare, but should be considered as an etiological factor of atelectasis.

  14. [Bronchial hyperresponsiveness and its importance for the clinician].

    PubMed

    Mihalache, A; Fitting, J-W

    2014-11-19

    Asthma is a chronic inflammatory airway disease, characterised by bronchial hyperresponsiveness causing bronchoconstriction, and thereby provoking typical symptoms (dyspnoea, cough, wheezing). Bronchial hyperres- ponsiveness indicates a temporary airflow limitation when exposed to a bronchoconstricting stimulus. Its measurement by challenge tests can be a valuable tool for confirming or excluding asthma, as well as for evaluating the efficacy of treatment. However, the origin of bronchial hyperresponsiveness is multifactorial and the different challenge tests are not equivalent. Direct challenge tests, like methacholine, mainly reflect chronic airway remo- delling, whereas indirect tests, like mannitol, better reflect bronchial inflammation.

  15. Malondialdehyde-acetaldehyde adducts decrease bronchial epithelial wound repair.

    PubMed

    Wyatt, Todd A; Kharbanda, Kusum K; Tuma, Dean J; Sisson, Joseph H; Spurzem, John R

    2005-05-01

    Most people who abuse alcohol are cigarette smokers. Previously, we have shown that malondialdehyde, an inflammation product of lipid peroxidation, and acetaldehyde, a component of both ethanol metabolism and cigarette smoke, form protein adducts that stimulate protein kinase C (PKC) activation in bronchial epithelial cells. We have also shown that PKC can regulate bronchial epithelial cell wound repair. We hypothesize that bovine serum albumin adducted with malondialdehyde and acetaldehyde (BSA-MAA) decreases bronchial epithelial cell wound repair via binding to scavenger receptors on bronchial epithelial cells. To test this, confluent monolayers of bovine bronchial epithelial cells were grown in serum-free media prior to wounding the cells. Bronchial epithelial cell wound closure was inhibited in a dose-dependent manner (up to 60%) in the presence of BSA-MAA than in media treated cells (Laboratory of Human Carcinogenesis [LHC]-9-Roswell Park Memorial Institute [RPMI]). The specific scavenger receptor ligand, fucoidan, also stimulated PKC activation and decreased wound repair. Pretreatment with fucoidan blocked malondialdehyde-acetaldehyde binding to bronchial epithelial cells. When bronchial epithelial cells were preincubated with a PKC alpha inhibitor, Gö 6976, the inhibition of wound closure by fucoidan and BSA-MAA was blocked. Western blot demonstrated the presence of several scavenger receptors on bronchial epithelial cell membranes, including SRA, SRBI, SRBII, and CD36. Scavenger receptor-mediated activation of PKC alpha may function to reduce wound healing under conditions of alcohol and cigarette smoke exposure where malondialdehyde-acetaldehyde adducts may be present.

  16. Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.

    PubMed

    Yasukawa, Atsushi; Hosoki, Koa; Toda, Masaaki; Miyake, Yasushi; Matsushima, Yuki; Matsumoto, Takahiro; Boveda-Ruiz, Daniel; Gil-Bernabe, Paloma; Nagao, Mizuho; Sugimoto, Mayumi; Hiraguchi, Yukiko; Tokuda, Reiko; Naito, Masahiro; Takagi, Takehiro; D'Alessandro-Gabazza, Corina N; Suga, Shigeru; Kobayashi, Tetsu; Fujisawa, Takao; Taguchi, Osamu; Gabazza, Esteban C

    2013-01-01

    Eosinophilic inflammation and remodeling of the airways including subepithelial fibrosis and myofibroblast hyperplasia are characteristic pathological findings of bronchial asthma. Epithelial to mesenchymal transition (EMT) plays a critical role in airway remodelling. In this study, we hypothesized that infiltrating eosinophils promote airway remodelling in bronchial asthma. To demonstrate this hypothesis we evaluated the effect of eosinophils on EMT by in vitro and in vivo studies. EMT was assessed in mice that received intra-tracheal instillation of mouse bone marrow derived eosinophils and in human bronchial epithelial cells co-cultured with eosinophils freshly purified from healthy individuals or with eosinophilic leukemia cell lines. Intra-tracheal instillation of eosinophils was associated with enhanced bronchial inflammation and fibrosis and increased lung concentration of growth factors. Mice instilled with eosinophils pre-treated with transforming growth factor(TGF)-β1 siRNA had decreased bronchial wall fibrosis compared to controls. EMT was induced in bronchial epithelial cells co-cultured with human eosinophils and it was associated with increased expression of TGF-β1 and Smad3 phosphorylation in the bronchial epithelial cells. Treatment with anti-TGF-β1 antibody blocked EMT in bronchial epithelial cells. Eosinophils induced EMT in bronchial epithelial cells, suggesting their contribution to the pathogenesis of airway remodelling.

  17. [Relationship between congenital heart disease and bronchial dysplasia].

    PubMed

    Zeng, Shuang-Lin; Li, Ya-Jun; Huang, Ting; Tan, Li-Hua; Mei, Xi-Long; Sun, Jian-Ning

    2011-11-01

    To study the relationship of the incidence of bronchial dysplasia (bronchial anomalous origin and bronchial stenosis) with congenital heart disease. A total of 185 children with congenital heart disease or bronchial dysplasia were enrolled. Bronchial dysplasia was identified by the 64-MSCT conventional scanning or thin slice scanning with three-dimensional reconstruction. Forty-five children (25.3%) had coexisting bronchial dysplasia and congenital heart disease. The incidence rate of bronchial dysplasia in children with congenital heart disease associated with ventricular septal defect was higher than in those without ventricular septal defect (33.7% vs 15.0%; P<0.05). There were no significant differences in the incidence rate of bronchial dysplasia between the children with congenital heart disease who had a large vascular malformation and who did not. Bronchial dysplasia often occurs in children with congenital heart disease. It is necessary to perform a tracheobronchial CT scanning with three-dimensional reconstruction to identify tracheobronchial dysplasia in children with congenital heart disease, especially associated with ventricular septal defect.

  18. Insight into the number of pre-malignancies and malignancies of the skin in a hospital population in the Netherlands.

    PubMed

    van Rijsingen, Margit; Seubring, Inge; Maessen-Visch, Birgitte; Lavrijsen, Sjan; van Bergen, Bert; Groenewoud, Johannes; Gerritsen, Marie-Jeanne

    2015-01-01

    Skin cancer incidence is rising, placing a burden on healthcare systems worldwide. This problem may even be more extensive than expected, since registration of (pre)malignancies of the skin is poor. To provide insight into the numbers of (pre)malignancies in patients with actinic keratosis (AK) or basal cell carcinoma (BCC) in 2 university and 2 general hospitals. The types and numbers of previous tumours and of tumours during a two-year follow-up were collected from 574 patients. Mean time between the first diagnosed (pre)malignancy and time of inclusion was 6.6 years. Overall, 60% had multiple types of (pre)malignancies. In BCC patients, 61% had multiple BCCs, in patients with squamous cell carcinoma (SCC), 40% had multiple SCCs. The combination 'BCC and SCC' occurred in 10%, 'BCC and AK' in 47%, 'SCC and AK' in 14%. High numbers of patients with multiple (pre)malignancies were found in this patient population in university and general hospitals, which may well reflect the Dutch hospital population. We conclude that skin cancer patients are more extensively affected than was expected up till now. Consequently, the management of skin cancer may be in need of adaptation in near future and the question arises whether dermatologists have the capacity for providing care for all these patients.

  19. Cutaneous malignant and premalignant conditions caused by chronic arsenicosis from contaminated ground water consumption: a profile of patients from eastern India.

    PubMed

    Ghosh, Sudip Kumar; Bandyopadhyay, Debabrata; Bandyopadhyay, Samik Kumar; Debbarma, Kuntal

    2013-01-01

    Natural arsenic pollution is a major global health problem. The two worst affected areas e Bangladesh and West Bengal, India. Arsenic is a well-documented human carcinogen that affects many organs including the skin. The authors sought to find out the clinical patterns of different malignant and premalignant conditions associated with chronic arsenicosis from drinking contaminated ground water in a group of patients from eastern India. This was a clinical observational study. Patients with chronic arsenicoses with suspected cutaneous malignancies for whom dermatology service was sought were enrolled in the study. A total of 24 patients (male to female ratio, 11:1; age range, 32-71 years; mean age, 52.2 years) were evaluated. Squamous cell carcinoma (SCC) was the commonest malignancies in our series, seen in 10 (41.7%) patients. This was followed by Bowen's disease (9 [37.5%]) and basal cell carcinoma (8 [33.3%]). Three patients (12.5%) had > 1 type of cutaneous malignancies. Multicentric lesions were seen in 3 cases. The most common site of involvement was the chest (8 [33.3%]). No statistically significant correlation was found between number of lesions and arsenic content in the hairs and nails of the patients.

  20. Oral White Lesions Associated with Chewing Khat

    PubMed Central

    Gorsky, Meir; Epstein, Joel B; Levi, Harel; Yarom, Noam

    2004-01-01

    Introduction Khat is a cultivated plant whose leaves when chewed elevate mood. Unlike the chewing of betel nut, no association between the white oral mucosal lesions in khat users and oral malignancies has been reported. Chewing of khat has been documented in many countries and has increased with worldwide migration. The impact of chewing khat upon the oral mucosa is essentially unknown. Purpose The purpose of this study was to assess the occurrence of oral white changes in chronic khat chewers. Oral mucosal changes in a group of 47 Yemenite Israeli men over 30 years of age, who had chewed khat more than 3 years, were compared to those of 55 Yemenite men who did not chew. Results White lesions were significantly more prevalent in the khat chewers (83%) compared to the non chewing individuals (16%) (P < 0.001). White oral lesions were identified primarily on the lower buccal attached gingival mucosa, the alveolar mucosa and the lower mucobuccal fold on the chewing side (p < 0.001). There was no significant association between the occurrence of the white lesions and smoking. Even though the majority of the white lesions (85.4%) were homogenous, 71.4% of the non homogenous lesions were identified in khat chewers. Vital staining with toluidine blue and exfoliative cytology was conducted on a subset of patients with homogenous and non-homogenous oral lesions, and there were no findings suspicious for pre-malignant or malignant changes. Discussion This study demonstrated a relationship between khat chewing and oral white lesions, which we attribute to chronic local mechanical and chemical irritation of the mucosa. Our findings also suggest that mucosal changes associated with khat are benign, however, this initial study requires further studies including follow-up of khat users to confirm the current findings, including the likely benign changes associated with chronic use and histologic findings of clinical lesions.

  1. Oral White Lesions Associated with Chewing Khat

    PubMed Central

    Gorsky, Meir; Epstein, Joel B; Levi, Harel; Yarom, Noam

    2004-01-01

    Introduction Khat is a cultivated plant whose leaves when chewed elevate mood. Unlike the chewing of betel nut, no association between the white oral mucosal lesions in khat users and oral malignancies has been reported. Chewing of khat has been documented in many countries and has increased with worldwide migration. The impact of chewing khat upon the oral mucosa is essentially unknown. Purpose The purpose of this study was to assess the occurrence of oral white changes in chronic khat chewers. Oral mucosal changes in a group of 47 Yemenite Israeli men over 30 years of age, who had chewed khat more than 3 years, were compared to those of 55 Yemenite men who did not chew. Results White lesions were significantly more prevalent in the khat chewers (83%) compared to the non chewing individuals (16%) (P < 0.001). White oral lesions were identified primarily on the lower buccal attached gingival mucosa, the alveolar mucosa and the lower mucobuccal fold on the chewing side (p < 0.001). There was no significant association between the occurrence of the white lesions and smoking. Even though the majority of the white lesions (85.4%) were homogenous, 71.4% of the non homogenous lesions were identified in khat chewers. Vital staining with toluidine blue and exfoliative cytology was conducted on a subset of patients with homogenous and non-homogenous oral lesions, and there were no findings suspicious for pre-malignant or malignant changes. Discussion This study demonstrated a relationship between khat chewing and oral white lesions, which we attribute to chronic local mechanical and chemical irritation of the mucosa. Our findings also suggest that mucosal changes associated with khat are benign, however, this initial study requires further studies including follow-up of khat users to confirm the current findings, including the likely benign changes associated with chronic use and histologic findings of clinical lesions. PMID:19570281

  2. Warburg and Crabtree Effects in Premalignant Barrett's Esophagus Cell Lines with Active Mitochondria

    PubMed Central

    Suchorolski, Martin T.; Paulson, Thomas G.; Sanchez, Carissa A.; Hockenbery, David; Reid, Brian J.

    2013-01-01

    Background Increased glycolysis is a hallmark of cancer metabolism, yet relatively little is known about this phenotype at premalignant stages of progression. Periodic ischemia occurs in the premalignant condition Barrett's esophagus (BE) due to tissue damage from chronic acid-bile reflux and may select for early adaptations to hypoxia, including upregulation of glycolysis. Methodology/Principal Findings We compared rates of glycolysis and oxidative phosphorylation in four cell lines derived from patients with BE (CP-A, CP-B, CP-C and CP-D) in response to metabolic inhibitors and changes in glucose concentration. We report that cell lines derived from patients with more advanced genetically unstable BE have up to two-fold higher glycolysis compared to a cell line derived from a patient with early genetically stable BE; however, all cell lines preserve active mitochondria. In response to the glycolytic inhibitor 2-deoxyglucose, the most glycolytic cell lines (CP-C and CP-D) had the greatest suppression of extra-cellular acidification, but were able to compensate with upregulation of oxidative phosphorylation. In addition, these cell lines showed the lowest compensatory increases in glycolysis in response to mitochondrial uncoupling by 2,4-dinitrophenol. Finally, these cell lines also upregulated their oxidative phosphorylation in response to glucose via the Crabtree effect, and demonstrate a greater range of modulation of oxygen consumption. Conclusions/Significance Our findings suggest that cells from premalignant Barrett's esophagus tissue may adapt to an ever-changing selective microenvironment through changes in energy metabolic pathways typically associated with cancer cells. PMID:23460817

  3. Pre-Cancerous Lesions in the Oral and Maxillofacial Region: A Literature Review with Special Focus on Etiopathogenesis.

    PubMed

    Irani, Soussan

    2016-01-01

    Many types of cancers develop in the oral and maxillofacial region. Squamous cell carcinoma is the most common cancer and constitutes over 90 percent of these tumors. Malignant transformation is a genetic process, which later makes a phenotyping change at the cellular level. Some cancers such as oral squamous cell carcinomas (OSCCs) develop from pre-malignant lesions and conditions. Despite advances in the treatment of OSCC, the 5-year survival rate remains approximately 50% due to inability of early detection of OSCC and precursor lesions. Early detection of oral cancer, especially in the premalignant stage, can decrease mortality and morbidity significantly. This article reviews some clinical, histopathological features and etiopathogenesis of pre-cancerous lesions of the oral cavity and skin of face and lip vermilion. A relevant English literature search in Pubmed, Science Direct, and Google Scholar was performed from 1930 to 2015. Full text of 191 articles met the specific inclusion criteria for this review.

  4. Pre-Cancerous Lesions in the Oral and Maxillofacial Region: A Literature Review with Special Focus on Etiopathogenesis

    PubMed Central

    Irani, Soussan

    2016-01-01

    Many types of cancers develop in the oral and maxillofacial region. Squamous cell carcinoma is the most common cancer and constitutes over 90 percent of these tumors. Malignant transformation is a genetic process, which later makes a phenotyping change at the cellular level. Some cancers such as oral squamous cell carcinomas (OSCCs) develop from pre-malignant lesions and conditions. Despite advances in the treatment of OSCC, the 5-year survival rate remains approximately 50% due to inability of early detection of OSCC and precursor lesions. Early detection of oral cancer, especially in the premalignant stage, can decrease mortality and morbidity significantly. This article reviews some clinical, histopathological features and etiopathogenesis of pre-cancerous lesions of the oral cavity and skin of face and lip vermilion. A relevant English literature search in Pubmed, Science Direct, and Google Scholar was performed from 1930 to 2015. Full text of 191 articles met the specific inclusion criteria for this review. PMID:28855922

  5. Expression of Stem Cell Markers in Preinvasive Tubal Lesions of Ovarian Carcinoma

    PubMed Central

    Chene, G.; Ouellet, V.; Rahimi, K.; Barres, V.; Meunier, L.; De Ladurantaye, M.; Provencher, D.; Mes-Masson, A. M.

    2015-01-01

    In order to better understand the ovarian serous carcinogenic process with tubal origin, we investigated the expression of stem cell markers in premalignant tubal lesions (serous tubal intraepithelial carcinoma or STIC). We found an increased stem cell marker density in the normal fallopian tube followed by a high CD117 and a low ALDH and CD44 expression in STICs raising the question of the role of the stem cell markers in the serous carcinogenic process. PMID:26504831

  6. Bronchial wall region extraction algorithm using multi-slice CT images

    NASA Astrophysics Data System (ADS)

    Akashi, Kengo; Saita, Shinsuke; Kubo, Mitsuru; Kawata, Yoshiki; Niki, Noboru; Nakano, Yasutaka; Niimi, Akio; Matsumoto, Hisako; Oguma, Tsuyoshi; Takiguchi, Yuichi; Kawata, Naoko; Tanabe, Nobuhiro; Ohmatsu, Hironobu; Eguchi, Kenji; Kaneko, Masahiro; Moriyama, Noriyuki

    2009-02-01

    As multi-slice CT develops, there are great expectations for an automatic and computer-support diagnoses. This research is on bronchial area which is composed of the bronchial wall regions and the air regions in the internal bronchial tube. Since to diagnose this is difficult, support diagnosis using CT images is desired. The thickness of bronchial wall changes as the airway of early lung cancer, bronchial asthma and the bronchial enhancing syndrome and others change into a malignant state. These changes are detected and the thickness of bronchial wall becomes important information. In this research, the extraction accuracy of the algorithm for bronchial wall evaluation is good.

  7. Quantitative skin prick and bronchial provocation tests with platinum salt.

    PubMed Central

    Merget, R; Schultze-Werninghaus, G; Bode, F; Bergmann, E M; Zachgo, W; Meier-Sydow, J

    1991-01-01

    Occupational asthma due to platinum salts is a frequent disease in platinum refineries. The diagnosis is based upon a history of work related symptoms and a positive skin prick test with platinum salts. Bronchial provocation tests have not been performed in epidemiological studies because the skin test is believed to be highly specific and sensitive. As no reliable data about this issue currently exist, this study assesses the use of skin prick and bronchial provocation tests with methacholine and platinum salt in platinum refinery workers. Twenty seven of 35 workers, who were referred to our clinic with work related symptoms and nine control subjects with bronchial hyperreactivity underwent a skin prick test and bronchial provocation with methacholine and platinum salt. For skin prick and bronchial provocation tests with platinum salt a 10(-2)-10(-8) mol/l hexachloroplatinic acid solution, in 10-fold dilutions was used. Four of the 27 subjects and all controls showed neither a bronchial reaction nor a skin reaction. Twenty three subjects were considered allergic to platinum salt; 22 of these showed a fall of 50% or more in specific airway conductance after inhalation of the platinum salt solution. Four workers experienced a positive bronchial reaction despite a negative skin prick test. No correlation of responsiveness to methacholine with responsiveness to platinum salt was found, but the skin prick test correlated with the bronchial reaction to platinum salt (rs = 0.50, p less than 0.023, n = 22). One dual reaction was seen in bronchial provocation tests. Side effects of both skin tests and bronchial provocation tests with platinum salt were rare and were not encountered in workers without a skin reaction to platinum salt. It is concluded that bronchial provocation tests with platinum salts should be performed on workers with work related symptoms but negative skin tests with platinum salts. PMID:1772797

  8. Surgical salvage of acquired lung lesions in extremely premature infants.

    PubMed

    Sacks, Greg D; Chung, Katherine; Jamil, Kevin; Garg, Meena; Dunn, James C Y; DeUgarte, Daniel A

    2014-05-01

    Acquired neonatal lung lesions including pneumatoceles, cystic bronchopulmonary dysplasia, and pulmonary interstitial emphysema can cause extrinsic mediastinal compression, which may impair pulmonary and cardiac function. Acquired lung lesions are typically managed medically. Here we report a case series of three extremely premature infants with acquired lung lesions. All three patients underwent aggressive medical management and ultimately required tube thoracostomies. These interventions were unsuccessful and emergency thoracotomies were performed in each case. Two infants with acquired pneumatoceles underwent unroofing of the cystic structure and primary repair of a bronchial defect. The third infant with pulmonary interstitial emphysema, arising from cystic bronchopulmonary dysplasia, required a middle lobectomy for severe and diffuse cystic disease. When medical management fails, tube thoracostomy can be attempted, leaving surgical intervention for refractory cases. Surgical options include oversewing a bronchial defect in the setting of a bronchopleural fistula or lung resection in cases of an isolated expanding lobe.

  9. The bronchial obstruction as a complication of endovascular repair of aortic pseudoaneurysm in Behçet’s disease

    PubMed Central

    Yesin, Mahmut; Toprak, Cüneyt; Acar, Emrah; Kalçık, Macit; Taşçı, Ahmet Erdal; Pala, Selçuk

    2016-01-01

    Behçet’s disease (BD) is an autoimmune disorder affecting multiple organs. Aortic pseudoaneurysm is the most catastrophic lesion in BD. This lesion type is considered as a complicated and challenging pathology by surgeons because of the technical operative difficulties and frequent recurrence. So, the endovascular repair of inflammatory aortic pseudoaneurysm has been used as an alternative to open surgical repair. It is particularly important in patients who are high-risk surgical candidates because of comorbidities. In this report, we present a case and treatment of bronchial obstruction, which caused progressive dyspnea after endovascular repair of aortic rupture, in patient with known history of BD. PMID:28203395

  10. [100 cases of bronchial mechanical sutures].

    PubMed

    Paolini, A; Lepore, M; Riccardelli, F; Canuti, W; Caminiti, A; Mucci, M; Ruggieri, M

    1990-03-01

    The Authors report their experience with stapler model T.A. 30 in lung resections; 100 stapled sutures were carried out in the IV Surgical Department of the University "La Sapienza" of Rome, during the period 1980-88. The use of stapler with two rows of staples allows a secure closure of the bronchial stump. Moreover, it prevents granulomas caused by suture material. The bronchopleural fistulas, serious complications of manual suturing, did not occur. Finally, this method is simpler and rapidly feasible in comparison with classic ones.

  11. [Recommendations of the Chilean Association for Digestive Endoscopy for the management of gastric pre-malignant lesions].

    PubMed

    Rollán, Antonio; Cortés, Pablo; Calvo, Alfonso; Araya, Raúl; Bufadel, María Ester; González, Robinson; Heredia, Carolina; Muñoz, Pablo; Squella, Freddy; Nazal, Roberto; Gatica, María de Los Ángeles; Gobelet, Jaquelina; Estay, René; Pisano, Raúl; Contreras, Luis; Osorio, Ingrid; Estela, Ricardo; Fluxá, Fernando; Parra-Blanco, Adolfo

    2014-09-01

    An expert panel analyzed the available evidence and reached a consensus to release 24 recommendations for primary and secondary prevention of gastric cancer (CG) in symptomatic patients, with indication for upper GI endoscopy. The main recommendations include (1) Search for and eradicate H. pylori infection in all cases. (2) Systematic gastric biopsies (Sydney protocol) in all patients over 40 years of age or first grade relatives of patient with CG, to detect gastric atrophy, intestinal metaplasia or dysplasia. (3) Incorporate the OLGA system (Operative Link on Gastritis Assessment) to the pathological report, to categorize the individual risk of CG. (4) Schedule endoscopic follow-up according to the estimated risk of CG, namely annual for OLGA III- IV, every 3 years for OLGA I- II or persistent H. pylori infection, every 5 years for CG relatives without other risk factors and no follow-up for OLGA 0, H. pylori (-). (4) Establish basic human and material resources for endoscopic follow-up programs, including some essential administrative processes, and (5) Suggest the early CG/total CG diagnosis ratio of each institution and the proportion of systematic recording of endoscopic images, as quality indicators. These measures are applicable using currently available resources, they can complement any future screening programs for asymptomatic population and may contribute to improve the prognosis of CG in high-risk populations.

  12. Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies

    PubMed Central

    Vici, P; Pizzuti, L; Mariani, L; Zampa, G; Santini, D; Di Lauro, L; Gamucci, T; Natoli, C; Marchetti, P; Barba, M; Maugeri-Saccà, M; Sergi, D; Tomao, F; Vizza, E; Di Filippo, S; Paolini, F; Curzio, G; Corrado, G; Michelotti, A; Sanguineti, G; Giordano, A; De Maria, R; Venuti, A

    2016-01-01

    ABSTRACT Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease. PMID:27063030

  13. Therapeutic effect of laser vaporization for vaginal intraepithelial neoplasia following hysterectomy due to premalignant and malignant lesions.

    PubMed

    Wang, Yan; Kong, Wei-Min; Wu, Yu-Mei; Wang, Jian-Dong; Zhang, Wei-Yuan

    2014-06-01

    The aim of this study was to evaluate the therapeutic effect of laser vaporization for vaginal intraepithelial neoplasia (VAIN) after hysterectomy in Chinese women and to identify factors affecting persistence/recurrence. Twenty-eight VAIN patients after hysterectomy due to cervical intraepithelial neoplasia (group 1) and 11 VAIN patients due to cervical cancer (group 2) were reviewed retrospectively. All patients were treated with at least one episode of laser vaporization between 2010 and 2011, and then followed up every 3 months for at least 1 year. Cox regression analysis was used to identify independent factors predicting persistence/recurrence. All VAIN patients achieved remission after two episodes of laser treatment, with 85.7% complete regression in group 1 and 54.5% in group 2. The first episode of the treatment had a significantly higher success rate in group 1 than in group 2 (46.2% vs 0.0%). All patients had no recurrence during a mean follow-up time of 22.8-27.8 months (range 12-39 months). However, infection persisted in 21 (61.8%) of 34 human-papillomavirus-positive patients after laser vaporization. Severity of VAIN was the only significant independent predictor of persistence/recurrence after one episode of the treatment (adjusted odds ratio, 4.08; 95% confidence interval, 1.28-12.96; P = 0.017). Laser treatments were well tolerated with no major side-effects. Laser vaporization may be a useful option for the treatment of VAIN after hysterectomy. However, a follow-up is required to assess the long-term efficacy of laser treatment. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  14. Increased number of IL-2, IL-2 receptor and IL-10 positive cells in premalignant lesions of the cervix.

    PubMed

    Mindiola, Raimy; Caulejas, Diana; Núñez-Troconis, José; Araujo, Mary; Delgado, Mariela; Mosquera, Jesús

    2008-12-01

    Previous studies have shown the involvement of the immune response in the progression of human uterine cervix cancer. The aim of this study was to determine the expression of Interleukin-2 (IL-2), IL-2 receptor (IL-2R) and Interleukin 10 (IL-10) in different grades of cervical intraepithelial neoplasias of the exocervix (CIN 1, 2 and 3), and its relationship with the serum cytokine profiles and human papilomavirus (HPV) infection status. Indirect immunofluorescence was used to study the expression of IL-2, IL-2R and IL-10 in human cervical samples from 50 patients and 9 normal controls. Serum IL-2, IL-2R and IL-10 were measured by ELISA and HPV DNA and HPV types were identified by PCR. Increased number of IL-2, IL-2R and IL-10 positive cells were observed in the cervix from patients with CIN, associated with the grades of dysplasia. A significant correlation was observed between IL-2 and IL-2R (p>0.0001), IL-2 and IL-10 (p>0.0001), as well as IL-10 and IL-2R (p>0.0001). Twenty percent of patients were HPV positive and 84% of those patients were tissue cytokine positive. These results suggest that IL-2, IL-2R and IL-10 tissue expression may play a role in the development of cervical intraepithelial dysplasias.

  15. Bronchial Aneurysms Mimicking Aortic Aneurysms: Endovascular Treatment in Two Patients

    SciTech Connect

    Vernhet, Helene; Bousquet, Claudine; Jean, Betty; Lesnik, Alvian; Durand, Gerard; Giron, Jacques; Senac, Jean Paul

    1999-05-15

    Bronchial artery dilatation and aneurysm formation is a potential complication of local inflammation, especially in bronchiectasis. When the bronchial artery has an ectopic origin from the inferior segment of the aortic arch, aneurysms may mimick aortic aneurysms. Despite this particular location, endovascular treatment is possible. We report two such aneurysms that were successfully embolized with steel coils.

  16. Inhaled dopamine induces bronchodilatation in patients with bronchial asthma.

    PubMed

    Cabezas, G A; Lezama, Y; Vidal, A; Velasco, M

    1999-10-01

    To determine the probable bronchodilating effect of dopamine administered by inhalation route in patients with crisis of bronchial asthma and the effect of dopamine on bronchial motor tone. We have studied eighteen (18) patients with crisis of bronchial asthma, ten (10) subjects with bronchial hyperreactivity and ten (10) healthy subjects. Patients with other pulmonary or cardiac disease were excluded. All received by inhalation placebo (0.9% saline solution), dopamine at 0.5 microg/kg/min (controlled by heart rate and arterial pressure with a dynamap), and placebo. Respiratory parameters: forced vital capacity (FVC), forced expiratory volume at the first second (FEV1), forced maximal expiratory flow (FEFmax) and forced expiratory flow at the 50% of vital capacity (FEF50) were measured in each protocol period. Student's paired t test, Wilcoxon and Mann Whitney analysis were performed. After dopamine inhalation, there was an increase of FVC by 23% (p<0.001); an increase of FEV1 by 39% (p<0.0001); an increase of FEF50 by 33% (p<0.001) and an increase of FEFmax by 31% (p<0.001). There were no respiratory parameter changes in both, subjects with bronchial hyperreactivity and normal after dopamine inhalation. Inhaled dopamine induces bronchodilatation in patients with crisis of bronchial asthma. Inhaled dopamine neither alters basal bronchial tone in healthy subjects nor in subjects with bronchial hyperreactivity.

  17. [Safe local anesthesia in patients with bronchial asthma].

    PubMed

    Anisimova, E N; Gromovik, M V

    The paper presents the analysis of studies of local anesthesia in patients with bronchial asthma. It was found that the diagnosis of hypersensitivity to sodium metabisulfite in patients with bronchial asthma must be optimized for development of local anesthesia selection algorithm in outpatient dentistry.

  18. Teriflunomide encourages cytostatic and apoptotic effects in premalignant and malignant cutaneous keratinocytes.

    PubMed

    Hail, Numsen; Chen, Ping; Rower, Joseph; Bushman, Lane R

    2010-10-01

    Teriflunomide (TFN) reportedly inhibits de novo pyrimidine synthesis and exhibits anti-inflammatory, disease-modifying activities in vivo. These qualities would suggest that TFN could be useful in skin cancer chemoprevention or therapy. We investigated some mechanistic aspects of this tenet by characterizing the effects of TFN on premalignant and malignant human cutaneous keratinocytes. TFN promoted a dose- and/or time-dependent cytostasis and in these cells, which was followed by apoptosis. These features occurred in the presence of a physiological concentration of uridine in the culture medium. The short-term S phase arrest triggered by TFN was reversible in the malignant keratinocytes, and the indirect apoptosis induction was apparently preceded by mitochondrial disruption and reactive oxygen species production in both the premalignant and malignant keratinocytes. Respiration deficient malignant keratinocytes were resistant to the acute cytostatic and latent apoptotic effects of TFN implicating de novo pyrimidine synthesis and mitochondrial bioenergetics as the primary targets for TFN in the respiring cells. These novel mechanistic findings support a role for TFN in skin cancer chemoprevention and therapy.

  19. Primary Sclerosing Cholangitis as a Premalignant Biliary Tract Disease: Surveillance and Management.

    PubMed

    Rizvi, Sumera; Eaton, John E; Gores, Gregory J

    2015-11-01

    Primary sclerosing cholangitis (PSC) is a premalignant biliary tract disease that confers a significant risk for the development of cholangiocarcinoma (CCA). The chronic biliary tract inflammation of PSC promotes pro-oncogenic processes such as cellular proliferation, induction of DNA damage, alterations of the extracellular matrix, and cholestasis. The diagnosis of malignancy in PSC can be challenging because inflammation-related changes in PSC may produce dominant biliary tract strictures mimicking CCA. Biomarkers such as detection of methylated genes in biliary specimens represent noninvasive techniques that may discriminate malignant biliary ductal changes from PSC strictures. However, conventional cytology and advanced cytologic techniques such as fluorescence in situ hybridization for polysomy remain the practice standard for diagnosing CCA in PSC. Curative treatment options of malignancy arising in PSC are limited. For a subset of patients selected by using stringent criteria, liver transplantation after neoadjuvant chemoradiation is a potential curative therapy. However, most patients have advanced malignancy at the time of diagnosis. Advances directed at identifying high-risk patients, early cancer detection, and development of chemopreventive strategies will be essential to better manage the cancer risk in this premalignant disease. A better understanding of dysplasia definition and especially its natural history is also needed in this disease. Herein, we review recent developments in our understanding of the risk factors, pathogenic mechanisms of PSC associated with CCA, as well as advances in early detection and therapies. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  20. [Increase of nonspecific bronchial reactivity after occupational exposure to vanadium].

    PubMed

    Pistelli, R; Pupp, N; Forastiere, F; Agabiti, N; Corbo, G M; Tidei, F; Perucci, C A

    1991-01-01

    A study was conducted to evaluate the level of bronchial responsiveness among workers recently exposed to vanadium pentoxide during periodical removal of ashes and clinker from the boilers of an oil-fired power station. A total of 11 male workers were examined 40-60 hours after the last exposure; male subjects, comparable as to age and smoking habits and not exposed to vanadium, were randomly chosen among the employees of the same power station as a control group. None of the subjects in the two groups had symptoms of bronchial inflammation or significant airways obstruction. However, bronchial responsiveness, investigated using a methacholine challenge test, was significantly higher in the exposed group. It is suggested that exposure to vanadium increases bronchial responsiveness even without clinical appearance of bronchial symptoms. The role of such increased level of airways responsiveness as a risk factor for chronic obstructive lung disease is speculated.

  1. Circulating Epithelial Cells in Patients with Pancreatic Lesions: Clinical and Pathologic Findings

    PubMed Central

    Cauley, Christy E; Pitman, Martha B; Zhou, Jiahua; Perkins, James; Kuleman, Birte; Liss, Andrew S; Castillo, Carlos Fernandez-del; Warshaw, Andrew L; Lillemoe, Keith D; Thayer, Sarah P

    2015-01-01

    Background Circulating epithelial cell (CEC) isolation has provided diagnostic and prognostic information for a variety of cancers, previously supporting their identity as circulating tumor cells in the literature. However, we report CEC findings in patients with benign, pre-malignant, and malignant pancreatic lesions using a size-selective filtration device. Study Design Peripheral blood samples were drawn from patients found to have pancreatic lesions on preoperative imaging at a surgical clinic. Blood was filtered using ScreenCell® devices, which were evaluated microscopically by a pancreatic cytopathologist. Pathological data and clinical outcomes of these patients were obtained from medical records over a one year follow-up period. Results Nine healthy volunteers formed the control group and were found to be negative for CECs. There were 179 patients with pancreatic lesions that formed the study cohort. CECs were morphologically similar in patients with a variety of pancreatic lesions. Specifically, CECs were identified in 51 of 105 pancreatic ductal adenocarcinomas (PDAC) (49%), 7 of 11 neuroendocrine tumors (64%), 13 of 21 intraductal papillary mucinous neoplasms (62%), and 6 of 13 patients with chronic pancreatitis. Rates of CEC identification were similar in patients with benign, premalignant, and malignant lesions (p=0.41). In addition, CECs findings in PDAC patients were not associated with poor prognosis. Conclusions While CECs were not identified in healthy volunteers, they were identified in patients with benign, premalignant, and malignant pancreatic lesions. The presence of CECs in patients presenting with pancreatic lesions is not diagnostic of malignancy, nor is it prognostic for patients with PDAC. PMID:26209458

  2. 3-D volume reconstruction of skin lesions for melanin and blood volume estimation and lesion severity analysis.

    PubMed

    D'Alessandro, Brian; Dhawan, Atam P

    2012-11-01

    Subsurface information about skin lesions, such as the blood volume beneath the lesion, is important for the analysis of lesion severity towards early detection of skin cancer such as malignant melanoma. Depth information can be obtained from diffuse reflectance based multispectral transillumination images of the skin. An inverse volume reconstruction method is presented which uses a genetic algorithm optimization procedure with a novel population initialization routine and nudge operator based on the multispectral images to reconstruct the melanin and blood layer volume components. Forward model evaluation for fitness calculation is performed using a parallel processing voxel-based Monte Carlo simulation of light in skin. Reconstruction results for simulated lesions show excellent volume accuracy. Preliminary validation is also done using a set of 14 clinical lesions, categorized into lesion severity by an expert dermatologist. Using two features, the average blood layer thickness and the ratio of blood volume to total lesion volume, the lesions can be classified into mild and moderate/severe classes with 100% accuracy. The method therefore has excellent potential for detection and analysis of pre-malignant lesions.

  3. Serum zinc, bronchiectasis, and bronchial carcinoma

    PubMed Central

    Beeley, J. M.; Darke, C. S.; Owen, G.; Cooper, R. D.

    1974-01-01

    Beeley, J. M., Darke, C. S., Owen, G., and Cooper, R. D. (1974).Thorax, 29, 21-25. Serum zinc, bronchiectasis, and bronchial carcinoma. Serum zinc levels were measured by atomic absorption spectrophotometry in 65 patients with proven bronchiectasis; the mean level was 93 μg/100 ml, while the levels in two groups of healthy control subjects were 88·6 and 92·7 μg/100 ml respectively. The range of individual values was similar in all groups and the differences between the mean serum zinc levels of the two groups of control subjects and the mean level of the group of patients with bronchiectasis were small and did not attain significance at the conventional 0·05 level. In contrast, the mean level in bronchial carcinoma patients (75·9 μg/100 ml) was significantly less than in each of the other groups of subjects. Zinc sulphate was administered for six weeks on a double-blind cross-over basis to patients with bronchiectasis and, although serum zinc levels rose, no detectable clinical improvement resulted. No definitive evidence of zinc deficiency in bronchiectasis has been established. PMID:4596632

  4. Bronchial reactions to exposure to welding fumes.

    PubMed Central

    Contreras, G R; Chan-Yeung, M

    1997-01-01

    OBJECTIVES: To study the airway response and its mechanism to welding fumes in six welders with respiratory symptoms. METHODS: Methacholine and welding challenge tests were carried out. The concentration of welding fumes during the exposure test was measured. On two subjects who developed bronchoconstricition to welding challenge, additional tests were carried out including prick, patch, and inhalation challenges with metal salt solutions. RESULTS: Three subjects developed immediate bronchial reaction to exposure to welding fume; one to mild steel and stainless steel welding, another to mild steel and galvanised welding, and one only to galvanised welding. They all had a moderate to pronounced degree of non-specific bronchial hyperresponsiveness. The concentration of fumes during welding tests, particularly to galvanised welding, was high. An inhalation challenge test with zinc chloride salt solution in two subjects who reacted to galvanised welding was negative. Prick and patch tests with zinc chloride were also negative. CONCLUSION: The airway response to welding in these subjects is non-specific and is due to irritation rather than to sensitisation. PMID:9538358

  5. Flexible bronchoscopic argon plasma coagulation for management of massive hemoptysis in bronchial Dieulafoy's disease

    PubMed Central

    Madan, Karan; Dhungana, Ashesh; Hadda, Vijay; Mohan, Anant; Guleria, Randeep

    2017-01-01

    Dieulafoy's disease is an uncommon condition, the usual site of occurrence being the gastrointestinal tract. The condition refers to the presence of a dysplastic submucosal artery with mucosal vascular branches that has propensity to cause recurrent bleeding. Dieulafoy's disease of the bronchus is rare. Herein, we describe the case of a 26-year-old male who presented with recurrent bouts of hemoptysis and bronchial Dieulafoy's disease was diagnosed. Flexible bronchoscopy was performed, and argon plasma coagulation (APC) of the bleeding lesion was done. The procedure was successful and was followed by complete eradication of the vascular malformation and cessation of hemoptysis. APC is a useful tool in the armamentarium of an interventional pulmonologist that can allow rapid and safe control of bleeding from superficially located and bleeding endobronchial lesions, and can be easily and effectively applied using a flexible bronchoscope. PMID:28144074

  6. Optimization of the spectral design used to detect early carcinoma in the human tracheo-bronchial tree by autofluorescence imaging

    NASA Astrophysics Data System (ADS)

    Gabrecht, Tanja; Glanzmann, Thomas; Freitag, Lutz; Grosjean, Pierre; Weber, Bernd C.; Monnier, Philippe; van den Bergh, Hubert; Wagnieres, Georges A.

    2003-10-01

    The early detection and localization of bronchial cancer remains a challenging task. Autofluorescence bronchoscopy is emerging as a useful diagnostic tool with improved sensitivity and specificity. Evidence exists that the native fluorescence or autofluorescence of bronchial tissues changes when they turn dysplastic or to carcinoma in situ (CIS). Early lesions in the bronchi tend to show a decrease in autofluorescence in the green region of the spectrum when excited with violet light and a relative increase in the red region of the spectrum. Several endoscopic imaging devices relying on these optical properties of bronchial mucosa have been developed. An industrial endoscopic autofluorescence imaging system for the detection of early cancerous lesions in the bronchi has been developed in collaboration with the firm Richard Wolf Endoskope GmbH, Knittlingen (Germany; its performance has been evaluated in a previous clinical study. A second study, presented in this article, aims to optimize the spectral design of the device. Twenty-four lung cancer or high risk patients were enrolled in this study to assess the influence of additional backscattered red light on the tumor-to-healthy tissue contrast and to compare the effect of a narrow band violet excitation to a large band violet excitation. In our study we observed a three times higher contrast between cancer and healthy tissue, when backscattered red light was added to the violet excitation. The comparison between a narrow and a large band violet excitation indicated an increase of the tumor-to-healthy tissue contrast by the narrow band excitation.

  7. Diagnostic cellular abnormalities in neoplastic and non-neoplastic lesions of the epidermis: a morphological and statistical study

    PubMed Central

    Malhotra, Saurabh; Kazlouskaya, Viktoryia; Andres, Christian; Gui, Jiang; Elston, Dirk

    2013-01-01

    Background Distinguishing cellular abnormalities in reactive and malignant lesions is challenging. We compared the incidence and severity of cytological abnormalities in malignant/premalignant and benign epidermal lesions. Methods One hundred fifty-two biopsies representing 69 malignant/premalignant squamous lesions and 83 benign conditions were studied. Cytological features, including nuclear hyperchromasia, nuclear overlap (crowding), irregular nuclei, high nuclear/cytoplasmic (N/C) ratio, conspicuous nucleoli, delicate inconspicuous nucleoli, clumped chromatin, pleomorphic parakeratosis, normal and abnormal mitotic figures and necrotic keratinocytes, were evaluated and graded. Statistical analysis was performed. Results Irregular nuclei, increased N/C ratio, conspicuous single prominent nucleoli, nuclear overlap (crowding), pleomorphic parakeratosis, nuclear hyperchromasia, necrotic keratinocytes, normal and abnormal mitotic figures and coarse chromatin were seen more frequently in malignant neoplasms (p < 0.05). Abnormal mitotic figures, although uncommon (20.3%), were only noted in the malignant/premalignant group. Certain cytological features were common among both malignant and benign lesions, suggesting that they are of little value. Conclusion In the setting of an atypical cutaneous squamous proliferation, nuclear irregularity, increased N/C ratio, conspicuous nucleoli, crowding and hyperchromasia are the most useful indicators of malignancy. In contrast, mitotic figures, necrotic cells and coarse chromatin are less useful. The presence of abnormal mitotic figures is very helpful when present; however, their overall rarity limits their utility. PMID:23398548

  8. Premalignant alteration assessment in liver-like tissue derived from embryonic stem cells by aristolochic acid I exposure

    PubMed Central

    Li, Tong; Jin, Ke; Zhu, Dan-yan; Li, Lu; Mao, Zheng-rong; Wu, Bo-wen; Wang, Yi-fan; Pan, Zong-fu; Li, Lan-juan; Xiang, Chun-sheng; Su, Kun-kai; Lou, Yi-jia

    2016-01-01

    The in vitro predictive evaluation of chemical carcinogenicity based on hepatic premalignance has so far not been established. Here, we report a novel approach to investigate the premalignant events triggered by human carcinogen aristolochic acid I (AAI) in the liver-like tissue derived from mouse embryonic stem cells. By AAI exposure, the liver-like tissue exhibited the paracrine interleukin-6 phenotypic characteristics. Hepatocytes expressed STAT3/p-STAT3, c-Myc and Lin28B in parallel. Some of them displayed the dedifferentiation characteristics, such as full of α-fetoprotein granules, increase in size, and nucleocytoplasmic shuttle of Oct4. When these cells were injected into mice, the xenografts mostly displayed the uniform area of hepatic-like tissue with malignant nuclei. The hepatic malignant markers, α-fetoprotein, cytokeratin 7 and cytokeratin 19, were co-expressed in albumin-positive areas, respectively. In conclusion, we established an approach to predict the hepatic premalignance triggered by carcinogen AAI. This premalignant assay system might aid to evaluate the effects of potential carcinogens in liver, and probably to screen the protecting against hepatocarcinogenic efficacy of pharmaceuticals in vitro. PMID:27713163

  9. Bronchial Artery Aneurysm with Associated Bronchial Artery to Pulmonary Artery Fistula: Treatment by Embolization

    PubMed Central

    Hsieh, Caleb G; Le, Thomas; Fogelfeld, Keren; Kamangar, Nader

    2017-01-01

    Bronchial artery aneurysm (BAA) is a rare vascular phenomenon. This review highlights a case of a BAA that was complicated by the presence of a bronchial artery to pulmonary artery (BA-PA) fistula, consequently presenting a unique challenge to management. BAAs have a strongly reported risk of rupture resulting in life-threatening hemoptysis. Embolization has thus become routine for the management such severe cases. The management of incidentally found anomalies is less obvious, but prophylactic embolization is a generally accepted practice. In this report, we review some of the risks and benefits associated with BAA embolization with specific consideration of the challenges in cases of co-existing BA-PA fistula. PMID:28217405

  10. A time- and matrix-dependent TGFBR3–JUND–KRT5 regulatory circuit in single breast epithelial cells and basal-like premalignancies

    PubMed Central

    Wang, Chun-Chao; Bajikar, Sameer S.; Jamal, Leen; Atkins, Kristen A.; Janes, Kevin A.

    2014-01-01

    Basal-like breast carcinoma is characterized by poor prognosis and high intratumor heterogeneity. In an immortalized basal-like breast epithelial cell line, we identified two anti-correlated gene-expression programs that arise among single extracellular matrix (ECM)-attached cells during organotypic 3D culture. The first contains multiple TGFβ-related genes including TGFBR3, whereas the second contains JUND and the basal-like marker, KRT5. TGFBR3 and JUND interconnect through four negative-feedback loops to form a circuit that exhibits spontaneous damped oscillations in 3D culture. The TGFBR3–JUND circuit appears conserved in some premalignant lesions that heterogeneously express KRT5. The circuit depends on ECM engagement, as detachment causes a rewiring that is triggered by RPS6 dephosphorylation and maintained by juxtacrine tenascin C, which is critical for intraductal colonization of basal-like breast cancer cells in vivo. Intratumor heterogeneity need not stem from partial differentiation and could instead reflect dynamic toggling of cells between expression states that are not cell autonomous. PMID:24658685

  11. FTIR microscopic comparative study on normal, premalignant, and malignant tissues of human intenstine

    NASA Astrophysics Data System (ADS)

    Mordechai, Shaul; Argov, Shmuel; Salman, Ahmad O.; Cohen, Beny; Ramesh, Jagannathan; Erukhimovitch, Vitaly; Goldstein, Jed; Sinelnikov, Igor

    2000-07-01

    Fourier-Transform Infrared Spectroscopy (FTIR) employs a unique approach to optical diagnosis of tissue pathology based on the characteristic molecular vibrational spectra of the tissue. The architectural changes in the cellular and sub-cellular levels developing in abnormal tissue, including a majority of cancer forms, manifest themselves in different optical signatures, which can be detected in infrared spectroscopy. The biological systems we have studied include normal, premalignant (polyp) and malignant human colonic tissues from three patients. Our method is based on microscopic infrared study (FTIR-microscopy) of thin tissue specimens and a direct comparison with normal histopathological analysis, which serves as a `gold' reference. The normal intestine tissue has a stronger absorption than polyp and cancerous types over a wide region in all three cases. The detailed analysis showed that there is a significant decrease in total phosphate and creatine contents for polyp and cancerous tissue types in comparison to the controls.

  12. Bronchial thermoplasty in asthma: current perspectives

    PubMed Central

    Laxmanan, Balaji; Hogarth, D Kyle

    2015-01-01

    Bronchial thermoplasty (BT) is a novel therapy for patients with severe asthma. Using radio frequency thermal energy, it aims to reduce the airway smooth muscle mass. Several clinical trials have demonstrated improvements in asthma-related quality of life and a reduction in the number of exacerbations following treatment with BT. In addition, recent data has demonstrated the long-term safety of the procedure as well as sustained improvements in rates of asthma exacerbations, reduction in health care utilization, and improved quality of life. Further study is needed to elucidate the underlying mechanisms that result in these improvements. In addition, improved characterization of the asthma subphenotypes likely to exhibit the largest clinical benefit is a critical step in determining the precise role of BT in the management of severe asthma. PMID:26028976

  13. [Serum immunoglobulin E level in bronchial asthma].

    PubMed

    Denchev, K; Radkov, M; Lipcheva, N

    1976-01-01

    Serum immunoglobulin E level was determined in 50 patients with bronchial asthma, treated in the out-patients department and clinical conditions at the Faculty Hospital--Varna. The quantitative determination of immunoglobulin E was carried out by radial immunodiffusion according to Mancini with monospecific anti-IgE globulin serum from Behringswerke (GFR). A considerable elevation of immunoglobulin E in the patients' sera was found, at an average of 394 IU (control 124 IU). A discrepancy in serum immunoglobulin E level was established with the different clinical forms of asthma. The highest are the values with infectious-allergic astmha-424 IU. High are the values both in the treated and not-treated with corticosteroids, without an essential difference between the two patient groups. Some of the rest immunoglobulins showed also an elevationppIgG 2620 mg% and IgA 366 mg%.

  14. Mainstem to mainstem bronchial fistula from broncholithiasis.

    PubMed

    Wiese, Tanya A

    2012-01-01

    Broncholithiasis is a rare condition in which calcified material erodes into the tracheobronchial tree. Most are caused from a fungal, nocardial, mycobacterial, or silicosis-related granulomatous lymphadenitis. Over time, the peribronchial lymph nodes become calcified; thereafter, with the normal repetitive motions of respiration, circulation, and deglutition, the calcifications erode into the lumen of the airway. This condition can be challenging to diagnose as its symptoms can mimic many more common diseases. The most common symptoms are wheezing, chronic cough, and dyspnea; thus, it was previously referred to as "stone asthma." More devastating complications can include massive hemoptysis, recurrent pneumonias, bronchiectasis, mediastinal abscess, and fistula formations. Only airways to mediastinal, esophageal, or vascular fistulas have been reported in the literature. This is the first reported case of a patient treated with electrocautery forceps, who developed a mainstem to mainstem bronchial fistula.

  15. [Single centre experience of endoscopic submucosal dissection (ESD) in premalignant and malignant gastrointestinal neoplasia].

    PubMed

    Höbel, S; Baumbach, R; Dautel, P; Oldhafer, K J; Stang, A; Feyerabend, B; Yahagi, N; Faiss, S

    2014-02-01

    Worldwide endoscopic submucosal dissection (ESD) of early GI cancers or premalignant neoplasia is becoming increasingly important. In Germany ESD is restricted to larger endoscopic institutions and only a few literature reports are available. The aim of the present study is to describe the results of 46 ESDs conducted in a German endoscopic centre. Between June 2007 and May 2012 46 ESDs in 45 patients (33 men, 12 women, mean age 66.1 years) were performed in the oesophagus (n = 17), stomach (n = 23) and rectum (n = 6). Data were collected for the en-bloc, R0 and R0 en-bloc resection rates as well as for complications, the curative resection and the local recurrence rates. In order to demonstrate a learning curve, results were evaluated for two periods (June 2007 to November 2010 vs. December 2010 to May 2012). ESD was technically possible in 93.5%. En-bloc, R0, R0 en-bloc and curative resection rates were 90.7%, 74.4%, 67.4% and 65.1%, respectively. The complication rate was 13%. In the second period en-bloc and R0 en-bloc resection rates increased from 81% to 100% and, respectively, from 52.4% to 81.8%. After a medium follow-up of 11.4 months, local tumour recurrence occurred in 10%. In cases of curative R0 en bloc resection of malignant tumours no tumour recurrence occurred. Despite the small number of patients, the present data underline the value of ESD, especially in cases of R0 en-bloc resections in the therapy for premalignant and early malignant GI tumours. Due to the required learning curve, ESD should be restricted to larger endoscopic centres in Germany. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Treatment of bronchial asthma with tianeptine.

    PubMed

    Lechin, F; van der Dijs, B; Lechin, A E

    2004-11-01

    Although circulating catecholamines and free serotonin in the plasma (f-5-HT) were found to be increased during asthma attacks, only f-5-HT levels correlated positively with bronchoconstriction and clinical severity. Tianeptine, a drug that enhances serotonin uptake by platelets and serotonergic axons at the central nervous system (CNS), provoked an abrupt disappearance of asthma attacks. This fact explains why tianeptine has proven to be a powerful therapeutic tool in controlling asthma. Its success has been demonstrated not only in two double-blind placebo, cross-over trials, but through an open study lasting more than seven years that included over 25,000 asthmatic patients. In the present article, we discuss the peripheral and central nervous system mechanisms that may explain the therapeutic success of tianeptine. These are summarized below. F-5-HT is taken up by pulmonary endocrine cells (PNEC) located at the parasympathetic terminals. A presynaptic element, these cells release serotonin and potentiate acetylcholine (ACh)-induced contraction of bronchial muscle. This effect is mediated by 5-HT(3) and 5-HT(4) postsynaptic receptors located at the bronchial muscle. According to the above, the increased f-5-HT plasma level, triggered by both platelet aggregation and nocturnal and/or diurnal hyperparasympathetic activity, potentiates ACh-induced bronchoconstriction. The fact that serotonin released by medullary serotonergic axons stimulates the medullary vagal cardiorespiratory neurons obliges us to think that serotonin-induced CNS mechanisms are also involved. Furthermore, the finding that drugs that interfere with serotonin uptake, by both platelets and 5-HT-terminals, worsen asthma symptoms and are able to provoke asthma attacks gives additional support to the above peripheral and CNS mechanisms.

  17. [Bronchial asthma due to storage mite allergy].

    PubMed

    Kroidl, R F; Schwichtenberg, U; Frank, E

    2007-08-01

    In a multicenter study (7 participating centres) 132 patients with bronchial asthma (grade II or III) and sensitization to storage mites (SM) and/or house dust mites (HSM) were screened and asked to undergo further allergological evaluation. 90 patients agreed. In addition to routine skin prick tests and RAST, quantitative skin prick tests (QSPT) and bronchial provocation tests (BPT) were also performed with the suspected mite allergens. The results were correlated with aspects of the domestic and working environments. Furthermore we questioned whether the outcome of BPT could be predicted from the results of the routine skin tests/RAST and QSPT respectively. Out of a total of 145 BPTs there were 79 positive results with SM and/or HSM. Three patients were mono-allergic to SM. The correlation with the domestic environment was unremarkable. Correlation with occupational factors revealed a strong predominance of farmers (42 of 90) and suggested the same for professions involved in work in dust-laden environments like bakers (5 of 90) and workers in wood- and paper industry (7 of 90). This also means, that SM-allergy occurs in persons not occupationally exposed to dust. A prediction as to the allergological relevance of SM-allergen was not possible from viewing the routine skin prick test however positive RAST data showed a significant correlation with positive BPT to SM Lepidoglyphus. Similarly it was possible to draw an inference from QSPT as to the relevant allergy. With a positive QSPT to the SM Lepidoglyphus destructor a positive result with a BPT was highly probable. Due to small numbers it is not possible to make a similar statement for the other SM species (Acarus and Tyrophagus).

  18. Photodynamic therapy (PDT) in advanced inoperable bronchial carcinoma

    NASA Astrophysics Data System (ADS)

    Moghissi, Keyvan; Dixon, Kate; Stringer, Mark R.; Brown, Stanley B.

    1996-12-01

    Objective: To assess the efficacy of PDT to: Palliate symptoms, control disease and extend survival in patients with advanced inoperable cancer. Subject and Method: 55 Males and 23 females aged between 45-81 years (mean 66 years) with inoperable and advanced lung cancer with > 5O. obstructive lesions of the main, lobar or segmental bronchi. Patients had pre-treatment routine clinical radiological, functional and endoscopic assessment with proven histological diagnosis. Protocol of PDT was; Intravenous injection of 2 mg/Kg bodyweight Polyhaematoporphyrin (equivalent to Photofrin) or Photofrin followed 24-72 hours later by illumination of tumour using 630 nm light (Oxford Laser) delivered via an optical fibre with end diffuser. Treatments were carried out under general anaesthesia as a day case procedure. Patients were rebronchoscoped for debridement/retreatment 4-7 days later. Results: There was no treatment related mortality. Two patients developed mild photosensitivity reaction. All patients showed symptomatic improvement with good initial functional and radiological amelioration. Every patient responded to treatment. Seven patients had complete response and negative histology for 3-12 months. After the first treatment average Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) improvement was 0.5 litres and 0.4 litres respectively. Twenty five percent of patients (nr 19) survived more than 2 years, 10'. (nr=8) between 1-2 years and the remaining 51 patients less than a year. Conclusion: PDT should be considered as a therapeutic modality for all stages of lung cancer and is an excellent treatment modality for palliation in advanced bronchial malignancies.

  19. [Optimal therapy of children with bronchial asthma at Pyatigorsk spa].

    PubMed

    Sokolova, M Iu; Ivanova, N A; Shabalov, N P

    2007-01-01

    The study of efficacy of bronchial asthma children's rehabilitation at Pyatigorsk spa with different schemes of treatment has shown that combined treatment with dry air-radon baths and halotherapy is more effective than each of these modalities alone.

  20. Bronchial epithelium in children: a key player in asthma.

    PubMed

    Carsin, Ania; Mazenq, Julie; Ilstad, Alexandra; Dubus, Jean-Christophe; Chanez, Pascal; Gras, Delphine

    2016-06-01

    Bronchial epithelium is a key element of the respiratory airways. It constitutes the interface between the environment and the host. It is a physical barrier with many chemical and immunological properties. The bronchial epithelium is abnormal in asthma, even in children. It represents a key component promoting airway inflammation and remodelling that can lead to chronic symptoms. In this review, we present an overview of bronchial epithelium and how to study it, with a specific focus on children. We report physical, chemical and immunological properties from ex vivo and in vitro studies. The responses to various deleterious agents, such as viruses or allergens, may lead to persistent abnormalities orchestrated by bronchial epithelial cells. As epithelium dysfunctions occur early in asthma, reprogramming the epithelium may represent an ambitious goal to induce asthma remission in children.

  1. Pink lesions.

    PubMed

    Giacomel, Jason; Zalaudek, Iris

    2013-10-01

    Dermoscopy (dermatoscopy or surface microscopy) is an ancillary dermatologic tool that in experienced hands can improve the accuracy of diagnosis of a variety of benign and malignant pigmented skin tumors. The early and more accurate diagnosis of nonpigmented, or pink, tumors can also be assisted by dermoscopy. This review focuses on the dermoscopic diagnosis of pink lesions, with emphasis on blood vessel morphology and pattern. A 3-step algorithm is presented, which facilitates the timely and more accurate diagnosis of pink tumors and subsequently guides the management for such lesions.

  2. [State of higher nervous activity in women with bronchial asthma].

    PubMed

    Zinchenko, T M

    2001-01-01

    A total of 103 women were examined with bronchial asthma, who demonstrated disturbances in the intrapsychic adaptation presenting as hystero-hypochondriacal and anxious alterations in the personality pattern with formation of a certain modus of thinking and behavior. Differences have been ascertained in the personality profile of patients with varying clinicopathogenetic forms of bronchial astma in those groups of patients differing in age, degree of severity of the condition duration of the analysis.

  3. Toxicities and early outcomes in a phase 1 trial of photodynamic therapy for premalignant and early stage head and neck tumors

    PubMed Central

    Ahn, Peter H.; Quon, Harry; O'Malley, Bert W.; Weinstein, Gregory; Chalian, Ara; Malloy, Kelly; Atkins, Joshua H.; Sollecito, Thomas; Greenberg, Martin; McNulty, Sally; Lin, Alexander; Zhu, Timothy C.; Finlay, Jarod C.; Cengel, Keith; Livolsi, Virginia; Feldman, Michael; Mick, Rosemarie; Busch, Theresa M.

    2016-01-01

    SUMMARY Objectives Management of early superficial lesions in the head and neck remains complex. We performed a phase 1 trial for high-grade premalignant and early superficial lesions of the head and neck using photodynamic therapy (PDT) with Levulan (ALA). Materials and methods Thirty-five subjects with high grade dysplasia, carcinoma in situ, or microinvasive (≤1.5 mm depth) squamous cell carcinoma were enrolled. Cohorts of 3–6 patients were given escalating intraoperative light doses of 50–200 J/cm2 4–6 h after oral administration of 60 mg/kg ALA. Light at 629–635 nm was delivered in a continuous (unfractionated) or fractionated (two-part) schema. Results PDT was delivered to 30/35 subjects, with 29 evaluable. There was one death possibly due to the treatment. The regimen was otherwise tolerable, with a 52% rate of grade 3 mucositis which healed within several weeks. Other toxicities were generally grade 1 or 2, including odynophagia (one grade 4), voice alteration (one grade 3), and photosensitivity reactions. One patient developed grade 5 sepsis. With a median follow-up of 42 months, 10 patients (34%) developed local recurrence; 4 of these received 50 J/cm2 and two each received 100, 150, and 200 J/cm2. Ten (34%) patients developed recurrence adjacent to the treated field. There was a 69% complete response rate at 3 months. Conclusions ALA-PDT is well tolerated. Maximum Tolerated Dose appears to be higher than the highest dose used in this study. Longer followup is required to analyze effect of light dose on local recurrence. High marginal recurrence rates suggest use of larger treatment fields. PMID:26865261

  4. Molecular Damage in the Bronchial Epithelium of Current and Former Smokers

    PubMed Central

    Wistuba, Ignacio I.; Lam, Stephen; Behrens, Carmen; Virmani, Arvind K.; Fong, Kwun M.; LeRiche, Jean; Samet, Jonathan M.; Srivastava, Sudhir; Minna, John D.; Gazdar, Adi F.

    2016-01-01

    Background Most lung cancers are attributed to smoking. These cancers have been associated with multiple genetic alterations and with the presence of preneoplastic bronchial lesions. In view of such associations, we evaluated the status of specific chromosomal loci in histologically normal and abnormal bronchial biopsy specimens from current and former smokers and specimens from nonsmokers. Methods Multiple biopsy specimens were obtained from 18 current smokers, 24 former smokers, and 21 nonsmokers. Polymerase chain reaction-based assays involving 15 polymorphic microsatellite DNA markers were used to examine eight chromosomal regions for genetic changes (loss of heterozygosity [LOH] and microsatellite alterations). Results LOH and microsatellite alterations were observed in biopsy specimens from both current and former smokers, but no statistically significant differences were observed between the two groups. Among individuals with a history of smoking, 86% demonstrated LOH in one or more biopsy specimens, and 24% showed LOH in all biopsy specimens. About half of the histologically normal specimens from smokers showed LOH, but the frequency of LOH and the severity of histologic change did not correspond until the carcinoma in situ stage. A subset of biopsy specimens from smokers that exhibited either normal or preneoplastic histology showed LOH at multiple chromosomal sites, a phenomenon frequently observed in carcinoma in situ and invasive cancer. LOH on chromosomes 3p and 9p was more frequent than LOH on chromosomes 5q, 17p (17p13; TP53 gene), and 13q (13q14; retinoblastoma gene). Microsatellite alterations were detected in 64% of the smokers. No genetic alterations were detected in nonsmokers. Conclusions Genetic changes similar to those found in lung cancers can be detected in the nonmalignant bronchial epithelium of current and former smokers and may persist for many years after smoking cessation. PMID:9308707

  5. Shared Gene Expression Alterations in Nasal and Bronchial Epithelium for Lung Cancer Detection.

    PubMed

    2017-07-01

    We previously derived and validated a bronchial epithelial gene expression biomarker to detect lung cancer in current and former smokers. Given that bronchial and nasal epithelial gene expression are similarly altered by cigarette smoke exposure, we sought to determine if cancer-associated gene expression might also be detectable in the more readily accessible nasal epithelium. Nasal epithelial brushings were prospectively collected from current and former smokers undergoing diagnostic evaluation for pulmonary lesions suspicious for lung cancer in the AEGIS-1 (n = 375) and AEGIS-2 (n = 130) clinical trials and gene expression profiled using microarrays. All statistical tests were two-sided. We identified 535 genes that were differentially expressed in the nasal epithelium of AEGIS-1 patients diagnosed with lung cancer vs those with benign disease after one year of follow-up ( P  < .001). Using bronchial gene expression data from the AEGIS-1 patients, we found statistically significant concordant cancer-associated gene expression alterations between the two airway sites ( P  < .001). Differentially expressed genes in the nose were enriched for genes associated with the regulation of apoptosis and immune system signaling. A nasal lung cancer classifier derived in the AEGIS-1 cohort that combined clinical factors (age, smoking status, time since quit, mass size) and nasal gene expression (30 genes) had statistically significantly higher area under the curve (0.81; 95% confidence interval [CI] = 0.74 to 0.89, P  = .01) and sensitivity (0.91; 95% CI = 0.81 to 0.97, P  = .03) than a clinical-factor only model in independent samples from the AEGIS-2 cohort. These results support that the airway epithelial field of lung cancer-associated injury in ever smokers extends to the nose and demonstrates the potential of using nasal gene expression as a noninvasive biomarker for lung cancer detection.

  6. [The measurement of bronchial hyperreactivity for military service fitness].

    PubMed

    Ferrante, E; Grasso, S; Corbo, G M; Ciappi, G

    1991-10-01

    The authors discuss the efficacy of methacholine challenge to discriminate fit subjects to military service. We evaluated the relation between bronchial hyperreactivity and clinical symptoms, airways caliber and atopic status in a group of italian conscripts who reported to have bronchial asthma. Five-hundred-four subjects were studied. Bronchial hyperreactivity was measured by methacholine test, and atopic status was assessed by skin-tests. A measurable PC20 FEV1 was detected in 424 subjects. On the basis of the methacholine threshold concentration the overall sample was divided in four categories. The four categories differed as regards onset of disease, lung function and skin reactivity towards Dermatophagoides Pter, whereas no difference was found as regards skin reactivity towards Grass. In the group evaluated in spring, the four categories differed as regards skin reactivity towards Grass. In conclusion we found that bronchial hyperreactivity is related to clinical history, lung function and atopic status; the measurement of bronchial hyperreactivity is important to evaluate conscripts referring bronchial asthma.

  7. Bronchial and extrabronchial factors in chronic airflow obstruction

    PubMed Central

    Leaver, D. G.; Tattersfield, A. E.; Pride, N. B.

    1974-01-01

    Leaver, D. G., Tattersfield, A. E., and Pride, N. B. (1974).Thorax, 29, 394-400. Bronchial and extrabronchial factors in chronic airflow obstruction. Chronic airflow obstruction may be due either to disease of the airway wall and lumen or to loss of airway-distending forces acting on the outer wall of the bronchus. In 17 patients with chronic airflow obstruction the relative importance of bronchial and extrabronchial factors was assessed by analysing the relation between airways conductance and static transpulmonary pressure over a range of lung volumes. Using previously established clinical, radiological, and functional criteria (which did not include measurements of the mechanical properties of the lungs), six of these patients had evidence of widespread emphysema and six patients had predominant `bronchial' disease. In four of the six `emphysematous' patients there was no functional evidence of disease of the bronchial wall or lumen during quiet breathing, and airway narrowing could be explained by loss of airway-distending forces. The six patients with characteristic `bronchial' features showed functional evidence of disease of the bronchial wall or lumen. Images PMID:4850829

  8. The role of cytology in oral lesions: a review of recent improvements.

    PubMed

    Mehrotra, Ravi

    2012-01-01

    Historically, sensitivity and specificity of oral cytology is poor. Using conventional oral cytology for the diagnosis of cancer and its precursors has not had the success that cytologists had hoped for; however, with improved methodology, oral cytology has enjoyed a resurgence of interest. This renewed interest is partly due to the introduction of a specialized brush that collects a full-thickness epithelial sample and not just superficially sloughed cells, as well as analysis of that sample with computer assistance; in addition, a variety of adjunctive techniques have been introduced to potentially enhance the diagnosis of the cytologic specimens including DNA analysis, immunocytochemistry, molecular analysis, and liquid-based preparations. An increase in sensitivity (>96%) and specificity (>90%) of the oral brush biopsy with computer-assisted diagnosis has been reported for identification of malignant and premalignant lesions. Brush cytology is valuable to prevent misdiagnosing doubtful oral lesions, i.e., those lesions without a definitive etiology, diagnosing large lesions where excision of the entire tissue is not possible or practicable, evaluating patients with recurrent malignancies, and monitoring premalignant lesions.

  9. Environmental risk factors and allergic bronchial asthma.

    PubMed

    D'Amato, G; Liccardi, G; D'Amato, M; Holgate, S

    2005-09-01

    The prevalence of allergic respiratory diseases such as bronchial asthma has increased in recent years, especially in industrialized countries. A change in the genetic predisposition is an unlikely cause of the increase in allergic diseases because genetic changes in a population require several generations. Consequently, this increase may be explained by changes in environmental factors, including indoor and outdoor air pollution. Over the past two decades, there has been increasing interest in studies of air pollution and its effects on human health. Although the role played by outdoor pollutants in allergic sensitization of the airways has yet to be clarified, a body of evidence suggests that urbanization, with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases observed in most industrialized countries, and there is considerable evidence that asthmatic persons are at increased risk of developing asthma exacerbations with exposure to ozone, nitrogen dioxide, sulphur dioxide and inhalable particulate matter. However, it is not easy to evaluate the impact of air pollution on the timing of asthma exacerbations and on the prevalence of asthma in general. As concentrations of airborne allergens and air pollutants are frequently increased contemporaneously, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of allergic respiratory allergy and bronchial asthma. Pollinosis is frequently used to study the interrelationship between air pollution and respiratory allergy. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc) can affect both components (biological and chemical) of this interaction. By attaching to the surface of pollen grains and of plant-derived particles of paucimicronic size, pollutants could modify not only the morphology of these antigen-carrying agents but also their allergenic

  10. Bronchial atresia: the hidden pathology within a spectrum of prenatally diagnosed lung masses.

    PubMed

    Kunisaki, Shaun M; Fauza, Dario O; Nemes, Luanne P; Barnewolt, Carol E; Estroff, Judy A; Kozakewich, Harry P; Jennings, Russell W

    2006-01-01

    This study was aimed at determining whether different congenital lung masses represent diverse manifestations of a single developmental abnormality associated with fetal airway obstruction. We conducted a 3-year retrospective review of patients who underwent surgical resection of a prenatally diagnosed lung mass. Prenatal imaging was used to define mass position and its effect on adjacent organs. Lung specimens were examined through careful full-specimen microdissections, as well as by plain and contrast roentgenograms. Twenty-five patients underwent lung resection during this study period. Based on the final pathology reports, 56% were congenital cystic adenomatoid malformations, 12% were congenital lobar emphysemas, 8% were bronchopulmonary sequestrations, and 24% had features of both cystic adenomatoid malformation and bronchopulmonary sequestrations. No bronchogenic cysts were present in this series. Overall, bronchial atresia was identified in 77% of the examined specimens (n = 22) and was associated with all types of lung malformations. Bronchial atresia is a common, unrecognized component of prenatally diagnosed congenital cystic adenomatoid malformations, bronchopulmonary sequestrations, congenital lobar emphysemas, and lesions of mixed pathology. Most congenital lung masses may be part of a spectrum of anomalies linked to obstruction of the developing fetal airway as an underlying component in their pathogenesis.

  11. Roles of sonography and hysteroscopy in the detection of premalignant and malignant polyps in women presenting with postmenopausal bleeding and thickened endometrium.

    PubMed

    Cavkaytar, Sabri; Kokanali, Mahmut Kuntay; Ceran, Ufuk; Topcu, Hasan Onur; Sirvan, Levent; Doganay, Melike

    2014-01-01

    To assess the role of sonographic endometrial thickness and hysteroscopic polyp size in predicting premalignant and malignant polyps in postmenopausal women. A total of 328 postmenopausal women with abnormal uterine bleeding and thickened endometrium underwent operative hysteroscopy due to detection of endometrial polyps were included in this retrospective study. Preoperative endometrial thickness measured by transvaginal ultrasonography and polyp size on hysteroscopy were noted. Hysteroscopic resection with histology was performed for endometrial polyps. Endometrial thickness and polyp size were evaluated on the basis of final diagnosis established by histologic examination. Receiver operator characteristic curves were calculated to assess the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of endometrial thickness and polyp size for detecting premalignant and malignant polyps. Premalignant and malignant polyps were identified in 26 (7.9%) of cases. Sonographic measurement showed a greater endometrial thickness in cases of premalignant and malignant polyps when compared to benign polyps. On surgical hysteroscopy, premalignant and malignant polyps were also larger. Endometrial thickness demonstrated a sensitivity of 53.8%, specificity of 85.8%, PPV of 24.6% and NPV of 95.6% at a cut-off limit of 11.5 mm with diagnostic accuracy of 83.2%. Polyp size has a diagnostic accuracy of 94.8% with a sensitivity of 92.3%, specificity of 95.0%, PPV of 61.5% and NPV of 99.3% at a cut-off point of 19.5mm. Endometrial thickness measured by transvaginal ultrasonography is not sufficient in predicting premalignant and malignant endometrial polyps in postmenopausal women with abnormal uterine bleeding and thickened endometrium. Polyp size on hysteroscopy is a more accurate parameter, because of better sensitivity and specificity. However, while polyp size ≥ 19.5mm seems to have a great accuracy for predicting premalignancy and

  12. Elastic Deformation Properties of Implanted Endobronchial Wire Stents in Benign and Malignant Bronchial Disease: A Radiographic In Vivo Evaluation

    SciTech Connect

    Hautmann, Hubert; Rieger, Johannes; Huber, Rudolf M.; Pfeifer, Klaus J.

    1999-03-15

    Purpose: To evaluate the long-term mechanical behavior in vivo of expandable endobronchial wire stents, we imaged three different prostheses in the treatment of tracheobronchial disease. Methods: Six patients with bronchial stenoses (three benign, three malignant) underwent insertion of metallic stents. Two self-expandable Wallstents, two balloon-expandable tantalum Strecker stents and two self-expandable nitinol Accuflex stents were used. Measurements of deformation properties were performed during voluntary cough by means of fluoroscopy, at 1 month and 7-10 months after implantation. The procedures were videotaped, their images digitized and the narrowing of stent diameters calculated at intervals of 20 msec. Results: After stent implantation all patients improved with respect to ventilatory function. Radial stent narrowing during cough reached 53% (Wallstent), 59% (tantalum Strecker stent), and 52% (nitinol Accuflex stent) of the relaxed post-implantation diameter. Stent compression was more marked in benign compared with malignant stenoses. In the long term permanent deformation occurred with the tantalum Strecker stents; the other stents were unchanged. Conclusion: Endobronchial wire stents can be helpful in the treatment of major airway collapse and obstructing bronchial lesions. However, evidence of material fatigue as a possible effect of exposure to recurrent mechanical stress on the flexible mesh tube may limit their long-term use. This seems to be predominantly important in benign bronchial collapse.

  13. A rare case of multiple bronchial artery aneurysms associated with a double aortic arch

    PubMed Central

    Mahmood, Rameysh Danovani; Chen, Zhi Yong; Low, Teck Boon; Ng, Keng Sin

    2015-01-01

    Bronchial artery aneurysm is uncommon, and the occurrence of multiple aneurysms arising from a bronchial artery is even rarer. To date, there has been only one published case report describing double bronchial artery aneurysms. We herein describe a case of three aneurysms arising from a left bronchial artery, accompanied by multiple bilateral hypertrophied bronchial and intercostobronchial arteries, as well as a double aortic arch. Bronchial artery aneurysm is potentially life-threatening, and immediate treatment is recommended to minimise the potential risk of rupture. The aneurysms in our case were successfully treated via transcatheter arterial embolisation using coils. PMID:25820859

  14. [Effects of high altitude on bronchial asthma].

    PubMed

    Schultze-Werninghaus, G

    2008-03-01

    Sojourns in the high mountains have been recommended to patients with asthma for many decades. It is the aim of this contribution to summarise the published studies about the effects of a stay at > 1500 m above sea level on asthmatic patients. These data from 428 adolescent and adult patients indicate an improvement of asthma symptoms and lung function during sojourns at high altitude. In many patients a reduction of the steroid therapy was achievable. Profound changes in the immune system have been demonstrated at high altitude, with a reduction of B- and T-helper cell activation. Total and mite-specific immunoglobulin E antibodies decrease significantly during longer sojourns. These changes are associated with a reduction of airway inflammation (e. g., reduction of eosinophil activation, NO exhalation and bronchial hyper-responsiveness). The fact that also patients with non-allergic asthma demonstrate a reduction of their airway inflammation at high altitude suggests that the high altitude climate has beneficial effects on asthma beyond the effects of allergen avoidance. High UV exposure and low humidity could be important additional factors, to explain the reductions in asthma severity in the high mountain climate. Larger controlled studies should be performed to prove the positive effects of the high altitude climate on asthma.

  15. Delphi project in bronchial asthma. Two stages.

    PubMed

    Fernández-Benítez, M; Ibero Iborra, M; Sanz Ortega, J; Garde Garde, J

    2010-01-01

    From the paediatric point of view, we have undertaken two Delphi studies into bronchial asthma. The first is related to the consensus known as the consensus document of the five associations. The second is more recent and has been undertaken with GEMA (the Spanish Guidelines on the Management of Asthma). The aim of this paper is to carry out a descriptive study comparing the 2 Delphi processes and to objectively assess if in some way behaviour over the past two years has changed as far as expert opinion is concerned. In the consensus document those points giving rise to most controversy were the treatment of children under three years of age and treatment with immunotherapy in allergic asthma. It is also necessary to highlight how important it was at that particular point in time to define the phenotypes of wheezing and the predictive index of asthma in children of less than 3 years of age. Of the 52 questions in the questionnaire, in 13.6% the panel of experts reached no consensus in their positions. Following GEMA the Delphi methodology, 56 questions were asked in the first round of the questionnaire, and consensus was reached in 87.5%. As regards the paediatric part relating to diagnosis and treatment in children, agreement was reached on all the questions in the first round. Agreement was reached in 8.92% questions in the second round. Clinical guidelines and consensus documents can modify behaviour towards an illness, both in the diagnosis and treatment.

  16. Effect of acupuncture on bronchial asthma.

    PubMed

    Yu, D Y; Lee, S P

    1976-11-01

    1. Needle acupuncture was performed at three sites in twenty patients in a clinical attack of bronchial asthma. 2. In all patients the symptoms of bronchoconstriction improved during the attacks when the correct site was stimulated, and in five patients wheezing was abolished. 3. Stimulation at the correct site produced a significant increase in the mean FEV1-0 (58%) and FVC (29%) but not in maximal mid-expiratory flow rate (MMFR; 76%), when compared with the findings before acupuncture, along with a significant fall in the Pa,CO2 and an insignificant fall in Pa,O2. A mild tachycardia was also observed. 4. After acupuncture a greater improvement in FEV1-0, FVC and MMFR was produced by inhalation of isoprenaline. 5. No significant changes in FEV1-0, FVC, MMFR, pulse rate or arterial blood gas tensions occurred after acupuncture at control sites. 6. In four of the patients during clinical remission acupuncture was performed before and after histamine aerosol challenge, but there was no effect on either the severity or the duration of the histamine-induced bronchoconstriction. 7. It is concluded that acupunture probably reduced the reflex component of the bronchoconstriction, but failed to influence direct smooth muscle constriction caused by histamine.

  17. Comparison of molecular abnormalities in bronchial brushings and tumor touch preparations.

    PubMed

    Barkan, Güliz A; Caraway, Nancy P; Jiang, Feng; Zaidi, Tanweer M; Fernandez, Ricardo; Vaporcyin, Ara; Morice, Rodolfo; Zhou, Xian; Bekele, Benjamin Nebiyou; Katz, Ruth L

    2005-02-25

    Preneoplastic lung lesions and early-stage lung carcinomas are associated with molecular abnormalities. The authors performed a pilot study to evaluate the use of DNA fluorescence in situ hybridization (FISH) probes to ascertain whether these biomarkers can predict nonsmall cell lung carcinoma (NSCLC). Fourteen bronchial brushings ipsilateral to the tumor (BB/Ts), tumor touch imprints, and touch imprints of the bronchus adjacent to the tumor obtained from 15 patients with early-stage NSCLC were analyzed. The LAVysion multicolor probe set consisting of probes to 5p15, 6, 7p12, and 8q2 and the in-house probes 3p22.1 and 10q22 was used. Using the LAVysion multicolor probe set, 25 epithelial cells were counted and considered positive if > 5 cells were abnormal. Using 3p22.1 and 10q22, > or = 100 nuclei per slide were scored. The results were tabulated as the percentage of cells with deletions compared with the centromeric probes 3 and 10. Greater than 2% of the deletions were positive for 3p22.1 and 10q22. Bronchial washings from patients without lung tumors were used as controls. The BB/Ts were negative for malignant cells by cytologic evaluation and the LAVysion probe set; however, the combined in-house probes for 3p22.1 and 10q22 tested on BB/Ts predicted cancer in 100% of cancer patients. FISH positivity in the lung cancers was 100% for 3p22.1 deletions, 79% for 10q22 deletions, and 57% for LAVysion probes. When compared with the bronchial epithelium, tumor cells showed a 3.7-fold excess of 3p22.1 deletions, a 2-fold excess of 10q22 deletions, and a 12.6-fold excess of abnormal cells. The current study indicated that detection of molecular abnormalities in bronchial epithelial cells via FISH was very useful in identifying patients at high risk for developing lung carcinoma. The molecular abnormalities identified in the BB/Ts were detected at elevated levels in the tumor specimens. 2004 American Cancer Society

  18. High wavenumber Raman spectroscopy in the characterization of urinary metabolites of normal subjects, oral premalignant and malignant patients

    NASA Astrophysics Data System (ADS)

    Brindha, Elumalai; Rajasekaran, Ramu; Aruna, Prakasarao; Koteeswaran, Dornadula; Ganesan, Singaravelu

    2017-01-01

    Urine has emerged as one of the diagnostically potential bio fluids, as it has many metabolites. As the concentration and the physiochemical properties of the urinary metabolites may vary under pathological transformation, Raman spectroscopic characterization of urine has been exploited as a significant tool in identifying several diseased conditions, including cancers. In the present study, an attempt was made to study the high wavenumber (HWVN) Raman spectroscopic characterization of urine samples of normal subjects, oral premalignant and malignant patients. It is concluded that the urinary metabolites flavoproteins, tryptophan and phenylalanine are responsible for the observed spectral variations between the normal and abnormal groups. Principal component analysis-based linear discriminant analysis was carried out to verify the diagnostic potentiality of the present technique. The discriminant analysis performed across normal and oral premalignant subjects classifies 95.6% of the original and 94.9% of the cross-validated grouped cases correctly. In the second analysis performed across normal and oral malignant groups, the accuracy of the original and cross-validated grouped cases was 96.4% and 92.1% respectively. Similarly, the third analysis performed across three groups, normal, oral premalignant and malignant groups, classifies 93.3% and 91.2% of the original and cross-validated grouped cases correctly.

  19. Bronchial reactivity to histamine before and after sodium cromoglycate in bronchial asthma.

    PubMed Central

    Kang, B; Townley, R G; Lee, C K; Miller Kolotkin, B

    1976-01-01

    Out of 19 patients with extrinsic bronchial asthma challenged with 123 mug histamine acid phosphate by intravenous infusion only 13 responded with a fall in FEV1 of over 10% (mean 16%). Seventeen of these patients were given histamine 2 mg/ml by aerosol, and all responded with a mean decrease in FEV1 of 37.8%. When challenged with allergen extract by aerosol the mean decrease in FEV1 was 37.5%. After 40 mg sodium cromoglycate 15 of the 17 patients showed significant protection against allergen challenge with a mean decrease in FEV1 of only 23.6%. Inhalation of 40 mg sodium cromoglycate, however, failed to protect against histamine given by either the intravenous or aerosol route. Histamine given intravenously to asthmatic patients produces less of a bronchial response than when given by aerosol, even though the intravenous route produces many more systemic symptoms, such as flushing and throbbing headache. The protection of sodium cromoglycate against an allergen inhalation challenge is not due to histamine antagonsim. PMID:816411

  20. Determining bronchial morphology for the purposes of segregating so-called heterotaxy.

    PubMed

    Loomba, Rohit S; Pelech, Andrew N; Shah, Parinda H; Anderson, Robert H

    2016-04-01

    Introduction Heterotaxy is a unique clinical entity in which lateralisation of the thoraco-abdominal organs is abnormal, typically with isomerism of the bronchial tree and atrial appendages. This study was carried out to determine whether routine clinical imaging such as chest radiographs, angiographic images, and CT/MRI can determine bronchial isomerism, and how sidedness of bronchial isomerism correlates with overall features anticipated in hearts with isomeric atrial appendages. Methods and results We identified 73 patients with heterotaxy, in whom imaging clearly demonstrated the bronchial tree, seen at our institution since 1998. We calculated bronchial angles and lengths using all the available imaging modalities to determine the presence and sidedness of bronchial isomerism. This was then compared with the anticipated presence of isomeric atrial appendages based on the overall clinical findings, as the appendages themselves had not specifically been imaged. The ratio of bronchial lengths revealed bronchial isomerism in all patients, with bronchial angles permitting distinction of right as opposed to left isomerism. We noted discordances between the identified bronchial isomerism and the presumed arrangement of the atrial appendages in nearly 20% of the patients in our cohort. Routine clinical imaging with chest radiographs, angiographic imaging, and CT/MRI can determine the presence of bronchial isomerism in patients with so-called heterotaxy. Right as opposed to left isomerism can be distinguished based on bronchial angles. The finding of bronchial isomerism correlates well, but not totally, with the presumed isomerism of the atrial appendages as predicted from the identified intra-cardiac morphology.

  1. Herniation of unruptured tuberculous lung abscess into chest wall without pleural or bronchial spillage

    PubMed Central

    Magazine, Rahul; Mohapatra, Aswini K.; Manu, Mohan K.; Srivastava, Rajendra K.

    2011-01-01

    A 22-year-old unmarried man presented to the chest outpatient department with a history of productive cough of two-month duration. He also complained of pain and swelling on the anterior aspect of right side of chest of one-month duration. Imaging studies of the thorax, including chest roentgenography and computerized tomography, revealed an unruptured lung abscess which had herniated into the chest wall. Culture of pus aspirated from the chest wall swelling grew Mycobacterium tuberculosis. He was diagnosed to have a tuberculous lung abscess which had extended into the chest wall, without spillage into the pleural cavity or the bronchial tree. Antituberculosis drugs were prescribed, and he responded to the treatment with complete resolution of the lesion. PMID:22084547

  2. Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies.

    PubMed

    Hellner, Karin; Miranda, Fabrizio; Fotso Chedom, Donatien; Herrero-Gonzalez, Sandra; Hayden, Daniel M; Tearle, Rick; Artibani, Mara; KaramiNejadRanjbar, Mohammad; Williams, Ruth; Gaitskell, Kezia; Elorbany, Samar; Xu, Ruoyan; Laios, Alex; Buiga, Petronela; Ahmed, Karim; Dhar, Sunanda; Zhang, Rebecca Yu; Campo, Leticia; Myers, Kevin A; Lozano, María; Ruiz-Miró, María; Gatius, Sónia; Mota, Alba; Moreno-Bueno, Gema; Matias-Guiu, Xavier; Benítez, Javier; Witty, Lorna; McVean, Gil; Leedham, Simon; Tomlinson, Ian; Drmanac, Radoje; Cazier, Jean-Baptiste; Klein, Robert; Dunne, Kevin; Bast, Robert C; Kennedy, Stephen H; Hassan, Bassim; Lise, Stefano; Garcia, María José; Peters, Brock A; Yau, Christopher; Sauka-Spengler, Tatjana; Ahmed, Ahmed Ashour

    2016-08-01

    Current screening methods for ovarian cancer can only detect advanced disease. Earlier detection has proved difficult because the molecular precursors involved in the natural history of the disease are unknown. To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points over three years from a single patient during treatment for high-grade serous ovarian cancer (HGSOC). The functional and clinical significance of the identified mutations was examined using a combination of population-based whole genome sequencing, targeted deep sequencing, multi-center analysis of protein expression, loss of function experiments in an in-vivo reporter assay and mammalian models, and gain of function experiments in primary cultured fallopian tube epithelial (FTE) cells. We identified frequent mutations involving a 40kb distal repressor region for the key stem cell differentiation gene SOX2. In the apparently normal FTE, the region was also mutated. This was associated with a profound increase in SOX2 expression (p<2(-16)), which was not found in patients without cancer (n=108). Importantly, we show that SOX2 overexpression in FTE is nearly ubiquitous in patients with HGSOCs (n=100), and common in BRCA1-BRCA2 mutation carriers (n=71) who underwent prophylactic salpingo-oophorectomy. We propose that the finding of SOX2 overexpression in FTE could be exploited to develop biomarkers for detecting disease at a premalignant stage, which would reduce mortality from this devastating disease.

  3. Effect of pre-cardiac and adult stages of Dirofilaria immitis in pulmonary disease of cats: CBC, bronchial lavage cytology, serology, radiographs, CT images, bronchial reactivity, and histopathology.

    PubMed

    Ray Dillon, A; Tillson, D M; Wooldridge, A; Cattley, R; Hathcock, J; Brawner, W R; Cole, R; Welles, B; Christopherson, P W; Lee-Fowler, T; Bordelon, S; Barney, S; Sermersheim, M; Garbarino, R; Wells, S Z; Diffie, E B; Schachner, E R

    2014-11-15

    A controlled, blind study was conducted to define the initial inflammatory response and lung damage associated with the death of precardiac stages of Dirofilaria immitis in cats as compared to adult heartworm infections and normal cats. Three groups of six cats each were used: UU: uninfected untreated controls; PreS I: infected with 100 D. immitis L3 by subcutaneous injection and treated topically with selamectin 32 and 2 days pre-infection and once monthly for 8 months); IU: infected with 100 D. immitis L3 and left untreated. Peripheral blood, serum, bronchial lavage, and thoracic radiographic images were collected from all cats on Days 0, 70, 110, 168, and 240. CT images were acquired on Days 0, 110, and 240. Cats were euthanized, and necropsies were conducted on Day 240 to determine the presence of heartworms. Bronchial rings were collected for in vitro reactivity. Lung, heart, brain, kidney, and liver tissues were collected for histopathology. Results were compared for changes within each group. Pearson and Spearman correlations were performed for association between histologic, radiographic, serologic, hematologic and bronchoalveolar lavage (BAL) results. Infected cats treated with selamectin did not develop radiographically evident changes throughout the study, were heartworm antibody negative, and were free of adult heartworms and worm fragments at necropsy. Histologic lung scores and CT analysis were not significantly different between PreS I cats and UU controls. Subtle alveolar myofibrosis was noted in isolated areas of several PreS I cats and an eosinophilic BAL cytology was noted on Days 75 and 120. Bronchial ring reactivity was blunted in IU cats but was normal in PreS I and UU cats. The IU cats became antibody positive, and five cats developed adult heartworms. All cats with heartworms were antigen positive at one time point; but one cat was antibody positive, antigen negative, with viable adult females at necropsy. The CT revealed early involvement

  4. Lung malignancy: Diagnostic accuracies of bronchoalveolar lavage, bronchial brushing, and fine needle aspiration cytology

    PubMed Central

    Sareen, Rateesh; Pandey, C L

    2016-01-01

    Background: Early diagnosis of lung cancer plays a pivotal role in reducing lung cancer death rate. Cytological techniques are safer, economical and provide quick results. Bronchoscopic washing, brushing and fine needle aspirations not only complement tissue biopsies in the diagnosis of lung cancer but also comparable. Objectives: (1) To find out diagnostic yields of bronchioalveolar lavage, bronchial brushings, FNAC in diagnosis of lung malignancy. (2) To compare relative accuracy of these three cytological techniques. (3) To correlate the cytologic diagnosis with clinical, bronchoscopic and CT findings. (4) Cytological and histopathological correlation of lung lesions. Methods: All the patients who came with clinical or radiological suspicion of lung malignancy in two and a half year period were included in study. Bronchoalveolar lavage was the most common type of cytological specimen (82.36%), followed by CT guided FNAC (9.45%) and bronchial brushings (8.19%). Sensitivity, specificity, positive and negative predictive value for all techniques and correlation with histopathology was done using standard formulas. Results: The most sensitive technique was CT FNAC – (87.25%) followed by brushings (77.78%) and BAL (72.69%). CT FNAC had highest diagnostic yield (90.38%), followed by brushings (86.67%) and BAL (83.67%). Specificity and positive predictive value were 100 % each of all techniques. Lowest false negatives were obtained in CT FNAC (12.5%) and highest in BAL (27.3%). Highest negative predictive value was of BAL 76.95 % followed by BB 75.59% and CT FNAC 70.59%. Conclusion: Before administering antitubercular treatment every effort should be made to rule out malignancy. CT FNAC had highest diagnostic yield among three cytological techniques. BAL is an important tool in screening central as well as in accessible lesions. It can be used at places where CT guided FNAC is not available or could not be done due to technical or financial limitations PMID:27890992

  5. [Air distribution in the bronchial tree of human lungs].

    PubMed

    Lai, Wei; Tan, Xiaoping; Pei, Juemin

    2004-04-01

    A three-element model of lumped parameter based on the statistic data of Weible's symmetric model and on the reference anatomic figures of the bronchial tree of the lungs has been proposed using the fluid network theory. It was assumed that the upper five or seven generations of the twenty-four generations of the respiratory airway are asymmetric, while the rest are symmetric. GEAR method was used to solve the ordinary differential equations. The pressure and flow rate distributions in different positions of the lungs during normal respiration and partial bronchial obstruction were compared, respectively. This model has great significance in finding out the air distribution in the human bronchial tree under various physiological and pathological conditions.

  6. Comparison of bronchial washing, brushing and biopsy for diagnosis of pulmonary tuberculosis.

    PubMed

    Palenque, E; Amor, E; Bernaldo de Quiros, J C

    1987-04-01

    The diagnostic yields of bronchial washings, bronchial brushings and lung biopsy specimens were compared in 50 patients with positive Mycobacterium tuberculosis cultures. The number of positive results obtained with cultures of bronchial brushings was significantly higher than that with bronchial washings (p less than 0.001). The histological study of biopsy lung material improved the rate of immediate or rapid diagnosis of tuberculosis (p less than 0.001).

  7. Adjunctive screening devices for oral lesions: their use by Canadian Dental Hygienists and the need for knowledge translation.

    PubMed

    Laronde, D M; Corbett, K K

    2015-12-22

    Screening for oral cancer and other mucosal conditions is a knowledge-to-action objective that should be easy: there is supportive evidence, it is fast and non-invasive, and the oral cavity is easy to visualize. However, over 60% of oral cancers are diagnosed late, when treatment is complex and prognosis poor. Adjunctive screening devices (ASDs), e.g. toluidine blue (TB), fluorescence visualization (FV), chemiluminescence (CL) and brush biopsies, were designed to assess risk of oral lesions or aid in identification and localization of oral premalignant and malignant lesions. Little is known on how clinicians feel about using ASDs.

  8. 21 CFR 868.5740 - Tracheal/bronchial differential ventilation tube.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tracheal/bronchial differential ventilation tube.../bronchial differential ventilation tube. (a) Identification. A tracheal/bronchial differential ventilation tube is a device used to isolate the left or the right lung of a patient for anesthesia or...

  9. 21 CFR 868.5740 - Tracheal/bronchial differential ventilation tube.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tracheal/bronchial differential ventilation tube.../bronchial differential ventilation tube. (a) Identification. A tracheal/bronchial differential ventilation tube is a device used to isolate the left or the right lung of a patient for anesthesia or...

  10. 21 CFR 868.5740 - Tracheal/bronchial differential ventilation tube.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tracheal/bronchial differential ventilation tube.../bronchial differential ventilation tube. (a) Identification. A tracheal/bronchial differential ventilation tube is a device used to isolate the left or the right lung of a patient for anesthesia or...

  11. 21 CFR 868.5740 - Tracheal/bronchial differential ventilation tube.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tracheal/bronchial differential ventilation tube.../bronchial differential ventilation tube. (a) Identification. A tracheal/bronchial differential ventilation tube is a device used to isolate the left or the right lung of a patient for anesthesia or...

  12. 21 CFR 868.5740 - Tracheal/bronchial differential ventilation tube.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tracheal/bronchial differential ventilation tube.../bronchial differential ventilation tube. (a) Identification. A tracheal/bronchial differential ventilation tube is a device used to isolate the left or the right lung of a patient for anesthesia or...

  13. Tracheal and bronchial stenoses and other obstructive conditions

    PubMed Central

    Schweiger, Claudia; Cohen, Aliza P.

    2016-01-01

    Although tracheal stenosis and bronchial stenosis are relatively rare in the pediatric population, they are both associated with significant morbidity and mortality. While most cases of congenital tracheal stenosis in children present as complete tracheal rings (CTRs), other congenital tracheal obstructions are also encountered in clinical practice. In addition, acquired obstructive tracheal conditions stemming from endotracheal trauma or previous surgical interventions may occur. Many affected children also have associated cardiovascular malformations, further complicating their management. Optimal management of children with tracheal or bronchial stenoses requires comprehensive diagnostic evaluation and optimization prior to surgery. Slide tracheoplasty has been the operative intervention of choice in the treatment of the majority of these children. PMID:28066618

  14. Isolating bronchial epithelial cell preparations from gross lung specimens.

    PubMed

    Kwon, Yong-Jae; Lee, Seog Joo; Koh, Jae Soo; Kim, Young-Joon; Park, Jong Ho

    2009-10-01

    Tissue microdissection is appropriate for separating pure cells from heterogeneous tissues. Recently, we have focused on whole genome DNA methylation patterns of lung squamous cell carcinoma (SCC) and needed to obtain the appropriate counterpart cells of lung SCC. However, in some regions of human tissues, such as in bronchial epithelium, it is difficult to apply tissue microdissection as a means to isolate pure cells from a heterogenous mixture of cells. Accordingly, we developed the pop brush method to retrieve sufficient amounts of pure bronchial epithelium from gross lung specimens, and this method enables us to study epigenetic variations of lung SCC.

  15. Persistent specific bronchial reactivity to occupational agents in workers with normal nonspecific bronchial reactivity.

    PubMed

    Lemière, C; Cartier, A; Malo, J L; Lehrer, S B

    2000-09-01

    Specific bronchial reactivity (SBR) to common inhalants is related to the degree of nonspecific bronchial reactivity (NSBR) and to specific allergen sensitivity. We investigated 16 workers with normal NSBR who had been previously diagnosed with occupational asthma caused by high-molecular-weight agents. The agents were flour in seven workers, psyllium in five, and guar gum in four. The subjects had been removed from exposure to these agents for a mean of 5.7 (+/- 4.0 SD) yr, no longer showed evidence of persisting asthma, and had a normal lung function. In the present study, the workers were reexposed to the sensitizing agent by specific inhalation challenges, in the same way they were as at the time of the diagnosis, to assess their current SBR to the sensitizer. SBR was estimated as the duration of exposure that induced a 20% decrease in FEV(1). Eleven of the 16 subjects had an asthmatic reaction at the time of the study; the duration of exposure necessary to induce the asthmatic reaction was the same as that needed at the time of diagnosis (3.55 +/- 0.5 min and 4.2 +/- 0.7 min, respectively, p = 0.8). The decrease in specific IgE levels between the two events was much greater in the subjects who failed to react to the second challenge test (from 24.2 +/- 37.5% to 3.0 +/- 16.9% binding) than in those who reacted on both occasions (from 31.2 +/- 27.0% to 21.6 +/- 36.7% binding); however, in both groups the change was significant (p = 0.05 and 0.04, respectively). We conclude that SBR to high-molecular-weight agents persists in most cases despite a normalization of NSBR, and that this persistence is associated with a persistence of specific immunization to the agent.

  16. Characterization of tuberculous lesions in naturally infected African buffalo (Syncerus caffer).

    PubMed

    Laisse, Cláudio J M; Gavier-Widén, Dolores; Ramis, Guillermo; Bila, Custódio G; Machado, Adelina; Quereda, Juan J; Agren, Erik O; van Helden, Paul D

    2011-09-01

    Tuberculosis pathology was studied on 19 African buffalo (Syncerus caffer) from a herd in the Hluhluwe-iMfolozi Park in South Africa. The animals tested positive with the comparative intradermal tuberculin test and were euthanized during a test-and-cull operation to decrease prevalence of bovine tuberculosis (bTB) in the park. The lymph nodes and lungs were examined grossly for presence of tuberculous lesions, which were scored on a 0-5 scale for macroscopic changes. The gross lesions were examined histologically and classified into grade I, II, III, or IV according to a grading system used for bTB lesions in domestic cattle. Macroscopic lesions were limited to the retropharyngeal, bronchial, and mediastinal lymph nodes and the lungs. The most frequently affected lymph nodes were the bronchial (in 16 animals) and mediastinal (in 11 animals). All four grades of microscopic lesions were observed, grade II lesions were the most frequent. Mycobacterium bovis was detected by PCR in 8 out of 19 animals, and acid-fast bacilli were seen in 7 out of 19 animals, together both techniques identified mycobacteria in 5 out of 19 animals. Lesions were paucibacillary, as acid-fast bacilli were only rarely observed. The absence of lesions in the mesenteric lymph nodes and the high frequency of lesions in respiratory tract associated lymph nodes suggest that the main route of M. bovis infection in African buffalo is by inhalation.

  17. Neo-angiogenesis and the premalignant micro-circulatory augmentation of early colon carcinogenesis.

    PubMed

    Tiwari, Ashish K; Crawford, Susan E; Radosevich, Andrew; Wali, Ramesh K; Stypula, Yolanda; Kunte, Dhananjay P; Mutyal, Nikhil; Ruderman, Sarah; Gomes, Andrew; Cornwell, Mona L; De La Cruz, Mart; Brasky, Jeffrey; Gibson, Tina P; Backman, Vadim; Roy, Hemant K

    2011-07-28

    Spectroscopic techniques have demonstrated that in the microscopically normal mucosa, there is an increase in mucosal micro-circulation in patients harboring neoplasia elsewhere in the colon (i.e. marker of field carcinogenesis). However, the physiological and molecular basis of this early increase in blood supply (EIBS) has not been elucidated. We, therefore, investigated the microvessel density (MVD) and angiogenic gene expression in the premalignant colonic mucosa from the well-validated azoxymethane (AOM)-treated rat experimental model of colon carcinogenesis. Fisher 344 rats were treated with AOM (15 mg/kg i.p.) or saline and euthanized 14 weeks later (a time-point that precedes carcinoma development). Colon sections were studied for MVD via immunohistochemical assessment for CD31 and location was compared with optical assessment of mucosal hemoglobin with low-coherence enhanced backscattering spectroscopy (LEBS). Finally, we performed a pilot real-time PCR angiogenesis microarray (84 genes) from the microscopically normal colonic mucosa of AOM and age-matched saline treated rats. AOM treatment increased MVD in both the mucosa and submucosa of the rats (125% increase in mucosa; p<0.007, and 96% increase in submucosa; p<0.02) but the increase was most pronounced at the cryptal base consistent with the LEBS data showing maximal hemoglobin augmentation at 200-225 μm depth. Microarray analysis showed striking dysregulation of angiogenic and anti-angiogenic factors. We demonstrate, for the first time, that neo-angiogenesis occurs in the microscopically normal colonic mucosa and was accentuated at the bottom of the crypt. This finding has potential implications as a biomarker for risk-stratification and target for chemoprevention. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. Neo-Angiogenesis and the Premalignant Micro-Circulatory Augmentation of Early Colon Carcinogenesis

    PubMed Central

    Tiwari, Ashish K.; Crawford, Susan E.; Radosevich, Andrew; Wali, Ramesh K.; Stypula, Yolanda; Kunte, Dhananjay P.; Mutyal, Nikhil; Ruderman, Sarah; Gomes, Andrew; Cornwell, Mona L; De La Cruz, Mart; Brasky, Jeffrey; Gibson, Tina; Backman, Vadim; Roy, Hemant K.

    2013-01-01

    Spectroscopic techniques have demonstrated that in the microscopically normal mucosa, there is an increase in mucosal micro-circulation in patients harboring neoplasia elsewhere in the colon (i.e. marker of field carcinogenesis). However, the physiological and molecular basis of this early increase in blood supply (EIBS) has not been elucidated. We, therefore, investigated the microvessel density (MVD) and angiogenic gene expression in the premalignant colonic mucosa from the well-validated azoxymethane (AOM)-treated rat experimental model of colon carcinogenesis. Fisher 344 rats were treated with AOM (15 mg/kg i.p.) or saline and euthanized 14 weeks later (a time-point that precedes carcinoma development). Colon sections were studied for MVD via immunohistochemical assessment for CD31 and location was compared with optical assessment of mucosal hemoglobin with low-coherence enhanced backscattering spectroscopy (LEBS). Finally, we performed a pilot real-time PCR angiogenesis microarray (84 genes) from the microscopically normal colonic mucosa of AOM and age-matched saline treated rats. AOM treatment increased MVD in both the mucosa and submucosa of the rats (125% increase in mucosa; p<0.007, and 96% increase in submucosa; p<0.02) but the increase was most pronounced at the cryptal base consistent with the LEBS data showing maximal hemoglobin augmentation at 200-225μm depth. Microarray analysis showed striking dysregulation of angiogenic and anti-angiogenic factors. We demonstrate, for the first time, that neo-angiogenesis occurs in the microscopically normal colonic mucosa and was accentuated at the bottom of the crypt. This finding has potential implications as a biomarker for risk-stratification and target for chemoprevention. PMID:21493000

  19. Human mammary cancer progression model recapitulates methylation events associated with breast premalignancy.

    PubMed

    Dumont, Nancy; Crawford, Yongping G; Sigaroudinia, Mahvash; Nagrani, Shefali S; Wilson, Matthew B; Buehring, Gertrude C; Turashvili, Gulisa; Aparicio, Samuel; Gauthier, Mona L; Fordyce, Colleen A; McDermott, Kimberly M; Tlsty, Thea D

    2009-01-01

    We have previously identified a rare subpopulation of variant human mammary epithelial cells (vHMEC) with repressed p16INK4A that exist in disease-free women yet display premalignant properties, suggesting that they have engaged the process of malignant transformation. In order to gain insight into the molecular alterations required for vHMEC to progress to malignancy, and to characterize the epigenetic events associated with early progression, we examined the effect of oncogenic stress on the behavior of these cells. HMEC that express p16INK4A and vHMEC that do not, were transduced with constitutively active Ha-rasV12 and subsequently exposed to serum to determine whether signals from the cellular microenvironment could cooperate with ras to promote the malignant transformation of vHMEC. Epigenetic alterations were assessed using methylation-specific polymerase chain reaction (PCR). vHMEC expressing Ha-rasV12 (vHMEC-ras) bypassed the classic proliferative arrest that has been previously documented in normal fibroblasts following oncogenic stress, and that we also observe here in normal HMEC. Moreover, vHMEC-ras cells exhibited many additional alterations that are observed during progression to malignancy such as the generation of chromosomal abnormalities, upregulation of telomerase activity, immortalization following exposure to serum, and anchorage-independent growth, but they did not form tumors following orthotopic injection in vivo. Associated with their early progression to malignancy was an increase in the number of genes methylated, two of which (RASSF1A and SFRP1) were also methylated in other immortalized mammary cell lines as well as in breast cancer cells and tissues. We have characterized a mammary progression model that recapitulates molecular and methylation alterations observed in many breast cancers. Our data suggest that concomitant methylation of RASSF1A and SFRP1 marks an early event in mammary transformation and may thus have prognostic

  20. Human mammary cancer progression model recapitulates methylation events associated with breast premalignancy

    PubMed Central

    2009-01-01

    Introduction We have previously identified a rare subpopulation of variant human mammary epithelial cells (vHMEC) with repressed p16INK4A that exist in disease-free women yet display premalignant properties, suggesting that they have engaged the process of malignant transformation. In order to gain insight into the molecular alterations required for vHMEC to progress to malignancy, and to characterize the epigenetic events associated with early progression, we examined the effect of oncogenic stress on the behavior of these cells. Methods HMEC that express p16INK4A and vHMEC that do not, were transduced with constitutively active Ha-rasV12 and subsequently exposed to serum to determine whether signals from the cellular microenvironment could cooperate with ras to promote the malignant transformation of vHMEC. Epigenetic alterations were assessed using methylation-specific polymerase chain reaction (PCR). Results vHMEC expressing Ha-rasV12 (vHMEC-ras) bypassed the classic proliferative arrest that has been previously documented in normal fibroblasts following oncogenic stress, and that we also observe here in normal HMEC. Moreover, vHMEC-ras cells exhibited many additional alterations that are observed during progression to malignancy such as the generation of chromosomal abnormalities, upregulation of telomerase activity, immortalization following exposure to serum, and anchorage-independent growth, but they did not form tumors following orthotopic injection in vivo. Associated with their early progression to malignancy was an increase in the number of genes methylated, two of which (RASSF1A and SFRP1) were also methylated in other immortalized mammary cell lines as well as in breast cancer cells and tissues. Conclusions We have characterized a mammary progression model that recapitulates molecular and methylation alterations observed in many breast cancers. Our data suggest that concomitant methylation of RASSF1A and SFRP1 marks an early event in mammary

  1. Use of 90° Hopkin's Telescopic Examination as an OPD Tool to Clinically Evaluate and Record Oral Cavity Lesions: Our Experience in Early Detection, Especially in Patients with Limited Mouth Opening.

    PubMed

    Mandlik, Dushyant; Gupta, Karan; Patel, Daxesh; Patel, Purvi; Toprani, Rajendra; Patel, Kaustubh

    2015-06-01

    Restricted mouth opening due to premalignant lesions like oral sub-mucous fibrosis, malignancies of oral cavity and postoperative status is very common in Indian patients. It is very difficult to evaluate, document and biopsy the lesions due to inability to access, vast area and diversity of premalignant lesions and subject variations. 90° Hopkin's slender out-patient examination telescope was found useful tool in this. The aim of the study was to evaluate the use of magnified view and reach of a slender telescope to document and examine the oral cavity for any premalignant and malignant lesions, especially for patients with restricted mouth opening and to study its impact on management. A 90(0) Hopkin's telescope was used to evaluate and document oral cavity examination in the Out Patients Department (OPD). The data of first 2000 patients was analysed. Difficult to reach areas, where mouth opening was severely restricted was the significant subset. A total of 1394 patients approached OPD for primary diagnosis at our tertiary cancer care centre. Six hundred and six patients were the ones in follow up after treatment in form of Surgery, Chemotherapy or Radiotherapy, or combination. Five twenty three patients (of 1394) with mouth opening ≤ 20mm formed the study group. Telescope guided biopsies were also taken in 50 patients from 56 sites. Serial recordings were compared objectively in premalignant, treatment evaluation and close watch groups. An increase of 5.6% in rate of diagnosis of malignancy was made possible with the help of telescopic examination in patients with mouth opening ≤ 20mm. A 90(0) Hopkin's telescopic examination is a useful tool to evaluate and record oral cavity lesions, especially in patients with restricted mouth openings. It is a useful tool for screening high risk group, giving definite advantage of objective evaluation and recording of the lesion. It can also be used to objectively evaluate response of neo-adjuvant chemotherapy and as a

  2. Office-based biopsies for laryngeal lesions: Analysis of consecutive 581 cases.

    PubMed

    Cha, Wonjae; Yoon, Byung-Woo; Jang, Jeon Yeob; Lee, Jin Choon; Lee, Byung Joo; Wang, Soo-Geun; Cho, Jae Keun; Cho, Ilyoung

    2016-11-01

    Office-based biopsy (OBB) is widely used to diagnose suspicious laryngeal lesions. However, its routine use is still controversial and the algorithm for clinical strategy is not concrete. We tried to evaluate the accuracy of OBB as a diagnostic tool for laryngeal malignancy. Medical data of 581 patients undergoing OBB were reviewed. Diagnostic values of OBB were analyzed for malignancy and malignancy/premalignancy. False negative rates (FNRs) were analyzed according to subsites, lesion sizes, and morphology. The collection rate of adequate specimens was 99.1%, and there were no complications during OBB. The false omission rates for malignancy of benign lesion; mild, moderate, and severe dysplasia; and carcinoma in situ (CIS) were 5.1%, 11.9%, 14.3%, 50.0%, and 100.0%, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for malignancy in OBB were 78.2%, 100.0%, 100.0%, and 87.3%, respectively. Those for malignancy/premalignancy in OBB were 88.2%, 86.7%, 85.7%, and 89.1%, respectively. The high FNRs were reported in glottis lesions (27.0%) and small lesions below 1 cm (27.5%). Morphologically fungating lesions showed low FNR (9.1%) compared to nonfungating ones. Office-based biopsy could be used as an initial diagnostic tool for laryngeal malignancy for early detection and avoidance of general anesthesia. However, operative re-biopsy should be considered when severe dysplasia or CIS were reported in OBB, or when the lesions are clinically suspicious for malignancy. 4. Laryngoscope, 126:2513-2519, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  3. Cystic lesions in the pancreas: when to watch, when to resect.

    PubMed

    Balcom IV, J H; Fernandez-Del Castillo, C; Warshaw, A L

    2000-04-01

    The diagnosis of cystic lesions in the pancreas is becoming more common, largely due to the increases in diagnostic imaging done for other reasons. This review considers pseudocysts, mucinous cystic neoplasms, intraductal papillary mucinous tumors, and serous cystadenomas in some detail. The emphasis is on the fact that, through a careful history, physical examination, radiologic studies, and, often, cyst fluid analysis, a diagnosis can be reached expeditiously. This pursuit is important because two thirds of pancreatic cystic neoplasms are malignant or premalignant and should be resected, whereas pseudocysts and serous cystadenomas are benign, and, depending on the case, may be treated through observation, resection, or, for pseudocysts, by internal drainage.

  4. Processing bronchial sonograms to detect respiratory cycle fragments

    NASA Astrophysics Data System (ADS)

    Bureev, A. Sh; Zhdanov, D. S.; Zemlyakov, I. Yu; Svetlik, M. V.

    2014-10-01

    This article describes the authors' results of work on the development of a method for the automated assessment of the state of the human bronchopulmonary system based on acoustic data. In particular, the article covers the method of detecting breath sounds on bronchial sonograms obtained during the auscultation process.

  5. Accurate 3D quantification of the bronchial parameters in MDCT

    NASA Astrophysics Data System (ADS)

    Saragaglia, A.; Fetita, C.; Preteux, F.; Brillet, P. Y.; Grenier, P. A.

    2005-08-01

    The assessment of bronchial reactivity and wall remodeling in asthma plays a crucial role in better understanding such a disease and evaluating therapeutic responses. Today, multi-detector computed tomography (MDCT) makes it possible to perform an accurate estimation of bronchial parameters (lumen and wall areas) by allowing a quantitative analysis in a cross-section plane orthogonal to the bronchus axis. This paper provides the tools for such an analysis by developing a 3D investigation method which relies on 3D reconstruction of bronchial lumen and central axis computation. Cross-section images at bronchial locations interactively selected along the central axis are generated at appropriate spatial resolution. An automated approach is then developed for accurately segmenting the inner and outer bronchi contours on the cross-section images. It combines mathematical morphology operators, such as "connection cost", and energy-controlled propagation in order to overcome the difficulties raised by vessel adjacencies and wall irregularities. The segmentation accuracy was validated with respect to a 3D mathematically-modeled phantom of a pair bronchus-vessel which mimics the characteristics of real data in terms of gray-level distribution, caliber and orientation. When applying the developed quantification approach to such a model with calibers ranging from 3 to 10 mm diameter, the lumen area relative errors varied from 3.7% to 0.15%, while the bronchus area was estimated with a relative error less than 5.1%.

  6. Congenital bronchial atresia with regional emphysema associated with pectus excavatum.

    PubMed Central

    van Klaveren, R J; Morshuis, W J; Lacquet, L K; Cox, A L; Festen, J; Heystraten, F M

    1992-01-01

    Two cases of congenital bronchial atresia with pectus excavatum are reported. Costosternal retraction during the efforts to overcome the airway obstruction due to encroachment on normal lung tissue by the hyperinflated segments may play a part in causing pectus excavatum. Images PMID:1494776

  7. Inhaled Mannitol as a Laryngeal and Bronchial Provocation Test.

    PubMed

    Tay, Tunn Ren; Hoy, Ryan; Richards, Amanda L; Paddle, Paul; Hew, Mark

    2017-03-01

    Timely diagnosis of vocal cord dysfunction (VCD), more recently termed "inducible laryngeal obstruction," is important because VCD is often misdiagnosed as asthma, resulting in delayed diagnosis and inappropriate treatment. Visualization of paradoxical vocal cord movement on laryngoscopy is the gold standard for diagnosis, but is limited by poor test sensitivity. Provocation tests may improve the diagnosis of VCD, but the diagnostic performance of current tests is less than ideal. Alternative provocation tests are required. This pilot study demonstrates the feasibility of using inhaled mannitol for concurrent investigation of laryngeal and bronchial hyperresponsiveness. Consecutive patients with suspected VCD seen at our institution's asthma clinic underwent flexible laryngoscopy at baseline and following mannitol challenge. VCD was diagnosed on laryngoscopy based on inspiratory adduction, or >50% expiratory adduction of the vocal cords. Bronchial hyperresponsiveness after mannitol challenge was also assessed. We evaluated the interrater agreement of postmannitol laryngoscopy between respiratory specialists and laryngologists. Fourteen patients with suspected VCD in the context of asthma evaluation were included in the study. Mannitol provocation demonstrated VCD in three of the seven patients with normal baseline laryngoscopy (42.9%). Only two patients had bronchial hyperresponsiveness. There was substantial interrater agreement between respiratory specialists and laryngologists, kappa = 0.696 (95% confidence interval: 0.324-1) (P = 0.006). Inhaled mannitol can be used to induce VCD. It is well tolerated and can evaluate laryngeal and bronchial hyperresponsiveness at the same setting. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  8. A modified bronchial anastomosis technique for lung transplantation.

    PubMed

    Schröder, Carsten; Scholl, Frank; Daon, Emmanuel; Goodwin, Andrea; Frist, William H; Roberts, John R; Christian, Karla G; Ninan, Mathew; Milstone, Aaron P; Loyd, James E; Merrill, Walter H; Pierson, Richard N

    2003-06-01

    Low rates of major complications have been reported for the intussuscepting bronchial anastomotic technique but stenosis, malacia, and granulation tissue at the anastomosis may cause clinically important morbidity. We hypothesized that a modification of the telescoping technique that improves bronchial wall apposition might be associated with improved bronchial healing and clinical outcomes. The telescoping horizontal mattress "U-stitch" suture technique was modified to incorporate figure-of-eight sutures placed in the cartilaginous wall between each of three intussuscepting U stitches. Serial videotape records of 152 individual anastomoses (99 modified, 53 telescoped) in 118 consecutive operative survivors were retrospectively reviewed by examiners blinded with respect to technique used. Stenosis, airway instability, mucosa quality, and devascularized luminal tissue were graded at 4 to 14 days (initial), 4 to 12 weeks (early), and 6 to 12 months (late) after transplantation. The incidence of anastomotic stenosis was significantly lower using the modified technique at the initial (p = 0.025) and late (p = 0.015) observations. In the initial phase airway instability (p = 0.015) and devascularization grades (p = 0.001) were also significant lower in the modified group. There were no significant differences in mucosal condition between techniques. The modified telescoping technique was associated with significant survival advantage (mean 17.7%; p = 0.029) by multivariate analysis. The incidence of major airway complications (dehiscences and stenoses required stents) tended to be lower (3% versus 6%) in the modified group. The modified telescoping bronchial anastomosis technique is associated with improved early and late bronchial healing and higher 5-year survival without increased major airway complications.

  9. PERSISTENCE OF BRONCHIAL DYSPLASIA IS ASSOCIATED WITH DEVELOPMENT OF INVASIVE SQUAMOUS CELL CARCINOMA

    PubMed Central

    Merrick, Daniel T.; Gao, Dexiang; Miller, York E.; Keith, Robert L.; Baron, Anna E.; Feser, William; Kennedy, Timothy C.; Blatchford, Patrick J.; Braudrick, Sarah; Hirsch, Fred R.; Heasley, Lynn; Bunn, Paul A.; Franklin, Wilbur A.

    2015-01-01

    Background Bronchial dysplasia (BD), a presumed precursor of pulmonary squamous cell carcinoma (SCC), rarely progresses to invasive cancer. A high risk cohort at the University of Colorado provided an opportunity to directly sample airway epithelium at mapped sites on successive bronchoscopies. We have hypothesized that persistent dysplastic lesions showing a similar or higher level of dysplasia on follow-up biopsy, are associated with increased risk for the development of SCC. Methods and Material Endoscopic biopsies from 188 high risk subjects were histologically classified according to the current WHO classification for BD utilizing a numeric histology score ranging from 1-8 representing normal bronchial mucosa through invasive lung cancer. Differences in follow-up histology scores were compared between sites classified by clinical, histologic and immunohistochemical variables. Results Subjects with a higher frequency of sites that persist or progress to high grade dysplasia (≥37.5% persist/progress, N=35 versus <37.5% persist/progress, N=114) show a significant association with development of incident invasive SCC (adjusted hazard ratio: 7.84; 95% confidence interval: 1.56, 39.39), and those with incident lung SCC have adjusted mean follow-up histology scores 1.55 units higher than in subjects without lung cancer. Current smoking, elevated Ki-67 growth fraction, histologic features of angiogenic squamous dysplasia (ASD) and higher histology score in baseline biopsies are significantly associated with increased follow up histology scores. Conclusions These results show that persistent BD is associated with the development of invasive SCC. Furthermore, increased expression of Ki-67, the presence of angiogenic change and degree of baseline atypia are associated with persistence of BD. PMID:26542061

  10. Bronchial thermoplasty for moderate or severe persistent asthma in adults.

    PubMed

    Torrego, Alfons; Solà, Ivan; Munoz, Ana Maria; Roqué I Figuls, Marta; Yepes-Nuñez, Juan Jose; Alonso-Coello, Pablo; Plaza, Vicente

    2014-03-03

    Bronchial thermoplasty is a procedure that consists of the delivery of controlled radiofrequency-generated heat via a catheter inserted into the bronchial tree of the lungs through a flexible bronchoscope. It has been suggested that bronchial thermoplasty works by reducing airway smooth muscle, thereby reducing the ability of the smooth muscle to bronchoconstrict. This treatment could then reduce asthma symptoms and exacerbations, resulting in improved asthma control and quality of life. To determine the efficacy and safety of bronchial thermoplasty in adults with bronchial asthma. We searched the Cochrane Airways Group Specialised Register of Trials (CAGR) up to January 2014. We included randomised controlled clinical trials that compared bronchial thermoplasty versus any active control in adults with moderate or severe persistent asthma. Our primary outcomes were quality of life, asthma exacerbations and adverse events. Two review authors independently extracted data and assessed risk of bias. We included three trials (429 participants) with differences regarding their design (two trials compared bronchial thermoplasty vs medical management and the other compared bronchial thermoplasty vs a sham intervention) and participant characteristics; one of the studies included participants with more symptomatic asthma compared with the others.The pooled analysis showed improvement in quality of life at 12 months in participants who received bronchial thermoplasty that did not reach the threshold for clinical significance (3 trials, 429 participants; mean difference (MD) in Asthma Quality of Life Questionnaire (AQLQ) scores 0.28, 95% confidence interval (CI) 0.07 to 0.50; moderate-quality evidence). Measures of symptom control showed no significant differences (3 trials, 429 participants; MD in Asthma Control Questionnaire (ACQ) scores -0.15, 95% CI -0.40 to 0.10; moderate-quality evidence). The risk of bias for these outcomes was high because two of the studies did not

  11. Treatment of premalignancy: prevention of lymphoma in radiation leukemia virus-inoculated mice by cyclosporin A and immunotoxin.

    PubMed Central

    Yefenof, E; Abboud, G; Epszteyn, S; Vitetta, E S

    1992-01-01

    Radiation leukemia virus (RadLV)-induced preleukemic (PL) latency is characterized by the appearance of virus-infected PL cells in the thymus. The survival of these PL cells is dependent upon autostimulation with interleukin 4 (IL-4). We have intervened prophylactically in RadLV-induced preleukemia by using cyclosporin-A (CSA), which inhibits IL-4 production, and an immunotoxin (ITx) that kills PL cells. CSA efficiently inhibited IL-4 secretion from RadLV-induced PL and leukemic cells, and its administration to PL mice caused a significant delay in their death. An ITx consisting of anti-RadLV glycoprotein-70 (gp70) antibody coupled to ricin A chain efficiently inhibited protein synthesis in virus-infected cells in vitro and, when injected into PL mice, also delayed their death. Combined treatment with CSA and ITx prevented 75% of the treated PL mice from developing lymphoma. These results show that the development of malignancy from a premalignant state can be averted by a combination of therapeutic modalities that decrease the size and growth rate of the premalignant cell population. PMID:1731346

  12. Proteomic analysis of estrogen response of premalignant human breast cells using a 2-D liquid separation/mass mapping technique.

    PubMed

    Zhao, Jia; Zhu, Kan; Lubman, David M; Miller, Fred R; Shekhar, Malthy P V; Gerard, Brigitte; Barder, Timothy J

    2006-07-01

    A 2-D liquid-phase separation method based on chromatofocusing and nonporous silica RP-HPLC followed by ESI-TOF-MS was used to analyze proteins in whole cell lysates from estrogen-treated and untreated premalignant, estrogen-responsive cell line MCF10AT1 cells. 2-D mass maps in the pH range 4.6-6.0 were generated with good correlation to theoretical M(r) values for intact proteins. Proteins were identified based on intact M(r), pI and PMF, or MS/MS sequencing. About 300 unique proteins were identified and 120 proteins in mass range 5-75 kDa were quantified upon treatment of estrogen. Around 40 proteins were found to be more highly expressed (>four-fold) and 17 were down-regulated (>four-fold) in treated cells. In our study, we found that many altered proteins have characteristics consistent with the development of a malignant phenotype. Some of them have a role in the ras pathway or play an important role in signal pathways. These changed proteins might be essential in the estrogen regulation mechanism. Our study highlights the use of the MCF10AT1 cell line to examine estrogen-induced changes in premalignant breast cells and the ability of the 2-D mass mapping technique to quantitatively study protein expression changes on a proteomic scale.

  13. The efficacy of oral brush biopsy with computer-assisted analysis in identifying precancerous and cancerous lesions

    PubMed Central

    2011-01-01

    Background Cancer of the oral cavity is the sixth most common malignancy reported worldwide and one with the highest mortality rate among all malignancies. There is a paucity of reliable diagnostic methods to detect early malignancies. This study was performed to evaluate the sensitivity and specificity of brush biopsy in identifying oral premalignant and malignant lesions. Methods Oral brush and scalpel biopsies were performed on 85 consecutive patients presenting with an oral lesion deemed to be minimally suspicious by clinical examination and the results were compared. Results Of 79 patients with adequate brush biopsy samples with matching scalpel biopsies, 27 revealed histopathologic evidence of dysplasia or carcinoma, 26 of which were independently identified with the oral brush biopsy (sensitivity: 96.3% - 95% CI, 87%-100%). 52 oral lesions did not reveal any histopathologic evidence of dysplasia or carcinoma and of these, brush biopsy reported 47 as "negative" and 5 as "atypical"(specificity of "positive" brush biopsy result is 100%- 95% CI, 93%-100%; specificity for "atypical" brush biopsy result is 90.4%- 95% CI, 82%-97%. The positive predictive value of an abnormal oral brush biopsy was 84% and the negative predictive value was 98%. Conclusion Our study demonstrated that the oral brush biopsy is an accurate test in identifying oral premalignant and malignant lesions, even if minimally suspicious. PMID:21864339

  14. Possible role of WT1 in a human fetus with evolving bronchial atresia, pulmonary malformation and renal agenesis.

    PubMed

    Loo, Christine K C; Algar, Elizabeth M; Payton, Diane J; Perry-Keene, Joanna; Pereira, Tamara N; Ramm, Grant A

    2012-01-01

    The association of peripheral bronchial atresia and congenital pulmonary airway malformation (CPAM) has recently been recognised, but the pathology of the lesions evolving together has not been described. We present autopsy findings in a 20 week fetus showing areas of peripheral bronchial destruction and airway malformation consistent with developing CPAM in the right lung supporting a causal relationship between these lesions. This fetus also had congenital heart defect, bilateral renal agenesis and syndactyly. We identified another fetus from our autopsy files, with bilateral renal agenesis, similar right sided pulmonary malformation and cardiac defects. Similar bilateral renal agenesis and defects of the heart and lungs are found in wt1(-/-) mice and we have investigated the expression of WT1 in these fetuses. We hypothesise that the cardiac, liver, renal and possibly lung lesions in these two cases may arise due to mesenchymal defects consequent to WT1 misexpression and discuss evidence for this from the scientific literature. We used immunoperoxidase stains to analyse WT1 expression in autopsy hepatic tissue in both fetuses. We also investigated the expression of α-smooth muscle actin (α-SMA), a marker of activated hepatic stellate cells/myofibroblasts, and desmin in hepatic mesenchyme and compare these findings with control fetuses, without congenital malformations. We found reduced WT1 expression in hepatic mesothelium in both fetuses with malformations. There was also increased expression of α-SMA in liver perisinusoidal cells, as seen in the wt1(-/-) mouse model. We therefore propose that abnormality of WT1 signalling may be an underlying factor, as WT1 is expressed in coelomic lining cells from which mesenchyme is derived in many organs.

  15. Different CO2 laser vaporization protocols for the therapy of oral precancerous lesions and precancerous conditions: a 10-year follow-up.

    PubMed

    Deppe, Herbert; Mücke, Thomas; Hohlweg-Majert, Bettina; Hauck, Wolfgang; Wagenpfeil, Stefan; Hölzle, Frank

    2012-01-01

    Use of the CO(2) laser (λ = 10.6 μm, continuous wave, defocused) is an established procedure for the treatment of premalignant lesions. Through employment of the sp-mode as well as scanners, thermal laser effects can be reduced but, on the other hand, a lesser degree of destruction of dysplastic cells could lead to an increased recurrence rate. The purpose of this study was to prospectively evaluate the recurrence rates resulting from different methods of CO(2) laser vaporization. From May 1995 to May, 2005, 145 patients with a total of 148 premalignant lesions of the oral mucosa were treated in a prospective clinical study. Sixty-two lesions in 62 patients were vaporized with the defocused CO(2) laser (group 1). In a further 45 lesions (43 patients, group 2), a scanner was additionally employed. In the remaining 41 lesions (40 patients, group 3), vaporization was carried out in the sp-mode in which the scanner was also used. In September, 2005, recurrence rates in the three groups were evaluated. Use of the scanner in sp-mode resulted in the most irregular tissue vaporization. This can be accounted for by the irregular paths of the laser beam and the pulsed delivery of the laser energy. Statistically significant lowest recurrence rates were yielded by the defocused cw-technique followed by the cw-scanner and the sp-mode. These results indicate that for CO(2) laser treatment of premalignant lesions of the oral mucosa, the best results can be achieved with the defocused technique. It may be assumed that other methods with lesser penetration of thermal effects (e.g. sp, scanner) do not reach the deeper-lying cells and, consequently, render higher rates of recurrence.

  16. Thermodynamical analysis of acoustical perturbations in the bronchial tree

    NASA Astrophysics Data System (ADS)

    Puente, Margarita; Perez-Guerrero, Armando; Alvarado, Manuel

    2002-11-01

    In the airways, very complex flows occur because of different conditions and the existence of a lot of complications: constantly changing temperature and pressure during the respiration process, a normally turbulent flow in the trachea which, in heavy breathing, remains so in the first three or four generations of airways, changes of the direction of the flow over the breathing cycle, from inspiration to expiration, etc. We also know the air that flows in the bronchial tree is perturbed by several sources such as the heart and the circulatory system, the diaphragm and stomach movements, etc., which produce sound waves. Thus an acoustical analysis of the phenomenon can lead us to a physical model which could help us to better understand the phenomena and to demonstrate the importance to clinical applications such as the pneumocardiograms. To this purpose we use a thermodynamical model that originally was developed to analyze supersonic air jets to explain the production of shock waves in the bronchial tree.

  17. Inhaled mannitol as a test for bronchial hyper-responsiveness.

    PubMed

    Brannan, John D; Porsbjerg, Celeste; Anderson, Sandra D

    2009-10-01

    Bronchial provocation tests (BPTs) are useful for identifying one of the key features of asthma: bronchial hyper-responsiveness (BHR). The symptoms of asthma are not always reflective of the underlying pathophysiology of asthma and there is a need for objective tests to identify the presence and severity of BHR. A new BPT, involving the inhalation of dry powder mannitol, has recently been approved to identify BHR and is now in use as a diagnostic tool for currently active asthma. Airway sensitivity to mannitol identifies BHR that is dependent upon the presence of airway inflammation and would probably benefit from treatment with inhaled corticosteroids. The mannitol BPT is available commercially as a (single-use) test kit (Aridol/Osmohale), with the only additional requirement to perform the test being a spirometer. Accordingly, the mannitol BPT provides a point-of-need tool to identify BHR to assist in the diagnosis of asthma.

  18. Oral tartrazine challenge in childhood asthma: effect on bronchial reactivity.

    PubMed

    Hariparsad, D; Wilson, N; Dixon, C; Silverman, M

    1984-01-01

    Ten asthmatic children who gave a history of cough or wheeze after orange drinks, were tested for tartrazine sensitivity. On separate days, either oral tartrazine (1 mg) or a placebo capsule were administered double blind. Bronchial reactivity was measured before, 30 and 60 min after ingestion by means of a histamine-inhalation challenge test. There was no change in baseline lung function after tartrazine, but histamine sensitivity (PC20) increased significantly in four of the children. No response was obtained to a larger dose of tartrazine (10 mg) in four of the non-responders. Alteration in the bronchial reactivity after an oral challenge, appears to be a sensitive means of detecting tartrazine sensitivity.

  19. Bilateral Renal Dysplasia, Nephroblastomatosis, and Bronchial Stenosis. A New Syndrome?

    PubMed Central

    Rodriguez, Maria Matilde; Correa-Medina, Mayrin; Whittington, Elizabeth E.

    2015-01-01

    Bilateral nephroblastomatosis (NB) is an uncommon renal anomaly characterized by multiple confluent nephrogenic rests scattered through both kidneys, with only a limited number of cases reported in the medical literature. Some of these children may have associated either Perlman or Beckwith–Wiedemann syndrome and others do not demonstrate syndromic features. We report a full-term boy with anteverted nose, bilateral bronchial stenosis due to lack of cartilage, bilateral obstructive renal dysplasia and NB with glomeruloid features. The infant had visceromegaly, but neither gigantism nor hemihypertrophy. Immunohistochemistry for PAX2 (Paired box gene-2) and WT-1 (Wilms Tumor 1) were strongly positive in the areas of NB. GLEPP-1 (Glomerular Epithelial Protein) did not stain the areas of NB with a glomeruloid appearance, but was positive in the renal glomeruli as expected. We found neither associated bronchial stenosis nor the histology of NB resembling giant glomeruli in any of the reported cases of NB. PMID:25871299

  20. Bronchial rupture by an unusual mechanism of thoracic hyperextension.

    PubMed

    Soler, Xavier; Sell, Rebecca; Maestre, José; Ruiz-Manzano, Juan

    2012-05-01

    Tracheobronchial disruption usually occurs in the setting of blunt chest trauma and may be overlooked due to co-existing injuries and non-specific symptoms. Review the mechanism, diagnosis, and therapeutic management of tracheobronchial disruption. We present a case of a young woman with a bronchial rupture 3 weeks after accidental strangulation. Initial diagnosis was delayed due to the unusual presentation. She presented with acute respiratory failure and hemodynamic collapse after slowly progressive shortness of breath with exertion. This case report provides an overview of the clinical features of bronchial disruption by highlighting the varying degrees of clinical presentation and management. Urgent bronchoscopy is indicated for diagnosis, and surgical intervention for treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. [Antimicrobial treatment of bronchial infections in hospital emergency rooms].

    PubMed

    Vallano Ferraz, A; Danés Carreras, I; Ochoa Sangrador, C

    2004-08-01

    To analyze antimicrobial prescribing habits in children diagnosed with bronchial infections in hospital emergency rooms. A descriptive study was performed in a random sample of children diagnosed with acute bronchitis and bronchiolitis in the emergency rooms of 11 Spanish hospitals. Information about the type of bronchial infection diagnosed and the antimicrobial treatment prescribed was gathered. The appropriateness of antibiotic prescriptions was assessed by comparing clinical practice in the use of antibiotics for bronchial infections with consensus guidelines developed for this study. A total of 731 children were selected. The diagnosis was acute bronchitis in 531 (73 %) and bronchiolitis in 200 (27 %). Antimicrobial treatment was prescribed to 234 children (32 %; 95 % CI: 29-35 %). The most commonly prescribed antimicrobials were the aminopenicillins in 138 children (19 %; 95 % CI 16-22 %), cephalosporins in 54 (7 %; 95 % CI 5-9 %) and macrolides in 45 (6 % 95 % CI 4-8 %). The prescribed treatment was inappropriate in 26 % (95 % CI 23-29 %) of patients [31.5 % (95 % CI 27-35 %) of cases of acute bronchitis and 11.5 % (95 % CI 95 % 7-16 %) of cases of bronchiolitis]. Wide variability was observed in the inappropriate use of antimicrobial agents among the different hospitals, both in acute bronchitis (14-80 %) and in bronchiolitis (0-71 %). Inappropriate antimicrobial treatment is prescribed to a considerable proportion of the children with bronchial infections attended in hospital emergency rooms, although there is wide variability among different hospitals. Programs to improve the quality of antimicrobial prescription should be developed. These should combine regulatory and educational measures directed at health professionals and the general public.

  2. Temperament and stress coping styles in bronchial asthma patients

    PubMed Central

    Kuna, Piotr; Witusik, Andrzej; Wujcik, Radosław; Antczak, Adam; Pietras, Tadeusz

    2016-01-01

    Introduction Temperament, defined as the formal characteristics of behavior, is a personality trait which can influence the clinical presentation and course of bronchial asthma. It determines susceptibility to stress as well as stress coping styles. Aim The aim of the study was to assess whether healthy subjects differ from bronchial asthma patients with regard to temperamental variables and stress coping styles, and whether these factors may also differentiate patients with severe asthma from those with the milder form. The study also assesses whether the results of flow volume curve analysis correlate with temperamental traits and stress coping styles. Material and methods The study was conducted in a group of 65 asthma patients and 62 healthy controls. All underwent flow volume curve examination and psychological tests: Formal Characteristics of Behavior – Temperament Inventory (FCB-TI) and Coping in Stress Situations (CISS) questionnaire. Results Bronchial asthma patients were characterized by a lower level of briskness (“agility”) than healthy subjects (13.35 ±4.48 vs. 14.97 ±3.98, p = 0.031). The remaining temperamental traits and stress coping styles did not differ between the groups. Additionally, the forced expiratory volume in 1 s (FEV1) value was found to correlate negatively with the intensity of the emotion-oriented stress coping style, whereas FEV1 and forced vital capacity (FVC) were found to positively correlate with briskness, emotional reactivity and endurance, while a negative correlation was found with activity. Conclusions Briskness differentiates healthy subjects from bronchial asthma patients. The values obtained in FEV1 and FVC pulmonary function tests were also found to correlate with some temperamental variables. PMID:28035226

  3. Comparison between ketotifen and DSCG in bronchial challenge.

    PubMed

    Pauwels, R; Lamont, H; Van Der Straeten, M

    1978-05-01

    A double-blind cross-over study showed that orally taken ketotifen and inhaled DSCG have a comparable protective effect on allergen-induced bronchoconstriction. Both drugs significantly inhibit the immediate bronchial reaction after a 3 day treatment with either 1 mg ketotifen or 20 mg DSCG four times daily. Late reactions, which occurred in three out of the ten patients, were inhibited in two of the three patients by ketotifen as by DSCG.

  4. Benzalkonium Chloride Induced Bronchoconstriction in Patients with Stable Bronchial Asthma

    PubMed Central

    Lee, Byoung Hoon

    2007-01-01

    Background Although benzalkonium chloride (BAC)-induced bronchoconstriction occurs in patients with bronchial asthma, BAC-containing nebulizer solutions are still being used in daily practice in Korea. The aim of this study was to evaluate the effects of inhaled aqueous solutions containing BAC. Methods Thirty subjects with bronchial asthma and 10 normal controls inhaled up to three 600 µg nebulized doses of BAC using a jet nebulizer. FEV1 (forced expiratory volume at one second) was measured 15 minutes after each dose. Inhalations were repeated every 20 minutes until FEV1 decreased by 15% or more (defined as BAC-induced bronchoconstriction) or the 3 doses were administered. Results The percent fall in FEV1 in response to BAC inhalation was significantly higher in asthmatics than in normal subjects (p<0.05). BAC administration in subjects with asthma reached a plateau (maximal effect). BAC-induced bronchoconstriction was found in 6 asthmatics (20%), with two responders after the 2nd inhalation and after the 3rd inhalation. The percent fall in FEV1 in response to the 1st inhalation of BAC was significantly higher in asthmatics with higher bronchial hyperresponsiveness (BHR) than in those with lower BHR. Conclusions This study suggests that the available multi-dose nebulized solution is generally safe. However, significant bronchoconstriction can occur at a relatively low BAC dose in asthmatics with severe airway responsiveness. PMID:18309682

  5. Bronchial colonisation in patients with lung cancer: a prospective study.

    PubMed

    Laroumagne, Sophie; Lepage, Benoît; Hermant, Christophe; Plat, Gavin; Phelippeau, Michael; Bigay-Game, Laurence; Lozano, Stéphanie; Guibert, Nicolas; Segonds, Christine; Mallard, Valérie; Augustin, Nathalie; Didier, Alain; Mazieres, Julien

    2013-07-01

    Bronchial colonisation is frequently reported in patients with lung cancer, and has a potential impact on therapeutic management and prognosis. We aimed to prospectively define the prevalence and nature of bronchial colonisation in patients at the time of diagnosing lung cancer. 210 consecutive patients with lung cancer underwent a flexible bronchoscopy for lung cancer. The type and frequency of bacterial, mycobacterial and fungal colonisation were analysed and correlated with the patients' and tumours' characteristics. Potential pathogens were found in 48.1% of samples: mainly the Gram-negative bacilli Escherichia coli (8.1%), Haemophilus influenzae (4.3%) and Enterobacter spp. (2.4%); Gram-positive cocci, Staphylococcus spp. (12.9%) and Streptococcus pneumoniae (3.3%); atypical mycobacteria (2.9%); Candida albicans (42.9%); and Aspergillus fumigatus (6.2%). Aged patients (p=0.02) with chronic obstructive pulmonary disease (p=0.008) were significantly more frequently colonised; however, tumour stage, atelectasis, bronchial stenosis and abnormalities of chest radiography were not associated with a higher rate of colonisation. Squamous cell carcinoma tended to be more frequently colonised than other histological subtypes. Airway colonisation was reported in almost half of patients presenting with lung cancer, mainly in fragile patients, and was significantly associated with worse survival (p=0.005). Analysing colonisation status of patients at the time of diagnosis may help improve the management of lung cancer.

  6. [Electrophysiology and calcium signalling in human bronchial smooth muscle].

    PubMed

    Marthan, R; Hyvelin, J M; Roux, E; Savineau, J P

    1999-01-01

    Recently, cells isolated from airways have been used to characterize precisely the electrophysiological properties of this smooth muscle and to describe the changes in cytosolic calcium concentration ([Ca2+]i) occurring upon agonist stimulation. Although most studies have produced consistent results in terms of types of ion channel and pathways of calcium signalling implicated in the mechanical activity of airways, there are differences according to (i) the site along the bronchial tree (trachea vs. bronchi); (ii) the proliferating status of the cells (freshly isolated vs. cultured) and (iii) the species (human vs. animals). With regard to the electrophysiological properties of airway smooth muscle, the contribution to [Ca2+]i rise of Ca2+ influx through L-type voltage-dependent calcium channels depends on the balance between depolarization related to non-specific cation channel and/or chloride channel activation and hyperpolarization related to activation of a variety of potassium channels. Most of the above-mentioned channels appear to be controlled, directly or indirectly, by agonists in human bronchial smooth muscle. With regard to calcium signalling, the pattern of agonist-induced [Ca2+]i responses, the so-called [Ca2+]i oscillations, has been observed recently in freshly isolated airway smooth muscle cells. The role and the calcium sources involved in these oscillations in human bronchial smooth muscle are currently being investigated.

  7. Reduced in vitro erythroid progenitor cell growth in bronchial cancer.

    PubMed Central

    Masters, G S; Baines, P; Bailey-Wood, R; Gorvett, T; Littlewood, T; Bentley, P; Parry-Jones, H; Jacobs, A

    1987-01-01

    Peripheral blood and bone marrow were studied in 21 men with disseminated untreated bronchial cancer in an attempt to define abnormalities of erythropoiesis associated with the development of anaemia. Haemoglobin concentration at or below 13 g/dl was present in 13 cases. Marrow morphology was normal in all cases except one, in which small numbers of tumour cells were found. Clonal assay of erythroid progenitors showed a significant decrease in the number of BFU-E (p = 0.03) and CFU-E (p = 0.01) compared with cultures from normal marrow (12 subjects). The growth of granulocyte and macrophage progenitors (GM-CFCs) was similar in patients with bronchial cancer and normal subjects. When normal marrow was incubated in the presence of serum from bronchial cancer patients, no inhibitory factors could be detected either for BFU-E or CFU-E growth. In all patients circulating T8 numbers were significantly raised (p = 0.0002). Consequently, the median T4:T8 ratio in blood was 1.2, and this was significantly lower than the ratio of 1.7 found in 20 normal subjects (p = 0.036). In 18 patients the bone marrow T4:T8 ratio of 1.1 was significantly lower than the ratio of 2.9 found in seven normal subjects (p = 0.04). Total blood white cell counts, neutrophils, and monocyte numbers were also increased (p = 0.0001; p = 0.0001; p = 0.002). PMID:3818975

  8. Increased resting bronchial tone in normal subjects acclimatised to altitude

    PubMed Central

    Wilson, C; Bakewell, S; Miller, M; Hart, N; McMorrow, R; Barry, P; Collier, D; Watt, S; Pollard, A

    2002-01-01

    Background: Normal subjects frequently experience troublesome respiratory symptoms when acclimatised to altitude. Bronchial hyperresponsiveness (BHR) and full and partial flow-volume loops were measured before and after ascent to 5000 m altitude to determine if there are changes in resting bronchial tone and BHR that might explain the symptoms. Methods: BHR to histamine was measured using a turbine spirometer to record partial and full flow-volume curves and expressed as log dose slopes. Twenty one subjects were tested at sea level and after acclimatisation at 5000 m altitude. Results: No significant change in log dose slope measurements of forced expiratory volume in 1 second occurred after acclimatisation, and the maximal expiratory flow with 30% of forced vital capacity remaining (MEF30%) rose on the full loop and fell on the partial loop. Their ratio (full divided by partial) rose on average by 0.28 (95% confidence limits 0.14 to 0.42) from the mean (SD) sea level value of 0.87 (0.20). Conclusions: There is no increase in BHR in normal subjects acclimatised to altitude but an increase in resting bronchial tone occurs that could be released by deep inspiration. This may be the result of increased cholinergic tone. PMID:11978915

  9. Alterations in vitamin D signaling pathway in gastric cancer progression: a study of vitamin D receptor expression in human normal, premalignant, and malignant gastric tissue

    PubMed Central

    Wen, Yanghui; Da, Mingxu; Zhang, Yongbin; Peng, Lingzhi; Yao, Jibin; Duan, Yaoxing

    2015-01-01

    Amount of studies in cells and animal models have proved vitamin D has multifarious antitumor effects. However, epidemiological studies showed inconsistent result on gastric cancer. The antitumor role is mainly mediated by the vitamin D receptor (VDR). Our hypothesis is that VDR may be abnormally (poorly) expressed in gastric cancer tissue. Present study is aimed at discovering and analyzing VDR expression in a series of human gastric tissues, including normal, premalignant, and malignant gastric tissue, and correlated VDR to the clinicopathological parameters of gastric cancer patients. VDR expression was detected by immunohistochemistry. The χ2 test was used to analyze the VDR expression as well as the relationship between VDR and the clinicopathological factors of gastric cancer patients. Compared with normal (82.61%) and premalignant tissues (73.64%), VDR was lower expressed in cancer tissues (57.61%), with a statistically significant difference (P = 0.001). Among cancer tissues, VDR was higher expressed in well and moderate differentiated tissues contrasted with tissues with poor differentiation, and higher expressed in small tumors (< 5 cm) compared with large tumors (≥ 5 cm), with a statistically significant difference respectively (P = 0.016, P = 0.009). A decline linear trend appeared when analyzing the statistical difference of VDR expression among normal, premalignant, and malignant gastric tissues. VDR expression has been on the decline from the premalignant stage, finally low expressed in gastric cancer tissues, especial in poorly differentiated tissues. VDR could be a potential prognostic factor for patients with gastric cancer. PMID:26722516

  10. Alterations in vitamin D signaling pathway in gastric cancer progression: a study of vitamin D receptor expression in human normal, premalignant, and malignant gastric tissue.

    PubMed

    Wen, Yanghui; Da, Mingxu; Zhang, Yongbin; Peng, Lingzhi; Yao, Jibin; Duan, Yaoxing

    2015-01-01

    Amount of studies in cells and animal models have proved vitamin D has multifarious antitumor effects. However, epidemiological studies showed inconsistent result on gastric cancer. The antitumor role is mainly mediated by the vitamin D receptor (VDR). Our hypothesis is that VDR may be abnormally (poorly) expressed in gastric cancer tissue. Present study is aimed at discovering and analyzing VDR expression in a series of human gastric tissues, including normal, premalignant, and malignant gastric tissue, and correlated VDR to the clinicopathological parameters of gastric cancer patients. VDR expression was detected by immunohistochemistry. The χ(2) test was used to analyze the VDR expression as well as the relationship between VDR and the clinicopathological factors of gastric cancer patients. Compared with normal (82.61%) and premalignant tissues (73.64%), VDR was lower expressed in cancer tissues (57.61%), with a statistically significant difference (P = 0.001). Among cancer tissues, VDR was higher expressed in well and moderate differentiated tissues contrasted with tissues with poor differentiation, and higher expressed in small tumors (< 5 cm) compared with large tumors (≥ 5 cm), with a statistically significant difference respectively (P = 0.016, P = 0.009). A decline linear trend appeared when analyzing the statistical difference of VDR expression among normal, premalignant, and malignant gastric tissues. VDR expression has been on the decline from the premalignant stage, finally low expressed in gastric cancer tissues, especial in poorly differentiated tissues. VDR could be a potential prognostic factor for patients with gastric cancer.

  11. Immune Suppression in Premalignant Respiratory Papillomas: Enriched Functional CD4+Foxp3+ Regulatory T-cells And PD-1/PD-L1/L2 Expression

    PubMed Central

    Hatam, Lynda J.; DeVoti., James A; Rosenthal, David W.; Lam, Fung; Abramson, Allan L.; Steinberg, Bettie M; Bonagura, Vincent R.

    2012-01-01

    Purpose Respiratory papillomas, caused by human papillomaviruses types 6 and 11 (HPV6/11), are premalignant lesions with potential for malignant conversion. The cytokine and chemokine micromilieu of papillomas is TH2-like with a marked absence of IFN-γ expression. To illuminate why patients with recurrent respiratory papillomatosis (RRP) fail to effectively control their disease, we further investigated the suppressive cellular microenvironment in papillomas. Experimental Design CD4+CD25+CD127low/−Foxp3+ Tregs, and CD4+CD25−CD127low/−Foxp3− T-cells within papillomas were characterized and isolated. Their suppressor function was measured by inhibition of PBMC proliferation. Expression of PD-1, CD69, and Helios was identified on these T-cells. PD-L1, PD-L2, CCL17, and CCL22 mRNA was also identified in papillomas. by QPCR. Results Functional Tregs were markedly enriched in papillomas and strongly inhibited anti-CD3 and anti-CD28 antibody activated PBMC proliferation. The natural Treg marker Helios was reduced on Tregs from papillomas, indicating that the majority of Tregs in papillomas are adaptive. The majority of the papilloma-derived CD4+ T-cells expressed the CD4+CD25−CD127low/−Foxp3−PD1+CD69+ phenotype and failed to suppress PBMC proliferation, suggesting that they are chronically activated and exhausted. The Treg-attracting chemokine CCL22 was equally expressed by all laryngeal tissues examined. However CCL17 was robustly expressed by papillomas compared to unaffected laryngeal tissues from RRP patients and individuals without RRP. PD-L1 was elevated in papillomas compared to control laryngeal tissues. Conclusions Papilloma CD4+ T-cells are enriched with functional Tregs, and the adaptive Helios− Treg fraction was increased within the TH2-like papilloma micromilieu. CD4+CD25−CD127low/−Foxp3− T-cells failed to suppress PBMC proliferation and may be exhausted. The PD-1/PDL-1 pathway may represent an additional immunosuppressive mechanism

  12. Temperature differences are associated with malignancy on lung lesions: a clinical study

    PubMed Central

    Stefanadis, Christodoulos; Chrysohoou, Christina; Panagiotakos, Demosthenes B; Passalidou, Elisabeth; Katsi, Vasiliki; Polychronopoulos, Vlassios; Toutouzas, Pavlos K

    2003-01-01

    Background Although new endoscopic techniques can enhance the ability to detect a suspicious lung lesion, the primary diagnosis still depends on subjective visual assessment. We evaluated whether thermal heterogeneity of solid tumors, in bronchial epithelium, constitutes an additional marker for the diagnosis of benign and malignant lesions. Methods A new method, developed in our institute, is introduced in order to detect temperature in human pulmonary epithelium, in vivo. This method is based on a thermography catheter, which passes the biopsy channel of the fiber optic bronchoscope. We calculated the temperature differences (ΔT) between the lesion and a normal bronchial epithelium area on 22 lesions of 20 subjects, 50 – 65 years old. Results Eleven lesions were benign and 11 were malignant, according to the biopsy histology followed the thermography procedure. We found significant differences of ÄT between patients with benign and malignant tumor (0.71 ± 0.6 vs. 1.23 ± 0.4°C, p < 0.05). Logistic regression analysis showed that 1-Celsius degree differences between normal tissue and suspicious lesion six-fold the probability of malignancy (odds ratio = 6.18, 95% CI 0.89 – 42.7). Also, ΔT values greater than 1.05°C, constitutes a crucial point for the discrimination of malignancy, in bronchial epithelium, with sensitivity (64%) and specificity (91%). Conclusion These findings suggest that the calculated ΔT between normal tissue and a neoplastic area could be a useful criterion for the diagnosis of malignancy in tumors of lung lesions. PMID:12515579

  13. [Frequency and distribution of oral lesions in elderly patients].

    PubMed

    Crivelli, M R; Domínguez, F V; Adler, I L; Keszler, A

    1990-01-01

    In this study the relative frequency of oral lesions was evaluated in a group of 526 patients, 55 years old or elder. Clinical and pathological data were obtained from 244 patients who attended to a clinic of Medical and Social Assistance Program (PAMI) ad from 282 cases registered in the files of the Surgical Pathology Laboratory F.O.U.B.A. (LAP) since 1984 to 1986. The mean age of the groups was 63 years old. The most frequency lesions were the pseudotumors (44.6%) in LAP and (17.2%) in PAMI; premalignant lesions were (20.5%) in LAP, while in PAMI (2.4%). The cysts in LAP found (15.6%) in PAMI were (2.4%). The groups of PAMI showed (90%) of Candidiasis. Traumatic ulcer (30.7%) and afthae (28.8%). In LAP were (4.6%) the traumatic ulcer. The malignant tumors the most frequency was carcinoma espinocelular (8.16%) LAP and (6.56%) PAMI. It was remarkable that stomatodine as represented in PAMI (72.2%) and Candidiasis were (90%). Candidiasis were 90% of the specific inflammations. Results suggest that oral mobility in elderly patients correlates with the findings in this type of social assisted groups. The figures of the importance of methodical collaboration of Stomatologists and Oral Pathologists for differential diagnosis.

  14. Genomic Instability at Premalignant and Early Stages of Breast Cancer Development

    DTIC Science & Technology

    1999-08-01

    affected in 60 - 70% of in situ breast lesions. Positional cloning strategies are currently being employed to clone the target genes for such...have mapped to this region a large number previously reported ESTs. Several new cDNA clones were isolated and mapped. We sequenced almost 400,000 DNA...individuals to risk of developing familial breast cancer. These genes include the recently cloned BRCA1, BRCA2, PTEN and TP53 in the case of Li

  15. Effect of Rebamipide on the Premalignant Progression of Chronic Gastritis: A Randomized Controlled Study.

    PubMed

    Han, Xue; Jiang, Kui; Wang, Bangmao; Zhou, Lu; Chen, Xin; Li, Shu

    2015-10-01

    Chronic gastritis frequently progresses into precancerous intestinal metaplasia and intraepithelial neoplasia lesions. Rebamipide is a free radical scavenger and we assessed its efficacy on clinical symptoms, gastric mucosal lesions, pathologic grade, and immunohistochemistry in chronic gastritis patients. 178 eligible patients were randomized into treatment and control groups. Both groups followed an optimized lifestyle for 26 weeks, but the treatment group was additionally medicated with rebamipide 0.1 g three times per day. Upper gastrointestinal endoscopy was performed in all patients to evaluate the severity of gastritis by the Modified Lanza Scoring (MLS) and histological changes were evaluated by the Updated Sydney System Score (USSS). Gastric mucosa immunohistochemistry in the treatment group was performed using the intestinal metaplasia markers caudal type homeobox transcription factor 2 (CDX2) and trefoil factor 3 (TFF3) detection. There were significant outcome differences between the treatment and control groups regarding the clinical symptom scores (2.62 ± 1.86 vs. 1.55 ± 1.61, P = 0.0001), gastric mucosal lesion scores (0.57 ± 1.05 vs. 0.16 ± 0.90, P = 0.002), and inflammation (P < 0.05). Only in the treated patients were the rates of intestinal metaplasia (P = 0.017 vs. P = 0.123) and low-grade intraepithelial neoplasia (P = 0.005 vs. P = 0.226) significantly reduced after 26 weeks. The percentages of CDX2 (31.5 vs. 15.7%, P = 0.021) and TFF3 (44.9 vs. 25.8%, P = 0.012) expressing gastric mucosa cells were significantly lower after rebamipide medication than pre-treatment values. Rebamipide improved the clinical symptoms, gastric mucosal lesions, and pathological grades of chronic gastritis patients and decreased the expression rates of CDX2 and TFF3 in gastric cells.

  16. High resolution computed tomographic evaluation of bronchial wall thickness in healthy and clinically asthmatic cats

    PubMed Central

    WON, Sungjun; YUN, Sookyung; LEE, Jeosoon; LEE, Mikyung; CHOI, Mincheol; YOON, Junghee

    2017-01-01

    The objective of study is to determine the thickness of bronchial walls of clinically diagnosed asthmatic cats using high resolution computed tomography (HRCT) compared to that of healthy cats. The bronchial walls and pulmonary arteries were measured in healthy 16 cats and clinically asthmatic 4 cats. The bronchial walls and pulmonary arteries were measured under general anesthesia with positive pressure inspiration using HRCT. In healthy and asthmatic cats, bronchial lumen to the artery ratio (BA ratio), the ratio of bronchial wall thickness to bronchial diameter (TD ratio) and ratio of bronchial wall thickness to pulmonary artery (TA ratio) were measured. The mean BA ratio, TD ratio and TA ratio in healthy cats were 0.86 ± 0.12, 0.18 ± 0.02 and 0.25 ± 0.05, respectively. Under the same condition, the mean BA ratio, TD ratio and TA ratio in asthmatic cats were 0.93 ± 0.21, 0.22 ± 0.24 and 0.37 ± 0.06. The TD ratio and TA ratio in asthmatic cats were significantly higher than healthy cats (P<0.001). BA ratio was not significantly different in both groups (P>0.05). The evaluation of bronchial wall thickness by HRCT could be useful for diagnosis of disease of bronchial wall thickening, such as feline asthma. PMID:28163274

  17. Bronchial rupture and fatal tension pneumothorax following routine venipuncture in a kitten.

    PubMed

    Godfrey, D R

    1997-01-01

    A five-month-old Siamese kitten suffered a bronchial tear and subsequently a fatal tension pneumothorax during routine venipuncture. No other injuries and no underlying diseases were identified upon gross postmortem and histopathological examinations. The pathogenesis of the bronchial tear was undetermined. Bronchial ruptures are unreported in animals; they are well recognized as rare injuries in humans with chest trauma. The pathogenesis of the bronchial rupture most likely was due to occlusion of the upper airways (directly or due to laryngospasm), along with pressure on the chest, or due to stretching and twisting of the tracheobronchial tree.

  18. Free Vascularized Fibular Graft Transfer in the Reconstruction of Defects for Premalignant and Malignant Musculoskeletal Conditions of the Femur in a Tertiary Care Setting in Pakistan: A Series of Six Cases

    PubMed Central

    Manzoor, Hana; Saqib, Imad-ud-din; Jan, Waqar; Rashid, Mamoon

    2016-01-01

    Objective To determine the application, success and complications of the utilization of free vascularized fibular grafts (FVFG) in the reconstruction of lower limb defects after resection of primary lower limb musculoskeletal tumors. Methodology This descriptive retrospective case series analysis was conducted at Shifa International Hospital from January 2011 to January 2016. It included patients who had premalignant and malignant conditions of the lower limb and subsequently had the lesion resected followed by FVFG surgery. The data collected was to outline the demographic profile, clinical features, and post-procedure outcomes and complications. Results There was a total of six patients. The mean age of the patients was 25.8 ± 11.8 years (range: 15-40 years). The patients presented with pain, swelling, inability to bear weight and/or restriction of movement at the joint. Postoperatively, one patient had proximal wound necrosis and one patient had a thrombus in the anastomosed vessels, both of which were managed successfully. Conclusion With a success rate of 100% at the end of the six-month follow-up period, FVFG surgery is a reliable procedure that may be successfully carried out for musculoskeletal tumors of the lower limb with minimal complications. PMID:27924251

  19. [Benign vocal fold lesions].

    PubMed

    Pickhard, A; Reiter, R

    2013-05-01

    Benign vocal fold lesions are grouped in lesions arising from the epithelium like papillomas, lesions affecting the Reinke's space (nodules, polyps, cysts, Reinkes's edema as a form of chronic laryngitis) and lesions affecting the arytenoid (granulomas). A multifactorial genesis is assumed. Main symptoms are dysphonia and hyperfunctional vocal behavior that might also be a cause of these lesions. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Reliability of commercially available immunocytochemical markers for identification of neuroendocrine differentiation in bronchoscopic biopsies of bronchial carcinoma.

    PubMed Central

    Gosney, J. R.; Gosney, M. A.; Lye, M.; Butt, S. A.

    1995-01-01

    BACKGROUND--Although neuroendocrine differentiation occurs quite commonly in non-small cell bronchial malignancies, its biological significance and implications for management remain uncertain. Determining these facts requires its recognition early, ideally at diagnosis, which is usually made on tissue from bronchoscopy, but the best means of its detection in such material is unclear. A prospective comparative study was performed of 10 commercially available antisera to a series of markers of neuroendocrine differentiation, to test their efficacy when applied to fibreoptic bronchoscopy biopsy specimens. METHODS--Expression of chromogranin A, synaptophysin, neurone-specific enolase, protein gene product 9.5, the BB isoenzyme of creatine kinase, gastrin releasing peptide, adrenocorticotrophic hormone, calcitonin, calcitonin gene related peptide, and leucine enkephalin was sought by immunolabelling of bronchoscopic biopsy tissue from 83 primary bronchial carcinomas, 22 of them of small cell type. RESULTS--Only synaptophysin and chromogranin were sensitive and specific enough for neuroendocrine differentiation to discriminate between small cell and non-small cell lesions, whereas protein gene product 9.5 and creatine kinase were neither particularly sensitive nor specific and neurone-specific enolase actually labelled more non-small cell tumours than small cell lesions. Of the five secretory products sought, only gastrin releasing peptide was detectable in just one tumour. Three squamous and two morphologically undifferentiated tumours immunolabelled for synaptophysin and chromogranin, almost certainly indicating neuroendocrine differentiation in the absence of small cell morphology. CONCLUSIONS--Of the markers studied, only synaptophysin and chromogranin were sufficiently specific and sensitive for neuroendocrine differentiation to justify their inclusion in any panel of antibodies used in its detection in tissue obtained at fibreoptic brochoscopy. Images PMID:7701447

  1. Non-alcoholic steatohepatitis and preneoplastic lesions develop in the liver of obese and hypertensive rats: suppressing effects of EGCG on the development of liver lesions.

    PubMed

    Kochi, Takahiro; Shimizu, Masahito; Terakura, Daishi; Baba, Atsushi; Ohno, Tomohiko; Kubota, Masaya; Shirakami, Yohei; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

    2014-01-01

    Non-alcoholic steatohepatitis (NASH), which involves hepatic inflammation and fibrosis, is associated with liver carcinogenesis. The activation of the renin-angiotensin system (RAS), which plays a key role in blood pressure regulation, promotes hepatic fibrogenesis. In this study, we investigated the effects of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins, on the development of glutathione S-transferase placental form (GST-P)-positive (GST-P(+)) foci, a hepatic preneoplastic lesion, in SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP-ZF) obese and hypertensive rats. Male 7-week-old SHRSP-ZF rats and control non-obese and normotensive WKY rats were fed a high fat diet and received intraperitoneal injections of carbon tetrachloride twice a week for 8weeks. The rats were also provided tap water containing 0.1% EGCG during the experiment. SHRSP-ZF rats presented with obesity, insulin resistance, dyslipidemia, an imbalance of adipokines in the serum, and hepatic steatosis. The development of GST-P(+) foci and liver fibrosis was markedly accelerated in SHRSP-ZF rats compared to that in control rats. Additionally, in SHRSP-ZF rats, RAS was activated and inflammation and oxidative stress were induced. Administration of EGCG, however, inhibited the development of hepatic premalignant lesions by improving liver fibrosis, inhibiting RAS activation, and attenuating inflammation and oxidative stress in SHRSP-ZF rats. In conclusion, obese and hypertensive SHRSP-ZF rats treated with a high fat diet and carbon tetrachloride displayed the histopathological and pathophysiological characteristics of NASH and developed GST-P(+) foci hepatic premalignant lesions, suggesting the model might be useful for the evaluation of NASH-related liver tumorigenesis. EGCG might also be able to prevent NASH-related liver fibrosis and tumorigenesis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Impact of obesity on bronchial asthma in Indian population.

    PubMed

    Ramasamy, Anandha K; Gupta, Nitesh; Kumar, Raj

    2014-04-01

    Obesity and asthma are common inflammatory conditions, having presence of both local and systemic inflammation and this relationship is not well understood. This study was undertaken to compare pulmonary function parameters, inflammatory marker like C-reactive protein (hs-CRP), exhaled nitric oxide (FENO) and atopic profile between non-obese and obese bronchial asthma patients in Indian population. The study aims to elucidate the association between the systemic and local inflammatory response relating to obesity in asthmatics. Sixty bronchial asthma patients were recruited for the study, and were divided equally into obese (BMI>30 kg/m(2)) and non-obese (BMI<25 kg/m(2)) groups. These were assessed for pulmonary function parameters, blood hs-CRP levels, exhaled breath analysis of nitric oxide and skin prick testing for atopic profile. The study was approved by institutional ethical committee. The mean body mass index (BMI) for the non-obese and obese group was 21.64 kg/m(2) and 34.1 kg/m(2) respectively (P = 0.001). The functional residual capacity (FRC% predicted) (100.9 ± 4.21 vs 80.40 ± 4.03; P = 0.009) and expiratory reserve volume (ERV% predicted) (95.13 ± 6.71 vs. 67.03 ± 4.54; P = 0.001) both were significantly lower in the obese group. The non-obese and obese group had hs-CRP levels of 3.01 mg/L and 4.07 mg/L, respectively; the difference being statistically insignificant (P = 0.15). Similarly, FENO levels of non-obese and obese group were 63.20 ppb and 63.75 ppb, respectively; difference was not statistically significant (P = 0.95). Atopic profile of both the groups did not differ significantly. Obesity does not appear to increase the local and systemic inflammatory responses in bronchial asthma patients in Indian population.

  3. Increased myoepithelial cells of bronchial submucosal glands in fatal asthma.

    PubMed

    Green, F H Y; Williams, D J; James, A; McPhee, L J; Mitchell, I; Mauad, T

    2010-01-01

    Fatal asthma is characterised by enlargement of bronchial mucous glands and tenacious plugs of mucus in the airway lumen. Myoepithelial cells, located within the mucous glands, contain contractile proteins which provide structural support to mucous cells and actively facilitate glandular secretion. To determine if myoepithelial cells are increased in the bronchial submucosal glands of patients with fatal asthma. Autopsied lungs from 12 patients with fatal asthma (FA), 12 patients with asthma dying of non-respiratory causes (NFA) and 12 non-asthma control cases (NAC) were obtained through the Prairie Provinces Asthma Study. Transverse sections of segmental bronchi from three lobes were stained for mucus and smooth muscle actin and the area fractions of mucous plugs, mucous glands and myoepithelial cells determined by point counting. The fine structure of the myoepithelial cells was examined by electron microscopy. FA was characterised by significant increases in mucous gland (p = 0.003), mucous plug (p = 0.004) and myoepithelial cell areas (p = 0.017) compared with NAC. When the ratio of myoepithelial cell area to total gland area was examined, there was a disproportionate and significant increase in FA compared with NAC (p = 0.014). Electron microscopy of FA cases revealed hypertrophy of the myoepithelial cells with increased intracellular myofilaments. The NFA group showed changes in these features that were intermediate between the FA and NAC groups but the differences were not significant. Bronchial mucous glands and mucous gland myoepithelial cell smooth muscle actin are increased in fatal asthma and may contribute to asphyxia due to mucous plugging.

  4. Importance of education in bronchial asthma treatment - gender differences.

    PubMed

    Jankowska-Polańska, Beata; Pleśniak, Justyna; Seń, Mariola; Uchmanowicz, Izabella; Rosińczuk, Joanna

    2015-01-01

    Despite significant progress in understanding mechanisms and effective treatment there are still therapeutic failures in patients treated for bronchial asthma. Education is vital in the therapeutic process. It improves the control of the disease at the individual level by influencing the adherence and compliance. The study included 100 patients suffering from bronchial asthma and treated according to GINA 2002 guidelines in Allergy Clinic. Asthma control test (ACT), analysis of patients' medical documentation and a self-constructed questionnaire concerning health promotion and education were used in the study. Aim of this work was to assess differences in the influence of education on results of bronchial asthma control between sexes. Average duration of asthma was similar in women and men (13.0 ± 11.16 vs.12.7 ± 9.74 years). Weaker asthma control was found in women (ACT 17.7 vs. 20.4), as well as lower FEV1 values (80-50% of predicted value in 60.3% of women vs. 43.25 of men). In women an analysis of correlation concerning patients' knowledge and conducted health education with asthma control revealed a statistically significant positive correlation of knowledge acquired from the allergologist with asthma control, information about proceeding in acute attack, whereas negative correlation with asthma control with knowledge passed on by family doctor was found. Among the male respondents positive correlations of knowledge with asthma control within the scope of knowledge from allergologist and information concerning proceeding in asthmatic attack were found, while negative correlation with information coming from family doctor was revealed. Health education in patients with asthma should be conducted by a specialist in allergic diseases and well-prepared healthcare professionals.

  5. Bronchial Reactivity and Lung Function After World Trade Center Exposure.

    PubMed

    Aldrich, Thomas K; Weakley, Jessica; Dhar, Sean; Hall, Charles B; Crosse, Tesha; Banauch, Gisela I; Weiden, Michael D; Izbicki, Gabriel; Cohen, Hillel W; Gupta, Aanchal; King, Camille; Christodoulou, Vasilios; Webber, Mayris P; Zeig-Owens, Rachel; Moir, William; Nolan, Anna; Kelly, Kerry J; Prezant, David J

    2016-12-01

    World Trade Center (WTC)-exposed rescue/recovery workers endured massive respiratory insult from inhalation of particulate matter and gases, resulting in respiratory symptoms, loss of lung function, and, for many, bronchial hyperreactivity (BHR). The persistence of respiratory symptoms and lung function abnormalities has been well-documented, whereas persistence of BHR has not been investigated. A total of 173 WTC-exposed firefighters with bronchial reactivity measured within 2 years after September 11, 2001 (9/11) (baseline methacholine challenge test), were reevaluated in 2013 and 2014 (follow-up methacholine challenge test). FEV1 measurements were obtained from the late pre-9/11, early post-9/11, and late post-9/11 periods. Respiratory symptoms and corticosteroid treatment were recorded. Bronchial reactivity remained stable (within 1 doubling dilution) for most (n = 101, 58%). Sixteen of 28 (57%) with BHR (provocative concentration of methacholine producing a 20% decline in FEV1 <8 mg/mL) at baseline had BHR at follow-up, and an additional 27 of the 145 (19%) without BHR at baseline had BHR at follow-up. In multivariable models, we found that BHR baseline was strongly associated with BHR follow-up (OR, 6.46) and that BHR at follow-up was associated with an estimated 15.4 mL/y greater FEV1 decline than experienced by those without BHR at follow-up. Annual FEV1 decline was moderated by corticosteroid use. Persistent BHR and its deleterious influence on lung function suggest a role for airway inflammation in perpetuation of WTC-associated airway disease. In future massive occupational exposure to inorganic dust/gases, we recommend early and serial pulmonary function testing, including measurements of bronchial reactivity, when possible, and inhaled corticosteroid therapy for those with symptoms or pulmonary function tests consistent with airway disease. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  6. [Flexible bronchoscopy techniques: bronchoalveolar lavage, bronchial biopsy and transbronchial biopsy].

    PubMed

    Escribano Montaner, A; Moreno Galdó, A

    2005-04-01

    This article completes previous recommendations of the Techniques Group of the Spanish Society of Pediatric Pulmonologists on the practice of flexible bronchoscopy in children. We review the most frequently performed diagnostic and therapeutic procedures applied through the flexible bronchoscope: bronchoalveolar lavage, bronchial biopsy and transbronchial biopsy. Recommendations are also provided on the practice of nonbronchoscopic bronchoalveolar lavage. We review the indications and contraindications of these techniques, the equipment required, and the preparation and monitoring of the patient before, during and after the procedure. The complications of these techniques are also discussed. These recommendations may be adopted, modified or rejected according to clinical needs and constraints.

  7. [Research advances in association between pediatric obesity and bronchial asthma].

    PubMed

    Zhu, Lian; Xu, Zhi-Liang; Cheng, Yan-Yang

    2016-07-01

    This review article introduces the research advances in the pathophysiological mechanism of obesity in inducing pediatric bronchial asthma, including the role of leptin in obesity and asthma, the association of plasminogen activator inhibitor-1 with obesity and asthma, the association of adiponectin and interleukins with obesity and asthma, and the influence of neurotransmitter on asthma. In particular, this article introduces the latest research on the inhibition of allergic asthma through targeting at the nociceptor of dorsal root ganglion and blocking the signaling pathway of the nociceptor.

  8. Typhoid fever as a triggering factor in acute and intractable bronchial asthma attack.

    PubMed

    Wardhana; Surachmanto, Eko E; Datau, E A

    2013-10-01

    Typhoid fever is an enteric infection caused by Salmonella typhi. In Indonesia, typhoid fever is endemic with high incidence of the disease. In daily practice we frequently have patients with bronchial asthma, and it is becoming worse when these patients get typhoid fever. After oral ingestion, Salmonella typhi invades the the intestine mucosa after conducted by microbial binding to epithelial cells, destroying the microfold cells (M cell) then passed through the lamina propria and detected by dendritic cells (DC) which express a variety of pathogen recognition receptors on the surfaces, including Toll-Like Receptor (TLR). expressed on macrophages and on intestinal epithelial cells inducing degradation of IB, and translocation of NF-B (Nuclear Factor-Kappa Beta). This process initiates the induction of pro-inflammatory gene expression profile adhesion molecules, chemokines, adhesion molecules, and other proteins that induce and perpetuate the inflammation in host cells then will induce acute ant intractable attack of bronchial asthma. The role of typhoid fever in bronchial asthma, especially in persons with acute attack of bronchial asthma, is not well understood. In this article, we will discuss the role of typhoid fever in the bronchial asthma patients which may cause bronchial asthma significantly become more severe even triggering the acute and intractable attack of bronchial asthma. This fact makes an important point, to treat completely the typhoid fever in patients with bronchial asthma.

  9. A Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer.

    PubMed

    Silvestri, Gerard A; Vachani, Anil; Whitney, Duncan; Elashoff, Michael; Porta Smith, Kate; Ferguson, J Scott; Parsons, Ed; Mitra, Nandita; Brody, Jerome; Lenburg, Marc E; Spira, Avrum

    2015-07-16

    Bronchoscopy is frequently nondiagnostic in patients with pulmonary lesions suspected to be lung cancer. This often results in additional invasive testing, although many lesions are benign. We sought to validate a bronchial-airway gene-expression classifier that could improve the diagnostic performance of bronchoscopy. Current or former smokers undergoing bronchoscopy for suspected lung cancer were enrolled at 28 centers in two multicenter prospective studies (AEGIS-1 and AEGIS-2). A gene-expression classifier was measured in epithelial cells collected from the normal-appearing mainstem bronchus to assess the probability of lung cancer. A total of 639 patients in AEGIS-1 (298 patients) and AEGIS-2 (341 patients) met the criteria for inclusion. A total of 43% of bronchoscopic examinations were nondiagnostic for lung cancer, and invasive procedures were performed after bronchoscopy in 35% of patients with benign lesions. In AEGIS-1, the classifier had an area under the receiver-operating-characteristic curve (AUC) of 0.78 (95% confidence interval [CI], 0.73 to 0.83), a sensitivity of 88% (95% CI, 83 to 92), and a specificity of 47% (95% CI, 37 to 58). In AEGIS-2, the classifier had an AUC of 0.74 (95% CI, 0.68 to 0.80), a sensitivity of 89% (95% CI, 84 to 92), and a specificity of 47% (95% CI, 36 to 59). The combination of the classifier plus bronchoscopy had a sensitivity of 96% (95% CI, 93 to 98) in AEGIS-1 and 98% (95% CI, 96 to 99) in AEGIS-2, independent of lesion size and location. In 101 patients with an intermediate pretest probability of cancer, the negative predictive value of the classifier was 91% (95% CI, 75 to 98) among patients with a nondiagnostic bronchoscopic examination. The gene-expression classifier improved the diagnostic performance of bronchoscopy for the detection of lung cancer. In intermediate-risk patients with a nondiagnostic bronchoscopic examination, a negative classifier score provides support for a more conservative diagnostic

  10. Skin lesion of blastomycosis

    MedlinePlus

    ... gov/ency/article/000865.htm Skin lesion of blastomycosis To use the sharing features on this page, please enable JavaScript. A skin lesion of blastomycosis is a symptom of an infection with the ...

  11. In vivo expression of p53 and Bcl-2 and their role in programmed cell death in premalignant and malignant lung lesions.

    PubMed

    Koty, Patrick P; Zhang, Haifan; Franklin, Wilbur A; Yousem, Samuel A; Landreneau, Rodney; Levitt, Mark L

    2002-02-01

    Forty-four specimens of non-malignant and malignant human lung tissue, taken from patients with non-small cell lung cancer (NSCLC), were examined for the expression of wild-type p53, mutant p53, and bcl-2 and the occurrence of programmed cell death (apoptosis). Wild-type p53 expression peaked in peritumoral and metaplastic samples, whereas mutant p53, bcl-2 and apoptosis were first detected in metaplasia and increased with progression to carcinoma. Bcl-2 positive samples had lower levels of apoptosis than bcl-2 negative samples and was independent of wild-type or mutant p53 expression. These results suggest that the over-expression of wild-type p53 may be an early cellular response to an alteration in normal cellular homeostasis. The ensuing increase in apoptosis appears to be relatively independent of mutant or wild-type p53 expression, but does not occur in cells expressing bcl-2.

  12. Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia – a novel mouse model providing insights into geleophysic dysplasia

    PubMed Central

    Hubmacher, Dirk; Wang, Lauren W.; Mecham, Robert P.; Reinhardt, Dieter P.; Apte, Suneel S.

    2015-01-01

    ABSTRACT Mutations in the secreted glycoprotein ADAMTSL2 cause recessive geleophysic dysplasia (GD) in humans and Musladin–Lueke syndrome (MLS) in dogs. GD is a severe, often lethal, condition presenting with short stature, brachydactyly, stiff skin, joint contractures, tracheal-bronchial stenosis and cardiac valve anomalies, whereas MLS is non-lethal and characterized by short stature and severe skin fibrosis. Although most mutations in fibrillin-1 (FBN1) cause Marfan syndrome (MFS), a microfibril disorder leading to transforming growth factor-β (TGFβ) dysregulation, domain-specific FBN1 mutations result in dominant GD. ADAMTSL2 has been previously shown to bind FBN1 and latent TGFβ-binding protein-1 (LTBP1). Here, we investigated mice with targeted Adamtsl2 inactivation as a new model for GD (Adamtsl2−/− mice). An intragenic lacZ reporter in these mice showed that ADAMTSL2 was produced exclusively by bronchial smooth muscle cells during embryonic lung development. Adamtsl2−/− mice, which died at birth, had severe bronchial epithelial dysplasia with abnormal glycogen-rich inclusions in bronchial epithelium resembling the cellular anomalies described previously in GD. An increase in microfibrils in the bronchial wall was associated with increased FBN2 and microfibril-associated glycoprotein-1 (MAGP1) staining, whereas LTBP1 staining was increased in bronchial epithelium. ADAMTSL2 was shown to bind directly to FBN2 with an affinity comparable to FBN1. The observed extracellular matrix (ECM) alterations were associated with increased bronchial epithelial TGFβ signaling at 17.5 days of gestation; however, treatment with TGFβ-neutralizing antibody did not correct the epithelial dysplasia. These investigations reveal a new function of ADAMTSL2 in modulating microfibril formation, and a previously unsuspected association with FBN2. Our studies suggest that the bronchial epithelial dysplasia accompanying microfibril dysregulation in Adamtsl2−/− mice

  13. Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia--a novel mouse model providing insights into geleophysic dysplasia.

    PubMed

    Hubmacher, Dirk; Wang, Lauren W; Mecham, Robert P; Reinhardt, Dieter P; Apte, Suneel S

    2015-05-01

    Mutations in the secreted glycoprotein ADAMTSL2 cause recessive geleophysic dysplasia (GD) in humans and Musladin-Lueke syndrome (MLS) in dogs. GD is a severe, often lethal, condition presenting with short stature, brachydactyly, stiff skin, joint contractures, tracheal-bronchial stenosis and cardiac valve anomalies, whereas MLS is non-lethal and characterized by short stature and severe skin fibrosis. Although most mutations in fibrillin-1 (FBN1) cause Marfan syndrome (MFS), a microfibril disorder leading to transforming growth factor-β (TGFβ) dysregulation, domain-specific FBN1 mutations result in dominant GD. ADAMTSL2 has been previously shown to bind FBN1 and latent TGFβ-binding protein-1 (LTBP1). Here, we investigated mice with targeted Adamtsl2 inactivation as a new model for GD (Adamtsl2(-/-) mice). An intragenic lacZ reporter in these mice showed that ADAMTSL2 was produced exclusively by bronchial smooth muscle cells during embryonic lung development. Adamtsl2(-/-) mice, which died at birth, had severe bronchial epithelial dysplasia with abnormal glycogen-rich inclusions in bronchial epithelium resembling the cellular anomalies described previously in GD. An increase in microfibrils in the bronchial wall was associated with increased FBN2 and microfibril-associated glycoprotein-1 (MAGP1) staining, whereas LTBP1 staining was increased in bronchial epithelium. ADAMTSL2 was shown to bind directly to FBN2 with an affinity comparable to FBN1. The observed extracellular matrix (ECM) alterations were associated with increased bronchial epithelial TGFβ signaling at 17.5 days of gestation; however, treatment with TGFβ-neutralizing antibody did not correct the epithelial dysplasia. These investigations reveal a new function of ADAMTSL2 in modulating microfibril formation, and a previously unsuspected association with FBN2. Our studies suggest that the bronchial epithelial dysplasia accompanying microfibril dysregulation in Adamtsl2(-/-) mice cannot be reversed

  14. Prevalence of fungal hyphae in potentially malignant lesions and conditions—does its occurrence play a role in epithelial dysplasia?

    PubMed Central

    Hongal, Bhagyalaxmi Praveen; Kulkarni, Venkatesh V; Deshmukh, Revati Shailesh; Joshi, Priya Shirish; Karande, Prasad Prakash; Shroff, Adil S

    2015-01-01

    Background: Oral cancer is a major public health problem in India. A key factor that has led to lack of improvement in prognosis of oral cancer over the years, is delay in diagnosis and treatment. In many instances, a significant proportion of oral squamous cell carcinomas develop from premalignant lesions and conditions. Identification of such lesions and conditions is very important in order to prevent malignant transformation. The role of fungal infections has been studied and holds promise as an indicator to predict malignant transformation. So we designed a study to analyze the prevalence of fungal hyphae in biopsies of patients with clinically diagnosed cases of premalignant lesions and conditions. Aims and Objectives: To determine and compare the prevalence of fungal hyphae in biopsies of patients with clinically diagnosed cases of potentially malignant lesions and conditions and to assess the possible association between the degree of epithelial dysplasia and presence or absence of fungal hyphae. Materials and Methods: Clinically suspected and histopathologically diagnosed 70 cases of potentially malignant lesions and conditions (29 leukoplakia, 16 submucous fibrosis and 25 lichen planus) made up the study group. Three tissue sections (5μm) of each were stained with hematoxylin and eosin (H and E), periodic acid–Schiff's reagent (PAS) and Grocott's methenamine silver (GMS) and evaluated for fungal hyphae. The data collected was statistically analyzed by using Chi-square test and Statistical Package for Social Sciences (SPSS) software. Results: The estimated prevalence of fungal hyphae in cases with or without dysplasia in leukoplakia was 41.4%, lichen planus 36% and submucous fibrosis 25%. There was a significant association between degree of epithelial dysplasia with presence or absence of fungal hyphae in all the study groups. Conclusion: Presence of fungal hyphae in potentially malignant lesions and conditions may prove to be a useful indicator in

  15. Prevalence of fungal hyphae in potentially malignant lesions and conditions-does its occurrence play a role in epithelial dysplasia?

    PubMed

    Hongal, Bhagyalaxmi Praveen; Kulkarni, Venkatesh V; Deshmukh, Revati Shailesh; Joshi, Priya Shirish; Karande, Prasad Prakash; Shroff, Adil S

    2015-01-01

    Oral cancer is a major public health problem in India. A key factor that has led to lack of improvement in prognosis of oral cancer over the years, is delay in diagnosis and treatment. In many instances, a significant proportion of oral squamous cell carcinomas develop from premalignant lesions and conditions. Identification of such lesions and conditions is very important in order to prevent malignant transformation. The role of fungal infections has been studied and holds promise as an indicator to predict malignant transformation. So we designed a study to analyze the prevalence of fungal hyphae in biopsies of patients with clinically diagnosed cases of premalignant lesions and conditions. To determine and compare the prevalence of fungal hyphae in biopsies of patients with clinically diagnosed cases of potentially malignant lesions and conditions and to assess the possible association between the degree of epithelial dysplasia and presence or absence of fungal hyphae. Clinically suspected and histopathologically diagnosed 70 cases of potentially malignant lesions and conditions (29 leukoplakia, 16 submucous fibrosis and 25 lichen planus) made up the study group. Three tissue sections (5μm) of each were stained with hematoxylin and eosin (H and E), periodic acid-Schiff's reagent (PAS) and Grocott's methenamine silver (GMS) and evaluated for fungal hyphae. The data collected was statistically analyzed by using Chi-square test and Statistical Package for Social Sciences (SPSS) software. The estimated prevalence of fungal hyphae in cases with or without dysplasia in leukoplakia was 41.4%, lichen planus 36% and submucous fibrosis 25%. There was a significant association between degree of epithelial dysplasia with presence or absence of fungal hyphae in all the study groups. Presence of fungal hyphae in potentially malignant lesions and conditions may prove to be a useful indicator in predicting malignant transformation.

  16. Sensitivity of detection of asbestos bodies in sputa and bronchial washings

    SciTech Connect

    Wheeler, T.M.; Johnson, E.H.; Coughlin, D.; Greenberg, S.D.

    1988-09-01

    While asbestos bodies (ABs) in sputum and/or bronchial washings are highly specific markers for significant asbestos exposure, comparison of the sensitivity between sputum cytology and bronchial washing cytology for the detection of ABs had not been documented. Review of the files of the Cytopathology Laboratory, Methodist Hospital, Houston, Texas, for the period 1973 to 1984 identified 11 patients with slides available for review who (1) had been examined by both sputum cytology and bronchial washing cytology and (2) had at least one specimen positive for ABs. Of the 11 evaluable cases, all had ABs in the bronchial washings but ony 6 had ABs in the sputum. In addition, iron stain (e.g., the Prussian blue stain) was found to be more sensitive than the Papanicolaou stain for the detection of ABs in these cases. These findings indicate that iron-stained bronchial washing specimens should be preferred for the cytologic detection of asbestos exposure.

  17. Radial Endobronchial Ultrasound (EBUS) Guided Suction Catheter-Biopsy in Histological Diagnosis of Peripheral Pulmonary Lesions

    PubMed Central

    Zaric, Bojan; Stojsic, Vladimir; Carapic, Vladimir; Kovacevic, Tomi; Stojanovic, Goran; Panjkovic, Milana; Kioumis, Ioannis; Darwiche, Kaid; Zarogoulidis, Konstantinos; Stratakos, Grigoris; Tsavlis, Drosos; Hohenforst-Schmidt, Wolfgang; Pitsiou, Georgia; Zissimopoulos, Athanasios; Sachpekidis, Nikos; Karapantzos, Ilias; Karapantzou, Chrysanthi; Zarogoulidis, Paul; Perin, Branislav

    2016-01-01

    Background: EBUS guided trans-bronchial biopsy became routine in diagnosis of peripheral pulmonary lesions (PPL). Suction catheter-biopsy is a technique for obtaining a tissue sample from peripheral lung parenchyma. Aim of this study was to evaluate diagnostic efficiency, feasibility and safety of EBUS guided suction catheter-biopsy (SCB) in comparison to trans-bronchial biopsy (TBB) in diagnosis of PPL. The main intention was to demonstrate non-inferiority of the technique over trans-bronchial biopsy, especially when used under navigation of the EBUS. Methods: Radial EBUS probe (UM-3R, Olympus Co, Japan.) without guiding sheath was used to navigate suction catheter and TBB forceps to the PPL. The catheter was connected to the collection canister via vacuum pump. The SCB specimens were fixed with 10% buffered formalin. Results: There were 168 patients enrolled in this study; 69.9% males and 30.1% females. Main lesion diameter was 4.1±1.9 cm. Majority of patients, 131(77.9%) were diagnosed with lung cancer. Per-biopsy calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for EBUS-SCB were 92.4%, 100%, 100% and 67.7%, respectively. Corresponding values for EBUS-TBB were 92.3%, 100%, 100% and 69.7%. Only the size of the lesion significantly influenced (p=0.005) diagnostic performance. Complications occurred in 2 patients; one pneumothorax and one excessive bleeding. Conclusion: EBUS guided SCB is efficient, feasible and safe in diagnosis of peripheral lung cancer. The technique is complementary to trans-bronchial biopsy. PMID:26722354

  18. Oral submucous fibrosis: a premalignant condition in a 14-year-old Indian girl

    PubMed Central

    Deshpande, Anshula; Kiran, Shital; Dhillon, Steffi; Mallikarjuna, Rachappa

    2013-01-01

    A 14-year-old Indian girl presented with difficulty in mouth opening and burning sensation while eating. On examination, blanching of the oral mucosa with diffuse white pigmented lesion of size 3.5 to 2 cm along with melanotic pigmentation was seen on the left buccal mucosa posteriorly. The patient was diagnosed with oral submucous fibrosis. A comprehensive treatment plan was made based on conservative management that included motivation and intense counselling of the patient and her parents so that she quits the habit of chewing areca nut and tobacco, along with systemic treatment of vitamin B complex supplements, antioxidants, multivitamins and oral physiotherapy. We present this case to highlight the difficulties faced by the clinical practitioners in providing treatment because of the taboos and myths associated with surgical treatment modality in rural population as well as to emphasise the menace of increasing consumption and availability of tobacco and areca nut to children. PMID:24334472

  19. Oral submucous fibrosis: a premalignant condition in a 14-year-old Indian girl.

    PubMed

    Deshpande, Anshula; Kiran, Shital; Dhillon, Steffi; Mallikarjuna, Rachappa

    2013-12-12

    A 14-year-old Indian girl presented with difficulty in mouth opening and burning sensation while eating. On examination, blanching of the oral mucosa with diffuse white pigmented lesion of size 3.5 to 2 cm along with melanotic pigmentation was seen on the left buccal mucosa posteriorly. The patient was diagnosed with oral submucous fibrosis. A comprehensive treatment plan was made based on conservative management that included motivation and intense counselling of the patient and her parents so that she quits the habit of chewing areca nut and tobacco, along with systemic treatment of vitamin B complex supplements, antioxidants, multivitamins and oral physiotherapy. We present this case to highlight the difficulties faced by the clinical practitioners in providing treatment because of the taboos and myths associated with surgical treatment modality in rural population as well as to emphasise the menace of increasing consumption and availability of tobacco and areca nut to children.

  20. Example based lesion segmentation

    NASA Astrophysics Data System (ADS)

    Roy, Snehashis; He, Qing; Carass, Aaron; Jog, Amod; Cuzzocreo, Jennifer L.; Reich, Daniel S.; Prince, Jerry; Pham, Dzung

    2014-03-01

    Automatic and accurate detection of white matter lesions is a significant step toward understanding the progression of many diseases, like Alzheimer's disease or multiple sclerosis. Multi-modal MR images are often used to segment T2 white matter lesions that can represent regions of demyelination or ischemia. Some automated lesion segmentation methods describe the lesion intensities using generative models, and then classify the lesions with some combination of heuristics and cost minimization. In contrast, we propose a patch-based method, in which lesions are found using examples from an atlas containing multi-modal MR images and corresponding manual delineations of lesions. Patches from subject MR images are matched to patches from the atlas and lesion memberships are found based on patch similarity weights. We experiment on 43 subjects with MS, whose scans show various levels of lesion-load. We demonstrate significant improvement in Dice coefficient and total lesion volume compared to a state of the art model-based lesion segmentation method, indicating more accurate delineation of lesions.

  1. P16(INK 4a) and Ki-67 expression in human papilloma virus-related head and neck mucosal lesions.

    PubMed

    Gültekin, Sibel Elif; Sengüven, Burcu; Klussmann, Jens Peter; Dienes, Hans Peter

    2015-03-01

    Human papilloma virus (HPV) is postulated as a risk factor in the etiology of some specific mucosal pathologies in the head and neck regions. Despite the frequent use of p16(INK4a) as a surrogate marker for HPV-infection, there is still controversy with respect to its reliability. This study has been undertaken to assess the potential role of p16(INK 4a) and Ki-67 expression in HPV-related lesions. The study was conducted on 71 specimens of oral, tonsillar and laryngeal lesions which comprised 25 dysplasia and 46 papilloma specimens. Specimens were immunohistochemically stained for p16(INK4A) and Ki-67 proteins. HPV DNA was determined by one step multiplex polymerase chain reaction. HPV DNA was detected in 33.8% of all lesions. Tonsil and larynx lesions showed significant differences with oral lesions for HPV positivity (p < 0.001). p16(INK 4a) over-expression was seen in 56.5% of papilloma and 60% of dysplasia specimens. HPV status showed a positive correlation with p16(INK 4a) expression in tonsillar dysplasias (p < 0.001). p16(INK 4a) expression may have a value as a marker in high risk HPV induced dysplasias, but not in low risk infected lesions. The proliferation index is not related to HPV-induced lesions and may be evaluated as an independent marker in head and neck premalignant lesions.

  2. [Granulomatous lung lesions after occupational exposure to glass fibers].

    PubMed

    Klimczak, A; Langfort, R; Zych, J; Bestry, I; Rowińska-Zakrzewska, E

    2000-01-01

    39 years old man with granulomatous lesions in both lungs caused by occupational contact with glass fibers was described. He has been working as an bricklayer-plasterer for 18 years and was in contact with lime, cement, plaster, asbestos, dust of coal and wood and with glass fibers. For the last two years before admission in 1993 he has had frequent bronchial infections. On admission he was in good general condition, his spirometric examination and blood gases were within normal limits. On chest x-ray disseminated lesions were found. Those lesions were of the round shapes on chest CT. Many sputum cultures for tubercle bacilli were negative. ANA and ANCA were not found in the serum. ACE was within normal limits. No precipitins to environmental antigens were found. Cancer metastases were suspected and lung biopsy during videothoracoscopy was done. Many foreign body type granulomas were found throughout the specimen. The character of the lesions was not typical for tuberculosis, sarcoidosis, extrinsic allergic alveolitis, silicosis or asbestosis. There are some reports concerning the possibility of development of such lesions after the exposition to glass fibers. We suspect that case is an example of such pathology. His occupational exposition was stopped in 1993 and he was observed without treatment. During the 5 years of observation (up till 1998) he was in good health with stable chest x-ray picture and results of respiratory system function.

  3. Bronchial elastic fibers in normal subjects and asthmatic patients.

    PubMed

    Bousquet, J; Lacoste, J Y; Chanez, P; Vic, P; Godard, P; Michel, F B

    1996-05-01

    Elastic fibers required to maintain bronchial patency during ventilation may be damaged in asthma as a result of repair following inflammation or stretching during exacerbations. Fifteen normal subjects and 40 asthmatics of variable severity were studied. Bronchial biopsies were obtained from a subsegmental bronchus using a flexible bronchoscope. The elastic fibers were examined using orceine-eosine sustaining and/or immunohistochemistry with two monoclonal antibodies against elastin or transmission electron microscopy (six asthmatics and four control subjects). Orceine-eosine staining revealed that most normal subjects had normal fibers throughout the submucosa whereas of the 21 asthmatics analyzed only three had a normal superficial elastin network. In five patients, elastin had virtually disappeared. In the remaining patients, fibers appeared fragmented. The deeper layer of elastic fibers was abnormal in 17 asthmatics, fibers being patchy, tangled, and thickened. The fragmentation of the superficial network of elastic fibers shown in asthmatics was confirmed by immunohistochemistry. Electron microscopy studies suggested that the elastinolytic process and fragmentation of elastic fibers occurred in asthmatics. Elastinolysis occurs in the airways of asthmatics possibly as a result of repair elicited by chronic inflammation. Mechanical stretch induced by breathing and edema may lead to the fragmentation of fibers in asthmatic airways.

  4. Laser-assisted solder closure of bronchial stumps

    NASA Astrophysics Data System (ADS)

    Oz, Mehmet C.; Williams, Matthew R.; Moscarelli, Richard D.; Kaynar, Murat; Fras, Christian I.; Libutti, Steven K.; Smith, Hillary; Setton, Adrianne J.; Treat, Michael R.; Nowygrod, Roman

    1992-06-01

    Broncho-pleural fistula is a difficult clinical problem without a simple solution. Laser-assisted solder techniques potentially offer a means to precisely fix tissue glues into the fistulae through a bronchoscopic approach. Using a canine model, secondary bronchi were sealed with cryoprecipitate made from solvent/detergent treated plasma (treated to inactivate membrane enveloped virus) mixed with indocyanine green (absorption 805 nm). Diode laser energy (emission 808 nm, 7.3 W/cm2) was applied to the solder until desiccation was observed. Leakage pressures ranged between 18 - 86 mmHg with a mean of 46 +/- 24 mmHg. Laser-assisted solder techniques provide a reliably strong seal over leaking bronchial stumps and use of dye enhancement prevents undesired collateral thermal injury to surrounding bronchial tissue. Solvent/detergent plasma, prepared by methods shown to inactivate large quantities of HIV, HBV, and HCV, is an effective source of cyroprecipitate and should allow widespread use of pooled human material in a clinical setting.

  5. Bronchial lability and skin reactivity in siblings of asthmatic children.

    PubMed

    Verity, C M; Vanheule, B; Carswell, F; Hughes, A O

    1984-09-01

    Seventy five children with asthma (42 boys and 33 girls; age range 4 years 2 months to 15 years) and 75 of their siblings (37 boys and 38 girls; age range 4 years 3 months to 17 years 8 months) were studied to elucidate the mechanisms involved in the increased prevalence of asthma in boys, a prevalence that tends to disappear after puberty. Immediate cutaneous hypersensitivity to five allergens and maximum fall in peak expiratory flow rate after six minutes of treadmill running (bronchial lability) were determined in patients and siblings. There was no significant difference between boys and girls in skin test reactivity to single or multiple allergens in the sibling group. The percentage fall in peak expiratory flow rate after exercise was significantly greater in male than in female siblings and when a positive test was defined as a fall after exercise of either 10% or 15% of the rate before exercise the number of positive tests was significantly greater in boys. The results suggest that more boys than girls in this age group have asthma because their bronchial lability is greater, and not because more boys are atopic.

  6. Optical low-coherence tomography of bronchial tissue

    NASA Astrophysics Data System (ADS)

    Bamford, Karl J.; James, Stephen W.; Barr, Hugh; Tatam, Ralph P.

    1999-12-01

    An optical fiber based low coherence interferometer for measuring the Epithelium thickness of Bronchial tissue, for early diagnosis of Carcinoma in situ, is presented. Previous simulation of laser induced fluorescence using an electromagnetic scattering model has extracted the relative permittivity value for the Submucosa and Epithelium layers indicating a difference of up to 0.14. The optical system presented here uses a low coherence source operating at 840 nm with a bandwidth of 30 nm, coupled into single mode optical fiber. A Fizeau cavity is formed between the fiber end and the tissue under investigation. A remote processing interferometer is used to monitor changes in permittivity between the different tissue layers. An initial experiment has demonstrated a sensitivity measurement of 40 dB for a permittivity difference measurement of 0.61. Preliminary results have shown that the discontinuity between the Bronchial Epithelium layer and its surrounding medium can be identified allowing the thickness of the Epithelium layer to be measured to an accuracy of 20 micrometers . Since interferometric noise contributions are only significant within the processing interferometer, the fiber optic Fizeau interferometer technique is a strong candidate for the development of an endoscope for the early detection of cancer within Gastrointestinal and Respiratory tracts.

  7. Estradiol Increases Mucus Synthesis in Bronchial Epithelial Cells

    PubMed Central

    Tam, Anthony; Wadsworth, Samuel; Dorscheid, Delbert; Man, Shu-Fan Paul; Sin, Don D.

    2014-01-01

    Airway epithelial mucus hypersecretion and mucus plugging are prominent pathologic features of chronic inflammatory conditions of the airway (e.g. asthma and cystic fibrosis) and in most of these conditions, women have worse prognosis compared with male patients. We thus investigated the effects of estradiol on mucus expression in primary normal human bronchial epithelial cells from female donors grown at an air liquid interface (ALI). Treatment with estradiol in physiological ranges for 2 weeks caused a concentration-dependent increase in the number of PAS-positive cells (confirmed to be goblet cells by MUC5AC immunostaining) in ALI cultures, and this action was attenuated by estrogen receptor beta (ER-β) antagonist. Protein microarray data showed that nuclear factor of activated T-cell (NFAT) in the nuclear fraction of NHBE cells was increased with estradiol treatment. Estradiol increased NFATc1 mRNA and protein in ALI cultures. In a human airway epithelial (1HAE0) cell line, NFATc1 was required for the regulation of MUC5AC mRNA and protein. Estradiol also induced post-translational modification of mucins by increasing total fucose residues and fucosyltransferase (FUT-4, -5, -6) mRNA expression. Together, these data indicate a novel mechanism by which estradiol increases mucus synthesis in the human bronchial epithelium. PMID:24964096

  8. [Bronchial carcinoma at the Zadar Medical Center 1982-1986].

    PubMed

    Mazzi, A; Mazzi, M

    1989-01-01

    In the period between 1982-1986, 2132 neoplasms were registered in the Zadar Medical Center, out of them 164 (7.7%) were primary bronchial carcinomas of which 138 (84.1%) were morphologically verified. The difference between the number of the registered and verified bronchial carcinomas is due to the difference in the registration criteria. The annual average incidence rate of the verified carcinomas was about 30 which is lower than in the Zagreb area and Croatia as a whole. The average number of cases diagnosed in other institutions was about 20 percent. An analysis by sex revealed a prevalence among males aged 55-75. Morphologically, the most common type of carcinoma was planocellular, followed by anaplastic, small cell carcinoma and adenocarcinoma. The greatest majority of the positive findings was obtained by bronchoscopy and sputum examination. The average number of sputa obtained per patient was 3.5; 63 percent of these were adequate and 40 percent of them were positive. In 86% of cases the diagnosis was established from the first three sputa. The most frequently used bronchoscopic method of material obtained was aspiration and the best diagnostic results were obtained by puncture biopsy and excision. The high percentage of positive results obtained by transtracheal biopsy justifies its use.

  9. Regional differences in bronchial reactivity assessed by respiratory impedance.

    PubMed

    Beretta, Egidio; Tana, Francesco; Grasso, Gabriele Simone; Bartesaghi, Manuela; Novelli, Luca; Pesci, Alberto; Miserocchi, Giuseppe

    2014-02-01

    We used the Impulse Oscillometric System (IOS) to gain information concerning the distribution of hyper-reactivity along the bronchial tree during methacholine challenge test (MCT). 37 subjects underwent MCT until reaching the provocative dose (PD20). At each dose, we estimated respiratory resistance at 5 and 20Hz (R5, R20), and reactance at 5Hz (X5). In non-responsive subjects (N=14) no changes in R5, R20, and X5 were observed during MCT. In responsive subjects, a wide spectrum of responses was found concerning frequency dependence and PD20. We describe two phenotypes representing the extremes of response. For PD20>400μg (N=13), MCT caused equal changes of resistance/reactance on varying oscillation frequencies, suggesting a homogeneous bronchoconstriction along the bronchial tree. For PD20<200μg (N=10), a remarkable frequency dependence was observed, with increase in R5, no change in R20, and decrease in X5, suggesting hyper-responsiveness of the distal airways paralleled by a change in visco-elastic properties of lung parenchyma.

  10. Parasympathetic Stimuli on Bronchial and Cardiovascular Systems in Humans.

    PubMed

    Zannin, Emanuela; Pellegrino, Riccardo; Di Toro, Alessandro; Antonelli, Andrea; Dellacà, Raffaele L; Bernardi, Luciano

    2015-01-01

    It is not known whether parasympathetic outflow simultaneously acts on bronchial tone and cardiovascular system waxing and waning both systems in parallel, or, alternatively, whether the regulation is more dependent on local factors and therefore independent on each system. The aim of this study was to evaluate the simultaneous effect of different kinds of stimulations, all associated with parasympathetic activation, on bronchomotor tone and cardiovascular autonomic regulation. Respiratory system resistance (Rrs, forced oscillation technique) and cardio-vascular activity (heart rate, oxygen saturation, tissue oxygenation index, blood pressure) were assessed in 13 volunteers at baseline and during a series of parasympathetic stimuli: O2 inhalation, stimulation of the carotid sinus baroreceptors by neck suction, slow breathing, and inhalation of methacholine. Pure cholinergic stimuli, like O2 inhalation and baroreceptors stimulation, caused an increase in Rrs and a reduction in heart rate and blood pressure. Slow breathing led to bradycardia and hypotension, without significant changes in Rrs. However slow breathing was associated with deep inhalations, and Rrs evaluated at the baseline lung volumes was significantly increased, suggesting that the large tidal volumes reversed the airways narrowing effect of parasympathetic activation. Finally inhaled methacholine caused marked airway narrowing, while the cardiovascular variables were unaffected, presumably because of the sympathetic activity triggered in response to hypoxemia. All parasympathetic stimuli affected bronchial tone and moderately affected also the cardiovascular system. However the response differed depending on the nature of the stimulus. Slow breathing was associated with large tidal volumes that reversed the airways narrowing effect of parasympathetic activation.

  11. Monitoring asthma in childhood: lung function, bronchial responsiveness and inflammation.

    PubMed

    Moeller, Alexander; Carlsen, Kai-Hakon; Sly, Peter D; Baraldi, Eugenio; Piacentini, Giorgio; Pavord, Ian; Lex, Christiane; Saglani, Sejal

    2015-06-01

    This review focuses on the methods available for measuring reversible airways obstruction, bronchial hyperresponsiveness (BHR) and inflammation as hallmarks of asthma, and their role in monitoring children with asthma. Persistent bronchial obstruction may occur in asymptomatic children and is considered a risk factor for severe asthma episodes and is associated with poor asthma outcome. Annual measurement of forced expiratory volume in 1 s using office based spirometry is considered useful. Other lung function measurements including the assessment of BHR may be reserved for children with possible exercise limitations, poor symptom perception and those not responding to their current treatment or with atypical asthma symptoms, and performed on a higher specialty level. To date, for most methods of measuring lung function there are no proper randomised controlled or large longitudinal studies available to establish their role in asthma management in children. Noninvasive biomarkers for monitoring inflammation in children are available, for example the measurement of exhaled nitric oxide fraction, and the assessment of induced sputum cytology or inflammatory mediators in the exhaled breath condensate. However, their role and usefulness in routine clinical practice to monitor and guide therapy remains unclear, and therefore, their use should be reserved for selected cases.

  12. Human Papillomavirus in Brazilian women with and without cervical lesions

    PubMed Central

    2011-01-01

    Background Human Papillomavirus (HPV) high-risk (HR) types are the causal factor for cervical cancer and premalignant dysplasia. Data on frequency of HPV types provide a basis to design and evaluate HPV prevention programs. Taking into account the heterogeneity of HPV types across and within populations this study aims to access the HPV frequency in Brazilian women. Results We identified 24 different types of HPV, including a Betapapillomavirus and a likely new type, previously reported, from 132 women positive for the virus analysed by Hybrid Capture II assay. These women were infected by a single or multiple HPV types and 142 HPV strains were identified. HR types were found in 75% of women and HPV types 16, 18, 45, 58, and 66 had the highest frequency. Significant differences in frequency of HR HPV types were found for presence of cervical lesions, and for different HPV species and women age. Conclusions Compared with previous studies in Brazil, our data indicated differences in frequency and HPV type diversity, a significant association of other HR-types but HPV16 and 18 and cervical lesions, and a trend for distinct distribution of HPV types by age. PMID:21208414

  13. [Etiology and pathogenesis of precancerous lesions and invasive cervical carcinoma].

    PubMed

    Panjković, Milana; Ivković-Kapicl, Tatjana

    2008-01-01

    Cervical cancer is the second most common gynecological malignancy in the world. Human papilloma virus (HPV) infection is the leading ethiologic agent in the development of premalignant and malignant cervical diseases. HPV is a member of the Papovaviridae family and until now over 100 types have been recognized There are two types of viral infection: latent and productive. Virus induced oncogenesis is the result of interaction between virus oncoproteins E6 and E7 and tumor supresor host genes p53 and Rb. Many cofactors such as immunosuppression, early sexual relationship, multiple sexual partners, other sexualy transsmited infections and smoking are contributing factors of the precancerous and invasive cervical lesions. According to the oncogenic potential HPV are divided into three groups: low, intermediate and high oncogenic risk viruses. Molecular technics which are used for the virus detection are: In situ hibridisation, Hyybrid capture test and polymerasa chain reaction. Human papilloma virus testing has an important role in the follow up and treatment of women with "atypical squamous cells of unknown significant" changes in cervical smears and low-grade squamous intraepithelial lesions, changes in punch biopsy.

  14. Mining Gene Expression Signature for the Detection of Pre-Malignant Melanocytes and Early Melanomas with Risk for Metastasis

    PubMed Central

    de Souza, Camila Ferreira; Xander, Patrícia; Monteiro, Ana Carolina; Silva, Amanda Gonçalves dos Santos; da Silva, Débora Castanheira Pereira; Mai, Sabine; Bernardo, Viviane; Lopes, José Daniel; Jasiulionis, Miriam Galvonas

    2012-01-01

    Background Metastatic melanoma is a highly aggressive skin cancer and currently resistant to systemic therapy. Melanomas may involve genetic, epigenetic and metabolic abnormalities. Evidence is emerging that epigenetic changes might play a significant role in tumor cell plasticity and metastatic phenotype of melanoma cells. Principal findings In this study, we developed a systematic approach to identify genes implicated in melanoma progression. To do this, we used the Affymetrix GeneChip Arrays to screen 34,000 mouse transcripts in melan-a melanocytes, 4C pre-malignant melanocytes, 4C11− non-metastatic and 4C11+ metastatic melanoma cell lines. The genome-wide association studies revealed pathways commonly over-represented in the transition from immortalized to pre-malignant stage, and under-represented in the transition from non-metastatic to metastatic stage. Additionally, the treatment of cells with 10 µM 5-aza-2′-deoxycytidine (5AzaCdR) for 48 hours allowed us to identify genes differentially re-expressed at specific stages of melan-a malignant transformation. Treatment of human primary melanocytes with the demethylating agent 5AzaCdR in combination to the histone deacetylase inhibitor Trichostatin A (TSA) revealed changes on melanocyte morphology and gene expression which could be an indicator of epigenetic flexibility in normal melanocytes. Moreover, changes on gene expression recognized by affecting the melanocyte biology (NDRG2 and VDR), phenotype of metastatic melanoma cells (HSPB1 and SERPINE1) and response to cancer therapy (CTCF, NSD1 and SRC) were found when Mel-2 and/or Mel-3-derived patient metastases were exposed to 5AzaCdR plus TSA treatment. Hierarchical clustering and network analyses in a panel of five patient-derived metastatic melanoma cells showed gene interactions that have never been described in melanomas. Significance Despite the heterogeneity observed in melanomas, this study demonstrates the utility of our murine melanoma

  15. Evaluation of p53, Caspase-3, Bcl-2, and Ki-67 markers in oral squamous cell carcinoma and premalignant epithelium in a sample from Alava Province (Spain)

    PubMed Central

    Rodríguez-Gutierrez, Carlos; Rodríguez-Gómez, Enrique; Gil-Montoya, José A.; Gómez-Font, Rafael; González-Moles, Miguel Á.

    2013-01-01

    Objectives: The objective of this study was to determine whether alterations in the expression of p53, caspase-3 Bcl-2, and ki-67 appear early in premalignant oral epithelium and show clonal behavior. Study Design: Samples from 41 tumors with their adjacent non-tumor epithelia were immunohistochemically analyzed using monoclonal antibodies that recognize p53, caspase-3, Bcl-2, and Ki-67 Results: A statistically significant association was found between the expression in tumor and adjacent epithelium of p53, caspase-3, and Bcl-2 but not of k-67. A significant association was observed between the expression of ki-67 and p53 in both localizations. In non-tumor (premalignant) epithelium samples, there was a significant inverse relationship between the expressions of p53 and caspase-3 and a significant direct relationship between the expressions of p53 and Bcl-2. Conclusions: Alterations in these proteins appear to operate in combination with premalignant epithelia to create hyperproliferative cell states that favor the acquisition of summative oncogenic errors that confer invasive capacity. Key words:Cell cycle, apoptosis, p53, caspase-3, Bcl-2, Ki-67. PMID:23722133

  16. Eosinophil cationic protein mRNA expression in children with bronchial asthma.

    PubMed

    Yu, H Y; Li, X Y; Cai, Z F; Li, L; Shi, X Z; Song, H X; Liu, X J

    2015-11-13

    Studies have shown that eosinophils are closely related to pathogenesis of bronchial asthma. Eosinophils release eosinophil cationic protein (ECP), which plays an important role in infection and allergic reactions. Serum ECP mRNA expression in children with bronchial asthma has not been adequately investigated. We analyzed serum ECP mRNA expression in 63 children with bronchial asthma and 21 healthy children by using reverse-transcriptase polymerase chain reaction to understand the role of ECP in children with bronchial asthma. The children with bronchial asthma were segregated into acute-phase and stable-phase groups, based on the severity of the illness. Serum ECP mRNA expression in children with bronchial asthma (0.375 ± 0.04) was significantly higher than that in healthy controls (0.20 ± 0.02; P < 0.05). Additionally, children in the acute-phase group showed higher ECP mRNA expression level (0.44 ± 0.06) than those in the stable-phase (0.31 ± 0.03) and healthy control groups (0.20 ± 0.02; P < 0.05), while the level in the stable-phase (0.31 ± 0.03) was markedly higher than that in the healthy control group (0.20 ± 0.02; P < 0.05). Detection of serum ECP mRNA expression level has possible applications in the diagnosis and treatment of children with bronchial asthma.

  17. [Response mechanisms of the airway smooth muscle tissue in experimental bronchial spasm].

    PubMed

    Zashikhin, A L; Agafonov, Iu V; Barmina, A O

    2009-01-01

    This investigation was aimed at the complex evaluation of the reactivity mechanisms of bronchial smooth muscle tissue (SMT) in experimental bronchial spasm. Morphometric, cytospectrophotometric and electron microscopical analysis demonstrated the presence of three types of smooth muscle cells (SMC) within the bronchial SMT (small, medium, large), that differed in their linear and metabolic parameters. The findings of this study indicate that under the conditions of experimental bronchial spasm development, the ratios of SMC in bronchial SMT are changed with the increase in proportion of small SMC and the elimination of large SMC. In the dynamics of experimental bronchial spasm development, the activation of cytoplasmic synthesis as well as of DNA synthesis was detected mainly in group of small SMC. The reactive-dystrophic changes were marked at the subcellular level, that were most often identified in large SMC resulting in their elimination from population in the dynamics of an experiment. The data obtained suggest that one of the important mechanisms of airway SMT adaptation to the bronchial spasm development is a dynamic reorganization of SMC population.

  18. A novel approach: treatment of bronchial stump fistula with a plugged, bullet-shaped, angled stent.

    PubMed

    Han, Xinwei; Wu, Gang; Li, Yongdong; Li, Minghua

    2006-05-01

    The purpose of this study was to evaluate the initial clinical efficacy of a plugged, bullet-shaped, angled stent for managing bronchial stump fistula. The stent consisted of two parts. The body part had a diameter of 18 approximately 25 mm and was 30 mm long in a tubular configuration covered with polyethylene at the lower part. The bronchial limb was a bullet-shaped configuration with a dead end, 11 approximately 14 mm in diameter, 10 approximately 30 mm long covered with polyethylene. The body part and the bronchial limb were connected at the angled portion without overlap with use of nitinol wire and polyethylene. The stents were placed in 6 patients under fluoroscopic guidance. Stent placement was technically successful in all patients without complications. Immediate closure of the bronchial stump fistula was achieved in all patients after stent placement. Follow-up of 4 approximately 16 months, permanent closure of the bronchial pleural fistula was achieved in 4 patients (66.67%), and permanent closure of the bronchial stump fistula was achieved in 5 patients (83.33%). No complications occurred. Closure of the bronchial stump fistula with the stent was a simple, safe, and effective procedure.

  19. Measurement of bronchial blood flow in the sheep by video dilution technique.

    PubMed Central

    Link, D P; Parsons, G H; Lantz, B M; Gunther, R A; Green, J F; Cross, C E

    1985-01-01

    Bronchial blood flow was determined in five adult anaesthetised sheep by the video dilution technique. This is a new fluoroscopic technique for measuring blood flow that requires only arterial catheterisation. Catheters were placed into the broncho-oesophageal artery and ascending aorta from the femoral arteries for contrast injections and subsequent videotape recording. The technique yields bronchial blood flow as a percentage of cardiac output. The average bronchial artery blood flow was 0.6% (SD 0.20%) of cardiac output. In one sheep histamine (90 micrograms) injected directly into the bronchial artery increased bronchial blood flow by a factor of 6 and histamine (90 micrograms) plus methacholine (4.5 micrograms) augmented flow by a factor of 7.5 while leaving cardiac output unchanged. This study confirms the high degree of reactivity of the bronchial circulation and demonstrates the feasibility of using the video dilution technique to investigate the determinants of total bronchial artery blood flow in a stable animal model avoiding thoracotomy. Images PMID:3883564

  20. Technetium 99m-labeled VQ peptide: a new imaging agent for the early detection of tumors or premalignancies.

    PubMed

    Shi, Jiyun; Cui, Liyang; Jia, Bing; Liu, Zhaofei; He, Peng; Dong, Chengyan; Jin, Xiaona; Zhao, Huiyun; Li, Fang; Wang, Fan

    2013-01-01

    There is a critical need to develop diagnostic procedures enabling early detection of tumors while at a curable stage. Technetium 99m (99mTc)-labeled VQ peptide (99mTc-HYNIC-VQ) identified through screening phage display peptide libraries against fresh human colonic adenomas was prepared and evaluated for tumor detection. 99mTc-HYNIC-VQ was prepared by a non-SnCl2 method with more than 99% radiochemical purity. The biodistribution in the HT-29 tumor model showed that although the absolute tumor uptake values were relatively low (0.60 ± 0.09, 0.41 ± 0.09, 0.36 ± 0.18, and 0.19 ± 0.08 %ID/g at 0.5, 1, 2, and 4 hours postinjection, respectively), the tumor uptake was higher than that of any of the other organs except for the kidneys at any time point examined, which led to the high tumor to nontarget ratios. The tumors and inflammation were clearly visualized with high contrast. Although the mechanism of accumulation of radiolabeled VQ peptide in tumors and inflammation needs to be further investigated, 99mTc-HYNIC-VQ is a promising imaging agent for the early detection of tumors or premalignancies, at least for screening patients with a high risk of developing cancers.

  1. Low-Dose Pesticide Mixture Induces Senescence in Normal Mesenchymal Stem Cells (MSC) and Promotes Tumorigenic Phenotype in Premalignant MSC.

    PubMed

    Hochane, Mazene; Trichet, Valerie; Pecqueur, Claire; Avril, Pierre; Oliver, Lisa; Denis, Jerome; Brion, Regis; Amiaud, Jerome; Pineau, Alain; Naveilhan, Philippe; Heymann, Dominique; Vallette, François M; Olivier, Christophe

    2017-03-01

    Humans are chronically exposed to multiple environmental pollutants such as pesticides with no significant evidence about the safety of such poly-exposures. We exposed mesenchymal stem cells (MSC) to very low doses of mixture of seven pesticides frequently detected in food samples for 21 days in vitro. We observed a permanent phenotype modification with a specific induction of an oxidative stress-related senescence. Pesticide mixture also induced a shift in MSC differentiation towards adipogenesis but did not initiate a tumorigenic transformation. In modified MSC in which a premalignant phenotype was induced, the exposure to pesticide mixture promoted tumorigenic phenotype both in vitro and in vivo after cell implantation, in all nude mice. Our results suggest that a common combination of pesticides can induce a premature ageing of adult MSC, and as such could accelerate age-related diseases. Exposure to pesticide mixture may also promote the tumorigenic transformation in a predisposed stromal environment. Abstract Video Link: https://youtu.be/mfSVPTol-Gk Stem Cells 2017;35:800-811. © 2016 AlphaMed Press.

  2. Analysis of silver binding nucleolar organizer regions in exfoliative cytology smears of potentially malignant and malignant oral lesions.

    PubMed

    Sowmya, G V; Nahar, P; Astekar, M; Agarwal, H; Singh, M P

    2017-01-01

    Nucleolar organizer regions are nucleolar components that contain proteins that are stained selectively by silver methods; they can be identified as black dots throughout the nucleolus and are known as silver binding nucleolar organizer regions (AgNOR). The number of AgNOR is related to the cell cycle and the proliferative activity of the cells. We investigated AgNOR using exfoliative cytology smears of potentially malignant oral lesions. Eighty individuals were divided into four equal groups: healthy controls, oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma. The mean number of AgNOR in each study group gradually increased from control to oral leukoplakia to oral submucous fibrosis to oral squamous cell carcinoma. The proliferative index was increased in the oral premalignant and malignant patients compared to normal subjects. The mean AgNOR size gradually increased from control to oral leukoplakia to oral submucous fibrosis to oral squamous cell carcinoma. Spherical shaped AgNOR were most common in controls, whereas large, clustered and kidney shapes were most common in oral squamous cell carcinoma. Multiparameter analysis of AgNOR in oral exfoliative smears is a simple, sensitive and cost-effective method for differentiating premalignant from malignant lesions and can be used in conjunction with routine cytomorphological evaluation.

  3. [Suppression of non-specific bronchial hyperreactivity by DSCG (Disodium cromoglycate) and ipratropium bromide (author's transl)].

    PubMed

    Götz, M; Popow, C

    1980-09-26

    The protective activity of DSCG was investigated in 18 children with established non-specific bronchial hyperreactivity induced by bronchial challenge with acetylcholine. Ipratropium bromide, the anticholinergic agent, was used for comparison. DSCG showed a statistically significant inhibitory action on the decrease in specific airway conductance. Besides the well-established inhibition of mast cell degranulation a direct action on cholinergic irritative receptors seems likely. Application of DSCG in immunologically ill-defined forms of bronchial asthma may be considered. As expected, the direct acetylcholine antagonist, ipratropium bromide, showed an overall protective effect.

  4. [The effect of the Finnish dry sauna on bronchial asthma in childhood].

    PubMed

    Preisler, B; Falkenbach, A; Klüber, B; Hofmann, D

    1990-10-01

    More than 400,000 sauna baths have been built in Germany. Frequently, children with bronchial asthma and their parents raise the question whether sauna bathing might be hazardous for the lungs. In present study the effects of sauna bathing on the ventilation have been evaluated by use of peak-flow meters. Only one 12-years old girl suffered an attack of bronchial asthma while using a cold shower, probably as a result of breathing cold air. No other complications have been observed. Sauna bathing can be recommended for children with bronchial asthma, since advantages in the resistance against infections and in psychosocial development can be expected.

  5. Congenital right intermediate bronchial stenosis with carina trifurcation: successful management with slide tracheobronchial plasty.

    PubMed

    Wu, En-Ting; Yang, Ming-Chun; Wang, Ching-Chia; Lin, Ming-Tai; Chen, Shyh-Jye; Huang, Chi-Hsiang; Hwang, Haw-Kwei; Chen, Ming-Ren; Huang, Shu-Chien

    2014-07-01

    Congenital bronchial stenosis is rarely described and is difficult to manage. Here we report two cases of right intermediate bronchial stenosis (stenotic orifice with complete cartilage rings). Both cases were associated with ventricular septal defects, and a "trifurcation" pattern was found in both carinas. Both patients underwent surgical repair of the ventricular septal defects but could not be separated from ventilator support despite successful cardiac operations. Slide tracheobronchial plasty was applied to the right intermediate bronchus and lower trachea. After correction of the bronchial stenosis, both patients could be extubated and live without supplementary ventilation support.

  6. Impact of a bronchial genomic classifier on clinical decision making in patients undergoing diagnostic evaluation for lung cancer.

    PubMed

    Ferguson, J Scott; Van Wert, Ryan; Choi, Yoonha; Rosenbluth, Michael J; Smith, Kate Porta; Huang, Jing; Spira, Avrum

    2016-05-17

    Bronchoscopy is frequently used for the evaluation of suspicious pulmonary lesions found on computed tomography, but its sensitivity for detecting lung cancer is limited. Recently, a bronchial genomic classifier was validated to improve the sensitivity of bronchoscopy for lung cancer detection, demonstrating a high sensitivity and negative predictive value among patients at intermediate risk (10-60 %) for lung cancer with an inconclusive bronchoscopy. Our objective for this study was to determine if a negative genomic classifier result that down-classifies a patient from intermediate risk to low risk (<10 %) for lung cancer would reduce the rate that physicians recommend more invasive testing among patients with an inconclusive bronchoscopy. We conducted a randomized, prospective, decision impact survey study assessing pulmonologist recommendations in patients undergoing workup for lung cancer who had an inconclusive bronchoscopy. Cases with an intermediate pretest risk for lung cancer were selected from the AEGIS trials and presented in a randomized fashion to pulmonologists either with or without the patient's bronchial genomic classifier result to determine how the classifier results impacted physician decisions. Two hundred two physicians provided 1523 case evaluations on 36 patients. Invasive procedure recommendations were reduced from 57 % without the classifier result to 18 % with a negative (low risk) classifier result (p < 0.001). Invasive procedure recommendations increased from 50 to 65 % with a positive (intermediate risk) classifier result (p < 0.001). When stratifying by ultimate disease diagnosis, there was an overall reduction in invasive procedure recommendations in patients with benign disease when classifier results were reported (54 to 41 %, p < 0.001). For patients ultimately diagnosed with malignant disease, there was an overall increase in invasive procedure recommendations when the classifier results were reported (50 to 64

  7. Tea polyphenols prevent lung from preneoplastic lesions and effect p53 and bcl-2 gene expression in rat lung tissues.

    PubMed

    Gu, Qihua; Hu, Chengping; Chen, Qiong; Xia, Ying

    2013-01-01

    Lung cancer is one of the cancers that have the highest incidence and the highest mortality rate, and it is of great interest to identify ways to prevent its occurrence. We had established an animal model by using 3,4-benzopyrene intra-pulmonary injection in our previous study, and had observed that the rats lung carcinoma incidence and multiplicity were significantly reduced by green tea administration. This study further investigated the effect of tea polyphenols on rat lung preneoplastic lesions using the lung carcinoma model established by 3,4-benzopyrene intra-pulmonary injection. Sprague-Dawley rats of the same age were randomly divided into 10 groups and treated with 3,4-benzopyrene by intra-pulmonary injection. Five groups were given 0.3% solution of tea polyphenols (equivalent to 1.2% of green tea) in drinking water, while the other 5 groups were given pure drinking water. The rats were sacrificed at 0, 1, 4, 8 and 16 weeks after carcinogen treatment. In the control groups of rats, local bronchial inflammation were observed at 1 week after 3,4-benzopyrene treatment. From 4 weeks to 16 weeks after carcinogen treatment, hyperplasia, cell hyperproliferation, heterogeneity were observed in the bronchial epithelium. Meanwhile, the expression of p53 mRNA and protein, as well as the level of bcl-2, increased in the bronchial epithelial lesion. Tea polyphenols treatment significantly alleviated the bronchial epithelial lesions. At the same time, tea polyphenols treatment enhanced p53 expression, but reduced bcl-2 expression. These results indicated that tea polyphenols may have preventive effect against lung preneoplasm lesions, possibly through regulating the expression of some critical genes such as p53 and bcl-2.

  8. [Amoxicillin and its excretion into bronchial secretion (author's transl)].

    PubMed

    Weingärtner, L; Richter, I; Patsch, R; Thiemann, H H; Brömme, W; Baum, W; Vorwald, U

    1977-02-01

    Various dates on amoxicillin (resorption, distribution, elimination, tissue passage, urinary excretion) are presented. The bacterial spectrum is more fully discussed. Amoxicillin is compared with ampicillin. Dosage and therapeutical results are presented. Within repeated bronchoscopic examinations necessary on account of bronchopulmonary affections determination of germs were done in 88 children. At the same time examination of ampicillin levels in bronchial secretions were performed after amoxicillin therapy with different high doses (3 x 125 mg to 3 x 750 mg) for 7 days. It could be shown that good antibiotic levels could be found in secretion specimens above all obtained 2 to 4 hours after the last amoxicillin administration. They could be found too, if there did not exist any purulent secretion or stronger inflammation. There are relations between the amount of dosage, the level in secretion as well as the influence on germs.

  9. Bronchoscopic resection of bronchial angiolipoma: A rare case report

    PubMed Central

    Wu, Zhiqiang; Wan, Hongli; Shi, Min; Li, Ming; Wang, Zhanpeng; Yang, Caixia; Gao, Wei; Li, Qingxin

    2016-01-01

    Angiolipoma is a rare benign tumor that most commonly occurs in the extremities and trunk. Angiolipomas originating in the bronchial tree are extremely rare. To the best of our knowledge, only one such case, confined to the bronchus intermedius, has been reported to date. The present study describes the case of an asymptomatic 74-year-old man with a yellowish round mass incidentally discovered at the orifice of the right lower bronchus during a routine health check. The tumor originated from the membranous part of the right inferior bronchus. Using a high-frequency electric snare and argon plasma coagulation under general anesthesia, successful bronchoscopic resection of the tumor was performed. At 15 months after the surgery, the patient remained recurrence- and symptom-free. PMID:28101361

  10. Intra-bronchial migration of peritoneal catheter of lumboperitoneal shunt

    PubMed Central

    Kawahara, Takashi; Yanagi, Masakazu; Hirano, Hirofumi; Arita, Kazunori

    2015-01-01

    Background: A rare case of intra-bronchial migration of peritoneal catheter of lumboperitoneal (LP) shunt was treated under the bronchoscopic and fluoroscopic observation. Case Description: A 71-year-old man, who underwent LP shunt installation due to idiopathic normal pressure hydrocephalus a year before, presented with history of high fever and sputum production. Roentgenography and computed tomography of the chest revealed migration of distal end of the peritoneal catheter into the left main bronchus. Migrated catheter was gently extracted through the abdominal wound incision under the bronchoscopic and fluoroscopic observation. Contrast material infused into the catheter did not spread into the pleural cavity. The patient was free of the symptoms within 2 postoperative weeks. Moreover, he underwent the ventriculo-peritoneal shunt surgery 1-month later. Conclusion: This is the first case of the migration of peritoneal catheter of LP shunt into the main bronchus. PMID:26962468

  11. Bronchial hypersecretion, chronic airflow limitation, and peptic ulcer.

    PubMed

    Kauffmann, F; Brille, D

    1981-11-01

    Men with and men without a history of peptic ulcers were compared using respiratory symptoms and spirographic measurements taken from data recorded in an epidemiologic study. Among the 1,049 men examined, 7% reported a history of peptic ulcer. A clear relationship appeared between bronchial hypersecretion and peptic ulcers. It persisted after adjustment for age, smoking habits, social class, and country of origin. Men with ulcers inhaled tobacco smoke more often. Ulcers, smoking, and chronic phlegm were independently related to a lower body build index. It seems that the relationship between smoking and ulcers was greater among men with chronic phlegm, and it is postulated that peptic ulcers and "chronic bronchitis" might be related to a "common secretory disorder." After adjustment for age, men with a history of peptic ulcers had, not a lower FEV1, but a higher vital capacity. A slightly lower FEV1/VC ratio cannot in such cases be considered as an index of chronic airflow limitation.

  12. The use of fish oil in bronchial asthma.

    PubMed

    Arm, J P; Lee, T H

    1989-01-01

    A fish-oil enriched diet has potential in modulating the humoral and inflammatory components of the allergic response by inhibiting the generation of pro-inflammatory mediators derived from arachidonic acid and by reducing the production of PAF-acether. In addition, EPA suppresses the responses of target cells and tissues. Studies in bronchial asthma confirm the anti-inflammatory potential of a fish-oil enriched diet. Dietary supplementation with EPA in subjects with asthma led to changes in leukocyte mediator generation and chemotactic responses. There was also a significant attenuation of the late asthmatic response to inhaled antigen. Further studies are needed to determine the full potential of such diets in effecting changes in the clinical aspects of allergic disease.

  13. Acute bronchial infection in chronic obstructive pulmonary disease.

    PubMed

    Dorca, J

    1995-10-01

    Bacterial bronchial infection is a frequent cause of COPD exacerbation but not its only aetiology. Increased purulent expectorant appears to be its best indicator rather than fever, non-productive cough or dyspnoea. The clinician must try to recognize this condition rather than systematically prescribe empirical antibiotics. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis are the major pathogens. Although atypical bacteria are not frequent, Chlamydia pneumoniae could play significant role. During the last years, new antibiotics, much more expensive than other regimens, are widely prescribed, often without a rational approach. In patients not already on antibiotics, sputum Gram stain is useful for deciding which patient should be treated and what would be the best anti-biotic. When it is not available, the chosen antibiotic must be at least active against three major pathogens according to the local susceptibility patterns. In patients not responding to the initial treatment, the consideration of its potential spectrum holes is then more useful than sputum examination.

  14. Bombesin-like peptide receptors in human bronchial epithelial cells.

    PubMed

    Kane, M A; Toi-Scott, M; Johnson, G L; Kelley, K K; Boose, D; Escobedo-Morse, A

    1996-01-01

    Northern blot and RNAse protection assays previously failed to detect bombesin-like peptide (BLP) receptors in normal human lung tissue, but by RT/PCR cultured human bronchial epithelial (HBE) cells expressed all three BLP receptor subtypes, predominantly neuromedin B (NMB) receptor. By RT/PCR, we found expression of all three BLP receptor subtypes by human lung tissue and confirmed NMB receptor expression in six out of six HBE samples. However, transformed HBE BEAS B2B cells expressed only gastrin-releasing peptide (GRP) receptors; saturable, high-affinity (Kd = 3.5 nM) specific [125I]GRP binding confirmed functional GRP receptor, with M(r) = 75 kDa and immunologic cross-reactivity with GRP receptor from human small-cell lung carcinoma (SCLC) NCI-H345 cells. Altered regulation of BLP receptors may accompany transformation of normal lung cells to cancer.

  15. Acupuncture for bronchial asthma? A double-blind crossover study.

    PubMed

    Tandon, M K; Soh, P F; Wood, A T

    1991-03-18

    The therapeutic effectiveness of classic Chinese acupuncture was compared with "placebo" acupuncture in 15 patients with stable bronchial asthma. The patients received treatments with real and placebo acupuncture in a randomly ordered, subject and evaluator-blind crossover fashion twice weekly for five weeks. Both real and placebo treatment periods were preceded by three week periods when no acupuncture was administered. Five patients felt better on real treatment, five patients preferred placebo and five did not feel any improvement on either of the two treatments. Treatment with real acupuncture when compared with no treatment and placebo treatment failed to provide any improvement in daily peak flow rates, asthma symptom scores, number of puffs of beta 2-agonist aerosol use, and pulmonary function results.

  16. Evolutional trends in the management of tracheal and bronchial injuries

    PubMed Central

    2017-01-01

    Tracheal and Bronchial injuries are potentially life threatening complications which require urgent diagnosis and therapeutic intervention. They typically occur in association with blunt and penetrating chest trauma although they are increasingly being encountered in patients following endobronchial intervention and percutaneous tracheostomy insertion. Their precise incidence is unknown. Presenting features include dyspnoea, stridor, respiratory and haemodynamic compromise, haemoptysis, surgical emphysema, pneumothorax and persistent significant airleak. There may be other additional injuries to consider in trauma patients with large airway injury. Familiarity with the diagnosis and management of large airway injuries is important for medical teams engaged in emergency medicine, thoracic surgery and medicine, anaesthesia and intensive care. Although early surgical intervention is the mainstay of treatment, endobronchial manoeuvres to seal defects are receiving increasing attention particularly for patients with medical co-morbidities which may contraindicate formal surgery or transfer or where local surgical expertise is not available. PMID:28203439

  17. [Efficiency of kinesi- and hydrokinesitherapy in children with bronchial asthma].

    PubMed

    Surovenko, T N; Iashchuk, A V; Iansons, T Ia; Ezhov, S N

    2003-01-01

    The authors review efficiency of various programs of kinesi and hydrokinesitherapy of children with atopic bronchial asthma (BA). Efficiency of the treatment was assessed by quality of life using the questionnaire by A. West, D. French "Childhood asthma questionnaire" (adapted for Russia by V. I. Petrov et al). Monitoring of the activity of allergic inflammation of the upper respiratory tracts was performed by examination of the nasal lavage fluid for nitric oxide metabolites, of the lower respiratory tracts--by the metabolites in the condensate of the expired air. It is shown that hydrokinesitherapy raises BA children's quality of life and declines inflammation activity leading to reduction of the number of BA exacerbations and hospitalizations. The above criteria of the treatment efficacy proved sensitive.

  18. Cell-mediated immunity in operable bronchial carcinoma: the effect of injecting irradiated autologous tumour cells and BCG.

    PubMed

    Stack, B H; McSwan, N; Stirling, J M; Hole, D J; Parratt, D; Spilg, W G; Gillis, C R; McHattie, I; Green, A G; White, R G; Turner, M A

    1979-02-01

    In 52 patients undergoing tests of cell-mediated immunity before surgical resection of bronchial carcinoma a positive tuberculin test result was found in 71% compared with 68% of age- and sex-matched controls. Sensitisation to DNCB occurred in 52% of 37 patients but in 78% of controls. There was depression of lymphocyte transformation by PPD in 19 patients compared with controls (P=0.001), but there was no difference in lymphocyte transformation by PHA or pokeweed mitogen between 34 patients and controls. In a pilot study patients were randomly allocated to autograft (eight) or non-autograft (seven) groups. The autograft group were given an intradermal injection of a suspension of irradiated autologous tumour-cells mixed with intradermal BCG on the day of operation. Tests of cell-mediated immunity were repeated two weeks after operation. Five patients in each group received a course of radiotherapy to the mediastinum three weeks after operation. There was a rise in cutaneous tuberculin reactivity (P=0.08) and total leucocyte count (P=0.09) in the autograft group postoperatively with a fall in total lymphocyte and T lymphocyte counts in the non-autograft group (P less 0.05). These differences, however, were not followed by any difference in the frequency of tumour recurrence or the survival rate two years after operation. The results show that the immunological surveillance mechanism is impaired even in patients with early bronchial carcinoma and that it is possible to overcome postoperative immunological depression with specific immunotherapy combined with BCG. This treatment did not produce any clinical advantage in this small number of patients and the skin lesions caused the patients considerable discomfort.

  19. [Effects and significance of methacholine bronchial provocation tests and salbutamol bronchial dilation test on measurements of fractional exhaled nitric oxide in patients with asthma].

    PubMed

    Liu, Jielu; Yu, Huapeng; Tan, Xiaomei; Wu, Shuhan; Zhang, Pan; Fang, Zekui; Wang, Cuilan; He, Xi

    2016-03-01

    To study the effects and significance of methacholine (Mch) bronchial provocation tests and salbutamol bronchial dilation test on measurements of fractional exhaled nitric oxide (FeNO) in patients with asthma. This was a prospective study conducted between November 2014 and August 2015. A total of 135 patients with asthma visiting the respiratory clinic of Zhujiang Hospital were enrolled. The patients received either Mch bronchial provocation test or salbutamol bronchial dilation test based on their FEV1/FVC values and cooperative degree. Mch bronchial provocation test was performed by using Astograph Jupiter-21 (Astograh group) or APS-Pro airway reaction testing apparatus (APS group), and salbutamol bronchial dilation test was performed by using Jaeger spirometer (Dilation group). We compared the differences between FeNO values measured before examinations (Pre-FeNO) and 5 min after completion of these examinations (Post-FeNO). The geometric mean of Pre-FeNO and Post-FeNO was 28.07 ppb and 24.08 ppb respectively in the Astograh group, with a significant decrease of the FeNO value after the examination (Z=-3.093, P=0.002). A significant difference between Pre-FeNO and Post-FeNO was found in patients who had positive provocation results in the Astograh group (Z=-2.787, P=0.005), but not in the patients with negative results (Z=-1.355, P=0.176). The geometric mean of FeNO in the APS group decreased significantly from 27.95 ppb to 23.15 ppb after the examination was completed (Z=-5.170, P=0.000); both in patients with positive saline or Mch provocation results and in patients with negative provocation results, the differences between Pre-FeNO and Post-FeNO in the APS group being significant (Z=-2.705, -3.709, -2.371, P=0.002, 0.000, 0.018). No difference of FeNO change(ΔFeNO) was observed between the 2 Mch bronchial provocation test groups (U<918.000, P=0.117). The geometric mean of Pre-FeNO was 36.74 ppb and that of Post-FeNO was 34.79 ppb in the Dilation group; the

  20. Activation by histamine of bronchial epithelial cells from nonasthmatic subjects.

    PubMed

    Vignola, A M; Campbell, A M; Chanez, P; Lacoste, P; Michel, F B; Godard, P; Bousquet, J

    1993-10-01

    Histamine is a major mediator of the mast cells that are present between epithelial cells in asthma. In asthma, there is an increased expression of ICAM-1 and HLA-DR and an increased spontaneous release of fibronectin. The effect of histamine was tested on bronchial epithelial cells obtained by bronchial brushing from 22 nonasthmatic subjects. The activation of epithelial cells was assessed by immunocytochemical analysis of the expression of membrane markers (ICAM-1 and HLA-DR) using the alkaline phosphatase-anti-alkaline phosphatase method and the release of fibronectin (enzyme immunoassay). Time-response (three experiments) and dose-response (six experiments) curves showed that the maximal effect was obtained after an incubation time of 24 h and a dose of 1 microM of histamine. For this time course and concentration, there was a highly significant increase in the number of cells expressing ICAM-1 (before histamine: 10 +/- 11%; after histamine: 32 +/- 20%; P < 0.001) and HLA-DR (before histamine: 8 +/- 7%; after histamine: 23 +/- 20%; P < 0.001) and in the release of fibronectin (before histamine: 30 +/- 20 ng/10(5) viable cells; after histamine: 61 +/- 35 ng/10(5) viable cells; P < 0.003). Cycloheximide blocked these effects, suggesting that histamine requires protein synthesis for its action. Pyrilamine (H1-blocker) and ranitidine (H2-blocker) at a concentration of 10 microM decreased the effect of histamine. However, there was no additive effect when both antagonists were added. This study suggests that mast cells present in the airways have a role in the activation of epithelial cells.

  1. Cytotoxicity of folpet fungicide on human bronchial epithelial cells.

    PubMed

    Canal-Raffin, Mireille; l'Azou, Béatrice; Jorly, Joana; Hurtier, Annabelle; Cambar, Jean; Brochard, Patrick

    2008-07-30

    Folpet, a widely used dicarboximide fungicide, has been detected in the ambient air of several vine-growing regions of France. It is present in particle form in the environment; however, no study exploring its potential health impact on airways and the respiratory system has been published. Here, the biological effect of these particles was investigated in vitro on human bronchial epithelial cells (16HBE14o-). To be close to the real-life conditions of exposure, Folpan 80WG, a commercial form of folpet, was tested. Folpan 80WG particles showed dose- and time-dependent cytotoxic effects on 16HBE14o- cells. This effect was compared to that produced by technical-grade folpet and both were found to induce a toxicity with similar IC(50) values after 24h of exposure. After 4h and at least until 48h of exposure, the IC(50) values of Folpan 80WG particles were between 2.4 and 2.8 microg/cm(2). Investigation of the cytotoxicity found that Folpan 80WG particles at 1.85 microg/cm(2) induced an increase in ROS production from the first hour of exposure. Evidence that oxidative processes occur in folpet-exposed cells was confirmed by the presence of membrane lipid peroxidation. Furthermore, early apoptosis and late apoptosis/necrosis were both present after the first hour of exposure. These findings indicate that exposure to Folpan 80WG particles result in a rapid cytotoxic effect on human bronchial epithelial cells in vitro that could be in part explained by oxidative stress, characterised by membrane lipid peroxidation and ROS production.

  2. Bronchial thermoplasty: reappraising the evidence (or lack thereof).

    PubMed

    Iyer, Vivek N; Lim, Kaiser G

    2014-07-01

    Bronchial thermoplasty (BT) involves the application of radiofrequency energy to visible proximal airways to selectively ablate airway smooth muscle. BT is the first nonpharmacologic interventional therapy approved by the US Food and Drug Administration (FDA) for severe asthma. This approval was based on the results of the pivotal Asthma Intervention Research (AIR)-2 trial, which is the only randomized, double-blind, sham-controlled trial of BT. The primary end point of the AIR-2 trial was improvement in the Asthma Quality of Life Questionnaire (AQLQ). The results of the AIR-2 trial have generated enormous interest, controversy, and confusion regarding the true efficacy of BT for severe asthma. Current marketing of BT highlights its use for patients with "severe" asthma, which is interpreted by most practicing clinicians as meaning oral corticosteroid dependence, frequent exacerbations, or a significantly reduced FEV1 with a poor quality of life. Did the AIR-2 trial include patients with a low FEV1, oral steroid dependence, or frequent exacerbations? Did the trial show efficacy for any of the primary or secondary end points? The FDA approved the device based on the reduction in severe asthma exacerbations. However, were the rates of asthma exacerbations, ED visits, or hospitalizations truly different between the two groups, and was this type of analysis even justified given the original study design? This commentary is designed to specifically answer these questions and help the practicing clinician navigate the thermoplasty literature with confidence and clarity. We carefully dissect the design, conduct, and results of the AIR-2 trial and raise serious questions about the efficacy of bronchial thermoplasty.

  3. Contractile properties of bronchial smooth muscle with and without cartilage.

    PubMed

    Jiang, H; Stephens, N L

    1990-07-01

    The majority of in vitro studies on airway smooth muscle have used the trachealis (TSM) as a convenient substitute for muscle from airways that constitute the flow-limiting segment. The latter are technically difficult to work with. However, because the site of maximum resistance to airflow is at the third to seventh generations of the bronchial tree, the trachealis preparation is of limited value. Length-tension and force-velocity properties were therefore studied at optimal length (lo) of canine bronchial smooth muscle (BSM) from which cartilage had been carefully removed. Normalized maximum isometric tension or stress (Po x 10(4) N/m2) for BSM was 7.1 +/- 0.19 (SE), which was similar to that of BSM with cartilage (BSM+C, 6.8 +/- 0.21) but lower than for TSM (18.2 +/- 0.81). At length greater than lo, the BSM+C was stiffer than the BSM. The values of maximum shortening capacity (delta Lmax), obtained directly from isotonic shortening at a load equal to the resting tension at lo, were 0.76 lo +/- 0.03, 0.41 lo +/- 0.02, and 0.24 +/- 0.02 lo for TSM, BSM, and BSM+C, respectively. The BSM and BSM+C delta Lmaxs were different (P less than 0.05). Maximal shortening velocities (Vo) for BSM, elicited at 2, 4, and 8 s by quick release in the course of an isometric contraction were significantly higher than for the BSM+C. Vos showed gradual decreases in all three groups in the later phase of contraction, suggesting the operation of latch bridges.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Functional Metagenomics of the Bronchial Microbiome in COPD.

    PubMed

    Millares, Laura; Pérez-Brocal, Vicente; Ferrari, Rafaela; Gallego, Miguel; Pomares, Xavier; García-Núñez, Marian; Montón, Concepción; Capilla, Silvia; Monsó, Eduard; Moya, Andrés

    2015-01-01

    The course of chronic obstructive pulmonary disease (COPD) is frequently aggravated by exacerbations, and changes in the composition and activity of the microbiome may be implicated in their appearance. The aim of this study was to analyse the composition and the gene content of the microbial community in bronchial secretions of COPD patients in both stability and exacerbation. Taxonomic data were obtained by 16S rRNA gene amplification and pyrosequencing, and metabolic information through shotgun metagenomics, using the Metagenomics RAST server (MG-RAST), and the PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) programme, which predict metagenomes from 16S data. Eight severe COPD patients provided good quality sputum samples, and no significant differences in the relative abundance of any phyla and genera were found between stability and exacerbation. Bacterial biodiversity (Chao1 and Shannon indexes) did not show statistical differences and beta-diversity analysis (Bray-Curtis dissimilarity index) showed a similar microbial composition in the two clinical situations. Four functional categories showed statistically significant differences with MG-RAST at KEGG level 2: in exacerbation, Cell growth and Death and Transport and Catabolism decreased in abundance [1.6 (0.2-2.3) vs 3.6 (3.3-6.9), p = 0.012; and 1.8 (0-3.3) vs 3.6 (1.8-5.1), p = 0.025 respectively], while Cancer and Carbohydrate Metabolism increased [0.8 (0-1.5) vs 0 (0-0.5), p = 0.043; and 7 (6.4-9) vs 5.9 (6.3-6.1), p = 0.012 respectively]. In conclusion, the bronchial microbiome as a whole is not significantly modified when exacerbation symptoms appear in severe COPD patients, but its functional metabolic capabilities show significant changes in several pathways.

  5. Functional Metagenomics of the Bronchial Microbiome in COPD

    PubMed Central

    Millares, Laura; Pérez-Brocal, Vicente; Ferrari, Rafaela; Gallego, Miguel; Pomares, Xavier; García-Núñez, Marian; Montón, Concepción; Capilla, Silvia

    2015-01-01

    The course of chronic obstructive pulmonary disease (COPD) is frequently aggravated by exacerbations, and changes in the composition and activity of the microbiome may be implicated in their appearance. The aim of this study was to analyse the composition and the gene content of the microbial community in bronchial secretions of COPD patients in both stability and exacerbation. Taxonomic data were obtained by 16S rRNA gene amplification and pyrosequencing, and metabolic information through shotgun metagenomics, using the Metagenomics RAST server (MG-RAST), and the PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) programme, which predict metagenomes from 16S data. Eight severe COPD patients provided good quality sputum samples, and no significant differences in the relative abundance of any phyla and genera were found between stability and exacerbation. Bacterial biodiversity (Chao1 and Shannon indexes) did not show statistical differences and beta-diversity analysis (Bray-Curtis dissimilarity index) showed a similar microbial composition in the two clinical situations. Four functional categories showed statistically significant differences with MG-RAST at KEGG level 2: in exacerbation, Cell growth and Death and Transport and Catabolism decreased in abundance [1.6 (0.2–2.3) vs 3.6 (3.3–6.9), p = 0.012; and 1.8 (0–3.3) vs 3.6 (1.8–5.1), p = 0.025 respectively], while Cancer and Carbohydrate Metabolism increased [0.8 (0–1.5) vs 0 (0–0.5), p = 0.043; and 7 (6.4–9) vs 5.9 (6.3–6.1), p = 0.012 respectively]. In conclusion, the bronchial microbiome as a whole is not significantly modified when exacerbation symptoms appear in severe COPD patients, but its functional metabolic capabilities show significant changes in several pathways. PMID:26632844

  6. HSP60 activity on human bronchial epithelial cells.

    PubMed

    Sangiorgi, Claudia; Vallese, Davide; Gnemmi, Isabella; Bucchieri, Fabio; Balbi, Bruno; Brun, Paola; Leone, Angelo; Giordano, Andrea; Conway de Macario, Everly; Macario, Alberto Jl; Cappello, Francesco; Di Stefano, Antonino

    2017-10-01

    HSP60 has been implicated in chronic inflammatory disease pathogenesis, including chronic obstructive pulmonary disease (COPD), but the mechanisms by which this chaperonin would act are poorly understood. A number of studies suggest a role for extracellular HSP60, since it can be secreted from cells and bind Toll-like receptors; however, the effects of this stimulation have never been extensively studied. We investigated the effects (pro- or anti-inflammatory) of HSP60 in human bronchial epithelial cells (16-HBE) alone and in comparison with oxidative, inflammatory, or bacterial challenges. 16-HBE cells were cultured for 1-4 h in the absence or presence of HSP60, H2O2, lipopolysaccharide (LPS), or cytomix. The cell response was evaluated by measuring the expression of IL-8 and IL-10, respectively, pro- and anti-inflammatory cytokines involved in COPD pathogenesis, as well as of pertinent TLR-4 pathway mediators. Stimulation with HSP60 up-regulated IL-8 at mRNA and protein levels and down-regulated IL-10 mRNA and protein. Likewise, CREB1 mRNA was up-regulated. H2O2 and LPS up-regulated IL-8. Experiments with an inhibitor for p38 showed that this mitogen-activated protein kinase could be involved in the HSP60-mediated pro-inflammatory effects. HSP60 showed pro-inflammatory properties in bronchial epithelial cells mediated by activation of TLR-4-related molecules. The results should prompt further studies on more complex ex-vivo or in-vivo models with the aim to elucidate further the role of those molecules in the pathogenesis of COPD.

  7. Parasympathetic Stimuli on Bronchial and Cardiovascular Systems in Humans

    PubMed Central

    Zannin, Emanuela; Pellegrino, Riccardo; Di Toro, Alessandro; Antonelli, Andrea; Dellacà, Raffaele L.; Bernardi, Luciano

    2015-01-01

    Background It is not known whether parasympathetic outflow simultaneously acts on bronchial tone and cardiovascular system waxing and waning both systems in parallel, or, alternatively, whether the regulation is more dependent on local factors and therefore independent on each system. The aim of this study was to evaluate the simultaneous effect of different kinds of stimulations, all associated with parasympathetic activation, on bronchomotor tone and cardiovascular autonomic regulation. Methods Respiratory system resistance (Rrs, forced oscillation technique) and cardio-vascular activity (heart rate, oxygen saturation, tissue oxygenation index, blood pressure) were assessed in 13 volunteers at baseline and during a series of parasympathetic stimuli: O2 inhalation, stimulation of the carotid sinus baroreceptors by neck suction, slow breathing, and inhalation of methacholine. Results Pure cholinergic stimuli, like O2 inhalation and baroreceptors stimulation, caused an increase in Rrs and a reduction in heart rate and blood pressure. Slow breathing led to bradycardia and hypotension, without significant changes in Rrs. However slow breathing was associated with deep inhalations, and Rrs evaluated at the baseline lung volumes was significantly increased, suggesting that the large tidal volumes reversed the airways narrowing effect of parasympathetic activation. Finally inhaled methacholine caused marked airway narrowing, while the cardiovascular variables were unaffected, presumably because of the sympathetic activity triggered in response to hypoxemia. Conclusions All parasympathetic stimuli affected bronchial tone and moderately affected also the cardiovascular system. However the response differed depending on the nature of the stimulus. Slow breathing was associated with large tidal volumes that reversed the airways narrowing effect of parasympathetic activation. PMID:26046774

  8. [Somatostatin receptor scintigraphy in pediatric bronchial carcinoid tumor].

    PubMed

    Hervás Benito, I; Bello Arques, P; Loaiza, J L; Vercher, J L; Velasco, R P; Rivas Sánchez, A; Ruiz Llorca, C; Martí Vidal, J F; Mateo Navarro, A

    2010-01-01

    Carcinoid tumor is a rare neuroendocrine neoplasm with different locations, the most frequent ones during the pediatric age being the appendix and lung. Scintigraphy with (111)In-DTPA-d-Phe(1)-octreotide has led to an importance advance in the diagnosis of extension in carcinoid tumor patients. We present three pediatric patients with bronchial carcinoid studied with somatostatin analogue scintigraphy (SSRS). The first patient (9 years) was studied using the SSRS after surgery due to carcinoid tumor in the right lower lobe in which tumor remains was observed (this being clearer in the tomography study). The second patient (10 years) presented due to endobronchial tumor in the left lower lobe together with atelectasis of the LUL and emphysema of the LLL. Radiology imaging techniques suggested the differential diagnosis between the endobronchial carcinoid tumor or plasma cells or foreign body gramuloma. The SSRS showed an abnormal deposit of activity in the left hemithorax consisted with carcinoid tumor. No other areas suggesting metastasis were observed. After the surgery (endobronchial resection), new controls with SSRS showed absence of disease. The third patient (12 years) came after a lobectomy (RUL) due to bronchial carcinoid. The SSRS did not show any abnormal areas of activity. In the subsequent control (3 months), a deposit of activity was observed in the middle third of the right hemithorax, after which a lobectomy was performed (RLL and ML) that showed small remains of neuroendocrine carcinoid. Subsequent controls were negative. The SSRS has demonstrated great utility in the diagnosis, follow-up and staging of pediatric patients, carriers of neuroendocrine carcinoid tumors. Copyright 2008 Elsevier España, S.L. y SEMNIM. All rights reserved.

  9. Effect of inhaled magnesium sulfate on bronchial hyperresponsiveness.

    PubMed

    Wang, Hui; Xiong, Yi; Gong, Caihui; Yin, Lijuan; Yan, Li; Yuan, Xiaoping; Liu, Sha; Shi, Tiantian; Dai, Jihong

    2015-04-01

    To determine the response of nebulized magnesium sulfate on the lung function of children with bronchial hyperresponsiveness. Eighty-four children with asthma were divided into three groups randomly: magnesium sulfate (M), albuterol (A), and a combination of magnesium sulfate and albuterol (M + A). All patients were nebulized with acetylcholine, and then treated as designed. Lung function was compared between the three groups. Forced expiratory volume in first second (FEV1) significantly improved in all the three groups but it was better in (A) and (M + A) compared to (M) at 10 min and 20 min [10 min: 1.26 L ± 0.53 (A) vs. 1.10 L ± 0.27 (M), 1.35 L ± 0.59 (M + A) vs. 1.10 L ± 0.27 (M), p < 0.05; 20 min: 1.32 L ± 0.61 (A) vs. 1.17 L ± 0.30 (M), 1.42 L ± 0.59 (M + A) vs. 1.17 L ± 0.30 (M), p < 0.05]. Variation of FEV1, as absolute value at 10 min or 20 min over post-Ach FEV1 was significantly different in (A) or (M + A) compared to (M). Nebulized albuterol and magnesium sulfate + albuterol can more effectively improve FEV1 in children with bronchial hyperresponsiveness than nebulized magnesium sulfate at 10 min and 20 min after inhalation. It is further suggested that addition of magnesium sulfate to albuterol does not result in additional benefit.

  10. Aetiology of abfraction lesions.

    PubMed

    Lyons, K

    2001-09-01

    The aetiology of abfraction lesions is complex. Most evidence indicates that physical loading forces are a major contributing factor, although they are unlikely to be entirely responsible. Intraoral chemical influences and toothbrush abrasion, combined with the dynamics of inter-occlusal activity such as chewing, swallowing, and parafunction, lead to stress corrosion and may contribute to abfraction lesions. The multifactorial aetiology that operates in the initiation and progression of these lesions has made investigation difficult. Various theories have been proposed and numerous surveys and studies conducted, but the primary causal factor has yet to be definitively determined. This review concludes that occlusal loading is the initiating factor in the development of abfraction lesions.

  11. [Bronchial carcinoid tumor and scintigraphy of somatostatin receptors: detection of bone metastasis].

    PubMed

    Banzo, J; Abós, M D; Prats, E; García, F; Freile, E; Razola, P; Escalera, T

    2001-10-01

    Surgery is the treatment of choice for bronchial carcinoid tumor (BCT), whenever the staging is adequate. There is little information about the capability of the somatostatin receptor scintigraphy (SRS) to detect bone metastases in the carcinoid tumor. This work has aimed to evaluate retrospectively the diagnostic accuracy of the SRS in the detection of bone metastases in BCT. Based on their clinical indication, the patients were classified into two different groups: Group A (n = 4), staging of a known BCT; and Group B (n = 6), treatment control. The SRS results could be correlated with the CT results in all 4 patients from the group A, and in one patient from the group B, and the SRS results were compared with the clinical follow up during at least one year in the other 5 patients. The SRS scan detected the 4 BCT from the group A; in 2 of them the patient staging was superior when the SRS was used than with the CT, whereas the scan overestimated the tumor stage (BCT + sarcoidosis) in another patient. During the clinical course, one of these patients developed bone and liver metastases. The SRS was normal in 5 asymptomatic patients from group B, whereas the scan showed disseminated metastatic disease (liver, bone, spleen and lymph nodes) in another patient. In the 2 patients with bone metastases, the total number of bone metastases detected by the bone scan was 12, and by the SRS 8. The four lesions that were not detected by SRS were located in the ribs (n = 3) and 12-D (n = 1). The capability of the SRS to detect bone metastases makes it more useful in BCT staging. Over the next few years, the role of the bone scan and SRS in the detection of bone metastases in carcinoid tumors needs to be established.

  12. Genetic damage induced by organic extract of coke oven emissions on human bronchial epithelial cells.

    PubMed

    Zhai, Qingfeng; Duan, Huawei; Wang, Yadong; Huang, Chuanfeng; Niu, Yong; Dai, Yufei; Bin, Ping; Liu, Qingjun; Chen, Wen; Ma, Junxiang; Zheng, Yuxin

    2012-08-01

    Coke oven emissions are known as human carcinogen, which is a complex mixture of polycyclic aromatic hydrocarbon. In this study, we aimed to clarify the mechanism of action of coke oven emissions induced carcinogenesis and to identify biomarkers of early biological effects in a human bronchial epithelial cell line with CYP1A1 activity (HBE-CYP1A1). Particulate matter was collected in the oven area on glass filter, extracted and analyzed by GC/MS. DNA breaks and oxidative damage were evaluated by alkaline and endonucleases (FPG, hOGG1 and ENDO III)-modified comet assays. Cytotoxicity and chromosomal damage were assessed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The cells were treated with organic extract of coke oven emissions (OE-COE) representing 5, 10, 20, 40μg/mL extract for 24h. We found that there was a dose-effect relationship between the OE-COE and the direct DNA damage presented by tail length, tail intensity and Olive tail moment in the comet assay. The presence of lesion-specific endonucleases in the assays increased DNA migration after OE-COE treatment when compared to those without enzymes, which indicated that OE-COE produced oxidative damage at the level of pyrimidine and purine bases. The dose-dependent increase of micronuclei, nucleoplasmic bridges and nuclear buds in exposed cells was significant, indicating chromosomal and genomic damage induced by OE-COE. Based on the cytotoxic biomarkers in CBMN-Cyt assay, OE-COE may inhibit nuclear division, interfere with apoptosis, or induce cell necrosis. This study indicates that OE-COE exposure can induce DNA breaks/oxidative damage and genomic instability in HBE-CYP1A1 cells. The FPG-comet assay appears more specific for detecting oxidative DNA damage induced by complex mixtures of genotoxic substances.

  13. Prevalence and Anatomic Distribution of Serrated and Adenomatous Lesions in Patients with Inflammatory Bowel Disease

    PubMed Central

    Lee, Lik Hang; Fort Gasia, Miriam; Ghosh, Subrata; Panaccione, Remo; Urbanski, Stefan

    2017-01-01

    Background. Sessile serrated adenomas/polyps (SSA/Ps) and traditional serrated adenomas (TSAs) have not been well characterized in patients with inflammatory bowel disease (IBD). This study assesses the prevalence and anatomic distribution of SSA/Ps, TSAs, and conventional adenomas/dysplasia (Ad/Ds) in IBD patients. Methods. IBD patients with serrated, adenomatous, or hyperplastic lesions between 2005 and 2009 were identified in the regional tertiary-care hospital database. Clinicopathological information was reviewed and the histology of biopsies was reevaluated. Results. Ninety-six Ad/Ds, 25 SSA/Ps, and 4 TSAs were identified in 83 patients. Compared to Ad/Ds, serrated lesions were more prevalent in females (p = 0.046). The prevalence of Ad/Ds was 4.95%, SSA/Ps was 1.39%, and TSAs was 0.31%. No relationship was identified between lesion type and IBD type. Comparing all IBD patients, the distribution of lesion types was significantly different (p = 0.02) with Ad/Ds more common distally, SSA/Ps more common proximally, and TSAs evenly distributed. Among Crohn's disease (CD) patients, a similar distribution difference was noted (p < 0.001). However, ulcerative colitis (UC) patients had a uniform distribution of lesion types (p = 0.320). Conclusions. IBD patients have a lower prevalence of premalignant lesions compared to the general population, and the anatomic distribution of lesions differed between CD and UC patients. These findings may indicate an interaction between lesion and IBD pathogenesis with potential clinical implications. PMID:28182112

  14. Relationship between Methacholine Challenge Testing and exhaled nitric oxide in adult patients with suspected bronchial asthma.

    PubMed

    Giovannini, M; Valli, M; Ribuffo, V; Melara, R; Cappiello, G; Businarolo, E; Andreani, A

    2014-05-01

    Usually, hyperresponsiveness to inhaled methacholine is considered closely associated with a diagnosis of bronchial asthma. Recently, it has been clearly pointed out that bronchial hyperreactivity (BHR) is not a constant feature of asthma and that this condition is not always related to airways inflammation. In the present study we evaluated 42 Patients (21 positive and 21 negative for bronchial hyperreactivity, BHR) with the aim to determine the effect of Methacholine Challenge Testing (MCT) on the levels of exhaled nitric oxide (NO). Higher FeNO levels were found before methacholine provocation in the group that eventually resulted positive to the challenge, while after the challenge in both groups FeNO decreased in similar way, with no statistical difference. These data confirm that MCT is a relevant test for asthma diagnosis, but it is not always related to the severity of bronchial inflammation, while FeNO levels in our study have limited clinical significance when evaluated out of asthma exacerbation.

  15. Current practice in assessment and treatment of bronchial asthma in young males in Italy.

    PubMed

    Ferrante, E; Pantaleo, C; Quatela, M; Fuso, L; Basso, S; Pistelli, R

    2000-10-01

    The aim of the study was to evaluate, in a sample of young asthmatics in Italy, the current practice in assessment and treatment of asthma after the publication of guidelines. Young soldiers who declared bronchial asthma at the beginning of the compulsory military service were evaluated. One-hundred and thirty-eight subjects with confirmed asthma were selected. Sixty-seven subjects (48.5%) had had at last one spirometry, and only one subject had underwent peak flow monitoring at home; most of the subjects (96.8%) had had prick tests. More of the 50% of the subjects with bronchial obstruction or with severe bronchial hyperresponsiveness, with clinical moderate or severe asthma, had used only bronchodilators or no therapy at all in the preceding year. In this sample of young asthmatics, the lung function tests were still underutilized for the diagnosis and follow-up of bronchial asthma; moreover, the inhaled anti-inflammatory drugs were still underutilized.

  16. Bronchial fistula to the mediastinum in a heart-lung transplant patient.

    PubMed

    Borro, J M; Ramos, F; Vicente, R; Sanchis, F; Morales, P; Caffarena, J M

    1992-01-01

    We present a case of heart-lung transplantation complicated by bronchial perforation as the cause or consequence of prolonged lung infection. Periodic bronchoscopic and radiological follow-up showed resolution of the condition following adequate antibiotic and physiotherapeutic treatment.

  17. Preinvasive lesions

    Cancer.gov

    This definition is for allocation of lesions with preinvasive/borderline properties. It is currently aimed at newly identified neoplasms, which may be similar to those described in humans. In mouse pathology, many adenomas may be preinvasive/borderline lesions. However, their inclusion in the preinvasive category can be justified only upon development of better diagnostic criteria.

  18. Imaging Pediatric Vascular Lesions

    PubMed Central

    Nguyen, Tuyet A.; Krakowski, Andrew C.; Naheedy, John H.; Kruk, Peter G.

    2015-01-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  19. Update on the diagnosis and treatment of tracheal and bronchial injury

    PubMed Central

    Zhao, Zhengwei; Zhang, Tianyi; Yin, Xunliang; Zhao, Jinbo; Li, Xiaofei

    2017-01-01

    Tracheal and bronchial injury, including iatrogenic injury and traumatic injury, the former usually occurred in the operation, intubation or bronchoscopy. The latter was occurred in a variety of blunt trauma, often combined with a variety of complex injuries. The therapeutic approach can be differentiated, surgical or conservative, no criteria has been universally accepted. Successful treatment of tracheobronchial injuries requires early diagnostic evaluation. This article aims to review the indications and therapeutic options for tracheal and bronchial injuries. PMID:28203437

  20. He-Ne laser radiation in combined therapy of children's bronchial asthma

    NASA Astrophysics Data System (ADS)

    Zhilnikov, Dmitriy V.; Varavva, Andrey S.; Tarasova, Olga N.; Plaksina, Galina V.; Barybin, Vitaliy F.; Khlutkova, Svetlana N.

    2004-02-01

    In this paper the medical application of He-Ne lasers for the treatment of bronchial asthma is described. Research objective of this work was the development of a treatment method for children with bronchial asthman of heavy and medium-heavy forms, resistant to the base therapy, with the help of low-intensive laser radiation with wave length λ=0,63 μm.

  1. Bronchial mucosa produced by tissue engineering: a new tool to study cellular interactions in asthma.

    PubMed

    Chakir, J; Pagé, N; Hamid, Q; Laviolette, M; Boulet, L P; Rouabhia, M

    2001-01-01

    The use of fiberoptic bronchial biopsies has improved our understanding of the immunopathology of asthma. However, this approach offers a limited ability to perform mechanistic studies observing cell-cell and cell-matrix interactions, which are a key issue in the study of airway remodeling. Tissue engineering is a technique that combines the use of biology and engineering expertise to generate a limitless amount of tissue from small samples. This technology allows for the study of cell interactions under conditions as close as possible to the natural environment. The aim of this study was to evaluate the feasibility of an engineered human bronchial mucosa as a model to study cellular interactions in asthma. Human bronchial fibroblasts from normal and asthmatic donors were incorporated into collagen gel. Bronchial epithelial cells were seeded over this gel and then cultured in an air-liquid interface in the presence or the absence of T lymphocytes. Biopsy specimens from these engineered mucosa were taken for structural and ultrastructural analysis, and T lymphocytes were harvested and used to localize IL-5. Histologic analysis showed that engineered mucosa with normal bronchial cells presented a pseudostratified ciliated epithelium with the presence of mucus secretory cells. The electron microscopy analysis confirmed these histologic results. These features were comparable with those observed in normal bronchial tissues. However, in engineered mucosa from asthmatic subjects, the tissue structure was disorganized, particularly the epithelial cell arrangement. The percentage of IL-5(+) lymphocytes was significantly (P =.03) higher in engineered bronchial mucosa from asthmatic subjects (87% +/- 2%) compared with mucosa from normal volunteers (2% +/- 0.3%). Using tissue engineering, we produced an in vitro model of bronchial mucosa from normal and asthmatic subjects. These models could be a valuable tool to better understand key mechanisms involved in inflammation and

  2. Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer

    DTIC Science & Technology

    2015-07-01

    injury” throughout the respiratory tract. We have previously shown that gene expression from bronchial epithelial cells reflects the physiologic...of lung cancer, creates a “field of injury” throughout the respiratory tract. We have previously shown that gene expression from bronchial epithelial...for lung cancer.   INTRODUCTION:   Cigarette smoking, the major cause of lung cancer, creates a “field of injury” throughout the respiratory tract

  3. Bronchial artery infusion of mitomycin C in carcinoma of the lung

    SciTech Connect

    Ekholm, S.; Albrechtsson, U.; Tylen, U.

    1983-06-01

    Fifteen patients with bronchial carcinoma were treated with infusions of 10 mg Mitomycin C (MMC) in the bronchial artery feeding the tumor. The treatment was repeated three times with 2-3 weeks interval between treatments. Half of the patients then received radiation to the tumor area and mediastinum. All tumors decreased in size, complete remission occurred in two and partial remission in five patients. Survival time, however, was not prolonged and esophageal complications occurred in several patients.

  4. The functional anatomy of the bronchial circulation of the domestic fowl.

    PubMed Central

    Abdalla, M A; King, A S

    1976-01-01

    The bronchial circulation was studied in 25 adult domestic fowls. The right and left bronchial arteries originated caudal to the syrinx from a bronchoesophageal artery which is a branch of the right common carotid artery. Each bronchial artery ramified on the wall of the extrapulmonary part of the corresponding primary bronchus and finally anastomosed directly with a branch of the pulmonary artery at the hilus of the lung. Thr bronchial artery did not accompany the intrapulmonary part of the primary bronchus. The branches of each bronchial artery formed an anastomosing network on the wall of the extrapulmonary part of the primary bronchus. The calibre of the bronchial artery at its anastomosis with the branch of the pulmonary artery was greater than at its origin from the bronchoesophageal artery. Intravenous injections of Lycopodium spores indicated that the blood flows from the pulmonary artery into the bronchial artery. Small bronchial veins drained the extrapulmonary part of the primary bronchus into the pulmonary vein and the oesophageal veins. The intrapulmonary part of the primary bronchus was supplied by branches of the pulmonary artery and drained by tributaries of the pulmonary vein. The blood supply to the primary bronchus could constitute a shunt capable of passing blood from the pulmonary artery into the pulmonary vein without going through the exchange tissue. The parabronchial (atrial) muscles received a blood supply directly from the exchange tissue via septal venules which formed a network underneath the muscle bundles, without actually penetrating between the muscle cells. These venules drained into atrial veins which were tributaries of the pulmonary vein. The atrial muscles probably also received oxygen by direct diffusion from the parabronchial lumen. The pleura was supplied by the oesophageal branches of the bronchoesophageal artery, and by small twigs from the internal thoracic and intercostal arteries. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 Fig

  5. Neonatal bronchial reconstruction after Norwood procedure for hypoplastic left heart syndrome.

    PubMed

    Gaughan, Colleen B; Nguyen, Dao; Ricci, Marco

    2009-03-01

    Left bronchial obstruction is a rare complication after neonatal aortic arch reconstruction. This article describes the surgical management of a neonate with hypoplastic left heart syndrome who underwent a stage 1 Norwood reconstruction. A mediastinal infection developed with an abscess that caused left bronchial obstruction and disruption. The left bronchus was repaired successfully by using a pedicle intercostal muscle flap that was used to cover the defect.

  6. Radial-probe EBUS for the diagnosis of peripheral pulmonary lesions

    PubMed Central

    Jacomelli, Marcia; Demarzo, Sergio Eduardo; Cardoso, Paulo Francisco Guerreiro; Palomino, Addy Lidvina Mejia; Figueiredo, Viviane Rossi

    2016-01-01

    ABSTRACT Objective: Conventional bronchoscopy has a low diagnostic yield for peripheral pulmonary lesions. Radial-probe EBUS employs a rotating ultrasound transducer at the end of a probe that is passed through the working channel of the bronchoscope. Radial-probe EBUS facilitates the localization of peripheral pulmonary nodules, thus increasing the diagnostic yield. The objective of this study was to present our initial experience using radial-probe EBUS in the diagnosis of peripheral pulmonary lesions at a tertiary hospital. Methods: We conducted a retrospective analysis of 54 patients who underwent radial-probe EBUS-guided bronchoscopy for the investigation of pulmonary nodules or masses between February of 2012 and September of 2013. Radial-probe EBUS was performed with a flexible 20-MHz probe, which was passed through the working channel of the bronchoscope and advanced through the bronchus to the target lesion. For localization of the lesion and for collection procedures (bronchial brushing, transbronchial needle aspiration, and transbronchial biopsy), we used fluoroscopy. Results: Radial-probe EBUS identified 39 nodules (mean diameter, 1.9 ∓ 0.7 cm) and 19 masses (mean diameter, 4.1 ∓ 0.9 cm). The overall sensitivity of the method was 66.7% (79.5% and 25.0%, respectively, for lesions that were visible and not visible by radial-probe EBUS). Among the lesions that were visible by radial-probe EBUS, the sensitivity was 91.7% for masses and 74.1% for nodules. The complications were pneumothorax (in 3.7%) and bronchial bleeding, which was controlled bronchoscopically (in 9.3%). Conclusions: Radial-probe EBUS shows a good safety profile, a low complication rate, and high sensitivity for the diagnosis of peripheral pulmonary lesions. PMID:27832231

  7. Malignant MCF10CA1 cell lines derived from premalignant human breast epithelial MCF10AT cells.

    PubMed

    Santner, S J; Dawson, P J; Tait, L; Soule, H D; Eliason, J; Mohamed, A N; Wolman, S R; Heppner, G H; Miller, F R

    2001-01-01

    The MCF10 series of cell lines was derived from benign breast tissue from a woman with fibrocystic disease. The MCF10 human breast epithelial model system consists of mortal MCF10M and MCF10MS (mortal cells grown in serum-free and serum-containing media, respectively), immortalized but otherwise normal MCF10F and MCF10A lines (free-floating versus growth as attached cells), transformed MCF10AneoT cells transfected with T24 Ha-ras, and premalignant MCF10AT cells with potential for neoplastic progression. The MCF10AT, derived from xenograft-passaged MCF10-AneoT cells, generates carcinomas in approximately 25% of xenografts. We now report the derivation of fully malignant MCF10CA1 lines that complete the spectrum of progression from relatively normal breast epithelial cells to breast cancer cells capable of metastasis. MCF10CA1 lines display histologic variations ranging from undifferentiated carcinomas, sometimes with focal squamous differentiation, to well-differentiated adenocarcinomas. At least two metastasize to the lung following injection of cells into the tail vein; one line grows very rapidly in the lung, with animals moribund within 4 weeks, whereas the other requires 15 weeks to reach the same endpoint. In addition to variations in efficiency of tumor production, the MCF10CA1 lines show differences in morphology in culture, anchorage-independent growth, karyotype, and immunocytochemistry profiles. The MCF10 model provides a unique tool for the investigation of molecular changes during progression of human breast neoplasia and the generation of tumor heterogeneity on a common genetic background.

  8. Fenretinide Perturbs Focal Adhesion Kinase in Premalignant and Malignant Human Oral Keratinocytes. Fenretinide's Chemopreventive Mechanisms Include ECM Interactions.

    PubMed

    Han, Byungdo B; Li, Suyang; Tong, Meng; Holpuch, Andrew S; Spinney, Richard; Wang, Daren; Border, Michael B; Liu, Zhongfa; Sarode, Sachin; Pei, Ping; Schwendeman, Steven P; Mallery, Susan R

    2015-05-01

    The membrane-associated protein, focal adhesion kinase (FAK), modulates cell-extracellular matrix interactions and also conveys prosurvival and proliferative signals. Notably, increased intraepithelial FAK levels accompany transformation of premalignant oral intraepithelial neoplasia (OIN) to oral squamous cell carcinoma (OSCC). OIN chemoprevention is a patient-centric, optimal strategy to prevent OSCC's comorbidities and mortality. The cancer chemopreventive and synthetic vitamin A derivative, fenretinide, has demonstrated protein-binding capacities, for example, mTOR- and retinol-binding protein interactions. These studies used a continuum of human oral keratinocytes (normal-HPV E6/E7-transduced-OSCC) to assess potential fenretinide-FAK drug protein interactions and functional consequences on cellular growth regulation and motility. Molecular modeling studies demonstrated that fenretinide has approximately 200-fold greater binding affinity relative to the natural ligand (ATP) at FAK's kinase domain. Fenretinide also shows intermediate binding at FAK's FERM domain and interacts at the ATP-binding site of the closest FAK analogue, PYK2. Fenretinide significantly suppressed proliferation via induction of apoptosis and G2-M cell-cycle blockade. Fenretinide-treated cells also demonstrated F-actin disruption, significant inhibition of both directed migration and invasion of a synthetic basement membrane, and decreased phosphorylation of growth-promoting kinases. A commercially available FAK inhibitor did not suppress cell invasion. Notably, although FAK's FERM domain directs cell invasion, FAK inhibitors target the kinase domain. In addition, FAK-specific siRNA-treated cells showed an intermediate cell migration capacity; data which suggest cocontribution of the established migrating-enhancing PYK2. Our data imply that fenretinide is uniquely capable of disrupting FAK's and PYK2's prosurvival and mobility-enhancing effects and further extend fenretinide

  9. Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells.

    PubMed

    Khafif, A; Schantz, S P; Chou, T C; Edelstein, D; Sacks, P G

    1998-03-01

    An in vitro model for oral cancer was used to examine the growth inhibitory effects of chemopreventive agents when used singly and in combination. The model consists of primary cultures of normal oral epithelial cells, newly established cell lines derived from dysplastic leukoplakia and squamous cell carcinoma. Two naturally occurring substances, (-)-epigallocatechin-3-gallate (EGCG) from green tea and curcumin from the spice turmeric were tested. Cells were treated singly and in combination and effects on growth determined in 5-day growth assays and by cell cycle analysis. Effective dose 50s and the combination index were calculated with the computerized Chou-Talalay method which is based on the median-effect principle. Agents were shown to differ in their inhibitory potency. EGCG was less effective with cell progression; the cancer cells were more resistant than normal or dysplastic cells. In contrast, curcumin was equally effective regardless of the cell type tested. Cell cycle analysis indicated that EGCG blocked cells in G1, whereas curcumin blocked cells in S/G2M. The combination of both agents showed synergistic interactions in growth inhibition and increased sigmoidicity (steepness) of the dose-effect curves, a response that was dose and cell type dependent. Combinations allowed for a dose reduction of 4.4-8.5-fold for EGCG and 2.2-2.8-fold for curcumin at ED50s as indicated by the dose reduction index (DRI). Even greater DRI values were observed above ED50 levels. Our results demonstrate that this model which includes normal, premalignant and malignant oral cells can be used to analyse the relative potential of various chemopreventive agents. Two such naturally-occurring agents, EGCG and curcumin, were noted to inhibit growth by different mechanisms, a factor which may account for their demonstrable interactive synergistic effect.

  10. Residential dampness problems and symptoms and signs of bronchial obstruction in young Norwegian children.

    PubMed

    Nafstad, P; Oie, L; Mehl, R; Gaarder, P I; Lødrup-Carlsen, K C; Botten, G; Magnus, P; Jaakkola, J J

    1998-02-01

    To assess the role of dampness problems and house dust mite exposure in the development of bronchial obstruction in early life, a cohort of 3,754 children born in Oslo during 1992 and 1993 was followed for 2 yr. Bronchial obstruction was defined as two or more episodes with symptoms and signs of obstruction or one lasting 1 mo or more. A matched case-control study was carried out in 251 cases of bronchial obstruction (response rate: 98%) and their 251 paired controls. Information on home dampness problem(s), house dust mite exposure, and potential confounders was collected during home visits and by questionnaires. Dampness problems were confirmed in the homes of 27% of the cases and 14% of the controls, while a concentration of Dermatophagoides pteronyssinus allergens > 2 microg/g dust was found in the beds of 11 (4.5%) cases and three (1.2%) controls. In conditional logistic regression analysis controlling for potential confounders, confirmed dampness problems increased the risk of bronchial obstruction (adjusted odds ratio: 3.8; 95% confidence interval: 2.0-7.2). Exposure to D. pteronyssinus allergens > 2 microg/g dust increased the risk of bronchial obstruction (adjusted odds ratio: 2.8; 95% confidence interval: 0.7-11.7). Residential dampness problems in Oslo dwellings seem to increase symptoms and signs of bronchial obstruction in young children, apparently without increasing their exposure to house dust mites.

  11. [Air pollution and hospital admission trends of children with bronchial obstruction in Tuzla Canton].

    PubMed

    Hadzć, Devleta; Mladina, Nada; Ljuca, Farid; Bazardzanović, Mustafa

    2009-01-01

    The prevalence of bronchial obstruction in children is continuously increasing at any age. Many studies have found associations between increase of respiratory diseases and air pollution. The aim of this paper was to establish possible connection between children hospital admission trends for bronchial obstruction and levels of measured concentration of air pollution agents in Tuzla Canton area. The results of investigation demonstrated that the distribution of hospital admissions of children with bronchial obstruction was different regarding place of inhabitants and season. Spatial distribution demonstrated that the highest number of children treated for bronchial obstruction was from Tuzla, Lukavac and Zivinice. The incidence of patients from these municipalities was significantly above the participation of these municipalities in total population. Seasonal distribution of hospital admissions of children with bronchial obstruction was different for single municipalities of Tuzla Canton and for different seasons. Air pollutants, sulfur oxide and dust deposition were significantly higher for heating season compared to season without heating. There is a link between frequency of hospital admission for bronchial obstruction and level of measured air pollutants.

  12. Squamous cell carcinoma arising from an oral lichenoid lesion: a case report.

    PubMed

    Taghavi Zenouz, Ali; Mehdipour, Masoumeh; Attaran, Rana; Bahramian, Ayla; Emamverdi Zadeh, Paria

    2012-01-01

    Lichenoid reactions represent a family of lesions with different etiologic factors and a common clinical and histologic ap-pearance. Lichen planus is included with lichenoid reactions and is a relatively common chronic mucocutaneous disorder. The most important complication of lichenoid reactions is the possibility of malignant transformation. That is why it has been considered a precancerous condition. Although the malignant transformation rate varies widely in the literature, from 0.4 to 6.5 percent, in most studies it does not exceed 1%. The aim of this paper is to report a rare case of squamous cell car-cinoma (SCC) arising within an oral lichenoid lesion in a 17-year-old woman, where SCC is very uncommon. The patient did not have any risk factors and was healthy. The lesion was located on the border of the tongue. In view of thecommon occurrence of OLP (oral lichen planus) and the unresolved issues regarding its premalignant potential, this case report illus-trates the need for histologic confirmation and a close follow-up of clinical lesions with lichenoid features.

  13. Actinic lesions in fishermen’s lower lip: clinical, cytopathological and histopathologic analysis

    PubMed Central

    Piñera-Marques, Karine; Lorenço, Silvia Vanessa; da Silva, Luiz Fernando Ferraz; Sotto, Mirian Nacagami; Carneiro, Paulo Campos

    2010-01-01

    INTRODUCTION Actinic cheilitis (AC) is considered to be a pre-malignant lesion or an incipient and superficial form of lip squamous cell carcinoma. It is commonly found in individuals whose occupational activities are related to chronic sun exposure and the definitive diagnosis is performed with biopsy. Althoug Exfoliative cytology has been used as a screening procedure to evaluate cancer of the oral cavity no studies have proposed the use of exfoliative cytologic analysis to evaluate and diagnose AC. OBJECTIVE The purpose of this study was to evaluate lower lip lesions on fishermen related to chronic solar exposure using clinical, cytologic and histopathologic analyses. PATIENTS AND METHODS Smears taken from the vermilion of the lower lips of 125 fishermen and 30 control individuals were subjected to cytologic analysis. RESULTS The harvested cells were sufficient for cytologic analysis in 83.2% of the samples. Sixteen fishermen exhibited prominent lower lip lesions that justified biopsy and histological studies. In total, 4 specimens were malignant (3.2%), and 12 displayed epithelial dysplasia, demonstrating that the prevalence of epithelial dysplasia and malignant lesions was high among the fishermen population. These conditions were strongly associated with infiltration and blurring of the vermilion margin of the lower lip. CONCLUSION The cytologic analysis was not useful for detecting epithelial dysplasia or malignant alterations. PMID:20454492

  14. In situ hybridization analysis of human papillomavirus DNA in oral mucosal lesions.

    PubMed

    Zeuss, M S; Miller, C S; White, D K

    1991-06-01

    Commercial biotinylated DNA probes specific for human papillomavirus (HPV) types 6 and 11; 16 and 18; and 31, 33, and 35 were used for in situ hybridization analysis of 105 oral mucosal specimens from 5 cases of verruca vulgaris, 15 cases of condyloma acuminatum, 30 cases of squamous papilloma, 20 cases of hyperkeratosis/acanthosis, 15 cases of epithelial dysplasia, 5 cases of carcinoma in situ, and 15 cases of squamous cell carcinoma. Positive hybridization signals were found in 26 specimens (24.8%). Only HPV-6/11 was detected. HPV DNA occurred significantly more often (p less than 0.005, chi-square analysis) in condyloma acuminatum (100%) and verruca vulgaris (100%) than squamous papilloma (13.3%), hyperkeratotic/acanthotic lesions (10%), and malignant and premalignant lesions (0%). The tongue (19.1%) and labial epithelium (17.1%) were infected most frequently. Nuclear reaction products indicating HPV infection were associated primarily with koilocytes. These results demonstrate the usefulness of commercial biotinylated probes for HPV DNA analysis in routine paraffin-embedded lesion specimens. They confirm HPV involvement in benign lesions of the oral mucosa but fail to associate HPV infection with oral cancer and precancer.

  15. Malignant lesions in the ventral prostate of alloxan-induced diabetic rats.

    PubMed

    Ribeiro, Daniele Lisboa; Marques, Silvio Fernando Guideti; Alberti, Sandra; Spadella, César Tadeu; Manzato, Antônio José; Taboga, Sebastião Roberto; Dizeyi, Nishtman; Abrahamsson, Per-Anders; Góes, Rejane Maira

    2008-08-01

    The aim of this study was to evaluate the changes caused by chronic diabetes in the rat ventral prostate and to establish a correlation between diabetes and the development of prostatic lesions. Male rats received alloxan (42 mg/kg b.w.) to induce diabetes. Ninety days after diabetes diagnosis, animals were sacrificed and the ventral prostate was removed and prepared for general and immunohistochemical analyses. The total area showing different types of lesions was estimated. Diabetes led to a decrease in the body and prostatic weights, as well as in testosterone levels. The prostate morphology and stereology showed high variation in the diabetic group. Some animals had light changes; the great majority had an intense epithelial atrophy; and other rats showed premalignant and malignant lesions in the prostate. Such epithelial atrophy was, in some samples, combined with chronic inflammation, similar to proliferative inflammatory atrophy (PIA). The diabetic group also presented high incidence of prostatitis, adenocarcinoma and prostatic intra-epithelial neoplasia (PIN). Samples with adenocarcinoma had poorly differentiated acini with high levels of cellular proliferation and nuclear atypia. These lesions exhibited an invasive feature showing Bcl-2-positive cells and interruptions in the basement membrane. An association of PIA, PIN and adenocarcinoma was detected in one sample. Reduced androgen levels have a synergic effect to insulin dysfunction promoting negative effects in the rat prostate. Diabetic individuals had a high incidence of prostatitis, and this inflammation could stimulate the incidence of other forms of prostatic pathology.

  16. Malignant lesions in the ventral prostate of alloxan-induced diabetic rats

    PubMed Central

    Ribeiro, Daniele Lisboa; Marques, Silvio Fernando Guideti; Alberti, Sandra; Spadella, César Tadeu; Manzato, Antônio José; Taboga, Sebastião Roberto; Dizeyi, Nishtman; Abrahamsson, Per-Anders; Góes, Rejane Maira

    2008-01-01

    The aim of this study was to evaluate the changes caused by chronic diabetes in the rat ventral prostate and to establish a correlation between diabetes and the development of prostatic lesions. Male rats received alloxan (42 mg/kg b.w.) to induce diabetes. Ninety days after diabetes diagnosis, animals were sacrificed and the ventral prostate was removed and prepared for general and immunohistochemical analyses. The total area showing different types of lesions was estimated. Diabetes led to a decrease in the body and prostatic weights, as well as in testosterone levels. The prostate morphology and stereology showed high variation in the diabetic group. Some animals had light changes; the great majority had an intense epithelial atrophy; and other rats showed premalignant and malignant lesions in the prostate. Such epithelial atrophy was, in some samples, combined with chronic inflammation, similar to proliferative inflammatory atrophy (PIA). The diabetic group also presented high incidence of prostatitis, adenocarcinoma and prostatic intra-epithelial neoplasia (PIN). Samples with adenocarcinoma had poorly differentiated acini with high levels of cellular proliferation and nuclear atypia. These lesions exhibited an invasive feature showing Bcl-2-positive cells and interruptions in the basement membrane. An association of PIA, PIN and adenocarcinoma was detected in one sample. Reduced androgen levels have a synergic effect to insulin dysfunction promoting negative effects in the rat prostate. Diabetic individuals had a high incidence of prostatitis, and this inflammation could stimulate the incidence of other forms of prostatic pathology. PMID:18715471

  17. Stratified Mucin-Producing Intraepithelial Lesion of the Cervix: Subtle Features Not to Be Missed.

    PubMed

    Schwock, Joerg; Ko, Hyang Mi; Dubé, Valérie; Rouzbahman, Marjan; Cesari, Matthew; Ghorab, Zeina; Geddie, William R

    2016-01-01

    Stratified mucin-producing intraepithelial lesion (SMILE) is an uncommon premalignant lesion of the uterine cervix. A detailed examination of preinvasive SMILE cases including a comparison of the cytologic features with usual-type adenocarcinoma in situ (AIS) and human papillomavirus (HPV) genotyping was performed. Excisions and preceding Papanicolaou (Pap) tests were retrieved from the files of 2 tertiary care centers. Histologic review estimated the lesional SMILE proportion. Pap tests were reviewed and assessed for architectural, cellular and background features. Cobas® HPV test was performed. 13 cases were identified. Mean/median patient age was 35/33 years (range 23-51 years). Concurrent high-grade squamous intraepithelial lesion was found in 10/13 (77%) and AIS in 8/13 (62%) cases. In 6 cases, SMILE was dominant (≥50%) and represented in 5/6 corresponding Pap tests. Cytology interpretations differed more often in the SMILE-dominant group (p < 0.05). SMILE and AIS had overlapping features. Feathering and prominent nucleoli were absent in SMILE. HPV DNA was detected in all 12 cases tested. HPV 18 was most common (7/12). Excisions with positive/suspicious margins were reported in 5/6 SMILE-dominant versus 3/7 nondominant cases. SMILE is best considered as an AIS variant for cytologic, etiologic and management purposes. Cytologic features overlap with AIS, but are more subtle and easily missed. HPV testing may play a role in facilitating SMILE detection. © 2016 S. Karger AG, Basel.

  18. Intracystic concentrations of tumour markers for the diagnosis of cystic liver lesions.

    PubMed

    Fuks, D; Voitot, H; Paradis, V; Belghiti, J; Vilgrain, V; Farges, O

    2014-03-01

    Imaging occasionally fails to differentiate hepatic simple cysts from malignant or premalignant mucinous cystic lesions such as biliary cystadenomas. Hepatic simple cysts can be treated conservatively, whereas malignant or premalignant cysts require complete resection. This study assessed the ability of intracystic tumour marker concentrations to differentiate these disease entities. Intracystic fluid was sampled in patients undergoing partial or complete resection of a cystic lesion of the liver. The indication for surgery in hepatic simple cysts was symptoms or suspicion of a biliary cystadenoma. Intracystic concentrations of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 and tumour-associated glycoprotein (TAG) 72 were measured to assess the diagnostic accuracy of these tumour markers. Cut-off values were defined by receiver operating characteristic (ROC) curves. The study population comprised 118 patients (94 women) with a median age of 59 years. There were 75 patients with hepatic simple cysts, 27 with mucinous cysts (19 biliary cystadenomas, 4 biliary cystadenocarcinomas, 4 intraductal papillary mucinous neoplasms of the bile duct) and 16 with miscellaneous cysts. Unlike CEA and CA19-9, a TAG-72 concentration of more than 25 units/ml differentiated hepatic simple cysts from mucinous cysts with a sensitivity and a specificity of 0·79 and 0·97 respectively. The area under the ROC curve was 0·98 for mucinous versus hepatic simple cysts. The concentration of TAG-72 in cyst fluid accurately identified hepatic cysts that required complete resection. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

  19. Biological behavior of CIN lesions is predictable by multiple parameter logistic regression models.

    PubMed

    van Hamont, D; Bulten, J; Shirango, H; Melchers, W J G; Massuger, L F A G; de Wilde, P C M

    2008-04-01

    Progression and regression of premalignant cervical lesions cannot be predicted using conventional cytomorphological or histomorphological parameters. However, markers such as human papillomavirus (HPV) or makers indicating proliferation, genetic instability and chromosomal aberration may be of predictive value assessing short-term biological behavior of cervical intraepithelial neoplasia. In this paper, we have studied the usage of logistic regression models with Ki-67 labeling index (LI), chromosome index for chromosome 1 (CI#1) and aneusomy for chromosome 1 in cervical smears to predict progressive and regressive behavior of premalignant cervical lesions. Retrospectively, the intake smears of 42 women showing regression in follow-up and of 31 women showing progression in follow-up were assessed. A multiparameter logistic regression model containing the parameters Ki-67 LI, CI#1 and the fraction of cells with four copies of chromosome 1 per nucleus appeared to be the best predicting model, overall correct classification of 93.2% (area under the receiver operating characteristic curve 0.96 +/- 0.02). After cross-validation, the model correctly classified 66 of 73 samples (90.4%). Moreover, the model predicted biological behavior perfectly assessing the smear taken subsequently to the intake smear of 46 women. Although measuring parameters indicating proliferation and chromosome 1 aberration is laborious, this study demonstrates that short-term progressive and regressive behavior is highly predictable using a model combing these parameters. We also showed that in the triage management of high-risk human papillomavirus-positive women with minimally abnormal smears applying a model as such can be useful.

  20. Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy.

    PubMed

    Chhetri, Raghav K; Phillips, Zachary F; Troester, Melissa A; Oldenburg, Amy L

    2012-01-01

    The human mammary gland is a complex and heterogeneous organ, where the interactions between mammary epithelial cells (MEC) and stromal fibroblasts are known to regulate normal biology and tumorigenesis. We aimed to longitudinally evaluate morphology and size of organoids in 3D co-cultures of normal (MCF10A) or pre-malignant (MCF10DCIS.com) MEC and hTERT-immortalized fibroblasts from reduction mammoplasty (RMF). This co-culture model, based on an isogenic panel of cell lines, can yield insights to understand breast cancer progression. However, 3D cultures pose challenges for quantitative assessment and imaging, especially when the goal is to measure the same organoid structures over time. Using optical coherence tomography (OCT) as a non-invasive method to longitudinally quantify morphological changes, we found that OCT provides excellent visualization of MEC-fibroblast co-cultures as they form ductal acini and remodel over time. Different concentrations of fibroblasts and MEC reflecting reported physiological ratios [1] were evaluated, and we found that larger, hollower, and more aspherical acini were formed only by pre-malignant MEC (MCF10DCIS.com) in the presence of fibroblasts, whereas in comparable conditions, normal MEC (MCF10A) acini remained smaller and less aspherical. The ratio of fibroblast to MEC was also influential in determining organoid phenotypes, with higher concentrations of fibroblasts producing more aspherical structures in MCF10DCIS.com. These findings suggest that stromal-epithelial interactions between fibroblasts and MEC can be modeled in vitro, with OCT imaging as a convenient means of assaying time dependent changes, with the potential for yielding important biological insights about the differences between benign and pre-malignant cells.

  1. [Occult bronchial foreign bodies - analysis of own material].

    PubMed

    Szafrański, Wojciech; Dobielski, Jarosław; Papiewski, Wojciech; Czechowska, Urszula

    2013-01-01

    The aspiration of a foreign body is usually combined with acute clinical symptoms requiring immediate medical intervention. Nevertheless, in approximately one third of patients the symptoms of aspiration are less prominent; such a clinical condition is called occult bronchial foreign body (OBFB). The aim of our study was to assess the frequency of OBFB in the pulmonary unit of a district hospital and to evaluate the diagnostic difficulties and treatment modalities in such patients. The examined group consisted of patients hospitalized in the Department of Lung Diseases in Radom District Hospital. A retrospective analysis of medical records was preformed. In the period 1978-2008 - 12 patients (10 males, 2 females) were hospitalized due to OBFB. The foreign bodies occluded the bronchi over 2 months (3 to 7) in 4 patients. The moment of aspiration was not remembered by 8 patients. Cases of OBFB were rare. In the presented material the frequency was 4 per 10,000 hospitalizations and 8 per 10,000 bronchoscopies. In our region of 600,000 population the index of hospitalization due to OBFB in adults (〉 14 years of age) was 0.07 per 100,000 inhabitants/year. Foreign bodies mainly included bone fragments (5 cases), vegetal remnants - clove of garlic, ear of corn (3 patients), and other food remnants (2 patients). Occasionally other aspirates were found, such as a wooden peg or a piece of plastic. The aspiration took place mostly during meals. The patients developed one or more of the following symptoms: purulent pneumonia (3 cases), pleural empyema (1 case), atelectasis (5 cases), and recurrent bronchitis and pneumonia (2 cases). The foreign body (fragments of plants) was mimicking a bronchial tumour in 4 patients. Fibre optic or rigid bronchoscopy was applied successfully in 11 patients. Only one patient needed surgical intervention. OBFB is a rare condition, but has to be taken into consideration as a cause of chest radiological pathology and in patients with chronic

  2. Effects of ouabain on human bronchial muscle in vitro.

    PubMed

    Cortijo, Julio; Sarria, Benjamín; Mata, Manuel; Naline, Emmanuel; Advenier, Charles; Morcillo, Esteban J

    2003-11-01

    The effects of ouabain, an inhibitor of the plasmalemmal Na(+)/K(+)-ATPase activity, were examined in human isolated bronchus. Ouabain produced concentration-dependent contraction with -logEC(50)=7.16+/-0.11 and maximal effect of 67+/-4% of the response to acetylcholine (1 mM). Ouabain (10 microM)-induced contraction was epithelium-independent and was not depressed by inhibitors of cyclooxygenase and lipoxygenase, antagonists of muscarinic, histamine H(1)-receptors and alpha-adrenoceptors, or neuronal Na(+) channel blockade. The inhibition of ouabain contraction in tissues bathed in K(+)-free medium, and the inhibition by ouabain of the K(+)-induced relaxation confirm that the contractile action of ouabain is mediated by inhibition of Na(+)/K(+)-ATPase. Furthermore, depolarization (16.4+/-0.9 mV) was observed in human isolated bronchus by intracellular microelectrode recording. Ouabain (10 microM)-induced contractions were abolished by a Ca(2+)-free solution but not by blockers of L-type Ca(2+) channels. In human cultured bronchial smooth muscle cells, ouabain (10 microM) produced a sustained increase in [Ca(2+)](i) (116+/-26 nM) abolished in Ca(2+)-free medium. Incubation with a Na(+)-free medium or amiloride (0.1 mM) markedly inhibited the spasmogenic effect of ouabain thus suggesting the role of Na(+)/Ca(2+) exchange in ouabain contraction while selective inhibitors of Na(+)/H(+)-antiport, Na(+)/K(+)/Cl(-)-antiport, or protein kinase C had no effect. Ouabain (10 microM) failed to increase inositol phosphate accumulation in human bronchus. Ouabain (10 microM) did not alter bronchial responsiveness to acetylcholine or histamine but inhibited the relaxant effects of isoprenaline, forskolin, levcromakalim, or sodium nitroprusside. These results indicate that ouabain acts directly to produce contraction of human airway smooth muscle that depends on extracellular Ca(2+) entry unrelated to L-type channels and involving the Na(+)/Ca(2+)-antiporter.

  3. Oral Lesions in Neonates

    PubMed Central

    Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

    2016-01-01

    ABSTRACT Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

  4. Multifocal vascular lesions.

    PubMed

    Levin, Laura E; Lauren, Christine T

    2016-09-01

    Multifocal vascular lesions are important to recognize and appropriately diagnose. Generally first noticed on the skin, multifocal vascular lesions may have systemic involvement. Distinguishing among the different types of multifocal vascular lesions is often based on clinical features; however, radiological imaging and/or biopsy are frequently needed to identify distinct features and guide treatment. Knowledge of the systemic associations that can occur with different vascular anomalies may reduce life-threatening complications, such as coagulopathy, bleeding, cardiac compromise, and neurologic sequelae. This review provides a synopsis of the epidemiology, pathogenesis, presentation, workup, and treatment of several well-recognized multifocal vascular tumors and malformations.

  5. Incidental vertebral lesions.

    PubMed

    Coumans, Jean-Valery C E; Walcott, Brian P

    2011-12-01

    Incidental vertebral lesions on imaging of the spine are commonly encountered in clinical practice. Contributing factors include the aging population, the increasing prevalence of back pain, and increased usage of MR imaging. Additionally, refinements in CT and MR imaging have increased the number of demonstrable lesions. The management of incidental findings varies among practitioners and commonly depends more on practice style than on data or guidelines. In this article we review incidental findings within the vertebral column and review management of these lesions, based on available Class III data.

  6. Pure cutting current for loop excision of squamous intraepithelial lesions.

    PubMed

    McLucas, B; McGill, J

    1994-05-01

    Clear margins are critical to the identification of complete excision of premalignant lesions on the cervix. Large loop excision of the transformation zone aids the pathologic evaluation of the excised specimen while it causes minimal thermal damage. Prior studies of loop excision were performed with a cutting current blended with a coagulating waveform to aid hemostasis. Blended current has higher voltage, which may cause tissue to stick to the electrode and produce thermal damage to the cervix. In this series, pure cutting current was used to excise the cervical transformation zone in 20 patients. The depth of thermal damage was studied in 6 patients; the average endocervical zone of damage was 0.47 mm and that of the exocervical zone, 0.43 mm. The base of the cervix could be examined with the colposcope for the presence of glands. None of our procedures was complicated by intraoperative or delayed bleeding. The preoperative injection of a vasoconstrictor into the cervical stroma is thought to aid the surgery by its hemostatic properties.

  7. Deformable image registration of heterogeneous human lung incorporating the bronchial tree.

    PubMed

    Al-Mayah, Adil; Moseley, Joanne; Velec, Mike; Hunter, Shannon; Brock, Kristy

    2010-09-01

    To investigate the effect of the bronchial tree on the accuracy of biomechanical-based deformable image registration of human lungs. Three dimensional finite element models have been developed using four dimensional computed tomography image data of ten lung cancer patients. Each model is built of a body, left and right lungs, tumor, and bronchial trees. Triangular shell elements are used for the bronchial trees while tetrahedral elements are used for other components. Hyperelastic material properties based on experimental investigation on human lungs are used for the lung parenchyma. Different material properties are assigned for the bronchial tree using five values for the modulus of elasticity of 0.01, 0.12, 0.5, 10, and 18 MPa. Lungs are modeled to slide inside chest cavities by applying frictionless contact surfaces between each lung and corresponding chest cavity. The accuracy of the models is examined using an average of 40 bronchial bifurcation points identified on inhale and exhale images. Relative accuracy is evaluated by comparing the displacement of all nodes within the lungs as well as the dosimetric difference at the exhale position predicted by the model. There is no significant effect of bronchial tree on the model accuracy based on the bifurcation points analysis. However, on the local level, using an average of 38 000 nodes, there is a maximum difference of 8.5 mm in the deformation of the bronchial trees, as the modulus of elasticity of the bronchial trees increases from 0.01 to 18 MPa; however, more than 96% of nodes are within a 2.5 mm difference in each direction. The average dose difference at the predicted exhale position is