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Sample records for high grade squamous

  1. High-grade cervical squamous intraepithelial lesion during pregnancy.

    PubMed

    Murta, Eddie Fernando Candido; de Souza, Flávio Henrique Caetano; de Souza, Maria Azniv Hazarabedian; Adad, Sheila Jorge

    2002-01-01

    An increasing incidence of high-grade squamous intraepithelial lesion (HSIL) has been observed among young women. Consequently, an increased number of cases are being discovered during pregnancy. We analyzed the clinical and therapeutic management of HSIL during pregnancy. A retrospective study was conducted from 1979 to 1998, and 58 registries of women with a cytological or histological diagnosis of HSIL during the pregnant-puerperal period were reviewed. Information obtained from medical records included age, gestational age at diagnosis, parity, age of first intercourse, number of sexual partners before pregnancy, tobacco use, cytologic and colposcopic findings, route of delivery, postpartum follow-up, and treatment. This information was compared with a non-pregnant control group with HSIL. The average age of pregnant women with HSIL was 27.9 +/- 5.2 years. The cytologic or histologic diagnosis of HSIL was made in the first trimester in 12 (20.7%) women and in the second trimester in 30 (51.7%) women. Average parity was 2.8 +/- 2 deliveries. Age of first intercourse ranged from 13 to 29 years (16.1 +/- 3.3). Thirty-two women (55.1%) had more than one sexual partner before pregnancy. Thirty-seven (63.8%) refereed tobacco use. According to the aforementioned aspects, no statistical difference was found in relation to control, except to cervical ectopia, which was more frequent in pregnant women (56.9% versus 42.6%). From the total of 58 pregnant women with cytologic or biopsy HSIL diagnosis, 53 had HSIL diagnosis made on cervical biopsy directed by colposcopy performed during the pregnancy; 44 (83%) of them were submitted to conservative management. HSIL was diagnosed by cervical biopsy in postpartum evaluation in 76% pregnant women with vaginal delivery and 78.6% women who underwent cesarean section. A conservative management of HSIL in pregnancy is proposed, with colposcopic evaluation during gestation and postpartum, regardless of route of delivery.

  2. Treatment options for high-grade squamous intraepithelial lesions.

    PubMed

    Long, Stephanie; Leeman, Lawrence

    2013-06-01

    The introduction of testing for high-risk HPV types and P16 immunostaining of CIN2 histologic specimens allows for determination of the risk of progression versus regression for a woman with a particular cytologic or histologic specimen. Observation with serial cytological or colposcopic examinations is now appropriate for women with low-grade histologic lesions as well as pregnant and young women with certain high-grade histologic lesions. Current recommendations for management of high-grade lesions, the efficacy of treatment options (cryotherapy and LEEP), and the immediate (bleeding, infection) and longer term complications (cervical incompetence, preterm delivery) of cervical dysplasia treatment are presented. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. High-grade squamous intraepithelial lesion arising adjacent to vulvar lymphangioma circumscriptum: a tertiary institutional experience

    PubMed Central

    Bae, Go Eun; Yoon, Gun; Song, Yong Jung; Kim, Hyun-Soo

    2016-01-01

    Lymphangioma circumscriptum of the vulva occurs in patients who have undergone radical hysterectomy, lymph node dissection, or radiation therapy for management of advanced uterine cancer. Since vulvar lymphangioma circumscriptum typically presents as multiple, grossly verrucous vesicles of various sizes, it may be impossible to clinically distinguish vulvar lymphangioma circumscriptum from other vulvoperineal cutaneous diseases. In the present study, 16 (1.6%) out of the 1,024 vulvar biopsy or excision specimens were diagnosed as lymphangioma circumscriptum. In two (12.5%) out of the 16 cases, unusual histopathological findings were observed. Both patients had previously undergone radical hysterectomy with lymph node dissection and postoperative radiation therapy or concurrent chemoradiation therapy for advanced cervical cancer. Microscopic examination revealed high-grade squamous intraepithelial lesions, which were located immediately adjacent to the normal squamous epithelium covering the dilated subepithelial lymphatic vessels. Further, human papillomavirus genotyping confirmed that both patients were infected with high-risk human papillomavirus. High-grade squamous intraepithelial lesion cannot be grossly distinguished from vulvar lymphangioma circumscriptum because the multiple, verrucous vesicles that constitute the characteristic gross appearance of vulvar lymphangioma circumscriptum hinder its distinction. In this regard, our cases of high-grade squamous intraepithelial lesion, located adjacent to vulvar lymphangioma circumscriptum, support the notion that active surgical excision is necessary for the treatment of vulvar lymphangioma circumscriptum. PMID:27329721

  4. Clinicopathologic and outcome features of superficial high-grade and deep low-grade squamous cell carcinomas of the penis.

    PubMed

    Chaux, Alcides

    2015-01-01

    To report the clinicopathologic and outcome features of superficial high-grade and deep low-grade penile squamous cell carcinomas. From a retrospectively-collected series of patients with penile cancer we identified 41 cases corresponding to 12 superficial high-grade tumors and 29 deep low-grade tumors. As outcomes we evaluated inguinal lymph node status, presence of tumor relapse, final nodal status, and cancer-specific death. Follow-up ranged from 0.8 to 386.7 months (mean 152.5 months, median 157.3 months). Clinicopathologic features were similar between superficial high-grade and deep low-grade tumors, except for a tendency (Fisher's exact [Formula: see text]) of the former to include tumors with a verruciform pattern of growth. A significantly higher proportion of inguinal lymph node metastasis was found in superficial high-grade tumors compared to deep low-grade tumors [4/5 (80%) vs. 1/5 (20%) respectively, Fisher's exact [Formula: see text

  5. Revised terminology for cervical histopathology and its implications for management of high-grade squamous intraepithelial lesions of the cervix.

    PubMed

    Waxman, Alan G; Chelmow, David; Darragh, Teresa M; Lawson, Herschel; Moscicki, Anna-Barbara

    2012-12-01

    In March 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology, in collaboration with 35 stakeholder organizations, convened a consensus conference called the Lower Anogenital Squamous Terminology (LAST) Project. The recommendations of this project include using a uniform, two-tiered terminology to describe the histology of human papillomavirus-associated squamous disease across all anogenital tract tissues: vulva, vagina, cervix, penis, perianus, and anus. The recommended terminology is "low-grade" or "high-grade squamous intraepithelial lesion (SIL)." This terminology is familiar to clinicians, because it parallels the terminology of the Bethesda System cytologic reports. Biopsy results using SIL terminology may be further qualified using "intraepithelial neoplasia" (IN) terminology in parentheses. Laboratory p16 tissue immunostaining is recommended to better classify histopathology lesions that morphologically would earlier have been diagnosed as IN 2. p16 is also recommended for differentiating between high-grade squamous intraepithelial lesions and benign mimics. The LAST Project recommendations potentially affect the application of current guidelines for managing cervical squamous intraepithelial lesions. The authors offer interim guidance for managing cervical lesions diagnosed using this new terminology with special attention paid to managing young women with cervical high-grade squamous intraepithelial lesions on biopsy. Clinicians should be aware of the LAST Project recommendations, which include important changes from prior terminology.

  6. Revised Terminology for Cervical Histopathology and Its Implications for Management of High-Grade Squamous Intraepithelial Lesions of the Cervix

    PubMed Central

    Waxman, Alan G.; Chelmow, David; Darragh, Teresa M.; Lawson, Herschel; Moscicki, Anna-Barbara

    2014-01-01

    In March 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology, in collaboration with 35 stakeholder organizations, convened a consensus conference called the Lower Anogenital Squamous Terminology (LAST) Project. The recommendations of this project include using a uniform, two-tiered terminology to describe the histology of human papillomavirus-associated squamous disease across all anogenital tract tissues: vulva, vagina, cervix, penis, perianus, and anus. The recommended terminology is “low-grade” or “high-grade squamous intraepithelial lesion (SIL).” This terminology is familiar to clinicians, because it parallels the terminology of the Bethesda System cytologic reports. Biopsy results using SIL terminology may be further qualified using “intraepithelial neoplasia” (IN) terminology in parentheses. Laboratory p16 tissue immunostaining is recommended to better classify histopathology lesions that morphologically would earlier have been diagnosed as IN 2. p16 is also recommended for differentiating between high-grade squamous intraepithelial lesions and benign mimics. The LAST Project recommendations potentially affect the application of current guidelines for managing cervical squamous intraepithelial lesions. The authors offer interim guidance for managing cervical lesions diagnosed using this new terminology with special attention paid to managing young women with cervical high-grade squamous intraepithelial lesions on biopsy. Clinicians should be aware of the LAST Project recommendations, which include important changes from prior terminology. PMID:23168774

  7. Cytohistological correlation of endocervical gland involvement with high-grade squamous intraepithelial lesions

    PubMed Central

    Kir, G; Karabulut, MH; Yilmaz, MS; Topal, CS; Gocmen, A

    2012-01-01

    Background: Diagnosis of endocervical glandular involvement by high-grade squamous intraepithelial lesion (HSIL-EGI) on Papanicolaou (Pap) smears can affect the clinical management of patients. Aim: The cytological criteria for the diagnosis of HSIL-EGI are described and the accuracy of this diagnosis was investigated. Materials and Methods: Seventeen patients diagnosed with HSIL-EGI and 40 patients with diagnosis of HSIL on Pap smears with follow-up cone or loop electrocautery excision procedure (LEEP) biopsies were included in the study. The following criteria were evaluated for the cytological diagnosis of HSIL-EGI: atypical cells with definite features of HSIL, three-dimensional atypical squamous cell clusters (TDCs) with attached benign endocervical epithelium, finger-like TDCs covered with intact epithelium on most sides, which represent the finger-like invaginations of the endocervical glandular area involved by HSIL, and the absence of cytological findings of in situ adenocarcinoma of the cervix. Results: On subsequent histopathological evaluation, 16 of 17 (94.1%) patients with a cytological diagnosis of HSIL-EGI and 17 of 40 (42.5%) patients with HSIL exhibited endocervical glandular involvement (P < 0.001, sensitivity: 48.5%, specificity: 95.8%, positive predictive value: 94.1%, negative predictive value: 57.5% and accuracy: 68.4%). Conclusion: Diagnosis of HSIL-EGI may be possible on Pap smears with a high positive predictive value and specificity but low sensitivity, possibly due to cytological sampling limitations. To clarify the results of the present study, more extensive studies with a particular emphasis on the sampling of the endocervical glandular area for cytological evaluation of the cervix are needed. PMID:22787292

  8. World wide web-based cytological analysis of atypical squamous cells cannot exclude high-grade intraepithelial lesions.

    PubMed

    Washiya, Kiyotada; Takamizu, Ryuichi; Kumagai, Yukie; Himeji, Yukari; Kobayashi, Takako; Iwai, Muneo; Watanabe, Jun

    2012-01-01

    It has been reported that the low level of consistency of diagnosis of atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions (ASC-H) in uterine cervical cancer screening using the Bethesda System, indicating the necessity of a large-scale survey. We presented cases cytologically judged as ASC-H on our website and invited our members to give their opinions regarding the diagnosis by voting online. The Web voting results were analyzed and ASC-H was cytologically investigated. Virtual slides of atypical cells in cytology preparations of 53 cases were prepared and presented on a website. ASC-H cases were divided into 42 cases sampled by brush scraping and 11 cases sampled by cotton swab scraping. Fifty-three cases cytologically judged as ASC-H were classified into benign and CIN2/3, and their patterns of arrangement of atypical cells and 8 cytological parameters were morphologically investigated. The frequency of ASC-H diagnosis in the Web votes was low: 29.2% for brush-scraped and 26.2% for cotton swab-scraped cases. Three-dimensionality, coarse chromatin and irregular nuclei were significantly different between high-grade squamous intraepithelial lesions and benign cases. Web-based surveys showed the difference of cytological findings between high-grade squamous intraepithelial lesions and benign cases. To increase interobserver consistency, it may be useful to share information online, which avoids geographical and temporal limitations. Copyright © 2012 S. Karger AG, Basel.

  9. Effect of Thin Prep® imaging system on laboratory rate and relative sensitivity of atypical squamous cells, high-grade squamous intraepithelial lesion not excluded and high-grade squamous intraepithelial lesion interpretations

    PubMed Central

    Koltz, Brooke R.; Russell, Donna K.; Lu, Naiji; Bonfiglio, Thomas A.; Varghese, Sharlin

    2013-01-01

    Introduction: Automated screening of Thin Prep® Papanicolaou Tests has become increasingly common in clinical practice. Increased productivity has initiated laboratory use of the Thin Prep® Imaging System (TIS). Increased sensitivity is a potential additional benefit of TIS. Published studies have shown an increase in discovery of dysplastic cells. This study evaluates the effect of TIS on the incidence of atypical squamous cells high-grade squamous intraepithelial lesion not excluded (ASC-H) and high-grade squamous intraepithelial lesion (HGSIL) results on Thin Prep® Pap Tests by comparing TIS-assisted and manual screening findings and the diagnoses on subsequent follow-up in a screening population over a 1-year time period. Materials and Methods: A compilation of all ASC-H and HGSIL cases was prepared by conducting a computerized search over a 1-year period (7/06-6/07). The accumulated cases include Thin Prep Pap tests that were both TIS and manually screened. Follow-up results of cytologic and histologic cervical specimens were obtained for a time period extending to 2010. Interpretation utilizing TIS was in place 10 months prior to the study's initiation. Results: During the study period 70,522 Pap tests were performed in our laboratory. One third (33%) of Pap tests were screened with assistance of TIS. Manual screening was performed on 47,380 Pap tests of which 153 (0.32%) were interpreted as ASC-H and 164 (0.35%) were interpreted as HGSIL. During the same time period automated screening (TIS) was performed on 23,111 Pap tests. Interpretation of 62 (0.27%) cases provided an ASC-H result, while 71 (0.31%) were HGSIL. Follow-up cervical dysplasia by colposcopic biopsy and cone biopsy was distributed proportionally between TIS and manual screening for both ASC-H and HGSIL categories. Cervical intraepithelial neoplasia (CIN II/III) was identified on follow-up biopsy of 41% TIS cases and 45% manually screened cases for ASC-H. In the HGSIL subset 71% of TIS cases

  10. Early detection of high-grade squamous intraepithelial lesions in the cervix with quantitative spectroscopic imaging

    PubMed Central

    Mirkovic, Jelena; Yu, Chung-Chieh; O’Donoghue, Geoff P.; Galindo, Luis; Dasari, Ramachandra; de las Morenas, Antonio; Feld, Michael; Stier, Elizabeth

    2013-01-01

    Abstract. Quantitative spectroscopy has recently been extended from a contact-probe to wide-area spectroscopic imaging to enable mapping of optical properties across a wide area of tissue. We train quantitative spectroscopic imaging (QSI) to identify cervical high-grade squamous intraepithelial lesions (HSILs) in 34 subjects undergoing the loop electrosurgical excision procedure (LEEP subjects). QSI’s performance is then prospectively evaluated on the clinically suspicious biopsy sites from 47 subjects undergoing colposcopic-directed biopsy. The results show the per-subject normalized reduced scattering coefficient at 700 nm (An) and the total hemoglobin concentration are significantly different (p<0.05) between HSIL and non-HSIL sites in LEEP subjects. An alone retrospectively distinguishes HSIL from non-HSIL with 89% sensitivity and 83% specificity. It alone applied prospectively on the biopsy sites distinguishes HSIL from non-HSIL with 81% sensitivity and 78% specificity. The findings of this study agree with those of an earlier contact-probe study, validating the robustness of QSI, and specifically An, for identifying HSIL. The performance of An suggests an easy to use and an inexpensive to manufacture monochromatic instrument is capable of early cervical cancer detection, which could be used as a screening and diagnostic tool for detecting cervical cancer in low resource countries. PMID:23843090

  11. Prevalence of abnormal anal cytology and high-grade squamous intraepithelial lesions among a cohort of HIV-infected men who have sex with men.

    PubMed

    Sendagorta, Elena; Herranz, Pedro; Guadalajara, Hector; Bernardino, Jose Ignacio; Viguer, Jose María; Beato, María José; García-Olmo, Damian; Peña, Jose María

    2014-04-01

    The incidence of anal cancer among HIV-infected patients is higher than that in other populations. Anal high-grade squamous intraepithelial lesions are considered precursors to invasive squamous-cell carcinomas and are strongly associated to high-risk human papillomavirus infection. The aim of this study is to determine the prevalence of anal high-grade squamous intraepithelial lesions through screening based on cytology and high-resolution anoscopy with biopsy in a cohort of HIV-infected men who have sex with men. This investigation is an observational cross-sectional cohort study. The study was conducted in the HIV unit of a tertiary hospital in Spain. Three hundred HIV-infected men who have sex with men participated. Physical examination led to a diagnosis of perianal squamous-cell carcinoma and high-grade squamous intraepithelial lesions in 2 patients who were then excluded. Anal liquid cytology was performed. Patients with cytological abnormalities underwent high-resolution anoscopy and biopsy. The primary outcome measured was biopsy-proven high-grade squamous intraepithelial lesions. The median age was 41 ± 10.5 years. The mean and nadir CD4 cell counts were 651 ± 205 cells/mm(3) (interquartile range, 438-800) and 273 ± 205 cells/mm(3) (interquartile range, 131-362). High-risk human papillomavirus was detected in 80.9% of patients, and human papillomavirus 16 was detected in 35.9% of patients. The mean number of human papillomavirus genotypes was 4.6 ± 2.9 (CI, 2-6). Anal cytology was abnormal in 40.9% of patients (n = 122/298; interquartile range, 35.4%-46.6%). High-resolution anoscopy and biopsies were performed in 119 patients. The results of histological analyses were as follows: normal, 7.7% (n = 23); condyloma, 4.3% (n = 13); anal intraepithelial neoplasia 1, 5.7% (n = 17); anal intraepithelial neoplasia 2, 14% (n = 42); and anal intraepithelial neoplasia 3, 8% (n = 24). The overall prevalence of high-grade squamous intraepithelial lesions among

  12. Infrared coagulator ablation of high-grade anal squamous intraepithelial lesions in HIV-negative males who have sex with males.

    PubMed

    Goldstone, Stephen E; Hundert, Joshua S; Huyett, Jeff W

    2007-05-01

    The incidence of anal squamous carcinoma in males who have sex with males is rising. We reported that infrared coagulation of high-grade squamous intraepithelial lesions in HIV-positive males who have sex with males yielded a recurrence rate after the first ablation of 65 percent and 58 percent after a second ablation. The cure rate of an individual lesion was 72 percent. We endeavored to determine whether this technique demonstrates improved results in HIV-negative males who have sex with males. We performed a retrospective review of medical records on HIV-negative males who have sex with males who had infrared coagulation ablation of anal high-grade squamous intraepithelial lesions. Patients had at least six months' follow-up with cytology, high-resolution anoscopy, and biopsy. Recurrent high-grade squamous intraepithelial lesions were retreated. Seventy-five patients were enrolled, with a median age of 36 years, and 113 lesions were treated. Forty patients (53 percent) developed a recurrence in a median time of 238 days and 35 patients (47 percent) were disease free for a median of 516 days. When patients were treated a second or third time, recurrence rates dropped to 28 and 0 percent, respectively. The probability of successfully treating an individual lesion at first infrared coagulation was 81 percent and 93 percent when retreated. HIV-positive patients were twice as likely to have lesions persist and 1.7 times more likely to develop a recurrent high-grade squamous intraepithelial lesion. No patient developed squamous-cell carcinoma, anal stenosis, or had a serious complication. Infrared coagulation is a safe and effective office-based procedure for treating anal high-grade squamous intraepithelial lesions. Although recurrence was high after the first infrared coagulation, repeated treatment led to resolution of high-grade squamous intraepithelial lesions. Treatment success with infrared coagulation is significantly superior in HIV-negative patients compared

  13. Endoscopic diagnosis of early squamous neoplasia of the esophagus with iodine staining: high-grade intra-epithelial neoplasia turns pink within a few minutes.

    PubMed

    Shimizu, Yuichi; Omori, Tai; Yokoyama, Akira; Yoshida, Takeshi; Hirota, Jojo; Ono, Yuji; Yamamoto, Junji; Kato, Mototsugu; Asaka, Masahiro

    2008-04-01

    The ability to detect early squamous neoplasia of the esophagus can be enhanced considerably by iodine staining during endoscopic examination; however, there has been no study on distinguishing high-grade intra-epithelial squamous neoplasia from low-grade dysplasia by endoscopic examination. We assumed that high-grade intra-epithelial neoplasia could be identified as iodine-unstained areas more distinct and reddish than low-grade dysplasia after the brown color of iodine solution has faded, because there is almost no remaining glycogen-containing epithelium in high-grade intra-epithelial neoplasia. Seventy-nine patients who were found to have demarcated iodine-unstained areas (0.5 cm to 1.5 cm at widest part, 121 lesions in total) were studied. After a target lesion was found, the lesion was observed for about 3 min and its discoloration was evaluated. If a light-pink part appeared in the iodine-unstained area, the lesion was regarded as being positive for pink color. If no light-pink part was observed in the lesion within 3 min, the lesion was regarded as being negative for pink color. Thirty-four (87.2%) of the 39 lesions diagnosed as pink-color positive were histologically confirmed to be high-grade intra-epithelial squamous neoplasia or squamous cell carcinoma, whereas only three (3.7%) of the 82 lesions diagnosed as negative for pink color were histologically confirmed to be high-grade intra-epithelial squamous neoplasia (P < 0.0001). Using the pink-color sign as a diagnostic index for high-grade intra-epithelial squamous neoplasia and squamous cell carcinoma, sensitivity was 91.9% and specificity was 94.0%. By using the pink-color sign for endoscopic diagnosis, accurate diagnosis without endoscopic biopsy for iodine-unstained areas was possible.

  14. DNA methylation in human papillomavirus-infected cervical cells is elevated in high-grade squamous intraepithelial lesions and cancer

    PubMed Central

    Lee, Ki-Heon; So, Kyeong A; Hong, Sung Ran; Hwang, Chang-Sun; Kee, Mee-Kyung; Rhee, Jee Eun; Kang, Chun; Hur, Soo Young; Park, Jong Sup

    2016-01-01

    Objective DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. Methods A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. Results Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). Conclusion DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies. PMID:26768780

  15. γH2Ax Expression as a Potential Biomarker Differentiating between Low and High Grade Cervical Squamous Intraepithelial Lesions (SIL) and High Risk HPV Related SIL

    PubMed Central

    Kefala, Maria; Kottaridi, Christine; Spathis, Aris; Gouloumi, Alina-Roxani; Pouliakis, Abraham; Pappas, Asimakis; Sioulas, Vasileios; Chrelias, Charalambos; Karakitsos, Petros; Panayiotides, Ioannis

    2017-01-01

    Background γH2AX is a protein biomarker for double-stranded DNA breakage; its expression was studied in cervical squamous intraepithelial lesions and carcinomas. Methods Immunostaining for phospho-γH2AX was performed in sections from histologically confirmed cervical SIL and carcinomas, as well as from normal cervices used as controls. In total, 275 cases were included in the study: 112 low grade SIL (LGSIL), 99 high grade SIL (HGSIL), 24 squamous cell carcinoma (SCC), 12 adenocarcinoma and 28 cervical specimens with no essential lesions. Correlation of histological grading, high risk vs. low risk HPV virus presence, activated vs. non-activated status (by high risk HPV mRNA expression) and γH2AX expression in both basal and surface segments of the squamous epithelium was performed. Results Gradual increase of both basal and surface γH2AX expression was noted up from normal cervices to LGSIL harboring a low risk HPV type, to LGSIL harboring a high risk virus at a non-activated state (p<0.05). Thereafter, both basal and surface γH2AX expression dropped in LGSIL harboring a high risk virus at an activated state and in HGSIL. Conclusions γH2AX could serve as a potential biomarker discriminating between LGSIL and HGSIL, as well as between LGSIL harboring high risk HPV at an activated state. PMID:28118377

  16. Impact of human papillomavirus coinfections on the risk of high-grade squamous intraepithelial lesion and cervical cancer.

    PubMed

    Carrillo-García, Adela; Ponce-de-León-Rosales, Sergio; Cantú-de-León, David; Fragoso-Ontiveros, Verónica; Martínez-Ramírez, Imelda; Orozco-Colín, Asunción; Mohar, Alejandro; Lizano, Marcela

    2014-09-01

    The molecular and epidemiologic effect of human papillomavirus (HPV) coinfections in the risk of developing cervical cancer is yet unclear. The aim of this study was to determine the frequency HPV coinfections at different stages of cervical lesions in the development of cervical cancer and the impact of HPV specific type interactions on high-grade squamous intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) risk. HPV testing was performed in 931 cervical samples diagnosed as: negative for intraepithelial lesion or malignancy (NILM); low-grade squamous intraepithelial lesion (LSIL); HSIL; and ICC. For HPV detection and typing two sets of primers from the L1 region were used in the polymerase chain reaction method (PCR) (MY09/MY11/HMB01 and L1C1/L1C2.1/L1C2.2) and HPV type was determined by PCR product sequence. To look for multiple HPV infections, the E6 nested multiplex PCR method was performed in all DNA samples. Odds ratios were calculated as indexes of the strength of the association between the sample category (LSIL/NILM or ICC/HSIL) and the presence of a given viral combination. In HPV positive samples, coinfections are as common in ICC/HSIL as in LSIL/NILM (47.12% and 40.17%, respectively). There is an increased risk to ICC/HSIL when multiple high-risk HPV types are present. The coinfection of HPV68 with HPV16 increases the risk of ICC/HSIL (OR=14.54, P=0.012, after multivariate adjustment), related to the presence of HPV16 or HPV68 alone. These results sustain that specific HPV coinfections confer an increased risk to develop ICC/HSIL. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men.

    PubMed

    Jin, Fengyi; Roberts, Jennifer M; Grulich, Andrew E; Poynten, Isobel M; Machalek, Dorothy A; Cornall, Alyssa; Phillips, Samuel; Ekman, Deborah; McDonald, Ross L; Hillman, Richard J; Templeton, David J; Farnsworth, Annabelle; Garland, Suzanne M; Fairley, Christopher K; Tabrizi, Sepehr N

    2017-06-01

    We evaluate the performance of human papillomavirus (HPV) biomarkers in prediction of anal histological high-grade squamous intraepithelial lesions in gay and bisexual men (GBM) in Sydney, Australia. Baseline analysis of a 3-year cohort study. The Study of the Prevention of Anal Cancer is natural history study of anal HPV infection in GBM aged at least 35 years. All participants completed cytological and histological assessments. Stored ThinPrep PreservCyt residua were tested for HPV genotyping (Linear Array and Cobas 4800) and viral load, E6/E7 mRNA expression (NucliSENS easyQ HPV v1) and dual cytology staining of p16/Ki 67 antibodies (CINtecPLUS). Performance of each biomarker was compared with liquid-based anal cytology. The hypothetical referral rates were defined as the proportion of men who had abnormal cytology or tested positive to each of the biomarkers. The median age of the 617 participants was 49 years (range: 35-79), and 35.7% were HIV-positive. All biomarkers were strongly associated with the grade of HPV-associated anal lesions (P < 0.001 for all). High-risk HPV (HR-HPV) viral load with a 33% cut-off and HR-HPV E6/E7 mRNA had similar sensitivity to anal cytology (78.4 and 75.4 vs. 83.2%, respectively), improved specificity (68.0 and 69.4 vs. 52.4%, respectively) and lower referral rates (47.0 and 45.0 vs. 59.2%, respectively). Specificity was significantly higher in the HIV-negative for HR-HPV viral load (72.3 vs. 58.2%, P = 0.005). HR-HPV viral load and E6/E7 mRNA had similar sensitivity and higher specificity in predicting histological anal high-grade squamous intraepithelial lesion with lower referrals in GBM than anal cytology.

  18. Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment.

    PubMed

    Hirai, Mariko; Kitahara, Hiroko; Kobayashi, Yutaka; Kato, Koroku; Bou-Gharios, George; Nakamura, Hiroyuki; Kawashiri, Shuichi

    2017-01-01

    Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients. Thus, it is important to understand the mechanisms underlying regulation of PD-L1 expression in the OSCC microenvironment. In this study, we showed that PD-L1 expression in high-grade invasive OSCC cell lines was lower than that in a low-grade invasive OSCC line and found a close correlation between PD-L1 expression and the epithelial-mesenchymal transition (EMT). PD-L1 expression was upregulated in macrophages and dendritic cells (DCs) in high-grade invasive human OSCC tissues or co-cultured with mesenchymal-phenotype OSCC cells in vitro. TLR4-inhibitory peptide successfully suppressed PD-L1 upregulation on macrophages and DCs co-cultured with mesenchymal-phenotype OSCC cells, suggesting that some EMT-induced tumour antigen is critical for PD-L1 induction on tumour-associated macrophages and DCs. Further studies are necessary to explore the impact of EMT on the tumour immune microenvironment and to identify potential biomarkers for selecting patients who might preferentially benefit from PD-1/PD-L1 blockade or immunotherapies more broadly.

  19. Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment

    PubMed Central

    Hirai, Mariko; Kitahara, Hiroko; Kobayashi, Yutaka; Kato, Koroku; Bou-Gharios, George; Nakamura, Hiroyuki; Kawashiri, Shuichi

    2017-01-01

    Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients. Thus, it is important to understand the mechanisms underlying regulation of PD-L1 expression in the OSCC microenvironment. In this study, we showed that PD-L1 expression in high-grade invasive OSCC cell lines was lower than that in a low-grade invasive OSCC line and found a close correlation between PD-L1 expression and the epithelial-mesenchymal transition (EMT). PD-L1 expression was upregulated in macrophages and dendritic cells (DCs) in high-grade invasive human OSCC tissues or co-cultured with mesenchymal-phenotype OSCC cells in vitro. TLR4-inhibitory peptide successfully suppressed PD-L1 upregulation on macrophages and DCs co-cultured with mesenchymal-phenotype OSCC cells, suggesting that some EMT-induced tumour antigen is critical for PD-L1 induction on tumour-associated macrophages and DCs. Further studies are necessary to explore the impact of EMT on the tumour immune microenvironment and to identify potential biomarkers for selecting patients who might preferentially benefit from PD-1/PD-L1 blockade or immunotherapies more broadly. PMID:27922697

  20. Phosphorylated mTOR expression correlates with podoplanin expression and high tumor grade in esophageal squamous cell carcinoma

    PubMed Central

    Chuang, Wen-Yu; Chang, Yu-Sun; Chao, Yin-Kai; Yeh, Chi-Ju; Ueng, Shir-Hwa; Chang, Chiu-Yueh; Liu, Yun-Hen; Tseng, Chen-Kan; Chang, Hsien-Kun; Wan, Yung-Liang; Hsueh, Chuen

    2015-01-01

    Mechanistic (or mammalian) target of rapamycin (mTOR) plays important roles in cell growth and proliferation. In esophageal squamous cell carcinoma (SCC), high expression of phosphorylated (activated) mTOR (p-mTOR) has been reported as an adverse prognostic factor in some but not all studies. The signals of mTOR pathway and mitogen-activated protein kinase (MAPK) pathway converge on 4E-binding protein 1 (4EBP1), which drives the downstream proliferative signals. We previously found that high expression of phosphorylated 4EBP1 (p-4EBP1) is an adverse prognostic factor in esophageal SCC. Podoplanin is a type-1 transmembrane glycoprotein expressed in various normal human tissues, including lymphatic endothelium. Our previous study showed that high podoplanin expression correlates with clinical nodal metastasis, which is associated with short survival in esophageal SCC. In current study, we investigated p-mTOR expression by immunohistochemistry in 75 cases of surgically resected esophageal SCC. The result was correlated with p-4EBP1 expression, podoplanin expression, clinicopathologic features and patient survival. We found that high p-mTOR expression was significantly associated with high podoplanin expression (P = 0.0030) and high tumor grade (P = 0.0014). No correlation with p-4EBP1 expression, patient survival or other clinicopathologic features was found. Recently, podoplanin expression in astrocytic brain tumors was found to be regulated by the phosphatidylinositol 3-kinase (PI3K)/AKT/activator protein-1 (AP-1) pathway. Similarly, mTOR is activated by a PI3K/AKT/mTOR pathway. The association of p-mTOR and podoplanin expression in our study could be due to a common upstream pathway. Since both mTOR and podoplanin are potential therapeutic targets, the possible benefit of combined targeted therapy warrants further investigation. PMID:26722465

  1. Endocervical glandular involvement, positive endocervical surgical margin and multicentricity are more often associated with high-grade than low-grade squamous intraepithelial lesion.

    PubMed

    Kır, Gozde; Karabulut, Murat Hakan; Topal, Cumhur Selçuk; Yılmaz, Müberra Segmen

    2012-09-01

    The aim of this study was to compare the relative frequencies of endocervical glandular involvement (EGI), multicentricity, positive endocervical surgical margins (ESM) and positive vaginal surgical margins (VSM), and adenocarcinoma in situ of the cervix (AIS) between high-grade and low-grade squamous intraepithelial lesions (HSIL and LSIL, respectively). We identified 238 patients with squamous intraepithelial lesions/cervical intraepithelial neoplasia (CIN) who were treated by loop electrocautery excision (LEEP) or conventional cold-knife conization (CKC). A total of 223 (72 [32.3%] LSIL/CIN I; 85 [38.1%] HSIL/CIN II; 66 [29.6%] HSIL/CIN III; and 151 [67.7%], HSIL/CIN II + III) LEEP/CKC slides were histologically reviewed. The frequencies of EGI, positive ESM, and multicentricity were significantly higher in the HSIL/CIN II + III group than in the LSIL/CIN I group (P = 0.001, 0.001, and 0.025, respectively). Eighteen of the 72 (25%) LSIL/CIN I patients, 44 of the 85 (51.8%) HSIL/CIN II patients, and 60 of the 66 (90.9%) HSIL/CIN III patients (P = 0.001) showed EGI. In four of the 72 (5.6%) LSIL/CIN I patients, 18 of the 85 (21.2%) HSIL/CIN II patients, and 42 of the 66 (63.6%) HSIL/CIN III patients (P = 0.001), ESM was positive. Two of the 72 (2.8%) LSIL/CIN I patients, seven of the 85 (8.2%) HSIL/CIN II patients, and 11 of the 66 (16.7%) HSIL/CIN III patients (P = 0.016) were multicentric. The current study showed that EGI, positive ESM and multicentricity were more often associated with HSIL/CIN II + III than with LSIL/CIN I. Moreover, the frequencies of EGI, multicentricity, and positive ESM increased with increasing severity of the cervical lesion. This result may influence the preference for the type of surgical procedure used for patients with cytological diagnosis of HSIL. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  2. High-grade squamous intraepithelial lesion (HSIL) of the cervix with bizarre cytological appearances ('pleomorphic HSIL'): a review of 19 cases.

    PubMed

    Stewart, Colin J R

    2017-08-01

    Cervical high-grade squamous intraepithelial lesions (HSILs) are typically characterised by a proliferation of immature basaloid cells with relatively uniform hyperchromatic nuclei. In this report we describe 19 cases of HSIL exhibiting focal but very marked nuclear atypia often associated with multinucleation ('pleomorphic HSIL'). The bizarre cytological changes mainly involved the basal epithelium particularly in endocervical crypts where the neoplastic cells undermined the native glandular epithelial cells. Superficially invasive squamous cell carcinoma (SISCCA) was present in three cases (16%) and while this was more common than in a comparative series of 40 'conventional' HSIL excision specimens (5%), the difference was not statistically significant. All three invasive cases demonstrated additional histological features that have been associated with increased risk of SISCAA (expansile crypt involvement by HSIL, luminal necrosis, and/or intraepithelial squamous maturation), and the invasive foci were associated microanatomically with conventional-type rather than pleomorphic HSIL. The bizarre cells expressed p16 and p63 proteins but usually lacked mitotic activity and showed less Ki-67 labelling than adjacent conventional HSIL. These findings suggest that pleomorphic epithelial changes in HSIL do not necessarily indicate more aggressive biological behaviour and may, in some cases, represent a degenerative phenomenon. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

  3. Anal and perianal squamous carcinomas and high-grade intraepithelial lesions exclusively associated with "low-risk" HPV genotypes 6 and 11.

    PubMed

    Cornall, Alyssa M; Roberts, Jennifer M; Garland, Suzanne M; Hillman, Richard J; Grulich, Andrew E; Tabrizi, Sepehr N

    2013-11-01

    Anal squamous cell carcinomas are predominantly associated with high-risk human papillomaviruses (HPVs), particularly HPV 16, similar to cervical, vaginal and vulvar cancers. Although the presence of "low-risk" HPVs, in particular genotypes 6 and 11, have occasionally been reported in various HPV-related anogenital cancers, the overall distribution of these genotypes in the anal canal and perianal tissue may differ to that in the cervix. In addition, although the majority of anal and perianal cancers are associated with HPV, some are not; hence, confirmation of direct association of the virus within a lesion is important. Using laser capture microdissection, anal and perianal invasive carcinomas and high-grade squamous intraepithelial lesions (HSILs) in biopsies previously associated with HPV 6 or 11 alone were isolated from tissue sections and HPV genotype tested. Of seven cases tested, four invasive carcinomas were positive for HPV 6 only, one invasive carcinoma was negative for HPV and two HSILs were positive for HPV 11 only. All samples were confirmed as HPV 16/18 negative using two different DNA targets (E6 and L1). From these results, we confirm that HPV 6 and 11 can occasionally be associated with high-grade lesion and anal cancer.

  4. p16 Is Superior to ProEx C in Identifying High-grade Squamous Intraepithelial Lesions (HSIL) of the Anal Can

    PubMed Central

    Bala, Rajeev; Pinsky, Benjamin A.; Beck, Andrew H.; Kong, Christina S.; Welton, Mark L.; Longacre, Teri A.

    2016-01-01

    Although the incidence of human papillomavirus (HPV)-associated anal neoplasia is increasing, interobserver and intraobserver reproducibility in the grading of biopsy specimens from this area remains unacceptably low. Attempts to produce a more reproducible grading scheme have led to the use of biomarkers for the detection of high-risk HPV (HR-HPV). We evaluated the performance of standard morphology and biomarkers p16, ProEx C, and Ki-67 in a set of 75 lesions [17 nondysplastic lesions, 23 low-grade squamous intraepithelial lesions (LSIL)/condyloma, 20 high-grade squamous intraepithelial lesions (HSIL), 15 invasive squamous cell carcinomas] from the anal and perianal region in 65 patients and correlated these findings with HPV subtype on the basis of a type-specific multiplex real-time polymerase chain reaction assay designed to detect HR-HPV. A subset of cases with amplifiable HPV DNA was also sequenced. HSIL was typically flat (15/20), and only a minority (4/20) had koilocytes. In contrast, only 1 LSIL was flat (1/23), and the remainder were exophytic. The majority of LSIL had areas of koilocytic change (20/23). HR-HPV DNA was detected in the majority (89%) of invasive carcinomas and HSIL biopsies, 86% and 97% of which were accurately labeled by strong and diffuse block-positive p16 and ProEx C, respectively. LSIL cases, however, only infrequently harbored HR-HPV (13%); most harbored low-risk HPV (LR-HPV) types 6 and 11. Within the LSIL group, p16 outperformed ProEx C, resulting in fewer false-positive cases (5% vs. 75%). Ki-67 was also increased in HR-HPV-positive lesions, although biopsies with increased inflammation and reactive changes also showed higher Ki-67 indices. These data suggest that strong and diffuse block-positive nuclear and cytoplasmic labeling with p16 is a highly specific biomarker for the presence of HR-HPV in anal biopsies and that this finding correlates with high-grade lesions. PMID:23552383

  5. Differentiating between endocervical glandular neoplasia and high grade squamous intraepithelial lesions in endocervical crypts: cytological features in ThinPrep and SurePath cervical cytology samples.

    PubMed

    Thiryayi, Sakinah A; Marshall, Janet; Rana, Durgesh N

    2009-05-01

    A recent audit at our institution revealed a higher number of cases diagnosed as endocervical glandular neoplasia on ThinPrep (TP) cervical cytology samples (9 cases) as opposed to SurePath (SP) (1 case), which on histology showed only high-grade cervical intraepithelial neoplasia (CIN) with endocervical crypt involvement (CI). We attempted to ascertain the reasons for this finding by reviewing the available slides of these cases, as well as slides of cases diagnosed as glandular neoplasia on cytology and histology; cases diagnosed as high-grade squamous intraepithelial lesions (HSIL) on cytology which had CIN with CI on histology and cases with mixed glandular and squamous abnormalities diagnosed both cytologically and histologically. Single neoplastic glandular cells and short pseudostratified strips were more prevalent in SP than TP with the cell clusters in glandular neoplasia 3-4 cells thick, in contrast to the dense crowded centre of cell groups in HSIL with CI. The cells at the periphery of groups can be misleading. Cases with HSIL and glandular neoplasia have a combination of the features of each entity in isolation. The diagnosis of glandular neoplasia remains challenging and conversion from conventional to liquid based cervical cytology requires a period of learning and adaptation, which can be facilitated by local audit and review of the cytology slides in cases with a cytology-histology mismatch. (c) 2009 Wiley-Liss, Inc.

  6. Relevance of the Pap Test: A Report of HPV-DNA Test-Negative High-Grade Squamous Intraepithelial Lesions of the Female Lower Genital Tract.

    PubMed

    Hui, Yiang; Hansen, Katrine; Murthy, Jayasimha; Chau, Danielle; Sung, C James; Quddus, M Ruhul

    2016-01-01

    A vast majority of cervicovaginal intraepithelial lesions are caused by high-risk human papillomaviruses (HPVs). The Pap test has been the sole method used for the screening of cervicovaginal squamous intraepithelial lesions (SIL). Recently, the FDA approved an HPV-DNA assay as a method of primary screening. We report on a series of FDA-approved HPV-DNA test-negative SIL with HPV genotyping, using an alternative method on the corresponding surgical biopsy specimens. A retrospective review identified cytology-positive HPV-negative cases over a 15-month period at a tertiary care gynecologic oncology institution. Corresponding biopsies were reviewed and genotyped for high-risk HPVs. Of the 18,200 total cases, 17 patients meeting the study criteria were selected with 27 surgical specimens corresponding to their cytologic diagnoses. Four patients with high-grade lesions were identified, 3 of whom (75%) were positive for HPV. One of these 4 patients (25%) showed high-grade SIL on biopsies from 4 separate sites in the cervix and vagina. Multiviral HPV infections were frequent. We discuss the relevance of cotesting for screening cervical SILs and emphasize that false-negative results are possible with the FDA-approved HPV screening assay, also in patients with high-grade SIL. These cases may be detectable by cytologic examination and this suggests that the Pap test remains an important diagnostic tool. © 2016 S. Karger AG, Basel.

  7. Limiting factors for cytopathological diagnosis of high-grade squamous intraepithelial lesions: a cytohistological correlation between findings in cervical smears and loop electrical excision procedure.

    PubMed

    Pinto AP, Alvaro P; Tuon, Felipe F B; Torres, Luiz Fernando Bleggi; Collaço, Luiz Martins

    2002-01-01

    The present study sought possible factors leading to the cytological diagnosis of atypical squamous cells of uncertain significance (ASCUS) in cases of high-grade squamous intraepithelial lesions (HSIL). Based on retrospective histopathological analysis of loop electrical excision procedure (LEEP) products that diagnosed HSIL, two study groups were randomly selected. The first was consisted of cases with two consecutive Papanicolaou (Pap) smears with the diagnosis of ASCUS. The second (control) group was represented by cases diagnosed as HSIL by cytology. From the Pap smears diagnosed as ASCUS, the sampling limitations was different from control group (P < 0.05). The median size of the largest lesion in each case with ASCUS was 2.66 mm (+/- 1.71 mm). In the control group, the median size of the largest lesion was 5.15 mm (+/-2.58 mm) (P < 0.05). The size of the lesion and sample limitations led patients with cervical intraepithelial neoplasms to be diagnosed as ASCUS for two consecutive times, after a 6-mo period. Copyright 2002 Wiley-Liss, Inc.

  8. Utility of p16(ink4a) immunocytochemistry in liquid-based cytology specimens from women treated for high-grade squamous intraepithelial lesions.

    PubMed

    Carydis, Vasiliki Bessie; Walker, Todd; Wing, Anthony; Colgan, Terence J

    2007-01-01

    To examine whether p16(ink4a) immunocytochemical (ICC) expression detected intraepithelial disease in liquid-based cytology (LBC) specimens from women with high-grade squamous intraepithelial lesions (HSIL), whose specimen was labeled negative for intraepithelial lesion or malignany (NILM). Residual LBC specimens from women treated for HSIL (n = 21), whose LBC test was interpreted as NILM including marked benign inflammatory changes (BCC) were used. The control (n = 25) consisted of residual LBC specimens from women with documented HSIL. ICC for p16p(16k4a) was performed on a second ThinPrep (ThinPrep 2000, Cylyl Corporation, Boxborough, Massachusetts, U.S.A.) preparation; the percentage ofpositive cells and intensity of immunostaining were recorded. Standard LBC preparations for p16(ink4a) ICC-positive and ICC-negative control cases were reviewed. Twenty-four of 25 (96%) of the HSIL control group were ICC p16(ink4a) positive. In the NILM/BCC group, 2 of 21 with adequate LBC residua were ICC p16(ink4a) positive; on review both were reclassified as epithelial abnormality--1 HSIL and 1 atypical squamous cells cannot exclude HSIL. In both, subsequent colposcopic biopsy yielded HSIL. p16(ink4a) ICC positivity on NILM/BCC LBC residua from patients with HSIL may identify cases that merit cytologic review and possible reclassification. The utility of p16(ink4a) ICC in this situation requires further study.

  9. High Rates of Anal High-Grade Squamous Intraepithelial Lesions in HIV-Infected Women Who Do Not Meet Screening Guidelines.

    PubMed

    Gaisa, Michael; Ita-Nagy, Fanny; Sigel, Keith; Arens, Yotam; Hennessy, Mary Ann; Rodriguez-Caprio, Gabriela; Mullen, Michael; Aberg, Judith A; Cespedes, Michelle

    2017-02-01

    Human immunodeficiency virus (HIV)-infected women have a higher burden of anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) compared with HIV-uninfected women. Guidelines for AC screening in this population are heterogeneous. Here we report outcomes and risk factors for anal HSIL following implementation of universal AC screening offered to all HIV-infected women. Data from women who underwent AC screening with anal cytology from April 2009 to July 2014 were analyzed. Routine clinical data included anal and cervical cytology, demographic/behavioral data, and high-resolution anoscopy (HRA) results. We evaluated the association of cytology with HRA results, and predictors of HSIL pathology, and compared rates of HSIL pathology among women meeting screening guidelines to those who did not. Seven hundred forty-five HIV-infected women were screened with anal cytology. Thirty-nine percent had abnormal anal cytology on initial screen and 15% on secondary screen; 208 women underwent HRA following abnormal anal cytology. HSIL was found in 26% and 18% of anal biopsies following initial and secondary screening, respectively. One woman had AC. Cigarette smoking more than doubled HSIL risk. Among women who underwent AC screening despite not meeting existing guideline criteria, 21% and 10%, respectively, were found to have HSIL on biopsy. Neither meeting criteria for screening nor history of receptive anal sex was significantly associated with HSIL. Anal HSIL is common in HIV-infected women. Substantial numbers of HSIL would have been missed by strictly adhering to existing AC screening guidelines. These results support routine screening of all HIV-infected women regardless of human papillomavirus history or sexual practices. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  10. Comparison of self-collected vaginal, vulvar and urine samples with physician-collected cervical samples for human papillomavirus testing to detect high-grade squamous intraepithelial lesions

    PubMed Central

    Sellors, John W.; Lorincz, Attila T.; Mahony, James B.; Mielzynska, Iwona; Lytwyn, Alice; Roth, Paula; Howard, Michelle; Chong, Sylvia; Daya, Dean; Chapman, William; Chernesky, Max

    2000-01-01

    Background Certain types of human papillomavirus (HPV) in cervical samples are strongly associated with squamous intraepithelial lesions (SIL) and invasive cervical carcinoma. We determined and compared the test characteristics of testing for HPV with samples obtained by patients and with samples obtained by their physicians. Methods In a consecutive series of women referred to a colposcopy clinic at a teaching hospital because of abnormalities on cervical cytologic screening, 200 agreed to collect vulvar, vaginal and urine samples for HPV testing. The physician then collected cervical samples for HPV testing, and colposcopy, with biopsy as indicated, was performed. Presence of HPV was evaluated using the hybrid capture II assay (Digene Corp., Silver Spring, Md.) with a probe cocktail for 13 carcinogenic types. Cervical specimens were also tested for HPV by polymerase chain reaction and hybridization with type-specific probes. Cervical smears for cytologic examination were obtained from all women. Results High-grade lesions (high-grade squamous intraepithelial lesions [HSIL], equivalent to cervical intraepithelial neoplasia [CIN] grade 2 or 3, and adenocarcinoma) were found in 58 (29.0%) of the 200 women. Carcinogenic types of HPV were detected in the self-collected vaginal samples of 50 (86.2%) of these 58 women, in the self-collected vulvar samples of 36 (62.1%) and in the self-collected urine samples of 26 (44.8%). Carcinogenic types of HPV were detected in the cervical samples collected by physicians for 57 (98.3%) of these 58 women. The remaining 142 women (71.0%) had normal findings or low-grade squamous intraepithelial lesions (LSIL, CIN grade 1). Test results were negative or noncarcinogenic types of HPV were detected in the self-collected vaginal samples of 76 (53.5%) of these 142 women, in the self-collected vulvar samples of 89 (62.7%) and in the self-collected urine samples of 99 (69.7%). The sensitivity for self-collected samples ranged from 44.8% to

  11. Limitations on the detection rate of high-risk HPV by hybrid capture 2 methodology in high grade intraepithelial (HSIL) or atypical squamous cells-cannot exclude HSIL (ASC-H) cytological lesions with proved CIN2.

    PubMed

    Noël, Jean-Christophe; Simon, Philippe

    2015-01-01

    Recent literature data suggest that the high-risk human papillomaviruses (HR-HPVs) testing with several molecular techniques could be an alternative to cytology in the detection of cervical intraepithelial neoplasias of grade 2 or worse (CIN2+). However, any molecular techniques have its own limits and may give false negative results which must be clearly known before undertaking a primary HPV screening. This study aims to evaluate the performance of the high-risk HPV hybrid capture II detection kit (HCII) which is considered as a "gold standard technique" in a series of 100 women having proved both cytological lesions of atypical squamous cells-cannot exclude an HSIL (ASC-H) or high-grade squamous intraepithelial lesion (HSIL) and histological lesions of CIN2+. The clinical sensitivity of HCII in women with a cytological diagnosis of ASC-H/HSIL and a diagnosis of CIN2+ is high but not absolute and estimated at 96% (95,6% and 100% of women with a diagnosis of CIN2/3 or invasive squamous cell carcinoma, resp.). These data although they are infrequent must be clearly referred before to start an HPV primary screening of CIN2+ especially with HCII methodology.

  12. Punch biopsy guided by both colposcopy and HR-HPV status is more efficient for identification of immediate high-grade squamous intraepithelial lesion or worse among HPV-infected women with atypical squamous cells of undetermined significance.

    PubMed

    Ding, Z; Li, Y; Chen, A; Song, M; Zhang, Y

    2016-12-01

    To investigate the accuracy of colposcopy for diagnosing high-grade squamous intraepithelial lesion (HSIL) or worse (HSIL+) in human papillomavirus (HPV)-infected patients with atypical squamous cells of undetermined significance (ASCUS) cytology, and determine whether genotyping and viral load quantitation can be useful for detecting immediate HSIL+ risk in these patients. This study included 620 cases with ASCUS and positive for high-risk (HR)-HPV within 1 month before or after cervical cytology at Qilu Hospital between February 2013 and February 2014. Based on the colposcopic impression, lesion-targeted punch biopsy, endocervical curettage biopsy or random cervical punch biopsy in four quadrants was performed on these patients within 1 month. The accuracy of colposcopy for diagnosing HSIL+ was evaluated through comparison with the biopsy results. HR-HPV status determined by Hybrid Capture 2 or HPV genotyping was analysed retrospectively as a possible predictor of HSIL+. Agreement between colposcopic impression and cervical pathology was matched perfectly in 89.2% of cases (553/620), and the strength of agreement with the κ statistic was 0.698 (p<0.001). Colposcopy had high specificity (96.9%) but low sensitivity for detecting HSIL+ (67.5%). The risk of HSIL+ was significantly higher in patients with HPV-16 infection (52.3%) than in patients infected with other types of HPV (17.9%, p<0.001). HSIL+ and virus load was correlated at cut-offs (CO) of 50 relative light units (RLU)/CO and 100 RLU/CO (p=0.024 and 0.044, respectively). If considering HPV16 infection or high virus load (at 50 RLU/CO) as a diagnostic standard of HSIL+ when colposcopic impression was negative, sensitivity was improved to 74.7% and 81.0%, respectively. Good agreement was found between colposcopic and pathologic diagnosis. HR-HPV genotyping or virus load is relevant to the detection of HSIL+ among HPV-infected patients with ASCUS cytology. In these patients, biopsies considering HPV-16

  13. Immunoexpression of HPV 16/18 E6 and E7 oncoproteins in high-grade cervical squamous intraepithelial lesions in HIV-positive women.

    PubMed

    Rodrigues, L C; Speck, N M de Gois; Focchi, G R de Azevedo; Schimidt, M A; Marques, R M; Ribalta, J C Lascasas

    2016-02-19

    The aim of this study was to assess the immunoexpression of human papillomavirus genotypes 16 and 18 (E6 and E7) oncoproteins in cervical high-grade squamous intraepithelial lesions (HSIL) of human immunodeficiency virus (HIV)-positive women. These results were also compared to the persistence and/or recurrence of lesions after loop electrosurgical excision procedure. Cervical samples from 158 patients were divided into three groups according to the presence or absence of HSIL in women who were or were not HIV-positive. By using the tissue microarray technique, immunohistochemistry was performed to analyze the expression of HPV 16/18 E6 and E7 oncoproteins. Cervical samples from 95 HIV-positive women and 63 HIV-negative women were studied. A statistically significant difference was found in the immunoexpression of E6 and E7 oncoproteins in samples from HIV-positive women with HSIL and that of women with non-neoplastic tissue (P < 0.001). There was also a statistically significant correlation between the immunoexpression of E6 (P = 0.012) and E7 (P < 0.001) oncoproteins in lesion persistence among HIV-positive women. Within the limitations of this study, the immunoexpression of HPV 16/18 E6 and E7 oncoproteins may have prognostic value regarding lesion persistence in HIV-positive women.

  14. Anterior gradient protein 2 expression in high grade head and neck squamous cell carcinoma correlated with cancer stem cell and epithelial mesenchymal transition.

    PubMed

    Ma, Si-Rui; Wang, Wei-Ming; Huang, Cong-Fa; Zhang, Wen-Feng; Sun, Zhi-Jun

    2015-04-20

    Anterior gradient protein 2 (AGR2) is a novel biomarker with potential oncogenic role. We sought to investigate the diagnostic and prognostic role of AGR2 on head and neck squamous cell carcinoma (HNSCC) with an emphasis on its correlation of cancer stemloid cells (CSC) and epithelial mesenchymal transition (EMT). We found that AGR2 protein levels were higher in HNSCC than in normal oral mucosa. High levels of AGR2 were associated with the T category, pathological grade and lymph node metastasis of HNSCC. Expression of AGR2 increased in recurring HNSCC after radiotherapy and in post cisplatin-based chemotherapeutic tissues. In HNSCC cell lines, knock-down of AGR2 induced apoptosis, reduced sphere formation, and down-regulated Survivin, Cyclin D1, Bcl2, Bcl2l1, Slug, Snail, Nanog and Oct4. In addition, over-expressed AGR2 in transgenic mice with spontaneous HNSCC was associated with lost function of Tgfbr1 and/ or lost function of Pten. In vitro knockdown TGFBR1 in HNSCC cell lines increased AGR2 expression. These results suggest that AGR2 is involved in EMT and self-renewal of CSC and may present a potential therapeutic target (oncotarget) for HNSCC.

  15. Cytological grading: An alternative to histological grading in oral squamous cell carcinoma

    PubMed Central

    Namala, Srilekha; Guduru, Vijay Srinivas; Ananthaneni, Anuradha; Devi, Sabitha; Kuberappa, Puneeth Horrati; Udayashankar, Urmila

    2016-01-01

    Background: Micronuclei (MN) in oral exfoliative cells have been shown to indicate a disparaging change in genetic information of the cell. Recent studies showed correlation between the frequency of MN and severity of this damage. Grading of lesions can be used to determine the austerity of this damage. Aims: The aim of this study is to compare the MN frequency in oral exfoliated cells of normal and oral squamous cell carcinoma (OSCC) individuals and to cytologically grade the frequency of MN in cytological smears and to correlate it with histological grading. The objective is to ascertain whether MN frequency in oral exfoliated cells can be a parameter for grading of OSCC. Settings and Design: The study group comprises of 40 subjects (20 controls and 20 OSCC patients) in the age group of 45-85 years. Materials and Methods: The cytosmear was obtained from each group and stained with Papanicolaou (PAP) stain. Twenty cells from each slide were counted for MN and cytological grade of OSCC was assigned based on the average frequency of MN. Cytological grade was correlated with histological grading and the data were recorded. Student's t-test and Spearman's correlation were used for the analysis of the data. Results: Average frequency of MN was 2.5 times higher in OSCC patients when compared to that in controls and the difference was found to be highly significant. Sixty percent correlation was found between cytological grade and histological grade of OSCC and the difference between them was not significant. Conclusions: Cytological grading can be used in grading OSCC, and MN insinuates genotoxic damage occurring in the epithelial cells. PMID:27756984

  16. Cytokeratin7 and cytokeratin19 expression in high grade cervical intraepithelial neoplasm and squamous cell carcinoma and their possible association in cervical carcinogenesis.

    PubMed

    Lee, Hojung; Lee, Hyekyung; Cho, Yong Kyun

    2017-02-17

    High risk human papillomavirus (HR HPV) infects cells at the squamocolumnar junction (SCJ) of the cervix, causing cancer. Cytokeratin (CK)7 is an SCJ marker, and stains cervical neoplasia. CK19 is a binding partner of CK7 and expressed in cervical cancer. Despite this possible association between CK7/CK19 and cervical cancer, not much is known about the mechanism of CK7/CK19 involvement in HR HPV-mediated cervical carcinogenesis. We analyzed the expression pattern of CK7, CK19, and p16 by using immunohistochemistry and HPV infection by in situ hybridization in 25 cases of high grade cervical intraepithelial neoplasia (CIN3) and in 30 cases of squamous cell carcinoma (SCC). CK19, p16, and HPV expression was positive in all CIN3 and SCC cases. CK7 expression was positive in all CIN3 cases and in 20/30 (66%) SCCs. Each protein showed diffuse or patchy staining with topographic distinction. Patchy staining of CK7 and episomal HPV DNA overlapped in the upper layer of CIN3 and central portion of an invasive nest in the SCC, whereas patchy CK19 staining and integrated HPV DNA were usually noted in the lower layer of CIN3 and the periphery of the SCC nest. The p16 staining pattern coincided with that of CK19 in a subset of SCC. These results suggest that CK7 may be more related with viral episomal replication and CK19 with viral integration, contributing to viral replication and malignant transformation in HR HPV infected cells. In addition, coordinate CK7/CK19 staining may be used as a valuable marker for predicting physical status of HR HPV and E7 oncoprotein level in cervical tumor.

  17. No Evidence for Synergy Between Human Papillomavirus Genotypes for the Risk of High-Grade Squamous Intraepithelial Lesions in a Large Population-Based Study

    PubMed Central

    Wentzensen, Nicolas; Nason, Martha; Schiffman, Mark; Dodd, Lori; Hunt, William C.; Wheeler, Cosette M.

    2014-01-01

    Background. Multiple human papillomavirus (HPV) genotypes may be independently or synergistically associated with risk of high-grade squamous intraepithelial lesions (HSILs). We evaluated the risk of HSIL in women concomitantly infected with multiple HPV genotypes. Methods. A population-based stratified sample of 59 664 cervical cytology specimens from women residing in New Mexico were evaluated for cytologic abnormalities and HPV genotypes. We calculated the risk of HSIL in women infected with a single HPV genotype and the risk in those infected with multiple HPV genotypes. Results. The highest risk of HSIL was observed for HPV-16 (0.036), followed by HPV-33 (0.028), HPV-58 (0.024), and HPV-18 (0.022). For most types, we observed a greater risk of HSIL in women infected with multiple carcinogenic HPV types. In contrast, the risk of HSIL was similar in women infected with HPV-16 and other types, compared with women infected with HPV-16 only. We observed an increased but plateauing risk of HSIL in women infected with multiple types, compared with those infected with a single type, with risk ratios of 1.5 (95% confidence interval [CI], 1.2–1.8), 1.7 (95% CI, 1.3–2.4), and 1.4 (95% CI, 0.83–2.5) for women infected with 2, 3, and ≥4 genotypes, respectively. Conclusions. In the largest population-based study of HPV genotypes and cytologic outcomes so far, we did not see more than additive effects of HPV types on the risk of HSIL in women infected with multiple types. PMID:24179110

  18. Factors that influence persistence or recurrence of high-grade squamous intraepithelial lesion with positive margins after the loop electrosurgical excision procedure: a retrospective study.

    PubMed

    Zhu, Menghan; He, Yuan; Baak, Jan Pa; Zhou, Xianrong; Qu, Yuqing; Sui, Long; Feng, Weiwei; Wang, Qing

    2015-10-20

    In 5-20 % of patients with cervical high-grade squamous intraepithelial lesion (HSIL), a positive margin after the loop electrosurgical excision procedure (LEEP) is associated with persistence/recurrence, but the prognostic value of other clinico-pathological factors is less clear. Among 4336 patients with HSIL who underwent an initial LEEP, 275 (6 %) had HSIL-positive margins, 37 of whom were lost to follow-up. We evaluated the remaining 238 patients. Persistence/recurrence was defined as histopathological HSIL during follow-up. The age of the patients ranged from 21 to 69 years (median: 40). The median follow-up period was 25 months (range: 6-43). Of the 238 patients, 211 (88.7 %) patients remained free of persistence/recurrence, while 27 (11.3 %) experienced persistence/recurrence. According to a univariate analysis, age (P = 0.03) and maximum specimen diameter (P = 0.043) were associated with persistence/recurrence, but number/location of involved margin sections and the pathology of the endocervical curettage were not (P > 0.10). The relative risk of the subjects (greater than or equal to 35 years ages) was 4.6 times of the subject less than 35 years, the difference was statistically significant (14 % vs. 3 %, P < 0.05). A multivariate analysis indicated that an age of 35 years or older was the only independent risk factor (OR 4.97, 95 % CI 1.14-21.62, P = 0.03). In patients with HSIL and HSIL-involved margins after an initial LEEP, age is a strong independent predictor of persistence/recurrence. Follow-up with screening cytology and/or biopsy may be considered in younger patients, whereas a secondary LEEP/hysterectomy may be considered in older patients.

  19. The impact of using electrical impedance spectroscopy (ZedScan) on the performance of colposcopy in diagnosing high grade squamous lesions of the cervix.

    PubMed

    Muszynski, C; Dupont, E; Vaysse, B; Lanta, S; Tidy, J; Sergent, F; Gondry, J

    2017-09-01

    To determine the efficacy of colposcopy plus ZedScan, which measures changes in tissue electrical impedance, for detecting intraepithelial high-grade lesions compared to colposcopy alone. A prospective study conducted at a university hospital colposcopy clinic. Patients referred following abnormal cervical cytology or colposcopic follow up were examined by colposcopy plus ZedScan to assess the cervix. The results of ZedScan directed and colposcopically directed biopsies were compared. Ninety-one patients were included in this study. The median age was 33 years. Eighty (88%) were referred with abnormal cytology; LSIL 45%, ASCUS 27%, ACS-H 8%, HSIL 7%, AGC 1% and 12% follow-up postconisation or colposcopic follow up. Colposcopy alone detected 18 high-grade lesions with 64 women undergoing biopsy with a total of 115 biopsies being taken with a sensitivity of 60% and NPV estimated at 81.7%. ZedScan with colposcopy increased the detection of high-grade lesions by 47.3%, identifying 27 high-grade lesions and one case of invasive cancer. Sensitivity was 93.1% and NPV estimated at 91.3%. A combination of normal colposcopy practice and ZedScan had a sensitivity and NPV of 100%. ZedScan used in conjunction with the colposcopy improves sensitivity in detecting high-grade lesions at the expense of a moderate increase in the number of biopsies. Crown Copyright © 2017. Published by Elsevier Masson SAS. All rights reserved.

  20. The Role of Polymerase Chain Reaction of High-Risk Human Papilloma Virus in the Screening of High-Grade Squamous Intraepithelial Lesions in the Anal Mucosa of Human Immunodeficiency Virus-Positive Males Having Sex with Males

    PubMed Central

    Hidalgo-Tenorio, Carmen; Rivero-Rodriguez, Mar; Gil-Anguita, Concepción; Esquivias, Javier; López-Castro, Rodrigo; Ramírez-Taboada, Jessica; de Hierro, Mercedes López; López-Ruiz, Miguel A.; Martínez, R. Javier; Llaño, Juan P.

    2015-01-01

    Objectives To evaluate the advantages of cytology and PCR of high-risk human papilloma virus (PCR HR-HPV) infection in biopsy-derived diagnosis of high-grade squamous intraepithelial lesions (HSIL = AIN2/AIN3) in HIV-positive men having sex with men (MSM). Methods This is a single-centered study conducted between May 2010 and May 2014 in patients (n = 201, mean age 37 years) recruited from our outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for PCR HPV analysis and for cytology. Anoscopy was performed for histology evaluation. Results Anoscopy showed 33.8% were normal, 47.8% low-grade squamous intraepithelial lesions (LSIL), and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV had greater sensitivity than did cytology (88.8% vs. 75.7%) in HSIL screening, with similar positive (PPV) and negative predictive value (NPV) of 20.3 vs. 22.9 and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was, generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2) or low (<0.4). Area under the receiver operating characteristics (AUROC) curve analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6). Multivariate regression analysis showed protective factors against HSIL were: viral suppression (OR: 0.312; 95%CI: 0.099-0.984), and/or syphilis infection (OR: 0.193; 95%CI: 0.045-0.827). HSIL risk was associated with HPV-68 genotype (OR: 20.1; 95%CI: 2.04-197.82). Conclusions When cytology and PCR HR-HPV findings are normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV-positive patients. HPV suppression with treatment protects against the appearance of HSIL. PMID:25849412

  1. p16(INK4a) as a complementary marker of high-grade intraepithelial lesions of the uterine cervix. I: Experience with squamous lesions in 189 consecutive cervical biopsies.

    PubMed

    Dray, Michael; Russell, Peter; Dalrymple, Chris; Wallman, Neil; Angus, George; Leong, Adelyn; Carter, Jonathan; Cheerala, Bharathi

    2005-04-01

    To test the usefulness of p16(INK4a) immunostaining for improving the diagnostic accuracy of cervical punch biopsies referred to a routine laboratory setting during the investigation of women with abnormal Papanicolaou smears. A total of 188 consecutive and unselected colposcopically directed cervical biopsies and a single contemporaneous cervical polyp were accessioned prospectively over a 3-month period, step-serially sectioned and examined by H&E and immunostained for p16(INK4a). The clinical context, results of concurrent Papanicolaou smears/ThinPrep slides and Digene hybrid capture tests for high-risk human papillomavirus (HPV) subtypes, as well as follow-up cervical smears/ThinPrep, biopsies and loop excisions of transformation zones or cone biopsies were all correlated with the morphological and immunohistochemical findings. Seventy-seven biopsies (40.7%) displayed a high-grade squamous intraepithelial lesion (HGSIL; cervical intraepithelial neoplasia [CIN] 2-3), 27 (14.3%) showed a low grade squamous intraepithelial lesion (HPV +/- CIN1) and 85 (45%) showed a range of non-dysplastic (inflammatory or reactive) changes. Diffuse strong parabasal immunostaining for p16(INK4a), suggestive of integrated high-risk HPV DNA into the host genome, was observed in 81 biopsies (42.9%, including the cervical polyp) and correlated (>90%) with HGSIL in the H&E sections. Only one case revealed irreconcilable discordance between the histological features and this strong parabasal immunostaining pattern. Focal and weaker midzonal or superficial p16(INK4a) immunostaining, suggestive of episomal HPV infection, was noted in 19 biopsies (10%) and these biopsies exhibited a range of histological changes but predominantly low grade squamous intraepithelial lesion (LGSIL). No staining of the squamous epithelium was seen in 89 biopsies (47.1%). Again, only one case revealed irreconcilable discordance between the histological features and this negative immunostaining pattern. On

  2. p16 and MIB1 improve the sensitivity and specificity of the diagnosis of high grade squamous intraepithelial lesions: methodological issues in a report of 447 biopsies with consensus diagnosis and HPV HCII testing.

    PubMed

    Van Niekerk, Dirk; Guillaud, Martial; Matisic, Jasenka; Benedet, John L; Freeberg, J Adrian; Follen, Michele; MacAulay, Calum

    2007-10-01

    Many investigators are studying the additional value of biomarkers to improve histopathologic agreement, but few are using the same methodologies. Our objectives in this analysis to differentiate High-grade Squamous Intraepithelial lesions (HGSIL) from Low Grade Squamous Intraepithelial Lesions (LGSIL), atypia, and normal were: (1) to examine the rate of Human Papilloma Virus High-Risk positivity (HPV HR+), (2) to compare and grade the basal, parabasal, intermediate, and superficial layer staining of each marker, (3) to determine the optimal qualitative threshold for markers, (4) to compare p16 and MIB1 agreement, and (5) to examine the sensitivities and specificities using each markers alone and together. A sample of biopsies from 208 patients were chosen from a total of 1850 patients and 3735 biopsies obtained during the course of ongoing optical trials. At least two independent blinded reviews were performed for each biopsy. A third review was performed if there was a disagreement between the two reviews. Both endocervical and ectocervical samples were stained for p16 and MIB1. A grading system that is delineated in the text ranged from 0 to 3 for both markers and each biopsy was scored by each cell layer. Frequencies, sensitivities, and specificities were calculated using Statistica. An ANOVA was used to compare p16 and MIB1 staining in the epithelial layers. Finally the sensitivity and specificity of each marker alone and together were examined. 453 specimens from 208 patients whose final diagnoses were normal (n=244), low-grade (LG) (n=59), and high-grade (HG) (n=144) were selected for analysis. 447 of 453 specimens were available for staining. Most LG and HG lesions were HPV HR positive. Endocervical samples stained positive less often than ectocervix and often results were discordant from ectocervical results. The analysis by layers showed pronounced increases in staining of both p16 and MIB1 as lesions progressed from normal to LG to HG. The cutoff or

  3. Argon plasma coagulation treatment of anal high-grade squamous intraepithelial lesions in men who have sex with men living with HIV: results of a 2-year prospective pilot study.

    PubMed

    de Pokomandy, A; Rouleau, D; Lalonde, R; Beauvais, C; de Castro, C; Coutlée, F

    2017-08-23

    Men who have sex with men (MSM) living with HIV are at high risk for anal high-grade squamous intraepithelial lesions (HSILs) and cancer. The best management of anal HSIL remains unclear. Our objective was to assess whether argon plasma coagulation (APC) could be safe, well tolerated and efficient to treat anal HSILs in MSM living with HIV. A prospective phase II, open-label, pilot study was conducted to evaluate APC to treat anal HSILs in 20 HIV-positive MSM. Participants were followed for 2 years after their first treatment. Twenty men with persistent HSILs completed the 2-year study. Their baseline median CD4 count was 490 cells/μL and 85% had undetectable HIV viral loads. Overall, 65% (13/20) of participants were clear of HSILs at their 24-month visit. The initial response rates after the first, second and third APC treatments were 45%, 44% and 67%, respectively, but recurrences were common. The main side effect was pain during and within 1 week after the treatments. There were no long-term side effects, nor serious adverse events related to the procedure. Cost is a drawback. APC can be used to treat anal HSILs in HIV-seropositive MSM, and requires repeated treatment because of a high recurrence rate. As successful treatment of human papillomavirus (HPV) infection or eradication of the anal transitional zone remains impossible, HSIL treatment is challenging and requires long-term follow-up. © 2017 British HIV Association.

  4. Human papillomavirus detection by hybrid capture II and residual or recurrent high-grade squamous cervical intraepithelial neoplasia after large loop excision of the transformation zone (LLETZ).

    PubMed

    Sarian, Luís Otávio; Derchain, Sophie Françoise Mauricette; Pittal, Denise da Rocha; Andrade, Liliana Aparecida Angelo; Morais, Sirlei Siani; Figueiredo, Priscila Garcia

    2005-01-01

    The purpose of this study was to assess the association between highly-oncogenic types HPV DNA detection by Hybrid Capture II (HCII) and residual or recurrent high-grade cervical intraepithelial neoplasia (CIN 2 or 3) during the follow-up of women submitted to large loop excision of the transformation zone (LLETZ). In this cohort study, 94 women submitted to LLETZ because of CIN 2 or 3 between March 2001 and September 2002 were followed up twice yearly until September 2003. Follow-up visits consisted of an interview regarding clinical, social and demographic characteristics complemented with gynecological examination with specimen collection for Pap test and HCII and colposcopy. Eighty-one patients attended the first visit (mean 4.8 months, range 3-6) and 75 the second visit (mean 10.9 months, range 7-17 months). McNemar's test to assess the variation of HPV DNA detection following LLETZ, odds ratios (OR) to evaluate the correlation between HPV DNA positivity and residual/recurrent CIN during follow-up, and logistic regression to assess the risk of residual/recurrent CIN were used. There was a strong and significant reduction in HPV detection after LLETZ (P < 0.001). HPV DNA detection was correlated with residual/recurrent CIN at the first (OR = 103.4; 95% CI 5.5 to 1961.2) and second (OR = 12.7; 95% CI 1.1 to 345.5) follow-up visits. Multivariate analysis showed HPV persistence as a stand-alone risk factor for residual/recurrent CIN (OR = 50.3; 95% CI 3.8 to 663.1). High risk HPV DNA detection decreased substantially after CIN treatment with LLETZ, but HPV persistence was strongly correlated with residual/recurrent CIN.

  5. Human Papillomavirus (HPV) DNA Triage of Women with Atypical Squamous Cells of Undetermined Significance with cobas 4800 HPV and Hybrid Capture 2 Tests for Detection of High-Grade Lesions of the Uterine Cervix

    PubMed Central

    Lapierre, Simon Grandjean; Sauthier, Philippe; Mayrand, Marie-Hélène; Dufresne, Simon; Petignat, Patrick; Provencher, Diane; Drouin, Pierre; Gauthier, Philippe; Dupuis, Marie-Josée; Michon, Bertrand; Ouellet, Stéphan; Hadjeres, Rachid; Ferenczy, Alex; Franco, Eduardo L.

    2012-01-01

    The triage of women with high-risk (HR) human papillomavirus (HPV)-positive smears for atypical squamous cells of undetermined significance (ASC-US) to colposcopy is now an integrated option in clinical guidelines. The performance of cobas 4800 HPV and that of Hybrid Capture 2 (HC2) for HR HPV DNA detection in cervical samples in PreservCyt were compared in 396 women referred to colposcopy for ASC-US. Of these, 316 did not have cervical intraepithelial neoplasia (CIN), 47 had CIN1, 29 had CIN2 or CIN3 (CIN2+), and 4 had CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 149 (37.6%) samples with HC2 and cobas 4800 HPV, respectively (P = 0.15). The clinical sensitivities and specificities for detecting CIN2+ were 89.7% (95% confidence interval [CI], 72.8 to 97.2%) and 66.7% (95% CI, 61.7 to 71.3%) with cobas 4800 HPV and 93.1% (95% CI, 77.0 to 99.2%) and 72.2% (95% CI 67.4 to 76.5%) with HC2. The performance of cobas 4800 HPV was similar to that of HC2 for identifying women with ASC-US who would benefit the most from colposcopy. PMID:22301023

  6. Human Papillomavirus Test for Triage of Japanese Women With Low-Grade Squamous Intraepithelial Lesions.

    PubMed

    Iwata, Takashi; Hasegawa, Toshihiko; Ochiai, Kazunori; Takizawa, Ken; Umezawa, Satoshi; Kuramoto, Hiroyuki; Ohmura, Mineo; Kubushiro, Kaneyuki; Arai, Hiroharu; Sakamoto, Masaru; Motoyama, Teiichi; Watanabe, Kayoko; Aoki, Daisuke

    2015-12-01

    We evaluated high-risk human papillomavirus (HR-HPV) DNA testing for high-grade cervical intraepithelial neoplasia (CIN) lesions by cobas HPV test and diagnostic HPV16/18 genotyping in Japanese women with low-grade squamous intraepithelial lesions. Of 357 patients, HR-HPV positivity prevalence was 75.6%, and 21.3% had grade 2 or higher CIN lesions (CIN2+), with the highest prevalence at 30 to 34 years. Negative predictive values of HR-HPV for CIN2+ in our patients were 93.1% (any age) and 94.9% (40-50 years). Absolute risk for CIN2+ in HR-HPV positive and HPV16/18 positive individuals was 25.9 and 35.1, respectively. Relative risk for CIN2+ lesions was 5.1 for HPV16/18 positive versus HR-HPV negative, and 3.8 for HR-HPV positive versus HR-HPV negative women. Predictive values of CIN2+ positive were higher for HPV16/18 positive women (any age) than 12 other HPV positive-genotypes, and highest (50%) at 40-50 years. The HPV16/18 genotyping might prevent women (>40 years) at risk of high-grade CIN lesions from undergoing unnecessary colposcopy/overtreatment of nonprogressive lesions. © The Author(s) 2015.

  7. Association of human papillomavirus, Neisseria gonorrhoeae and Chlamydia trachomatis co-infections on the risk of high-grade squamous intraepithelial cervical lesion

    PubMed Central

    de Abreu, André LP; Malaguti, Natália; Souza, Raquel P; Uchimura, Nelson S; Ferreira, Érika C; Pereira, Monalisa W; Carvalho, Maria DB; Pelloso, Sandra M; Bonini, Marcelo G; Gimenes, Fabrícia; Consolaro, Marcia EL

    2016-01-01

    The link between high-risk human Papillomavirus (HR-HPV) and other sexually transmitted diseases (STDs) in the risk of developing cervical cancer still unclear. Thus, in this report we investigated the rates of co-infections between HPV and other important non-HPV STDs in different cervical findings using a multiplex polymerase chain reaction (M-PCR) to simultaneously detect Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, HSV-1 and -2, and Treponema pallidum. A total of 838 women aged 18 to 68 years were screened using Papanicolaou smears for cervical abnormalities, HPV and non-HPV STDs using PCR and M-PCR methods. A total of 614 (73.3%) of the women had normal cytology (NILM) and 224 (26.7%) women exhibited abnormal cytology (≥ ASC-US). HPV-DNA prevalence was 33.9%, and HPV-16 was the most prevalent genotype in women with NILM and ≥ ASC-US cytology. Non-HPV STDs were detected in 30.4% women and T. vaginalis was the most prevalent one (11.6%). A higher increased risk of ≥ ASC-US and HSIL occurred in co-infections of HR-HPV with C. trachomatis and N. gonorrhoeae. Co-infections of HPV-DNA and HR-HPV with HSV-2 exhibited a similar increased risk but only with ≥ ASC-US. Co-infections of HPV-DNA and HR-HPV with T. vaginalis demonstrated a similar increased risk of ≥ ASC-US and HSIL. We found that C. trachomatis and N. gonorrhoeae were the primary pathogens associated with HR-HPV for the increased risk for all grades of cervical abnormalities but mainly for HSIL, suggesting a possible synergistic action in cervical lesions progression. Our results reinforce the hypothesis that some non-HPV STDs might play a role as co-factors in HPV-mediated cervical carcinogenesis. These data improve our understanding of the etiology of SCC and may also be useful for disease prevention. PMID:27429850

  8. Association of human papillomavirus, Neisseria gonorrhoeae and Chlamydia trachomatis co-infections on the risk of high-grade squamous intraepithelial cervical lesion.

    PubMed

    de Abreu, André Lp; Malaguti, Natália; Souza, Raquel P; Uchimura, Nelson S; Ferreira, Érika C; Pereira, Monalisa W; Carvalho, Maria Db; Pelloso, Sandra M; Bonini, Marcelo G; Gimenes, Fabrícia; Consolaro, Marcia El

    2016-01-01

    The link between high-risk human Papillomavirus (HR-HPV) and other sexually transmitted diseases (STDs) in the risk of developing cervical cancer still unclear. Thus, in this report we investigated the rates of co-infections between HPV and other important non-HPV STDs in different cervical findings using a multiplex polymerase chain reaction (M-PCR) to simultaneously detect Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, HSV-1 and -2, and Treponema pallidum. A total of 838 women aged 18 to 68 years were screened using Papanicolaou smears for cervical abnormalities, HPV and non-HPV STDs using PCR and M-PCR methods. A total of 614 (73.3%) of the women had normal cytology (NILM) and 224 (26.7%) women exhibited abnormal cytology (≥ ASC-US). HPV-DNA prevalence was 33.9%, and HPV-16 was the most prevalent genotype in women with NILM and ≥ ASC-US cytology. Non-HPV STDs were detected in 30.4% women and T. vaginalis was the most prevalent one (11.6%). A higher increased risk of ≥ ASC-US and HSIL occurred in co-infections of HR-HPV with C. trachomatis and N. gonorrhoeae. Co-infections of HPV-DNA and HR-HPV with HSV-2 exhibited a similar increased risk but only with ≥ ASC-US. Co-infections of HPV-DNA and HR-HPV with T. vaginalis demonstrated a similar increased risk of ≥ ASC-US and HSIL. We found that C. trachomatis and N. gonorrhoeae were the primary pathogens associated with HR-HPV for the increased risk for all grades of cervical abnormalities but mainly for HSIL, suggesting a possible synergistic action in cervical lesions progression. Our results reinforce the hypothesis that some non-HPV STDs might play a role as co-factors in HPV-mediated cervical carcinogenesis. These data improve our understanding of the etiology of SCC and may also be useful for disease prevention.

  9. CpG Methylation Analysis of HPV16 in Laser Capture Microdissected Archival Tissue and Whole Tissue Sections from High Grade Anal Squamous Intraepithelial Lesions: A Potential Disease Biomarker.

    PubMed

    Molano, Monica; Tabrizi, Sepehr N; Garland, Suzanne M; Roberts, Jennifer M; Machalek, Dorothy A; Phillips, Samuel; Chandler, David; Hillman, Richard J; Grulich, Andrew E; Jin, Fengyi; Poynten, I Mary; Templeton, David J; Cornall, Alyssa M

    2016-01-01

    Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC) are associated with human papillomavirus (HPV). Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS) and laser capture microdissected (LCM) tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL.

  10. CpG Methylation Analysis of HPV16 in Laser Capture Microdissected Archival Tissue and Whole Tissue Sections from High Grade Anal Squamous Intraepithelial Lesions: A Potential Disease Biomarker

    PubMed Central

    Molano, Monica; Tabrizi, Sepehr N.; Garland, Suzanne M.; Roberts, Jennifer M.; Machalek, Dorothy A.; Phillips, Samuel; Chandler, David; Hillman, Richard J.; Grulich, Andrew E.; Jin, Fengyi; Poynten, I. Mary; Templeton, David J.; Cornall, Alyssa M.

    2016-01-01

    Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC) are associated with human papillomavirus (HPV). Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS) and laser capture microdissected (LCM) tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL. PMID:27529629

  11. Characterization of a cluster of oncogenic mutations in E6 of a human papillomavirus 83 variant isolated from a high-grade squamous intraepithelial lesion.

    PubMed

    Cannavo, Isabelle; Benchetrit, Maxime; Loubatier, Céline; Michel, Gregory; Lemichez, Emmanuel; Giordanengo, Valérie

    2011-10-01

    We previously isolated human papillomavirus 83 (HPV83m) from a cervical smear. Sequence analysis of E6 and E7 proteins highlighted five mutations located in the second putative zinc-finger region of E6 (E6m), an important domain for protein-protein or protein-DNA interactions. Here, we show that E6m of HPV83m can trigger human primary cell proliferation and anchorage-independent growth properties, similarly to E6 of HPV16, a high-risk HPV (HR-HPV). Interestingly, we demonstrate that, in contrast to E6 of HPV16, E6m corrupts neither p53 stability nor telomerase activity, but acts as a specific modulator of the transcriptional machinery. By studying E6m reversion mutants, we confirmed the importance of the second zinc-finger domain in triggering the observed upregulation of cell growth and of the transcriptional machinery. Reversion of these mutations in E6m (to yield strain E6r) fully abolished the oncogenic potential of E6m, transforming the phenotype of E6 from a high-risk to a low-risk phenotype. Importantly, our data define the importance of a cluster of mutations in the second zinc finger of E6m in increasing the oncogenic potential of HPV83.

  12. Histologic grade in penile squamous cell carcinoma: visual estimation versus digital measurement of proportions of grades, adverse prognosis with any proportion of grade 3 and correlation of a Gleason-like system with nodal metastasis.

    PubMed

    Chaux, Alcides; Torres, José; Pfannl, Rolf; Barreto, Jose; Rodriguez, Ingrid; Velazquez, Elsa F; Cubilla, Antonio L

    2009-07-01

    Histologic grade has been reported as an important pathologic parameter predictive of nodal metastases and outcome in patients with penile squamous cell carcinoma. There is no consensus about the criteria for grading and the proportion of anaplastic cells required to classify a tumor as high grade. The incidence and management of heterogeneous tumors (tumors harboring more than 1 histologic grade) are not well established. The purposes of this study were to present a grading model for penile cancer, to test the practicality of the system by comparing a visual ("naked-eye") estimation of the proportions of grades with a digitally guided measuring system and to determine the influence on nodal metastasis of the various proportions of grades. A total of 117 penectomy and circumcision specimens with bilateral inguinal lymph node dissections were studied and 62 heterogeneous tumors were identified (53%). The following steps were taken: (1) design of a grading system model; (2) determination of proportions of histologic grades by naked-eye evaluation and by digital measurement; (3) evaluation of metastasis according to proportions of grades; (4) determination of the influence of site of grade 3 in nodal metastasis; (5) design of a Gleason-like scoring system; and (6) statistical evaluation. We designed a 3-tier grading system. Grade 1: well-differentiated cells, almost undistinguishable from normal squamous cells except for the presence of minimal basal/parabasal cell atypia. Grade 3: tumors predominantly composed of anaplastic cells. Grade 2: all tumors not fitting into criteria described for grade 1 or 3. A visual and digital-based (slides scanned and the corresponding areas measured with an image-editing software) proportions of grades were estimated and the metastatic rate between them were confronted using different proportions of grade 3. To evaluate the influence of site of grade 3 on nodal metastasis, we selected 20 heterogeneous tumors. We established 3 sites

  13. PCNA and grade in 13 canine oral squamous cell carcinomas: association with prognosis.

    PubMed

    Mestrinho, L A; Faísca, P; Peleteiro, M C; Niza, M M R E

    2017-03-01

    This study evaluated the prognosis factors of age, tumour size, anatomic location, histological grade and proliferating cell nuclear antigen (PCNA) expression in 13 dogs with oral squamous cell carcinoma (OSCC) with bone invasion and without signs of lymph node or distant metastasis. All animals were treated with radical excision performed with at least 1 cm margin, based on computed tomography images. In the 2-year follow-up, median disease-free survival was 138 days for dogs with grade 3 tumours and was not reached for those with grade 2 tumours. Grade 3 tumours and PCNA labelling index ≥65% were related with a shorter disease-free survival time and consequently poor prognosis (p = 0.003 and p = 0.034, respectively). Mean PCNA labelling index was significantly higher in recurrent cases (p = 0.011). Histological grade and PCNA expression may be important prognosis factors in canine OSCC.

  14. [Value of estrogen and progesterone receptors in the management of intraepithelial squamous lesions of low grade].

    PubMed

    González Sánchez, J L; Chávez Brambila, J; Maricela Román, A; Infante Martínez, R; Salazar Esquivel, L E

    2001-01-01

    The objective of this study was to know the prognostic value of estrogen receptors and progesterone receptors positives (ER+, PR+) in the management of low grade squamous intraepithelial lesions [(LGSIL), human papillomavirus (HPV) and cervical intraepithelial neoplasia grade 1 (CIN 1) and menopausal status]. From January 1995 to January of 1999, was studied in 144 women with abnormal citology to HPV and CIN grades 1, 2 or 3. Colposcopy was carried out and two biopsies were taken from the suspicious lesion, they were sent for histopathological study, and for ER/PR by the dextran-coated charcoal technique. In addition to the receptor status information, histological type of squamous intraepithelial lesions (SIL), and menopausal status were recorded and analyzed and were correlated later. In normal cervix, 89% and 60% of specimens were ER+, PR+ (+6 fmol/mg protein) There was significant difference in ER status between the normal cervix con HPV and CIN, (P < 0.003), but no with PR (P > 0.53). ER levels in premenopausal and postmenopausal patients there was no significant difference (P > 0.27) but PR levels there was significant difference (P < 0.04). ER/PR levels in HPV o CIN grade no correlated to the histologic grade and menopausal status (P > 0.35, > 0.97, respectively). The women with levels ER+ were significant higher in the normal cervix than SIL, ER+, PR+ levels no correlated to the prognostic value in the management of LGSIL and menopausal status.

  15. Concurrent primary peritoneal low-grade serous carcinoma and endometrial high-grade serous carcinoma.

    PubMed

    Lockyer, Megan G; Deavers, Michael T; Zarrin-Khameh, Neda

    2015-05-01

    A 64-yr-old postmenopausal woman with high-grade squamous intraepithelial lesion and atypical glandular cell of undetermined significance on her Pap test was found to have endometrial serous carcinoma (high grade) involving a polyp in a subsequent endometrial biopsy. She underwent hysterectomy and bilateral salpingo-oophorectomy with multiple biopsies of the peritoneum. Microscopic examination of the entirely submitted uterus showed no residual serous carcinoma. Multiple foci of low-grade serous tumor with extensive calcifications and psammoma bodies were identified on the surfaces of the left fallopian tube, ovaries, and biopsies of the peritoneum, consistent with peritoneal primary low-grade serous carcinoma. To our knowledge, this is the first reported case of low-grade serous carcinoma of the peritoneum with a concurrent (high-grade) serous carcinoma of the endometrium arising from an endometrial polyp.

  16. Synchronous high-grade squamous intraepithelial lesion and adenocarcinoma in situ of cervix in a young woman presenting with hyperchromatic crowded groups in the cervical cytology specimen: report of a case.

    PubMed

    Zafar, Nadeem; Balazs, Louisa; Benstein, Barbara D

    2008-11-01

    We report a 29-year-old woman who underwent routine gynecologic evaluation at a community clinic and had a cervical sample drawn for liquid-based cytologic evaluation. At cytology, many hyperchromatic crowded groups (HCG) were present, but a consensus could not be established whether the abnormal cells were primarily glandular or squamous with secondary endocervical glandular involvement. An interpretation of atypical endocervical cells, favor neoplastic, was rendered and biopsy advised if clinically appropriate. At biopsy, the cervix contained synchronous squamous cell carcinoma in situ, secondarily involving endocervical glands, and neighboring adenocarcinoma in situ. Immunohistochemistry for Ki-67 and p16(INK4A) crisply and precisely stained both the lesions, clearly separating them from the adjacent uninvolved mucosa. This case re-emphasizes the challenge associated with accurate evaluation of HCG at cytology, the significance of ancillary testing for surrogate markers of high-risk HPV (HR-HPV) infection, the need for adjunct testing for HPV-DNA in the setting of HCG at cervical cytology, and a recommendation to set up studies to evaluate the role of surrogate markers of HR-HPV infection in cytologic samples with HCG.

  17. Quantitative analysis of high-resolution microendoscopic images for diagnosis of esophageal squamous cell carcinoma.

    PubMed

    Shin, Dongsuk; Protano, Marion-Anna; Polydorides, Alexandros D; Dawsey, Sanford M; Pierce, Mark C; Kim, Michelle Kang; Schwarz, Richard A; Quang, Timothy; Parikh, Neil; Bhutani, Manoop S; Zhang, Fan; Wang, Guiqi; Xue, Liyan; Wang, Xueshan; Xu, Hong; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R

    2015-02-01

    High-resolution microendoscopy is an optical imaging technique with the potential to improve the accuracy of endoscopic screening for esophageal squamous neoplasia. Although these microscopic images can be interpreted readily by trained personnel, quantitative image analysis software could facilitate the use of this technology in low-resource settings. In this study, we developed and evaluated quantitative image analysis criteria for the evaluation of neoplastic and non-neoplastic squamous esophageal mucosa. We performed an image analysis of 177 patients undergoing standard upper endoscopy for screening or surveillance of esophageal squamous neoplasia, using high-resolution microendoscopy, at 2 hospitals in China and at 1 hospital in the United States from May 2010 to October 2012. Biopsy specimens were collected from imaged sites (n = 375), and a consensus diagnosis was provided by 2 expert gastrointestinal pathologists and used as the standard. Quantitative information from the high-resolution images was used to develop an algorithm to identify high-grade squamous dysplasia or invasive squamous cell cancer, based on histopathology findings. Optimal performance was obtained using the mean nuclear area as the basis for classification, resulting in sensitivities and specificities of 93% and 92% in the training set, 87% and 97% in the test set, and 84% and 95% in an independent validation set, respectively. High-resolution microendoscopy with quantitative image analysis can aid in the identification of esophageal squamous neoplasia. Use of software-based image guides may overcome issues of training and expertise in low-resource settings, allowing for widespread use of these optical biopsy technologies. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Quantitative Analysis of High-Resolution Microendoscopic Images for Diagnosis of Esophageal Squamous Cell Carcinoma

    PubMed Central

    Shin, Dongsuk; Protano, Marion-Anna; Polydorides, Alexandros D.; Dawsey, Sanford M.; Pierce, Mark C.; Kim, Michelle Kang; Schwarz, Richard A.; Quang, Timothy; Parikh, Neil; Bhutani, Manoop S.; Zhang, Fan; Wang, Guiqi; Xue, Liyan; Wang, Xueshan; Xu, Hong; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.

    2014-01-01

    Background & Aims High-resolution microendoscopy is an optical imaging technique with the potential to improve the accuracy of endoscopic screening for esophageal squamous neoplasia. Although these microscopic images can readily be interpreted by trained personnel, quantitative image analysis software could facilitate the use of this technology in low-resource settings. In this study we developed and evaluated quantitative image analysis criteria for the evaluation of neoplastic and non-neoplastic squamous esophageal mucosa. Methods We performed image analysis of 177 patients undergoing standard upper endoscopy for screening or surveillance of esophageal squamous neoplasia, using high-resolution microendoscopy, at 2 hospitals in China and 1 in the United States from May 2010 to October 2012. Biopsies were collected from imaged sites (n=375); a consensus diagnosis was provided by 2 expert gastrointestinal pathologists and used as the standard. Results Quantitative information from the high-resolution images was used to develop an algorithm to identify high-grade squamous dysplasia or invasive squamous cell cancer, based on histopathology findings. Optimal performance was obtained using mean nuclear area as the basis for classification, resulting in sensitivities and specificities of 93% and 92% in the training set, 87% and 97% in the test set, and 84% and 95% in an independent validation set, respectively. Conclusions High-resolution microendoscopy with quantitative image analysis can aid in the identification of esophageal squamous neoplasia. Use of software-based image guides may overcome issues of training and expertise in low-resource settings, allowing for widespread use of these optical biopsy technologies. PMID:25066838

  19. Prediction of clinical outcome using p16INK4a immunocytochemical expression in low-grade squamous intraepithelial lesions and high-risk HPV-positive atypical squamous cells of undetermined significance in patients with and without colposcopic evident cervical disease

    PubMed Central

    LUKIC, ANKICA; SBENAGLIA, GIORGIO; CARICO, ELISABETTA; DI PROPERZIO, MATILDE; GIARNIERI, ENRICO; FREGA, ANTONIO; NOBILI, FLAVIA; MOSCARINI, MASSIMO; GIOVAGNOLI, MARIA ROSARIA

    2011-01-01

    p16INK4a as a diagnostic marker of a cervical intraepithelial neoplasia of grade 2+ (CIN2+) in atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cytological samples has been analyzed, but has not yet been included in clinical routine practice. One hundred and ninety-one patients with an abnormal Pap test (84 ASC-US and 107 LSILs) who underwent colposcopy were selected for this study. At enrollment, 96 patients (Group 1) had a positive colposcopy and therefore underwent a cervical biopsy, while 95 (Group 2) had a negative colposcopy and were followed up for up to 1 year. Both groups were tested for p16INK4a using immunocytochemical methods, and the p16INK4a results were correlated with histology or follow-up outcome. In Group 1 ASC-US cases, 82% of lesions less than CIN2 were p16INK4a-negative and all CIN2 cases were p16INK4a-positive (p=0.00044). In Group 1 LSIL cases, 71% of lesions less than CIN2 were p16INK4a-negative and 87% of CIN2/3 were p16INK4a-positive (p=0.00033). Seventy-seven percent of Group 2 ASC-US patients with a negative 1-year follow-up (NF-U) were p16INK4a-negative at enrollment, while all patients with positive follow-up (PF-U) were p16INK4a-positive (p=0.00113). In Group 2 LSIL cases, 83% of patients with NF-U were p16INK4a-negative, while 65% of patients with PF-U were p16INK4a-positive at enrollment (p=0.0014). In fact, 39% of the positive p16INK4a LSIL patients had CIN2+ histological lesions. The positive predictive value of p16INK4a for CIN2+ was 50% in ASC-US and 52% in LSIL cases; the negative predictive value was 100 and 94%, respectively. In conclusion, in our patients, a negative p16INK4a appears to be a marker of the absence of CIN3, while a positive p16INK4a can be correlated with the presence of histological CIN2+ found at enrollment or during the subsequent follow-up. Thus, its clinical predictive value is independent from the colposcopic aspect at enrollment. PMID

  20. Association between aerobic vaginitis, bacterial vaginosis and squamous intraepithelial lesion of low grade.

    PubMed

    Jahic, Mahira; Mulavdic, Mirsada; Hadzimehmedovic, Azra; Jahic, Elmir

    2013-01-01

    To determine frequency of HPV infection, aerobic vaginitis and bacterial vaginosis in respondents with squamous intraepithelial lesion of lower grade comparing to respondents with normal PAP test results. Prospective research of 100 respondents has been conducted at University-Clinic Center Tuzla and Gynecology and Obstetrics Department at Primary Health Care Center Tuzla in period from May 2011 untill January 2012. Examination program included: anamnesis, clinical gynecological examination, HPV typization, microbiological examination of vaginal and cervical smear and PAP test. High risk HPV group has been found more frequently among the respondents with LG SIL 46% (23) than in those with normal PAP result 14% (7) p < 0.05. Aerobic vaginitis has been found in the respondents with LG SIL in 28% (14) and there is statistically significant difference of this vaginitis comparing to the respondents with normal PAP result (p < 0.05). Bacterial vaginosis has been found in 12% (6) of the respondents with LG SIL and in 4% (2) of those with normal PAP result which is not statistically significant. In women with LG SIL and aerobic vaginitis in 9 cases E. coli has been isolated, in 4 E. faecalis and in 1 Staphylococcus aureus, while in women with normal PAP test results 3 cases of E.coli have been isolated. Examining changes in pH value of vaginal environment, higher measured values have been found in the respondents with LG SIL- 5.26 while in the respondents with normal PAP test result was 4.94 (p < 0.05). There is also statistically significant increase in the number of leukocytes in the respondents with LG SIL in relation to those with normal result. In women with LG SIL aerobic vaginitis is very common but is not an indicator of HPV infection. An adequate treatment of aerobic vaginitis would decrease the frequency of LG SIL and number of precancerous lesions which may

  1. Histopathological grading systems analysis of oral squamous cell carcinomas of young patients

    PubMed Central

    Frare, Juliana-Cristina; Sawazaki-Calone, Iris; Ayroza-Rangel, Ana-Lucia-Carrinho; Bueno, Alexandre-Galvão; de Morais, Carlos-Floriano; Nagai, Hildebrando-Massahiro; Kunz, Reno

    2016-01-01

    Background To analyze the clinicopathological profile of young patients (≤ 40 years) with oral SCC and correlate with a control group (≥ 50 years) by means of histopathological grading systems. Material and Methods 14 young patients and 14 control patients were selected with similar clinical stage and tumor location. Demographic and clinical data were obtained from patient records and histological sections were evaluated according to four histopathological grading systems. Associations between categories of demographic and clinical data were performed through Chi-square test and Exact Fisher test. The survival analyzes were performed according to the Kaplan-Meier method. Results The comparison between groups showed a greater association of treatment modalities in younger patients (p=0.022), they had a higher incidence of local recurrence and regional metastasis (p=0.018) and lower disease-free survival in 5 years (p=0.069). There was no difference in 5-year overall survival among the studied groups. There was no difference in histological grading between studied groups according to the four used systems. Conclusions This study showed that, despite tumors had similar histological grade and more therapeutic modalities were used in the young group, tumors in young patients had a higher incidence of recurrence/metastasis, showing tendency to a more aggressive behavior. Key words:Squamous cell carcinoma, tumors histological grading, young. PMID:26946200

  2. Invasive Front Grading and Epithelial-Mesenchymal Transition in Canine Oral and Cutaneous Squamous Cell Carcinomas.

    PubMed

    Nagamine, E; Hirayama, K; Matsuda, K; Okamoto, M; Ohmachi, T; Uchida, K; Kadosawa, T; Taniyama, H

    2017-09-01

    Oral and cutaneous tissues are the most frequent origin in canine squamous cell carcinoma (SSC). In SCC, changes in adhesion molecule expression and transition from epithelial to mesenchymal phenotype are thought to be important in development of invasive behavior of neoplastic cells at the leading front of the tumor. We therefore investigated histological invasive front grading and epithelial-mesenchymal transition (EMT) in both oral SCCs and cutaneous SCCs. EMT was assessed by evaluating immunohistochemical expression of E-cadherin, β-catenin, desmoglein, vimentin, and N-cadherin. Regardless of the anatomic location, invasive front grading resulted in higher histological grades than grading of the surface. Most oral SCCs were of significantly higher histologic grade than cutaneous SCCs ( P < .01). Expression of E-cadherin, β-catenin, and desmoglein was significantly lower in oral SCC compared with cutaneous SCC ( P < .01). A significant association was found between invasive front grading and loss of E-cadherin, β-catenin, and desmoglein ( P < .01). Also, vimentin-positive neoplastic cells had low immunoreactivity of these adhesion molecules, and a few of these neoplastic cells were positive for N-cadherin. These results suggest not only E-cadherin and β-catenin but also desmoglein as markers for predicting biological behavior of canine SCC. Depending on their primary sites, EMT correlates with biological behavior and therefore histological grade of canine SCC. We suggest that combining invasive front grading with assessment of immunohistochemical expression of E-cadherin, β-catenin, and desmoglein may allow more accurate prediction of biological behavior of canine SCCs.

  3. Human Papillomavirus Type 16 Viral Load Is Higher in Human Immunodeficiency Virus-Seropositive Women with High-Grade Squamous Intraepithelial Lesions Than in Those with Normal Cytology Smears

    PubMed Central

    Lefevre, Jonas; Hankins, Catherine; Money, Deborah; Rachlis, Anita; Pourreaux, Karina; Coutlée, François

    2004-01-01

    Human papillomavirus type 16 (HPV-16) viral load in cervicovaginal lavage samples collected from 66 human immunodeficiency virus-seropositive women was inversely correlated with blood CD4 count (P = 0.002). HPV-16 viral load was 81-fold higher in women with cervical smears suggestive of high-grade lesions (median, 4,425,883 copies/μg of DNA) than in women with normal smears (median, 54,576), controlling for age (P = 0.006). PMID:15131192

  4. High-grade spondylolytic spondylolisthesis.

    PubMed

    Emary, Peter C; Eberspaecher, Stefan A; Taylor, John A

    2017-08-01

    Case reports of high-grade spondylolisthesis have been rarely published in the chiropractic literature. Documented here is a case involving a 28-year-old woman who presented to the World Spine Care clinic in the Dominican Republic with minimal neuromusculoskeletal symptoms despite a grade 4 spondylolytic spondylolisthesis. The key imaging and etiological features of this clinical disorder are presented.

  5. High-grade spondylolytic spondylolisthesis

    PubMed Central

    Emary, Peter C.; Eberspaecher, Stefan A.; Taylor, John A.

    2017-01-01

    Case reports of high-grade spondylolisthesis have been rarely published in the chiropractic literature. Documented here is a case involving a 28-year-old woman who presented to the World Spine Care clinic in the Dominican Republic with minimal neuromusculoskeletal symptoms despite a grade 4 spondylolytic spondylolisthesis. The key imaging and etiological features of this clinical disorder are presented. PMID:28928499

  6. Histologic grading and nucleolar organizer regions in oral squamous cell carcinomas

    PubMed Central

    HANEMANN, João Adolfo Costa; MIYAZAWA, Marta; SOUZA, Mireile São Geraldo dos Santos

    2011-01-01

    Objective The purposes of this study were to histologically assess different types of oral squamous cell carcinoma and the silver-binding nucleolar organizer region (AgNOR) morphology in neoplastic cells, as well as to quantify the number of AgNORs in each type of carcinoma in order to relate AgNOR count and histologic grading. Material and Methods Twenty-eight cases of oral squamous cell carcinoma were divided into 4 groups, namely well-differentiated, moderately differentiated, poorly differentiated, and undifferentiated. For NOR study, 3-µm-thick sections were stained with 50% aqueous silver nitrate solution. The predominant microscopic pattern of NORs was determined. Quantitative analyses of NORs were obtained of all cells present on each histological field using a 0.025 mm2 eyepiece graticule. Different histological fields were analyzed until the total number of NORs was 120 cells for each tumor. Kruskall-Wallis test was applied to compare the groups of sample data at a significance level of p=0.05. Results The mean number of AgNORs per nucleus was 3.20 for the well-differentiated group, 5.33 for the moderately differentiated one, 8.27 for the poorly differentiated one, and 10.08 for the undifferentiated one. AgNOR count was significantly different (p<0.05) among all of the studied groups. Conclusion AgNOR staining technique seems to be a useful diagnostic tool since differences in AgNOR numeric values can be identified in the different types of oral squamous cell carcinoma. This technique is easy to handle and inexpensive, thus justifying its large use in histopathology. PMID:21625747

  7. A Grading System Combining Tumor Budding and Nuclear Diameter Predicts Prognosis in Resected Lung Squamous Cell Carcinoma.

    PubMed

    Kadota, Kyuichi; Miyai, Yumi; Katsuki, Naomi; Kushida, Yoshio; Matsunaga, Toru; Okuda, Masaya; Yokomise, Hiroyasu; Kanaji, Nobuhiro; Bandoh, Shuji; Haba, Reiji

    2017-06-01

    For lung squamous cell carcinomas, there are no histologic findings that have been universally accepted as prognostic factors. Tumor budding and nuclear grade have been recognized as prognostic factors in other carcinomas. In this study, we investigated whether pathologic findings could determine clinical outcome in Japanese patients with lung squamous cell carcinomas. Tumor slides from surgically resected lung squamous cell carcinomas (1999 to 2012) were reviewed (n=216). Tumors were evaluated for histologic subtypes, differentiation, tumor budding, nuclear diameter, and mitosis. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the log-rank test and the Cox proportional hazards model. Tumor budding and large nuclei were independent prognostic factors of a worse RFS (P<0.001 and P=0.002, respectively) and a worse OS (P<0.001 and P=0.038, respectively) on multivariate analysis after adjustment for pathologic stage and lymphatic invasion. However, histologic subtypes, differentiation, and mitotic count did not correlate with prognosis. A grading system combining tumor budding and nuclear diameter was an independent prognostic factors of a worse RFS (grade 2 vs. 1, hazard ratio [HR]=2.91; P<0.001, and grade 3 vs. 1, HR=7.60, P<0.001) and a worse OS (grade 2 vs. 1, HR=2.15; P=0.014, and grade 3 vs. 1, HR=4.54, P<0.001). We found that a grading system combining tumor budding and nuclear diameter was a significant prognostic factor among Japanese patients with resected lung squamous cell carcinoma.

  8. Study of Collagen Birefringence in Different Grades of Oral Squamous Cell Carcinoma Using Picrosirius Red and Polarized Light Microscopy

    PubMed Central

    Arun Gopinathan, Pillai; Kokila, Ganganna; Jyothi, Mahadesh; Ananjan, Chatterjee; Pradeep, Linganna; Humaira Nazir, Salroo

    2015-01-01

    Objectives. The present study was done to evaluate birefringence pattern of collagen fibres in different grades of oral squamous cell carcinoma using Picrosirius red stain and polarization microscopy and to determine if there is a change in collagen fibres between different grades of oral squamous cell carcinoma. Materials and Methods. Picrosirius red stained 5 μm thick sections of previously diagnosed different grades of squamous cell carcinoma and normal oral mucosa were studied under polarization microscopy for arrangement as well as birefringence of collagen fibres around tumour islands. Results. It was found that thin collagen fibres increased and thick collagen fibres decreased with dedifferentiation of OSCC (P < 0.0001). It was observed that there was change in polarization colours of thick fibres from yellowish orange to greenish yellow with dedifferentiation of OSCC indicating loosely packed fibres (P < 0.0001). Conclusion. There was a gradual change of birefringence of collagen from yellowish orange to greenish yellow from well to poorly differentiated squamous cell carcinoma, indicating that there is a change from mature form of collagen to immature form as tumour progresses. Studying collagen fibres with Picrosirius red for stromal changes around tumour islands along with routine staining may help in predicting the prognosis of tumour. PMID:26587310

  9. Use of human papillomavirus DNA, E6/E7 mRNA, and p16 immunocytochemistry to detect and predict anal high-grade squamous intraepithelial lesions in HIV-positive and HIV-negative men who have sex with men.

    PubMed

    Phanuphak, Nittaya; Teeratakulpisarn, Nipat; Keelawat, Somboon; Pankam, Tippawan; Barisri, Jiranuwat; Triratanachat, Surang; Deesua, Amornrat; Rodbamrung, Piyanee; Wongsabut, Jiratchaya; Tantbirojn, Patou; Numto, Saranya; Ruangvejvorachai, Preecha; Phanuphak, Praphan; Palefsky, Joel M; Ananworanich, Jintanat; Kerr, Stephen J

    2013-01-01

    Men who have sex with men (MSM) are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL) is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV) infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM. A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA) with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43-46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7%) and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline. Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months.

  10. Use of Human Papillomavirus DNA, E6/E7 mRNA, and p16 Immunocytochemistry to Detect and Predict anal High-Grade Squamous Intraepithelial Lesions in HIV-Positive and HIV-Negative Men Who Have Sex with Men

    PubMed Central

    Phanuphak, Nittaya; Teeratakulpisarn, Nipat; Keelawat, Somboon; Pankam, Tippawan; Barisri, Jiranuwat; Triratanachat, Surang; Deesua, Amornrat; Rodbamrung, Piyanee; Wongsabut, Jiratchaya; Tantbirojn, Patou; Numto, Saranya; Ruangvejvorachai, Preecha; Phanuphak, Praphan; Palefsky, Joel M.; Ananworanich, Jintanat; Kerr, Stephen J.

    2013-01-01

    Background Men who have sex with men (MSM) are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL) is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV) infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM. Methodology/Principal Findings A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA) with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43–46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7%) and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline. Conclusions/Significance Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of

  11. Immunohistochemical expression of phosphatase and tensin homolog in histologic gradings of oral squamous cell carcinoma

    PubMed Central

    Jasphin, Shiny S. R.; Desai, Dinkar; Pandit, Siddharth; Gonsalves, Nithin M.; Nayak, Preethi B.; Iype, Amal

    2016-01-01

    Context: Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene located on chromosome 10q23. PTEN has its major function in the regulation of cell adhesion, cell cycle arrest, migration, apoptosis programming, and differentiation. This genomic region suffers loss of heterozygosity in many human cancers. Aims: The aim of this study was to compare the immunohistochemical expression of PTEN in normal oral mucosa and oral squamous cell carcinoma (OSCC) and to correlate the PTEN expression in gradings of OSCC. Materials and Methods: Thirty cases of paraffin tissue sections of previously diagnosed OSCC were taken. Of thirty cases, ten were well differentiated, ten were moderately differentiated, and ten were poorly differentiated. As a control, ten paraffin sections of oral normal mucosa tissue specimens were taken from patients undergoing extractions. The sections were stained for immunohistochemical expression of PTEN. The cells stained by PTEN antibody were counted, and an immunohistochemical score was obtained. Statistical Analysis Used: Statistical analysis was done using Mann–Whitney's test and Kruskal–Wallis test. Results: Statistical analysis revealed that there was a significant difference between normal mucosa and OSCC in immunohistochemistry staining. However, there was no significant difference in PTEN expression among gradings of OSCC. Conclusions: The study concluded that there was a decrease in PTEN expression in OSCC than normal mucosa. It also concluded that PTEN is a tumor suppressor gene which has a wide role in oral carcinogenesis. PMID:27994422

  12. High-grade focal areas in low-grade central osteosarcoma: high-grade or still low-grade osteosarcoma?

    PubMed

    Righi, Alberto; Paioli, Anna; Dei Tos, Angelo Paolo; Gambarotti, Marco; Palmerini, Emanuela; Cesari, Manuela; Marchesi, Emanuela; Donati, Davide Maria; Picci, Piero; Ferrari, Stefano

    2015-01-01

    High-grade foci (grade 3 according to Broder's grading system) are sometimes detected in low-grade (grade 1 and 2) central osteosarcoma. The aim of this study was to retrospectively evaluate the clinical outcome in patients upgraded to high grade (grade 3) after a first diagnosis of low-grade osteosarcoma, following the detection of high-grade areas (grade 3) in the resected specimen. Of the 132 patients with a diagnosis of low-grade central osteosarcoma at surgical biopsy at our Institute, 33 patients were considered eligible for the study. Median age was 37 (range 13-58 years). Location was in an extremity in 29 patients (88 %). Post-operative chemotherapy was given in 22 (67 %) patients. Follow-up data were available for all patients, with a median observation time of 115 months (range 4-322 months). After histological revision, areas of high-grade (grade 3) osteosarcoma accounting for less than 50 % of the tumor were found in 20 (61 %) patients, whereas the majority of the tumor was composed of a high-grade (grade 3) component in 13 (39 %) patients. In the 20 cases of low-grade osteosarcoma with high-grade foci (grade 3) in less than 50 % of the tumor, 9 patients did not receive adjuvant chemotherapy; only one of them died, of unrelated causes. In the adjuvant chemotherapy group (11 out of 20 patients), one patient developed multiple lung metastases and died of disease 39 months after the first diagnosis. In the other 13 cases of low-grade osteosarcoma with high-grade foci (grade 3) in more than 50 % of the tumor, 12 patients received adjuvant chemotherapy: 2 had recurrence, 4 developed multiple lung metastases and 3 died of disease. The only patient who did not receive chemotherapy is alive without disease 232 months after complete surgical remission. Our data indicate that patients with a diagnosis of low-grade osteosarcoma where the high-grade (grade 3) component is lower than 50 % of the resected specimen, may not require chemotherapy

  13. High Stakes for Medium Grades

    Treesearch

    Philip A. Araman

    1992-01-01

    This article discusses how the high demand for domestic and export logs, lumber, veneer, and other hardwood products might be solved by using dimension products and lesser-known species. It also discusses how the demands on U.S. hardwood forests for pulpwood and fuelwood will be filled primarily with low grade and small diameter hardwoods.

  14. Human papillomaviral load changes in low-grade squamous intraepithelial lesions of the uterine cervix

    PubMed Central

    Ho, C-M; Cheng, W-F; Chu, T-Y; Chen, C-A; Chuang, M-H; Chang, S-F; Hsieh, C-Y

    2006-01-01

    To better predict risk of progression of low-grade squamous intraepithelial lesions (LSILs) of the uterine cervix in women with human papillomavirus (HPV) infections, 294 baseline cervical specimens from women with LSILs were evaluated. Specimens were tested for HPV DNA using hybrid capture 2 (HC2) and PCR-reverse line blotting. 65 LSILs with HPV DNA types 16, 18, 52, or 58 were examined for physical status, E2/E6 ratio and viral load at two time points, along with patient age. Women with LSILs whose viral loads increased between baseline and 6 month follow-up had a 45% risk of developing HSIL (OR=7.6, 95% CI=1.9–29.4, P<0.01), as evaluated by real-time PCR and a 44% risk (OR=6.1, 95% CI=1.6–22.7, P<0.01), as evaluated by HC2. The two viral load measures correlated well (Person's coefficient, r=0.687, P<0.001). Such evaluations of viral load changes (increased or not increased) through repeat HPV DNA testing could predict progression of disease in LSIL cases of HPV types 16, 18, 52, and 58, which correlates to clinical implications. PMID:17060938

  15. Human papillomavirus false positive cytological diagnosis in low grade squamous intraepithelial lesion.

    PubMed

    Núñez-Troconis, José; Delgado, Mariela; González, Julia; Velásquez, Jesvy; Mindiola, Raimy; Whitby, Denise; Conde, Betty; Munroe, David J

    2009-12-01

    The purpose of this study was to investigate the number of Human Papillomavirus false positive cytological diagnosis in low grade squamous intraepithelial lesions (LSIL). Three hundred and two women who assisted to an Out-Patient Gynecologic Clinic in Maracaibo, Venezuela, were recruited for this study. Each patient had the Pap smear and a cervical swab for Hybrid Capture 2 (HC2). Three cytotechnologists reviewed the Pap smears and two pathologists rescreened all of them. The cytotechnologists reported 161 (53.3%) Pap smears negatives for intraepithelial lesion (IL) or malignancy, and 141 cases (46.7%) with epithelial abnormalities. They reported 46% of 302 patients with HPV infection in Pap smear slides. The pathologists found that 241 (79.8%) Pap smears were negatives for IL or malignancy and 61 (20.2%), with abnormal Pap smears. They found 14.6% HPV infection in all Pap smears (p<0.0001; 46% vs 14.6%). The HC2 study showed that 47 samples (15.6%) were positive for HPV. The study found that 114 Pap smears (False Positive: 85%) of 134 reported by the cytotechnologists and 24 (False Positive: 43%) of 56 cytologies reported by the pathologists as LSIL, were negative for HPV infection determined by HC2 (p<0.00003). The present study suggests that the cytotechnologists overdiagnosed cellular changes associated with HPV infection in the Pap smear, increasing the FP cytological diagnosis of LSIL.

  16. Histopathologic extent of cervical intraepithelial neoplasia 3 lesions in the atypical squamous cells of undetermined significance low-grade squamous intraepithelial lesion triage study: implications for subject safety and lead-time bias.

    PubMed

    Sherman, Mark E; Wang, Sophia S; Tarone, Robert; Rich, Laurie; Schiffman, Mark

    2003-04-01

    Cervical intraepithelial neoplasia 3 (CIN3) is the precursor of mostsquamous carcinomas and serves as a surrogate end point. However, small CIN3 lesions are rarely associated with concurrent invasion. We hypothesized that aggressive follow-up for cytology of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) leads predominantly to detection of smaller CIN3 lesions than those usually associated with cancer. We assessed this hypothesis in a masked histopathologic review of 330 CIN3 lesions in the ASCUS LSILTriage Study, focusing on ASCUS referrals. ASCUS referrals underwent randomized management [colposcopy for repeat cytology of high-grade squamous intraepithelial lesion (HSIL), colposcopy for oncogenic human papillomavirus (HPV) detection or repeat HSIL, or immediate colposcopy]; then all were followed with repeat cytology for 2 years, followed by colposcopy and aggressive treatment. We assessed all CIN3 lesions qualitatively and measured 39 of them. CIN3 lesions were overwhelmingly small. Compared with enrollment, lesions found at follow-up or exit involved fewer tissue fragments (P < 0.01) and showed less diffuse gland involvement (P = 0.03). CIN3 lesions found postenrollment after HPV testing involved the fewest tissue fragments [versus immediate colposcopy (P = 0.04) or repeat cytology of HSIL (P = 0.02)], and none showed diffuse gland involvement. The median distal-proximal length was 6.5 mm (median replacement of total epithelium = 5%) in the 39 measured cases. We conclude that CIN3 lesions underlying ASCUS or LSIL generally lack features associated with invasion, particularly if managed using HPV testing, suggesting that aggressive management leads to early detection of CIN3 but probably prevents relatively few cancers in screened populations.

  17. Inherent grading characteristics of individual pathologists contribute to clinically and prognostically relevant interobserver discordance concerning Broders' grading of penile squamous cell carcinomas.

    PubMed

    Gunia, Sven; Burger, Maximilian; Hakenberg, Oliver W; May, Dieter; Koch, Stefan; Jain, Anjun; Birnkammer, Kristina; Wieland, Wolf F; Otto, Wolfgang; Hofstädter, Ferdinand; Fritsche, Hans-Martin; Denzinger, Stefan; Gilfrich, Christian; Brookman-May, Sabine; May, Matthias

    2013-01-01

    We assessed the reproducibility and prognostic impact of the Broders' grading system (BGS) in a cohort of 147 patients with surgically treated penile squamous cell carcinomas. Conventionally stained histology slides were graded according to the BGS in two rounds by two study pathologists. Reproducibility was assessed using ĸ statistics. Multivariable analyses were calculated to predict cancer-specific survival (CSS). The 'mean grade' per pathologist per round was calculated by allocating grade points to each study case (G1-G4: 1-4 points) and dividing the sum of all grade points by the number of cases examined. The BGS showed substantial interobserver variation (59-87% with ĸ = 0.38-0.69) but almost perfect intraobserver reproducibility (91% with ĸ = 0.86 and 96% with ĸ = 0.94, respectively). The 'mean grade' per pathologist remained nearly constant in both rounds of examination (differences ≤0.05 grade points) but differed between the two pathologists (up to 0.4 grade points). In multivariable analyses, the prognostic impact of the BGS in terms of CSS was strongly pathologist-dependent. Clinically and prognostically relevant interobserver discordance concerning the BGS seems, at least in part, to be attributable to inherent 'aggressive' versus 'reserved' grading characteristics of individual pathologists. Copyright © 2012 S. Karger AG, Basel.

  18. High-Grading Lunar Samples

    NASA Technical Reports Server (NTRS)

    Allen, Carlton; Sellar, Glenn; Nunez, Jorge; Mosie, Andrea; Schwarz, Carol; Parker, Terry; Winterhalter, Daniel; Farmer, Jack

    2009-01-01

    Astronauts on long-duration lunar missions will need the capability to high-grade their samples to select the highest value samples for transport to Earth and to leave others on the Moon. We are supporting studies to define the necessary and sufficient measurements and techniques for high-grading samples at a lunar outpost. A glovebox, dedicated to testing instruments and techniques for high-grading samples, is in operation at the JSC Lunar Experiment Laboratory. A reference suite of lunar rocks and soils, spanning the full compositional range found in the Apollo collection, is available for testing in this laboratory. Thin sections of these samples are available for direct comparison. The Lunar Sample Compendium, on-line at http://www-curator.jsc.nasa.gov/lunar/compendium.cfm, summarizes previous analyses of these samples. The laboratory, sample suite, and Compendium are available to the lunar research and exploration community. In the first test of possible instruments for lunar sample high-grading, we imaged 18 lunar rocks and four soils from the reference suite using the Multispectral Microscopic Imager (MMI) developed by Arizona State University and JPL (see Farmer et. al. abstract). The MMI is a fixed-focus digital imaging system with a resolution of 62.5 microns/pixel, a field size of 40 x 32 mm, and a depth-of-field of approximately 5 mm. Samples are illuminated sequentially by 21 light emitting diodes in discrete wavelengths spanning the visible to shortwave infrared. Measurements of reflectance standards and background allow calibration to absolute reflectance. ENVI-based software is used to produce spectra for specific minerals as well as multi-spectral images of rock textures.

  19. Atypical squamous cells in the urine revealing endometrioid adenocarcinoma of the endometrium with squamous cell differentiation: a case report.

    PubMed

    Wang, Yinong; Otis, Christopher N; Florence, Roxanne R

    2015-01-01

    Urine cytology is mainly used to detect urothelial carcinoma (UC), especially for high-grade lesions including urothelial carcinoma in situ. Benign squamous cells are often seen in the urine specimens of women, they are either exfoliated from the trigone area of the bladder, the urethra, or the cervicovaginal region. However, abnormal squamous cells in the urine raise concerns of abnormalities of the urinary tract and cervicovaginal area which range from squamous metaplasia of the urothelium, a cervicovaginal squamous intraepithelial lesion, condyloma acuminatum of the bladder, UC with squamous differentiation, and squamous cell carcinoma. We present here a unique case of atypical squamous cells (ASCs) in the urine subsequently leading to the diagnosis of endometrioid adenocarcinoma of the endometrium with squamous differentiation. The presence of ASCs in voided urine is a rare finding that may indicate an underlying malignancy. Careful evaluation of squamous cells in the urine is an important part of our daily cytopathology practice.

  20. Stability and Change in High School Grades

    ERIC Educational Resources Information Center

    Guskey, Thomas R.

    2011-01-01

    This study investigated the stability of students' grades in high school courses during the academic year. Records of over 8,000 high school students from five large southeastern high schools were analyzed to determine the relationship between the first achievement grade students were assigned during an academic term and their final course grades.…

  1. Correlation of c-erbB-2 and S-100 expression with the malignancy grading and anatomical site in oral squamous cell carcinoma

    PubMed Central

    Albuquerque Júnior, Ricardo L C; Miguel, Márcia C C; Costa, Antonio L L; Souza, Lélia B

    2003-01-01

    An immunohistochemical analysis of 32 cases of oral squamous cell carcinoma (eight in the inferior lip, eight in the lateral angle of the tongue, eight in the palate and eight in the mouth floor) was performed to evaluate the expression pattern of c-erbB-2 protein and S-100-positive cells in the lesions. The immunohistochemical expression was correlated with the tumour anatomical site and histological grading of malignancy. A higher frequency of c-erbB-2-positive cases was found in the tongue, even though no correlation could be detected between the protein expression and the tumour histological grading. With respect to the S-100-positive cells, it was observed that a quantitative decrease was present in the cases classified as high-grade tumours when compared to the low ones (P = 0.0007). Thus, c-erbB-2 immunohistochemical expression is correlated with anatomical localization, and the expression of the S-100 Langerhans' cell markers is decreased significantly in high-grade carcinomas. PMID:14748745

  2. Peripheral blood lymphocytes from low-grade squamous intraepithelial lesions patients recognize vaccine antigens in the presence of activated dendritic cells, and produced high levels of CD8 + IFNγ + T cells and low levels of IL-2 when induced to proliferate

    PubMed Central

    2012-01-01

    Background Most infections with human papillomavirus (HPV) are resolved without clinical intervention, but a minority evolves into chronic lesions of distinct grades, including cervical-uterine cancer. It is known that in most cases the immune system mediates elimination of HPV infection. However, the mechanism of immune evasion leading to HPV persistence and development of early cervical lesions is not fully understood. The aim of the present work was to evaluate the potential of peripheral blood leukocytes (PBL) from low-grade squamous intraepithelial lesions (LSIL) patients to be activated ex-vivo by vaccine antigens, the participation of cytotoxic lymphocytes and regulatory T cells, and to determine the secretion of Th1 and Th2 cytokines mediated by stimulation of T cell receptors. Results We found that PBL from LSIL patients showed a significantly lower proliferation rate to vaccine antigens as compared to that of healthy donors, even though there was not a difference in the presence of antibodies to those antigens in sera from both groups. We did not find differences in either the frequency of CD4 + CD25 + FoxP3+ in PBL, or the levels of IL-4, IL-5 and IL-10 in plasma or conditioned media from PBL incubated with TcR agonists in vitro, between the two groups. However, we detected a lower production of IL-2 and a higher proportion of CD8 + IFNγ + cells in PBL from LSIL patients as compared with PBL from normal donors. We also observed that PBL from patients infected by HPV-16 and −18 were not able to proliferate in the presence of soluble HPV antigens added to the culture; however, a high level of proliferation was attained when these antigens were presented by activated dendritic cells. Conclusions Our results suggest that the immunodeficiency reported in LSIL patients could be due to the inability of specific cytotoxic T lymphocytes that for some unknown reason are present but unable to mount a response when challenged with their antigens

  3. Laryngeal Dysplasia, Squamous Cell Carcinoma, and Variants.

    PubMed

    Thompson, Lester D R

    2017-03-01

    Squamous cell carcinoma (SCC) is a malignant epithelial tumor showing evidence of squamous differentiation. It is the most common malignancy of the larynx, with several variants (verrucous, exophytic or papillary, spindle-cell, basaloid, acantholytic, adenosquamous) recognized, with well-established precursor lesions. Dysplasia is now separated into only low-grade and high-grade categories. Each SCC variant has unique cytomorphologic features and histologic differential diagnoses that are important to consider, as management and outcomes are different.

  4. [Incidence and physiopathology of high-grade dysplasia in Barrett's esophagus].

    PubMed

    Coriat, Romain; Perkins, Géraldine; Brezault, Catherine

    2011-05-01

    Barrett's esophagus is a well-known precursor of esophageal adenocarcinoma. Monitoring patients with Barrett's esophagus is recommended for detecting high-grade dysplasia or cancer. Gastroesophageal reflux disease affects approximately 20% of the population in developed countries. About 10-15% of patients with gastroesophageal reflux disease develop Barrett's esophagus, which can progress to adenocarcinoma. The esophagus is normally lined by squamous mucosa. Therefore, it is clear that for an adenocarcinoma, there is a prior sequence of events that lead to normal squamous mucosa transformation.

  5. Cervical Strip Biopsy for High-Grade Cervical Intraepithelial Lesions: a Valid Alternative to Conventional Punch Technique.

    PubMed

    Schneider, A; Wagner, K; Rakozy, C; Stolte, C; Bothur-Schäfer, P; Welcker, T; Choly, N; Roesgen, A; Rothe, H; Böhmer, G

    2015-10-01

    Introduction: To evaluate, if targeted strip biopsies decrease trauma/pain perception while maintaining diagnostic accuracy in patients with the diagnosis of high-grade squamous intraepithelial lesions of the uterine cervix. Patients and Methods: Between July 1st and December 31st 2014 we performed colposcopically directed strip biopsies in 102 patients with colposcopic suspicion of high-grade squamous intraepithelial lesions of the uterine cervix. We used a 3 mm curette for harvesting tissue samples under VITOM® videocolposcopy. So far, 60 patients underwent additional loop excision. Histologic examination of strip biopsies and loop specimens included routine hematoxylin and eosin staining as well as immunohistochemical staining for p16, Ki 67 and stathmin-1. Results: 55 patients (53 %), were histologically diagnosed with cervical intraepithelial neoplasia grade 3 on strip biopsies. Adenocarcinoma in situ was diagnosed in 2 patients (2 %), cervical intraepithelial neoplasia grade 2 in 35 patients (34 %), and cervical intraepithelial neoplasia grade 1 in 10 patients (10 %). The agreement between histologic results of strip biopsy and loop specimen was highly significant: In all 60 strip biopsies diagnosed with high-grade squamous intraepithelial lesions this diagnosis was confirmed histologically during follow-up loop specimen excision (high-grade squamous intraepithelial lesions in 58 patients, invasive disease in 2 patients). The pain level experienced during strip biopsy was rated on average 0.25 on a scale from 0 to 10. No clinically significant bleeding was reported. Conclusion: Targeted strip biopsies with a 3 mm curette are a reliable procedure to diagnose high-grade squamous intraepithelial lesions of the uterine cervix and yield high patient satisfaction (Video 1).

  6. Cytological Anal Squamous Intraepithelial Lesions Associated with Anal High-Risk Human Papillomavirus Infections among Men Who Have Sex with Men in Northern Thailand.

    PubMed

    Ruanpeng, Darin; Chariyalertsak, Suwat; Kaewpoowat, Quanhathai; Supindham, Taweewat; Settakorn, Jongkolnee; Sukpan, Kornkanok; Utaipat, Utaiwan; Miura, Toshiyuki; Kosashunhanan, Natthapol; Saokhieo, Pongpun; Songsupa, Radchanok; Wongthanee, Antika

    2016-01-01

    Anal cancer, one of human papillomavirus (HPV) related malignancies, has increased in recent decades, particularly among men who have sex with men (MSM) and HIV-infected (HIV+) persons. We aimed to explore the prevalence of anal squamous intraepithelial lesions (ASIL) using Papanicolau (Pap) screening among MSM in northern Thailand and its associated factors. Two hundreds MSM aged ≥18 years reporting receptive anal intercourse in the prior 6 months were recruited from July 2012 through January 2013. Medical history and behavioral data were collected by staff interview and computer-assisted self interview. Anal Pap smear, HPV genotyping, and HIV testing were performed. Two pathologists blinded to HPV and HIV status reported cytologic results by Bethesda classification. Mean age was 27.2 years (range 18-54). Overall, 86 (43.0%) had ASIL: 28 (14.2%) with atypical cells of undetermined significance (ASCUS), 1 (0.5%) with atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H), 56 (28.4%) with low-grade squamous intraepithelial lesion (LSIL), and 1 (0.5%) with high-grade squamous intraepithelial lesion (HSIL). ASIL was associated by univariate analysis (p ≤0.05) with older age, gender identity other than bisexual (i.e., gay men and transgender women), rectal douching, anal symptoms, genital warts, HIV positivity, and high-risk-HPV infection. However, on multiple logistic regression ASIL was associated only with high-risk HPV type (p = 0.002) and HIV infection (p = 0.01). ASIL is quite common in high-risk MSM in northern Thailand and is associated with high-risk HPV types and HIV infection. Routine anal Pap screening should be considered, given the high frequency of ASIL, particularly in the HIV+. High resolution anoscopy (HRA), not done here, should be to confirm PAP smears whose sensitivity and specificity are quite variable. Timely HPV vaccination should be considered for this population.

  7. Analysis of salivary antioxidant levels in different clinical staging and histological grading of oral squamous cell carcinoma: noninvasive technique in dentistry.

    PubMed

    Singh, Hanspal; Shetty, Pushparaja; S V, Sreelatha; Patidar, Madvikha

    2014-08-01

    To estimate and Compare of salivary antioxidant level {Uric acid (UA), Glutathione S Transferase (GST) and Superoxide dismutase (SOD)} between healthy control and study group (oral squamous cell carcinoma patients).Further comparison of sub division of study group on the basis of clinical staging and histological grading. The study group consists of 50 cases of squamous cell carcinoma and 50 healthy patients. These parameters were estimated by spectrophotometer. The biochemical values of this study were subjected to statistical analysis i.e. Independent t-test, ANOVA and Tukey test. UA suggested statistically significant changes in saliva of clinical staging and histological grading of oral squamous cell carcinoma (SCC) patients. Salivary SOD level between well to poorly differentiated SCC showed a progressive increase although it is not statistically significant. Salivary analysis of antioxidant is simple, non-invasive technique which may be useful as diagnostic, prognostic and therapeutic marker.

  8. Expression of alpha-dystroglycan correlates with tumour grade and predicts survival in oral squamous cell carcinoma.

    PubMed

    Sgambato, A; Caredda, E; Leocata, P; Rossi, G; Boninsegna, A; Vitale, A; Grandi, T; Cittadini, A; Migaldi, M

    2010-04-01

    Dystroglycan (DG) is a non-integrin adhesion molecule connecting the extracellular matrix to the actin cytoskeleton. Decreased expression of DG has been reported in several human cancers and related to tumour aggressiveness. Expression of the alpha-DG subunit was evaluated by immunostaining in a series of oral squamous cell carcinoma (OSCC) and its relation with traditional prognostic indicators and with the clinical outcome of the patients was evaluated. Alpha-DG expression was easily detected in normal epithelium with a mean percentage of positive cells >80% but was undetectable in a significant fraction (59%) of OSCC. Loss of alpha-DG staining correlated with higher tumour grade (p = 0.04) and stage (p = 0.01), with nodal involvement (p = 0.001) and with an increased risk of recurrence (p = 0.002) and death (p = 0.004) in a univariate analysis, but it was not confirmed as an independent predictor of clinical outcome in a multivariate analysis. Loss of alpha-DG expression, which corresponds to loss of a functional DG complex, is a frequent event in human OSCC. Further studies are warranted on the role of this molecule in the entire multistep process of oral squamous tumorigenesis.

  9. Genomic landscape of high-grade meningiomas

    PubMed Central

    Bi, Wenya Linda; Greenwald, Noah F.; Abedalthagafi, Malak; Wala, Jeremiah; Gibson, Will J.; Agarwalla, Pankaj K.; Horowitz, Peleg; Schumacher, Steven E.; Esaulova, Ekaterina; Mei, Yu; Chevalier, Aaron; Ducar, Matthew; Thorner, Aaron R.; van Hummelen, Paul; Stemmer-Rachamimov, Anat; Artyomov, Maksym; Al-Mefty, Ossama; Dunn, Gavin P.; Santagata, Sandro; Dunn, Ian F.; Beroukhim, Rameen

    2017-01-01

    High-grade meningiomas frequently recur and are associated with high rates of morbidity and mortality. To determine the factors that promote the development and evolution of these tumors, we analyzed the genomes of 134 high-grade meningiomas and compared this information with data from 587 previously published meningiomas. High-grade meningiomas had a higher mutation burden than low-grade meningiomas but did not harbor any statistically significant mutated genes aside from NF2. High-grade meningiomas also possessed significantly elevated rates of chromosomal gains and losses, especially among tumors with monosomy 22. Meningiomas previously treated with adjuvant radiation had significantly more copy number alterations than radiation-induced or radiation-naïve meningiomas. Across serial recurrences, genomic disruption preceded the emergence of nearly all mutations, remained largely uniform across time, and when present in low-grade meningiomas, correlated with subsequent progression to a higher grade. In contrast to the largely stable copy number alterations, mutations were strikingly heterogeneous across tumor recurrences, likely due to extensive geographic heterogeneity in the primary tumor. While high-grade meningiomas harbored significantly fewer overtly targetable alterations than low-grade meningiomas, they contained numerous mutations that are predicted to be neoantigens, suggesting that immunologic targeting may be of therapeutic value. PMID:28713588

  10. [Partial regression of Barret esophagus with high grade dysplasia and adenocarcinoma after photocoagulation and endocurietherapy under antisecretory treatment].

    PubMed

    Fremond, L; Bouché, O; Diébold, M D; Demange, L; Zeitoun, P; Thiefin, G

    1995-01-01

    Barrett's oesophagus is a premalignant condition. The possibility of eradicating at least partially the metaplastic epithelium has been reported recently. In this case report, a patient with Barrett's oesophagus complicated by high grade dysplasia and focal adenocarcinoma was treated by Nd:Yag laser then high dose rate intraluminal irradiation while on omeprazole 40 mg/day. A partial eradication of Barrett's oesophagus and a transient tumoural regression were obtained. Histologically, residual specialized-type glandular tissue was observed beneath regenerative squamous epithelium. Four months after intraluminal irradiation, a local tumoural recurrence was detected while the area of restored squamous epithelium was unchanged on omeprazole 40 mg/day. This indicates that physical destruction of Barrett's oesophagus associated with potent antisecretory treatment can induce a regression of the metaplastic epithelium, even in presence of high grade dysplasia. The persistence of specialized-type glands beneath the squamous epithelium raises important issues about its potential malignant degeneration.

  11. Clinical significance of CK7, HPV-L1, and koilocytosis for patients with cervical low-grade squamous intraepithelial lesions: a retrospective analysis.

    PubMed

    Cao, Lanqing; Sun, Ping-Li; Yao, Min; Chen, Shifan; Gao, Hongwen

    2017-07-01

    Most cervical low-grade squamous intraepithelial lesions (LSILs) do not progress to high-grade squamous intraepithelial lesions (HSILs); however, reliable biomarkers that predict LSIL progression are lacking. We investigated the association of cytokeratin 7 (CK7), human papillomavirus-L1 capsid protein (HPV-L1), and koilocytosis with clinical outcomes of patients with LSIL. CK7, HPV-L1, Ki67, and p16-INK4A expression was determined in 72 cervical LSIL and 28 HSIL biopsy samples; koilocytosis was evaluated by reviewing biopsy slides. Fifty patients with LSIL received follow-up. CK7, HPV-L1, and koilocytosis were detected in 48.6%, 44.4%, and 52.0% of LSIL tissues and in 78.6%, 10.7%, and 64.3% of HSIL tissues, respectively. Lesion grade was correlated directly with CK7 expression (P=.007) and inversely with HPV-L1 expression (P=.004). CK7 expression in LSILs was correlated inversely with HPV-L1 expression and directly with p16-INK4A and Ki67 status. Furthermore, koilocytosis was significantly associated with HPV-L1 and p16-INK4A expression. Progression to cervical intraepithelial lesions of grades ≥2 occurred in 34% of cases. CK7 negativity and HPV-L1 positivity were significantly associated with lower HSIL progression rates. HPV-L1-positive and CK7-negative LSILs showed significantly lower progression rates compared with HPV-L1-negative and CK7-positive LSILs (6.3% v-positive cases showed a significantly lower progression rate (17.6%) compared with nonkoilocytic and HPV-L1-negative cases (50%). CK7-negative, HPV-L1-positive, and koilocytic LSILs showed a progression rate of 7.7%. Koilocytosis and p16-INK4A were not significantly associated with clinical outcomes. Hence, evaluating HPV-L1, CK7, and koilocytosis profiles combined may be more reliable for LSIL prognostication. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Multiphoton imaging of low grade, high grade intraepithelial neoplasia and intramucosal invasive cancer of esophagus

    NASA Astrophysics Data System (ADS)

    Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

    2017-04-01

    Esophageal squamous cell carcinoma (ESCC) is devastating because of its aggressive lymphatic spread and clinical course. It is believed to occur through low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and intramucosal invasive cancer (IMC) before transforming to submucosal cancer. In particular, these early lesions (LGIN, HGIN and IMC), which involve no lymph node nor distant metastasis, can be cured by endoscopic treatment. Therefore, early identification of these lesions is important so as to offer a curative endoscopic resection, thus slowing down the development of ESCC. In this work, spectral information and morphological features of the normal esophageal mucosa are first studied. Then, the morphological changes of LGIN, HGIN and IMC are described. Lastly, quantitative parameters are also extracted by calculating the nuclear-to-cytoplasmic ratio of epithelial cells and the pixel density of collagen in the lamina propria. These results show that multiphoton microscopy (MPM) has the ability to identify normal esophageal mucosa, LGIN, HGIN and IMC. With the development of multiphoton endoscope systems for in vivo imaging, combined with a laser ablation system, MPM has the potential to provide immediate pathologic diagnosis and curative treatment of ESCC before the transformation to submucosal cancer in the future.

  13. Histopathological grading systems analysis of oral squamous cell carcinomas of young patients.

    PubMed

    Frare, J-C; Sawazaki-Calone, I; Ayroza-Rangel, A-L-C; Bueno, A-G; de Morais, C-F; Nagai, H-M; Kunz, R; Lopes, M-A

    2016-05-01

    To analyze the clinicopathological profile of young patients (≤ 40 years) with oral SCC and correlate with a control group (≥ 50 years) by means of histopathological grading systems. 14 young patients and 14 control patients were selected with similar clinical stage and tumor location. Demographic and clinical data were obtained from patient records and histological sections were evaluated according to four histopathological grading systems. Associations between categories of demographic and clinical data were performed through Chi-square test and Exact Fisher test. The survival analyzes were performed according to the Kaplan-Meier method. The comparison between groups showed a greater association of treatment modalities in younger patients (p=0.022), they had a higher incidence of local recurrence and regional metastasis (p=0.018) and lower disease-free survival in 5 years (p=0.069). There was no difference in 5-year overall survival among the studied groups. There was no difference in histological grading between studied groups according to the four used systems. This study showed that, despite tumors had similar histological grade and more therapeutic modalities were used in the young group, tumors in young patients had a higher incidence of recurrence/metastasis, showing tendency to a more aggressive behavior.

  14. MutSα and MutLα immunoexpression analysis in diagnostic grading of oral epithelial dysplasia and squamous cell carcinoma.

    PubMed

    Jessri, M; Dalley, A J; Farah, C S

    2015-01-01

    This study explored the expression of DNA mismatch repair (MMR) proteins in a range of oral biopsies. We further evaluated the significance of MMR protein expression combined with basic demographic data in differentiating grades of oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Immunohistochemical expression of MutSα (hMLH1 and hPMS2) and MutLα (hMSH2 and hMSH6) were compared in 98 formalin-fixed paraffin embedded oral biopsies: 21 normal, 24 mild-dysplasia (MD), 8 moderate-to-severe-dysplasia (SD), and 45 OSCC. Expression of hMLH1, hPMS2, and hMSH2 was reduced in MD, SD, and OSCC compared with the normal. Reduced hMSH2 immunoreactivity discriminated poorly differentiated OSCC from well-differentiated OSCC. The diagnostic model correctly classified 71.4% of cases and revealed that hPMS2-negative biopsies were more likely to be cancerous (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.000-0.813; P = .040). The results suggested a diagnostic role for MMR proteins in OED and OSCC. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Studies on high grade cerebral gliomas

    SciTech Connect

    Bleehen, N.M. )

    1990-04-01

    A brief review of attempts in the United Kingdom to improve the results of treatment of high grade (grade 3, 4) supra-tentorial astrocytomas is presented. The radiosensitizer misonidazole failed to improve the results of post-surgical radiotherapy, however, multivariate analysis of data from these patients has provided a prognostic index of use in defining good and poor prognosis patients. An overview study of adjuvant nitrosourea therapy trials has shown a small significant advantage for the chemotherapy. A study of chemosensitization by benznidazole of CCNU treatment of patients in relapse failed to demonstrate any effect. 13 references.

  16. Analysis of CD8+ and CD4+ cells in oral squamous cell carcinoma and their association with lymph node metastasis and histologic grade of malignancy.

    PubMed

    dos antos Pereira, Joabe; da Costa Miguel, Márcia Cristina; Guedes Queiroz, Lélia Maria; da Silveira, Éricka Janine Dantas

    2014-03-01

    This study aimed to analyze CD8 and CD4 cells in oral squamous cell carcinoma and to correlate it with prognostic indicators. The sample was composed of 50 cases. Clinical data and histologic grade of malignancy were obtained. Specimens were submitted to immunohistochemistry. Cells were counted in 10 fields at the tumor invasion front and expressed as median. CD8 cells were more frequent in nonmetastatic lesions (18.5) and in low-grade specimens (18.2) (P<0.05). CD4 cells were equally distributed in nonmetastatic and metastatic lesions (4.5). In addition, they were slightly more frequent in low-grade lesions (4.7). None of these correlations were significant (P>0.05). CD8/CD4 ratio was higher in cases without metastasis (3.57) and in low-grade lesions (3.62) (P>0.05). Probably, CD8 cells are the most effective and important cells in the host immune responses against oral squamous cell carcinoma. In addition, CD4 cells could indirectly influence the host protection through regulation of CD8 recruitment and activation.

  17. Self-Graded and Teacher-Graded Achievement in a BSCS High School Biology Course.

    ERIC Educational Resources Information Center

    Good, Wallace Martin

    The effect of self-grading on biology students exposed to the same instruction (except grading) in an upper-middle class public school was investigated by comparing self-graded and teacher-graded populations in (1) achievement in high school biology, (2) level of aspiration behavior, (3) critical thinking skills, and (4) productivity. The…

  18. Cell membrane CD44v6 levels in squamous cell carcinoma of the lung: association with high cellular proliferation and high concentrations of EGFR and CD44v5.

    PubMed

    Ruibal, Álvaro; Aguiar, Pablo; Del Río, María Carmen; Nuñez, Matilde Isabel; Pubul, Virginia; Herranz, Michel

    2015-02-18

    Membranous CD44v6 levels in tumors and surrounding samples obtained from 94 patients with squamous cell lung carcinomas were studied and compared to clinical stage, cellular proliferation, membranous CD44v5 levels, epidermal growth factor receptor EGFR and cytoplasmatic concentrations of CYFRA 21.1. CD44v6 positive values were observed in 33/38 non-tumor samples and in 76/94 tumor samples, but there were not statistically significant differences between both subgroups. In CD44v6 positive tumor samples, CD44v6 was not associated with clinical stage, histological grade, ploidy and lymph node involvement, but significant association was found with high cellular proliferation. Likewise, CD44v6 positive tumors had significantly higher levels of EGFR and CD44v5. In patients with squamous cell lung carcinomas and clinical stage I, positive CD44v6 cases were associated with the same parameters. Furthermore, positive CD44v5 squamous tumors were associated significantly with histological grade III and lower levels of CYFRA21.1. Our findings support the value of CD44v6 as a possible indicator of poor outcome in patients with squamous lung carcinomas.

  19. Improvement in High-Grade Osteosarcoma Survival

    PubMed Central

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H.; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-01-01

    Abstract The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995–2003 vs 2004–2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%–16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients. PMID:27082623

  20. Esophageal squamous cell cancer in a highly endemic region

    PubMed Central

    Asombang, Akwi W; Kayamba, Violet; Lisulo, Mpala M; Trinkaus, Kathryn; Mudenda, Victor; Sinkala, Edford; Mwanamakondo, Stayner; Banda, Themba; Soko, Rose; Kelly, Paul

    2016-01-01

    AIM: To identify risk factors associated with esophageal cancer in Zambia and association between dietary intake and urinary 8-iso prostaglandin F2α (8-isoPGF2α). METHODS: We conducted a prospective, case control study at the University Teaching Hospital. Subjects included both individuals admitted to the hospital and those presenting for an outpatient upper endoscopy. Esophageal cancer cases were compared to age and sex-matched controls. Cases were defined as patients with biopsy proven esophageal cancer; controls were defined as subjects without endoscopic evidence of esophageal cancer. Clinical and dietary data were collected using a standard questionnaire, developed a priori. Blood was collected for human immunodeficiency virus (HIV) serology. Urine was collected, and 8-isoPGF2α was measured primarily by enzyme-linked immunosorbent assay and expressed as a ratio to creatinine. RESULTS: Forty five controls (mean age 54.2 ± 15.3, 31 male) and 27 cases (mean age 54.6 ± 16.4, 17 males) were studied. Body mass index was lower in cases (median 16.8) than controls (median 23.2), P = 0.01. Histopathologically, 25/27 (93%) were squamous cell carcinoma and 2/27 (7%) adenocarcinoma. More cases smoked cigarettes (OR = 11.24, 95%CI: 1.37-92.4, P = 0.02) but alcohol consumption and HIV seropositivity did not differ significantly (P = 0.14 for both). Fruit, vegetables and fish consumption did not differ significantly between groups (P = 0.11, 0.12, and 0.10, respectively). Mean isoprostane level was significantly higher in cases (0.03 ng/mg creatinine) than controls (0.01 ng/mg creatinine) (OR = 2.35, 95%CI: 1.19-4.65, P = 0.014). CONCLUSION: Smoking and isoprostane levels were significantly associated with esophageal cancer in Zambians, but diet, HIV status, and alcohol consumption were not. PMID:26973419

  1. Spina bifida occulta in high grade spondylolisthesis.

    PubMed

    Babbi, L; Terzi, S; Bandiera, S; Barbanti Brodano, G

    2014-01-01

    A 14-year-old boy presented with symptomatic high-grade dysplastic type spondylolisthesis, with a presence of spina bifida occulta, not diagnosed by plain radiographs, but confirmed on preoperative CT and MR. Circumferential fusion with partial reduction of L5/S1 was performed. Awareness of the coexistence of spondylolisthesis and spina bifida by an accurate preoperative planning is paramount to avoid iatrogenic damage to neural elements during surgery.

  2. Low-grade and high-grade endometrial stromal sarcoma: A National Cancer Database study.

    PubMed

    Seagle, Brandon-Luke L; Shilpi, Arunima; Buchanan, Samuel; Goodman, Chelain; Shahabi, Shohreh

    2017-08-01

    To provide refined prognostic information from large cohorts of women with low-grade or high-grade endometrial stromal sarcoma (ESS). We performed an observational retrospective cohort analysis of women diagnosed with low-grade or high-grade ESS from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to identify prognostic factors after multiple imputation of missing data. Recursive partitioning methods were used to rank prognostic factors in high-grade ESS. Matched cohort analyses were performed to hypothesis-test effects of adjuvant treatments. We identified 2414 and 1383 women with low-grade or high-grade ESS, respectively. Women with high-grade ESS had markedly decreased survival compared to women with low-grade ESS (five-year survival (95% CI): 32.6 (30.1-35.3%) versus 90.5% (89.3-91.8%), P<0.001). Among women with high-grade ESS, median survival (95% CI) was only 19.9 (17.1-22.1) months. Increased age and tumor size were associated with decreased survival in low-grade ESS. In high-grade ESS, additional negative prognostic factors were distant or nodal metastasis, omission of lymphadenectomy, and pathologically-positive surgical margins (all P<0.001). Use of adjuvant chemotherapy (time ratio (TR) (95% CI): 1.36 (1.17-1.58), P<0.001) and radiotherapy (TR (95% CI): 1.57 (1.32-1.87), P<0.001) were associated with increased survival for high-grade ESS. The contrasting excellent versus poor prognosis of low-grade versus high-grade ESS, respectively, was confirmed. The best treatment of high-grade ESS is early and complete surgical resection including lymphadenectomy. Adjuvant chemotherapy and radiotherapy may increase survival of women with high-grade ESS. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 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

  4. Clinical characteristics of high grade foveal hypoplasia.

    PubMed

    Park, Kyung-Ah; Oh, Sei Yeul

    2013-02-01

    To report clinical characteristics of high grade foveal hypoplasia. Patients with foveal hypoplasia of grade 3 or 4 on spectral domain optical coherence tomography according to a previously published scheme were enrolled. All patients underwent a full ophthalmologic assessment including visual acuity testing, slit lamp biomicroscopy, fundus examination, and evaluation of ocular alignment. The underlying causes of foveal hypoplasia were identified as albinism in five patients and aniridia in six patients. The mean logMAR visual acuity was 0.57 ± 0.24 (range 0.22-1.00) in the right eyes and 0.58 ± 0.21 (range 0.30-1.00) in the left eyes. On fundus examination in patients with albinism, two patients showed marked transparency, one patient showed moderate transparency, and two patients showed minimal transparency. Among six patients with aniridia, five patients showed normal macular pigmentation without macular reflex and one patient showed decreased macular pigmentation with no macular reflex. Patients with high grade macular hypoplasia tended to have poor visual acuities; however, the range of visual acuity was quite variable. Other factors associated with underlying disease could be the reason of this variability. Therefore, careful consideration should be given when assessing visual prognosis in foveal hypoplasia using optical coherence tomography.

  5. Clinical response to glycyrrhizinic acid in genital infection due to human papillomavirus and low-grade squamous intraepithelial lesion

    PubMed Central

    Valencia, Marcelino Hernández; Pacheco, Adia Carrillo; Quijano, Tomás Hernández; Girón, Antonio Vargas; López, Carlos Vargas

    2011-01-01

    Human papilloma virus (HPV) can infect any of the mucosal areas of the body and cause cervical cancer. Until recently, no specific treatments were available for this condition; therefore, any damaged tissue had to be removed or destroyed, which may have presented obstetrical repercussions for some women. Recently, new drugs have been developed that have shown to be effective for the cure of HPV infection. Glycyrrhizinic acid (GA) has shown fewer side effects and its systemic use makes it possible to reach difficult-to-treat lesions. The purpose of this study was to evaluate the clinical outcome of GA to eliminate the epithelial lesion and HPV. We carried out a longitudinal, descriptive study that included women of reproductive age who were diagnosed with HPV associated with low-grade squamous intraepithelial lesion (LSIL). Subjects began treatment based on GA using two routes of administration - systemic (oral) and topical (spray) - with assessments every month to determine the clinical changes of the lesions through colposcopy and Papanicolaou (Pap) smear. Simple statistics were used along with two-tailed Student's t-test; P<0.05 was considered statistically significant before and after treatment. There were 70 eligible patients, of whom 62 fulfilled the inclusion criteria. Age of subjects was 27.8±9.5 years. At the time of the study, 100% of the patients had HPV infection, 40% were associated with LSIL, and only 16% used a barrier contraceptive (condom) method. Resolution was achieved in all patients from 4 weeks of treatment initiation and improvement was achieved in the majority of patients at 12 weeks (74%) (P<0.001). However, there was persistence of LSIL in 27.7% of patients and only one patient progressed to cervical intraepithelial neoplasia (CIN) II. The use of GA proved to be effective in resolving clinical HPV lesions. For cervical lesions with epithelial changes (LSIL), treatment may be required for a longer period as with other drugs used for this

  6. Clinical response to glycyrrhizinic acid in genital infection due to human papillomavirus and low-grade squamous intraepithelial lesion.

    PubMed

    Valencia, Marcelino Hernández; Pacheco, Adia Carrillo; Quijano, Tomás Hernández; Girón, Antonio Vargas; López, Carlos Vargas

    2011-09-28

    Human papilloma virus (HPV) can infect any of the mucosal areas of the body and cause cervical cancer. Until recently, no specific treatments were available for this condition; therefore, any damaged tissue had to be removed or destroyed, which may have presented obstetrical repercussions for some women. Recently, new drugs have been developed that have shown to be effective for the cure of HPV infection. Glycyrrhizinic acid (GA) has shown fewer side effects and its systemic use makes it possible to reach difficult-to-treat lesions. The purpose of this study was to evaluate the clinical outcome of GA to eliminate the epithelial lesion and HPV. We carried out a longitudinal, descriptive study that included women of reproductive age who were diagnosed with HPV associated with low-grade squamous intraepithelial lesion (LSIL). Subjects began treatment based on GA using two routes of administration - systemic (oral) and topical (spray) - with assessments every month to determine the clinical changes of the lesions through colposcopy and Papanicolaou (Pap) smear. Simple statistics were used along with two-tailed Student's t-test; P<0.05 was considered statistically significant before and after treatment. There were 70 eligible patients, of whom 62 fulfilled the inclusion criteria. Age of subjects was 27.8±9.5 years. At the time of the study, 100% of the patients had HPV infection, 40% were associated with LSIL, and only 16% used a barrier contraceptive (condom) method. Resolution was achieved in all patients from 4 weeks of treatment initiation and improvement was achieved in the majority of patients at 12 weeks (74%) (P<0.001). However, there was persistence of LSIL in 27.7% of patients and only one patient progressed to cervical intraepithelial neoplasia (CIN) II. The use of GA proved to be effective in resolving clinical HPV lesions. For cervical lesions with epithelial changes (LSIL), treatment may be required for a longer period as with other drugs used for this

  7. [Presence of high risk human papilomaviruses (HPV) in the low grade cervical lesion].

    PubMed

    Iljazović, Ermina; Mustadenagić-Mujanović, Jasminka; Karasalihović, Zinaida; Cickusić, E; Avdić, S

    2006-01-01

    Low grade squamous intraepithelial lesion (LGSIL) and atypical squamous cells undetermined significance (ASCUS) are the most frequent verified cellular abnormalities. Their management are still highly controversial mostly caused by uncertainty about their histology and nature of originate. Detection of HPV DNA in the absence of cytological abnormalities can also indicate presence of high-grade cervical intraepithelial neoplasia (CIN). The aim of this study was to show the association of the benign cellular changes, ASCUS and LGSIL with oncogenic types of HPV and to prove the necessity of more intensive screening of this group of patients. Cytology and pathomorphology analyses were performed first. Identification of the presence of human papiloma virus was carried out by the Digene Hybride Capture II test for all patients. Identification of different HPV types for the particular number of patients was carried out by RFLP (Rsetriction Fragments Length of Polymorphism). Out of the 101 patients in the first group 92 (91,08%) were HPV positive, and 41, 58% had no cellular abnormalities, ASCUS or LGSIL. Out of 509 patients of the second group 26.92% were positive for HRHPV, and 78,97% of them had no cellular abnormalities, ASCUS or LGSIL. HPV 16 was detected in 27.36% (ASCUS/LGSIL) of low risk cervical lesion of the first examined period. The combination of smears with the detection of high risk HPV types increases the triage sensitivity especially at patients with mild.

  8. Gene therapy for high-grade glioma

    PubMed Central

    Natsume, Atsushi

    2008-01-01

    The treatment of high-grade gliomas remains difficult despite recent advances in surgery, radiotherapy and chemotherapy. True advances may emerge from the increasing understanding in molecular biology and discovery of novel mechanisms for the delivery of tumoricidal agents. In an attempt to overcome this formidable neoplasm, molecular approaches using gene therapy have been investigated clinically since 1992. The clinical trials have mainly been classified into three approaches: suicide gene therapy, immune gene therapy and oncolytic viral therapy. In this article, we review these approaches, which have been studied in previous and ongoing clinical trials. PMID:19262115

  9. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false High-grade paper recovery. 246.200... SEPARATION FOR MATERIALS RECOVERY GUIDELINES Requirements and Recommended Procedures § 246.200 High-grade paper recovery....

  10. High expression levels of COX-2 and P300 are associated with unfavorable survival in laryngeal squamous cell carcinoma.

    PubMed

    Chen, Yan-Feng; Luo, Rong-Zhen; Li, Yong; Cui, Bo-Kang; Song, Ming; Yang, An-Kui; Chen, Wen-Kuan

    2013-03-01

    In order to provide a basis for clinical treatment decisions, we explored whether there was a correlation between the expression of COX-2 and P300 and clinical factors in a group of patients with laryngeal squamous cell carcinoma (LSCC). A retrospective analysis of clinicopathological data was conducted in 80 patients with LSCC who presented between January 1997 and December 1998. An immunohistochemistry tissue microarray was conducted of 80 surgically resected LSCC and 20 adjacent normal tissue specimens. Survival analysis and Kaplan-Meier curves were used to compare the effects of clinicopathological factors on survival. The Cox model was applied for multivariate analysis. The expression level of COX-2/P300 in LSCC tissues and adjacent normal tissues were 47.5/50.0 versus 0.0/15.0 %. The expression of COX-2 and P300 was correlated with higher T category, N category, clinical staging, histological grade and recurrence (P < 0.05). P300 expression was correlated with COX-2 expression (P < 0.05). Univariate survival analysis showed that P300, COX-2, N category, clinical staging and recurrence factors were closely correlated with unfavorable survival (P < 0.05). Multivariate analysis showed that COX-2 expression, histological grade and recurrence were independent prognostic factors for LSCC. High expression levels of COX-2 and P300 indicated poor survival outcomes for patients with LSCC.

  11. Reduced expression of autophagy markers correlates with high-risk human papillomavirus infection in human cervical squamous cell carcinoma

    PubMed Central

    WANG, HUA-YI; YANG, GUI-FANG; HUANG, YAN-HUA; HUANG, QI-WEN; GAO, JUN; ZHAO, XIAN-DA; HUANG, LI-MING; CHEN, HONG-LEI

    2014-01-01

    Infection by an oncogenic human papillomavirus (HPV), in particular HPV16 and 18, is a high risk factor for developing cervical cancer; however, viral infection alone is not sufficient for cancer progression. Autophagy is hypothesized to be an important process during carcinogenesis. The aim of the present study was to investigate the association between autophagy and high-risk HPV (hrHPV) infection in human cervical squamous cell carcinomas (SCCs), and to analyze the clinical significance of this association. Quantum dot (QD)-based immunofluorescence histochemistry was used to detect the expression of autophagy markers, Beclin-1 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) proteins, in 104 cases of cervical cancer (including 80 SCCs and 24 adenocarcinomas) and 20 normal cervical tissues. hrHPV (HPV16/18) infection was detected by QDs based fluorescence in situ hybridization in cervical cancers. The results revealed that the expression levels of Beclin-1 and LC3B were significantly lower in cervical cancer cells when compared with those of normal cervical squamous epithelial cells, and were found to negatively correlate with hrHPV infection. The expression levels of Beclin-1 and LC3B were not associated with age, tumor grade, tumor stage, tumor node metastasis stage or lymph node metastasis. However, a positive correlation was identified between Beclin-1 and LC3B protein expression. In addition, the absence of autophagy in combination with hrHPV infection may accelerate the progression of cervical SCC. In conclusion, decreased expression of Beclin-1 and LC3B may be important in cervical carcinogenesis. The hrHPV-host cell interaction may inhibit autophagy, which may aid virus duplication and infection, as well as cervical cancer development. PMID:25202355

  12. Are High School Grades Inflated? Issues in College Readiness

    ERIC Educational Resources Information Center

    ACT, Inc., 2005

    2005-01-01

    To find out whether high school grade inflation exists, data drawn from students who took the ACT in the eleventh or twelfth grades and graduated from public high schools were examined. Because grade inflation is by definition a factor that develops over time, data from a relatively long period, 1991 to 2003, or 13 years were used. The number of…

  13. High-resolution CT findings of primary lung cancer with cavitation: a comparison between adenocarcinoma and squamous cell carcinoma.

    PubMed

    Kunihiro, Y; Kobayashi, T; Tanaka, N; Matsumoto, T; Okada, M; Kamiya, M; Ueda, K; Kawano, H; Matsunaga, N

    2016-11-01

    To evaluate the high-resolution computed tomography (CT) findings of primary lung cancer with cavitation and compare the findings in adenocarcinoma and squamous cell carcinoma. The high-resolution CT findings of tumours with cavitation were retrospectively evaluated in 60 patients. Forty-seven of the lesions were diagnosed as adenocarcinomas; 13 were diagnosed as squamous cell carcinomas. The diameters of the tumour and cavity, the maximum thickness of the cavity wall, shape of the cavity wall, the number of cavities, and the presence of ground-glass opacity, bronchial obstruction, intratumoural bronchiectasis, emphysema, and honeycombing were evaluated. The mechanisms of cavity formation were examined according to the pathological features. The maximum thickness of the cavity wall was significantly greater in squamous cell carcinomas than in adenocarcinomas (p=0.002). Ground-glass opacity and intratumoural bronchiectasis were significantly more common in adenocarcinomas than in squamous cell carcinomas (p<0.001 and p=0.040, respectively). Regarding the pathological findings, intratumoural bronchiectasis with or without alveolar wall destruction contributed to a significant difference between adenocarcinoma and squamous cell carcinoma (p<0.001; odds ratio [OR], 20.35; 95% confidence interval [CI], 3.87-107.10). The cavity wall tends to be thicker in squamous cell carcinomas than in adenocarcinomas. The presence of ground-glass opacity and intratumoural bronchiectasis is strongly suggestive of adenocarcinoma. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  14. Posterior surgery in high-grade spondylolisthesis.

    PubMed

    Lengert, R; Charles, Y P; Walter, A; Schuller, S; Godet, J; Steib, J-P

    2014-09-01

    High-grade L5-S1 spondylolisthesis alters sagittal spinopelvic balance, which can cause low back pain and progressive neurologic disorder. The present study assessed spondylolisthesis reduction and maintenance over time with L4-S1 versus L5-S1 fusion using a lever-arm system and posterior fusion combined with lumbosacral graft. Forty patients were operated on for symptomatic high-grade spondylolisthesis, 34 of whom had full pre- and post-operative radiological analysis, with a mean follow-up of 5.4years. There were 9 L5-S1 and 25 L4-S1 instrumentations. Analysis of spinopelvic and slipping parameters and the evolution of segmental lordosis compared results between L5-S1 and L4-S1 instrumentation. Mean Taillard spondylolisthesis index decreased from 64% to 37% (P=0.0001). Overall sagittal spinopelvic balance was not significantly changed. Overall L1-S1 and segmental L4-L5 lordosis were not affected by instrumentation. Mean L5-S1 segmental lordosis increased from 11° to 18°. There was loss of reduction from 19° to 14° with L5-S1 instrumentation, in contrast to maintained reduction with L4-S1 instrumentation (P=0.006). The lever-arm system provided anterior-posterior reduction of spondylolisthesis and corrected slippage. Postoperative change in overall sagittal spinopelvic balance was slight and constant. Posterior L4-S1 fusion provided better long-term control of L5-S1 lordosis reduction than the shorter L5-S1 fusion. Retrospective study of level IV. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Increased incidence trend of low-grade and high-grade neuroendocrine neoplasms.

    PubMed

    Leoncini, Emanuele; Boffetta, Paolo; Shafir, Michail; Aleksovska, Katina; Boccia, Stefania; Rindi, Guido

    2017-03-16

    The incidence of neuroendocrine neoplasms is increasing. This work aimed at: (i) establishing worldwide incidence trend of low-grade neuroendocrine neoplasms; (ii) defining the incidence and temporal trend of high-grade neuroendocrine neoplasms in USA utilizing the Surveillance Epidemiology and End Results database; (iii) comparing trends for low-grade vs. high-grade neuroendocrine neoplasms. We conducted a literature search on MEDLINE and Scopus databases and incidence trends were plotted for 1973-2012. The Surveillance Epidemiology and End Results database was used to identify incidence rates in USA for 1973-2012. Incidence rates were stratified according to histological grade, gender and ethnicity. Trends were summarized as annual percent change and corresponding 95% confidence interval. 11 studies were identified involving 72,048 cases; neuroendocrine neoplasm incidence rates increased over time in all countries for all sites, except for appendix. In Surveillance Epidemiology and End Results low-grade neuroendocrine neoplasm incidence rate increased from 1.09 in 1973 to 3.51 per 100,000 in 2012. During this interval, high-grade neuroendocrine neoplasm incidence rate increased from 2.54 to 10.52 per 100,000. African Americans had the highest rates of digestive neuroendocrine neoplasms with male prevalence in high-grade. Our data indicate an increase in the incidence of neuroendocrine neoplasms as a worldwide phenomenon, affecting most anatomical sites and involving both low-grade and high-grade neoplasms.

  16. Reduced expression of cytokeratin 4 and 13 is a valuable marker for histologic grading of esophageal squamous intraepithelial neoplasia.

    PubMed

    Takashima, Masaki; Kawachi, Hiroshi; Yamaguchi, Tsukasa; Nakajima, Yutaka; Kitagaki, Keisuke; Sekine, Masaki; Iida, Tadatsune; Takemura, Kosuke; Kawano, Tatsuyuki; Eishi, Yoshinobu

    2012-03-13

    Histologic evaluation of low-grade or high-grade intraepithelial neoplasia (LG-IN or HG-IN) of the esophagus is important for estimating the risk of progression to invasive carcinoma. Discrimination between LG-IN and HG-IN, or neoplasia and non-neoplastic lesion (NNL), however, is occasionally difficult. This study was designed to evaluate whether cytokeratin expression can be used for discrimination of these lesions. Esophageal Iodine-unstained lesions (n=154), less than 10 mm, were classified into HG-IN, LG-IN, and NNL. These lesions together with 154 foci of normal esophageal epithelium (NEE) were examined by immunohistochemistry for cytokeratins (CK4 and CK13), p53 overexpression, and the MIB-1 labeling index. The ratios of CK4- and CK13-positive staining were scored from 1 to 3. The CK4- and CK13-positive staining ratios were decreased in NNL (73% and 78%), LG-IN (55% and 69%), and HG-IN (33% and 48%), compared to NEE (91% and 95%). The differences between LG-IN and HG-IN, neoplasia and NNL, and among these three lesions and NEE were statistically significant (p < 0.005). The cytokeratin scores correlated with the MIB-1 labeling index (both: p < 0.0001), but not with p53 overexpression. CK4 and CK13 immunohistochemistry could be an objective method for evaluating the risk for progression to invasive carcinoma.

  17. Loss of ELF3 immunoexpression is useful for detecting oral squamous cell carcinoma but not for distinguishing between grades of epithelial dysplasia.

    PubMed

    AbdulMajeed, Ahmad A; Dalley, Andrew J; Farah, Camile S

    2013-08-01

    Early diagnosis and targeted therapy are crucial to mitigating the morbidity and mortality of oral squamous cell carcinoma. Among the potentially malignant oral disorders, epithelial dysplasia has known association with malignant transformation, but defensible gradation of dysplasia severity presents unmet challenges. Published microarray data has denoted dysregulation of CLSP, ELF3, IFI44, USP18, and CXCL13 genes in potentially malignant oral disorders. The present study investigated the diagnostic potential of these gene products to grade oral epithelial dysplasia severity. Archived biopsies from independent patient cohorts comprised "training" (n=107) and "test" (n=278) sample sets. Immunoreactivity for candidate markers was determined in the "training" set of normal oral mucosa (NOM), mild dysplasia (MD), moderate to severe dysplasia, and oral squamous cell carcinoma (OSCC). The diagnostic potential of ELF3 immunoscoring to improve detection and severity gradation of epithelial dysplasia was assessed with the "test" set. A reciprocal relationship between disease severity and immunoreactivity score for CLSP and ELF3 was observed (MD/NOM to OSCC: P<.08, Mann-Whitney U test), whereas elevated IFI44 immunostaining was present for OSCC compared to MD/NOM (P<.08, Mann-Whitney U test). Loss of ELF3 immunostaining effectively distinguished OSCC from non-malignant tissues (sensitivity=0.81; specificity=0.56; area under the curve [AUC]=0.68) but did not distinguish dysplasia from NOM (sensitivity=0.55; specificity=0.40; AUC=0.47) or moderate to severe dysplasia from MD (sensitivity=0.63; specificity=0.51; AUC=0.57). The results confirm via immunohistochemistry the relevance of published CLSP, ELF3, and IFI44 (but not USP18 or CXCL13) gene expression data to potentially malignant oral lesion severity. Loss of ELF3 immunostaining discriminated OSCC from dysplasia but was unreliable for grading dysplasia severity.

  18. Whence High-Grade Serous Ovarian Cancer.

    PubMed

    Kohn, Elise C; Ivy, S Percy

    2017-01-01

    Our understanding of epithelial ovarian cancer has blossomed, and we now recognize that it is a collection of varied histologic and molecularly different malignancies, many of which may not derive from a true ovarian anatomic precursor. High-grade serous ovarian cancer (HGSOC) is a unique type of epithelial cancer. It is characterized by nearly universal mutation in and dysfunction of p53, genomic instability rather than driver mutations, advanced stage at onset, and probable fallopian tube epithelium origin, with a serous tubal in situ carcinoma precursor. Germline deleterious mutations in BRCA1 and BRCA2, as well as other less prevalent genes involved in DNA repair, such as PALB2 and RAD51c, are associated with its carcinogenesis and may predict susceptibility to classes of treatment agents, including DNA-damaging agents and DNA repair inhibitors. Loss of function of these genes is associated with homologous recombination dysfunction (HRD). It is now recognized that there may be HGSOC with wild-type BRCA1 and BRCA2 with an identifiable HRD phenotype. Such HRD tumors also may be more susceptible to certain classes of treatments and may be phenotypically detectable with a composite molecular biomarker that has been shown to be predictive for response to PARP inhibitors. Use of this new knowledge of the anatomic and molecular background of HGSOC has led to the rational design of novel combinations of treatment classes to create an HRD-like cellular environment and thus drive treatment benefits.

  19. Grades, Coursework, and Student Characteristics in High School Economics

    ERIC Educational Resources Information Center

    Rebeck, Ken; Walstad, William B.

    2015-01-01

    The authors use U.S. public and private high school transcripts to analyze grade distribution patterns in economics courses across student and school characteristics, and compare these grades to those earned in other selected high school courses. Results are reported for the 53 percent of 2009 high school graduates who took a basic economics…

  20. Grades, Coursework, and Student Characteristics in High School Economics

    ERIC Educational Resources Information Center

    Rebeck, Ken; Walstad, William B.

    2015-01-01

    The authors use U.S. public and private high school transcripts to analyze grade distribution patterns in economics courses across student and school characteristics, and compare these grades to those earned in other selected high school courses. Results are reported for the 53 percent of 2009 high school graduates who took a basic economics…

  1. Assessment of diffusion tensor imaging metrics in differentiating low-grade from high-grade gliomas.

    PubMed

    El-Serougy, Lamiaa; Abdel Razek, Ahmed Abdel Khalek; Ezzat, Amani; Eldawoody, Hany; El-Morsy, Ahmad

    2016-10-01

    The aim of this article is to assess diffusion tensor imaging (DTI) metrics in differentiating low-grade from high-grade gliomas. A prospective study was conducted on 35 patients with gliomas who underwent DTI. Gliomas were classified into low-grade and high-grade gliomas. The fractional anisotropy (FA), mean diffusivity (MD), linear coefficient (CL), planar coefficient (CP) and spherical coefficient (CS) of the solid tumoral part and peri-tumoral regions were calculated. There was significant difference (p = 0.001) in MD of the solid tumoral part of low-grade (1.78 ± 0.33 × 10(-3 )mm(2)/s) and high-grade (1.16 ± 0.22 × 10(-3 )mm(2)/s) gliomas. The selection of 1.42 × 10(-3 )mm(2)/s as a cutoff value of MD of the tumoral part was used to differentiate low-grade and high-grade gliomas; the best results were obtained with area under the curve (AUC) of 0.957 and accuracy of 91.4%. There was a significant difference in FA, MD, CP and CS of peri-tumoral regions of both groups with p values of 0.006, 0.042, 0.030 and 0.037, respectively. The cutoff values of MD, FA, CS and CP of the peri-tumoral region used to differentiate low-grade from high-grade gliomas were 1.24, 0.315, 0.726 and 0.321 with AUC of 0.694, 0.773, 0.734 and 0.724 and accuracy of 68.6%, 80.0%, 74.3% and 74.3%, respectively. The combined MD of the solid tumoral part and FA of the peri-tumoral region used to differentiate low-grade from high-grade gliomas revealed AUC of 0.974 and accuracy of 88.6%. We conclude that the combination of MD of the solid tumoral part and FA of the peri-tumoral region is a noninvasive method to differentiate low-grade from high-grade gliomas. © The Author(s) 2016.

  2. Richter syndrome and brain involvement: low-grade lymphoma relapsing as cerebral high-grade lymphoma.

    PubMed

    Stuplich, Moritz; Mayer, Karin; Kim, Young; Thanendrarajan, Sharmilan; Simon, Matthias; Schäfer, Niklas; Glas, Martin; Schmidt-Wolf, Ingo G H; Herrlinger, Ulrich

    2012-01-01

    Richter syndrome (RS) describes the development of high-grade non-Hodgkin's lymphoma (NHL) from low-grade NHL. RS isolated to the brain is very rare and has a poor prognosis. We describe the cases of high-grade large B-cell diffuse NHL in a 56-year-old male with chronic lymphocytic leukemia and in a 71-year-old female with previously unknown low-grade NHL, both with initial appearance of neurological symptoms. This report extends the literature of central nervous system RS and particularly highlights the importance of a thorough diagnostic evaluation of patients with low-grade NHL presenting with neurological symptoms. Copyright © 2011 S. Karger AG, Basel.

  3. Performance of Aptima and Cobas HPV testing platforms in detecting high-grade cervical dysplasia and cancer.

    PubMed

    Ge, Yimin; Christensen, Paul; Luna, Eric; Armylagos, Donna; Schwartz, Mary R; Mody, Dina R

    2017-08-01

    Human papillomavirus (HPV) tests and genotyping have been used in clinical risk assessment. The purpose of this study was to analyze the performance of 2 common HPV testing platforms in detecting high-grade cervical lesions (high-grade squamous intraepithelial lesion [HSIL] or worse [≥HSIL]). Between January 1 and December 31, 2015, 2041 Papanicolaou (Pap) tests with biopsy confirmation were analyzed along with HPV tests performed on Cobas or Aptima platforms. A biopsy diagnosis of grade 2 cervical intraepithelial neoplasia was confirmed with p16/Ki-67 immunohistochemistry. In total, 1866 and 175 Pap cases were tested on Cobas and Aptima platforms, respectively. Both platforms were highly sensitive (97% for both) for biopsy-confirmed ≥HSIL. Cobas HPV testing had higher positive rates for the diagnosis of benign lesions (84% vs 51%) and low-grade squamous intraepithelial lesions (89% vs 63%) on biopsy compared with Aptima. Aptima testing had significantly higher specificity for ≥HSIL than Cobas (41% vs 13%; P < .0001). Overall, performance of the Aptima platform was superior to that of the Cobas platform in detecting biopsy-confirmed ≥HSIL, resulting from its significantly higher positive predictive value (25% vs 16%; P < .03) and overall accuracy (50% vs 26%; P < .0001). Although both the Cobas and Aptima platforms offer highly sensitive tests for high-grade cervical lesions, Aptima HPV testing demonstrated significantly higher specificity and positive predictive value than Cobas testing for biopsy-confirmed ≥HSIL. The considerable difference may be related to the significant increase in E6/E7 expression after HPV DNA integration. The significantly higher specificity and overall accuracy of Aptima testing for ≥HSIL, resulting in the identification of high-risk populations that require immediate treatment and close follow-up, may prove useful in clinical risk stratification. Cancer Cytopathol 2017;125:652-7. © 2017 American Cancer Society. © 2017

  4. Terahertz reflectometry imaging for low and high grade gliomas

    PubMed Central

    Ji, Young Bin; Oh, Seung Jae; Kang, Seok-Gu; Heo, Jung; Kim, Sang-Hoon; Choi, Yuna; Song, Seungri; Son, Hye Young; Kim, Se Hoon; Lee, Ji Hyun; Haam, Seung Joo; Huh, Yong Min; Chang, Jong Hee; Joo, Chulmin; Suh, Jin-Suck

    2016-01-01

    Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes. PMID:27782153

  5. Terahertz reflectometry imaging for low and high grade gliomas

    NASA Astrophysics Data System (ADS)

    Ji, Young Bin; Oh, Seung Jae; Kang, Seok-Gu; Heo, Jung; Kim, Sang-Hoon; Choi, Yuna; Song, Seungri; Son, Hye Young; Kim, Se Hoon; Lee, Ji Hyun; Haam, Seung Joo; Huh, Yong Min; Chang, Jong Hee; Joo, Chulmin; Suh, Jin-Suck

    2016-10-01

    Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes.

  6. The clinical application of HPV E6/E7 mRNA testing in triaging women with atypical squamous cells of undetermined significance or low-grade squamous intra-epithelial lesion Pap smear: A meta-analysis.

    PubMed

    Yang, Li; Zhu, Yuanhang; Bai, Yang; Zhang, Xiaoan; Ren, Chenchen

    2017-01-01

    The aim is to evaluate the clinical application value and correlation with cervical lesions' progression of human papillomavirus (HPV) E6/E7 mRNA test in women with atypical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intraepithelial lesions (LSILs/mild dyskaryosis) cytological abnormalities. A meta-analysis was conduct by searching China National Knowledge Infrastructure (1979-2016), Wanfang Date (1998-2016), VIP (1989-2016), PubMed (1950-2016), Web of Science (1950-2016) and Elsevier Science Direct (1998-2016), for studies on effect of HPV E6/E7 mRNA detection in women with ASCUS/LSIL/dyskaryosis. Study selection and appraisal were conducted independently by three authors, according to inclusive and exclusive criteria. Then, a meta-analysis was performed using the RevMan4.2 software. The subgroups analysis was conducted according to women's initial HPV DNA test results. Six articles with a total of 1024 subjects were included in the study. It was concluded that a positive HPV E6/E7 mRNA tested result have a higher risk of progressing to CIN2+ in future 2 years than a negative result. The pooled relative risk (RR) is 3.08, (95% confidence interval [CI] = 1.57-6.07, P < 0.05). The same situation was also observed in the subgroup of HPV DNA tested positive group and HPV DNA tested unlimited group. The pooled RR value of the two subgroups was, respectively, 1.98, (95% CI = 1.19-1.19, P < 0.05) and 7.58, (95% CI = 3.64-3.64, P < 0.05). A positive HPV E6/E7 mRNA testing result suggested the women with ASCUS, or LSIL Pap smear was in a truly dangerous position, which is an adverse prognostic factor. It suggested that cervical lesions stay in a progressing status and these women should be referred for colposcopy and strengthen follow-up promptly. Whereas, women with a negative HPV E6/E7 mRNA testing result can increase follow-up interval, by comprehensively considering their situation, thus, avoiding unnecessary colposcopy and

  7. Comparison of Linear Array and Line Blot Assay for Detection of Human Papillomavirus and Diagnosis of Cervical Precancer and Cancer in the Atypical Squamous Cell of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study▿

    PubMed Central

    Castle, Philip E.; Gravitt, Patti E.; Solomon, Diane; Wheeler, Cosette M.; Schiffman, Mark

    2008-01-01

    We evaluated Linear Array (LA), a newly commercialized PGMY09/11 L1 consensus primer PCR test that detects 37 human papillomavirus (HPV) genotypes by reverse line blot hybridization, for the detection of individual HPV genotypes and carcinogenic HPV and its clinical performance for detecting 2-year cumulative cervical precancer and cancer using archived specimens from the Atypical Squamous Cell of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion Triage Study. LA testing was conducted on enrollment specimens from women referred because of an ASCUS Pap test. To gauge the performance of the new test, the results were compared to those of its prototype predecessor assay, Line Blot Assay (LBA), restricted to paired results (n = 3,335). LA testing was done masked to LBA results and clinical outcomes. The results of LA and LBA testing were compared for detection of carcinogenic HPV and clinical outcomes of cervical precancer and cancer. Overall, 50% and 55% of the women tested positive for carcinogenic HPV by LBA and LA, respectively (P < 0.0001). The percent agreement for carcinogenic HPV detection was 88%, percent positive agreement was 80%, and kappa was 0.76 for detection of carcinogenic HPV by the two assays. There was a significant increase in detection by LA for most of the 37 HPV genotypes targeted by both assays, including for 13 of 14 carcinogenic HPV genotypes. LA detected more multiple-genotype infections for all HPV genotypes among HPV-positive women (P < 0.0001) and for carcinogenic HPV genotypes among carcinogenic-HPV-positive women (P < 0.0001). LA was more sensitive (92.3% versus 87.1%; P = 0.003) and less specific (48.2% versus 54.0%; P < 0.0001) than LBA for 2-year cumulative cervical precancer and cancer as diagnosed by the Pathology Quality Control Group. In conclusion, we found LA to be a promising assay for the detection of HPV genotypes and carcinogenic HPV, and it may be clinically useful for the detection of

  8. Comparison of linear array and line blot assay for detection of human papillomavirus and diagnosis of cervical precancer and cancer in the atypical squamous cell of undetermined significance and low-grade squamous intraepithelial lesion triage study.

    PubMed

    Castle, Philip E; Gravitt, Patti E; Solomon, Diane; Wheeler, Cosette M; Schiffman, Mark

    2008-01-01

    We evaluated Linear Array (LA), a newly commercialized PGMY09/11 L1 consensus primer PCR test that detects 37 human papillomavirus (HPV) genotypes by reverse line blot hybridization, for the detection of individual HPV genotypes and carcinogenic HPV and its clinical performance for detecting 2-year cumulative cervical precancer and cancer using archived specimens from the Atypical Squamous Cell of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion Triage Study. LA testing was conducted on enrollment specimens from women referred because of an ASCUS Pap test. To gauge the performance of the new test, the results were compared to those of its prototype predecessor assay, Line Blot Assay (LBA), restricted to paired results (n = 3,335). LA testing was done masked to LBA results and clinical outcomes. The results of LA and LBA testing were compared for detection of carcinogenic HPV and clinical outcomes of cervical precancer and cancer. Overall, 50% and 55% of the women tested positive for carcinogenic HPV by LBA and LA, respectively (P < 0.0001). The percent agreement for carcinogenic HPV detection was 88%, percent positive agreement was 80%, and kappa was 0.76 for detection of carcinogenic HPV by the two assays. There was a significant increase in detection by LA for most of the 37 HPV genotypes targeted by both assays, including for 13 of 14 carcinogenic HPV genotypes. LA detected more multiple-genotype infections for all HPV genotypes among HPV-positive women (P < 0.0001) and for carcinogenic HPV genotypes among carcinogenic-HPV-positive women (P < 0.0001). LA was more sensitive (92.3% versus 87.1%; P = 0.003) and less specific (48.2% versus 54.0%; P < 0.0001) than LBA for 2-year cumulative cervical precancer and cancer as diagnosed by the Pathology Quality Control Group. In conclusion, we found LA to be a promising assay for the detection of HPV genotypes and carcinogenic HPV, and it may be clinically useful for the detection of

  9. MRI characteristics associated with high-grade myxoid liposarcoma.

    PubMed

    Gimber, L H; Montgomery, E A; Morris, C D; Krupinski, E A; Fayad, L M

    2017-07-01

    To identify magnetic resonance imaging (MRI) features differentiating high-grade (>5% round-cell component) from low-grade myxoid liposarcomas (LPS) (≤5% round-cell component). Informed consent was waived. Patients with myxoid LPS and MRI before biopsy, neoadjuvant therapy, and surgery were included retrospectively. High-grade components were recorded from histological specimens by a pathologist (24 years of experience). Images were evaluated by a senior radiologist (>12 years of experience) for tumour size, location, tissue layer, and MRI features (signal intensity, heterogeneity, margin, and perilesional characteristics). Descriptive statistics, Fisher's exact test to identify associations with a round-cell component, and multivariate logistic regression to identify independent predictors of high-grade tumours were used. Thirty-one patients (16 women [mean 51.1 years; range 19-79 years] and 15 men [mean 45.5 years; range 18-95 years]) with myxoid LPS (23 low-grade, eight high-grade) were included. All high-grade lesions had lipid signal, a peritumoural capsule and peritumoural contrast enhancement, and more commonly exhibited heterogeneous signal; however, the average size of ≥10 cm was the strongest independent indicator of high-grade status (odds ratio [OR], 14.6; 95% confidence interval [CI]: 1.6, 131). Size ≥10 cm is most strongly associated with high-grade myxoid LPS (round-cell component >5%). Other features possibly differentiating high-grade from low-grade status include lesion margin, lipid signal, and perilesional characteristics. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  10. High-grade invasive urothelial carcinoma of the ureter with systematic lymph node metastasis successfully treated by nephroureterectomy followed by chemotherapy

    PubMed Central

    Liu, Zhu-Qing; Zhang, Xi; Xu, Qing

    2015-01-01

    We report a case of high-grade invasive urothelial carcinoma with squamous differentiation of the urinary tract. A 72-year-old woman was referred to our hospital because of asymptomatic gross hematuria. A right-sided laparoscopic radical nephroureterectomy with bladder cuff removal and right-sided pelvic lymphadenectomy were performed at our institution. Postoperative pathological examination showed high-grade urothelial carcinoma with squamous differentiation. Five months later, CT scan of the neck diagnosed it as lymph nodes metastasis. Following the laparoscopic radical nephroureterectomy, chemotherapy with gemcitabine and cisplatin or nedaplatin was carried out. After several cycles’ chemotherapy, nearly all the enlarged lymph node disappeared. Seven years and five years passed, urothelial carcinoma has not recurred after the surgery and all the lymph node disappeared respectively. PMID:25932275

  11. Evaluation of myeloid cells (tumor-associated tissue eosinophils and mast cells) infiltration in different grades of oral squamous cell carcinoma

    PubMed Central

    Debta, Priyanka; Debta, Fakir Mohan; Chaudhary, Minal; Bussari, Smita

    2016-01-01

    Background: The multifunctional involvement and infiltration of myeloid cells (tumor-associated tissue eosinophils [TATE] and mast cells) can provide a unique opportunity to define relevant effectors functions that may represent novel, therapeutic options for modulation of tumor onset/growth. Aim: Our study aimed to evaluate infiltration of myeloid cells (TATE and Mast cells) infiltration in different grades (WHO grading) of oral squamous cell carcinoma (OSCC). Materials and Methods: Total 30 cases of OSCC were selected for this study. Hematoxylin and eosin stain and toluidine blue special stain, to evaluate TATE and the mast cells infiltration, were used. Three-year follow-up of OSCC cases was done. Result: Among 30 cases, 63.33% cases of OSCC showed TATE-positive and 36.66% cases showed TATE-negative. Regarding mast cells infiltration, 66.66% OSCC cases showed mast cells positive and 33.33% cases did not show significant mast cells infiltration. We found significant association of TATE and mast cells infiltration in OSCC cases. These myeloid cells infiltration significantly associated with age of patients but did not show any significant association with gender, site, and habit of cases. When we compared these cells infiltration with clinical stages and different histological grades of tumor, we found their infiltration is decreasing, from Stages 1 to Stage 3 of tumor and from well to poorly differentiated carcinoma. We have also found the less infiltration of these myeloid in recurrence cases of OSCC. Conclusion: As the infiltration of TATE and mast cells are correlated, along with evaluation of TATE, we should also evaluate the presence of mast cells infiltration in OSCC. The assessment of myeloid cells could become, in the future, useful for therapeutic approaches in this subset of the patient. PMID:27688609

  12. Middle Grades and High Schools Use Effective Strategies to Prepare Students for Challenging High School Studies.

    ERIC Educational Resources Information Center

    Southern Regional Education Board (SREB), 2011

    2011-01-01

    Middle grades schools have their hands full in working with elementary schools and high schools to improve the likelihood of success for middle grades students--accelerating learning, helping elementary students move seamlessly into the middle grades, preparing middle grades students for rigorous high school courses, changing organization and…

  13. Prevalence of Human Papillomavirus Genotypes Among Women With High-Grade Cervical Lesions in Beijing, China.

    PubMed

    Xiao, Meizhu; Xu, Qiuxiang; Li, Hongyan; Gao, Huiqiao; Bie, Yachun; Zhang, Zhenyu

    2016-01-01

    The aim of the study is to investigate the prevalence of high-risk human papillomavirus (hr-HPV) genotypes among Han women with high-grade cervical lesions in Beijing, China.Cervical cell specimens from patients with histopathologically confirmed cervical lesions at 7 hospitals in Beijing were examined with a validated HPV kit for 13 hr-HPV genotypes during the study period. The patients were divided into a low-grade cervical lesions group (cervical intraepithelial neoplasia grade 1, CIN1) and a high-grade cervical lesions group (CIN2+, including cervical intraepithelial neoplasia grade 2, CIN2; cervical intraepithelial neoplasia grade 3, CIN3; squamous cervical cancer, SCC; and adenocarcinoma of the cervix, ACC) based on the histopathology results.A total of 2817 eligible patients were enrolled, including 610 cases identified as CIN1 and 2207 as CIN2+. The hr-HPV positive rates in the CIN1 and CIN2+ groups were 78.2% (477/610) and 93.3% (2060/2207), respectively. The most frequently detected genotypes were HPV16, 58, 52 and18 in the CIN1 group and HPV16, 58, 33, and 52 in the CIN2+ group, in descending order of prevalence. In addition, the prevalence of HPV18 among the patients with ACC was 28.6% (14/49), significantly >7.2% (54/752) prevalence among the SCC patients (P < 0.001). Additionally, significantly more women in the CIN2+ group had multiple infections compared with those in the CIN1 group (38.1% and 24.9%, respectively; P < 0.001). However, as the cervical lesion grade increased, the prevalence of multiple hr-HPV infections gradually deceased to 44.2% in the CIN2 patients, 36.7% in the CIN3 patients, and 35.3% in the cervical cancer (CC) patients, which included SCC and ACC patients. In cases of multiple hr-HPV infections in the CIN2+ group, double infections accounted for ∼76.6%, and HPV16+58, HPV16+52, and HPV16+18 were the most common combinations, in descending order. The most frequent combination for triple infections was HPV16+58+31, with

  14. High dose rate brachytherapy in early stage squamous-cell carcinoma of the lip.

    PubMed

    Mut, Alejandro; Guinot, José Luis; Arribas, Leoncio; Díez-Presa, Lorena; Tortajada, María Isabel; Santos, Miguel Ángel; Samper, Josefa; Santamaría, Paula; Vendrell, Juan Bosco

    2016-01-01

    To analyze the results obtained after treatment of early stage (T1-T2) squamous cell carcinoma of the lip with high dose rate brachytherapy and evaluate the efficacy of this treatment in both local and regional control. Retrospective analysis of the treatments performed at our department from March 1999 to March 2013 with high dose rate brachytherapy with rigid needles. We included 68 patients, 63 men and 5 women; 37 patients (54.4%) presented a T1 tumour, less than or equal to 2cm, while the other 31 (45.6%) were classified as T2. Median total dose was 45Gy, with a median dose per fraction of 5Gy x 9 fractions twice a day for 5 days. With a mean follow-up of 56.4 months, local control was 96.9%. Stratifying by tumour size, local control of T1 cases was 100%, while T2 achieved 93.2% (2 local recurrences). Regional control at 5 years was 93.8% for T1, and 80.8% for T2. In 11 cases with elective cervical treatment, no regional failure happened. As for toxicity, no patient presented soft tissue, or bone, necrosis. All patients achieved good or excellent cosmetic and functional results. High dose rate brachytherapy allows effective, safe treatments for squamous cell carcinoma of the lip, with good aesthetic and functional results. It can be considered a valid alternative for surgery in early stage tumours. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  15. Nuclear fractal dimension in oral squamous cell carcinoma: a novel method for the evaluation of grading, staging, and survival.

    PubMed

    Mincione, Gabriella; Di Nicola, Marta; Di Marcantonio, Maria Carmela; Muraro, Raffaella; Piattelli, Adriano; Rubini, Corrado; Penitente, Enrico; Piccirilli, Marcello; Aprile, Giuseppe; Perrotti, Vittoria; Artese, Luciano

    2015-10-01

    Fractal dimension (FD) in tissue specimens from patients with oral squamous cell carcinoma (OSCC) was evaluated. FD values in different stages of OSCC, and the correlations with clinicopathological variables and patient survival were investigated. Histological sections from OSCC and control non-neoplastic mucosa specimens were stained with hematoxylin-eosin for pathological analysis and with Feulgen for nuclear evaluation. FD in OSCC groups vs. controls revealed statistically significant differences (P < 0.001). In addition, a progressive increase of FD from stage I and II lesions and stage III and IV lesions was observed, with statistically significant differences (P = 0.003). Moreover, different degrees of tumor differentiation showed a significant difference in the average nuclear FD values (P = 0.001). A relationship between FD and patients' survival was also detected with lower FD values associated to longer survival time and higher FD values with shorter survival time (P = 0.034). These data showed that FD significantly increased during OSCC progression. Thus, FD could represent a novel prognostic tool for OSCC, as FD values significantly correlated with patient survival. Fractal geometry could give insights into tumor morphology and could become an useful tool for analyzing irregular tumor growth patterns. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

    NASA Astrophysics Data System (ADS)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Lombardi, Welington; da Silva, Eduardo V.; Belotto, Renata; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-02-01

    Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer and associated with human papillomavirus (HPV) infection. Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors. PDT is based on the accumulation of a photosensitizer in target cells that will generate cytotoxic reactive oxygen species upon illumination, inducing the death of abnormal tissue and PDT with less damaging to normal tissues than surgery, radiation, or chemotherapy and seems to be a promising alternative procedure for CIN treatment. The CIN high grades (II and III) presents potential indications for PDT due the success of PDT for CIN low grade treatment. The patients with CIN high grade that were treated with new clinic protocol shows lesion regression to CIN low grade 60 days after the treatment. The new clinical protocol using for treatment of CIN high grade shows great potential to become a public health technique.

  17. Reliability of Grading High School Work in English

    ERIC Educational Resources Information Center

    Brimi, Hunter M.

    2011-01-01

    This research replicates the work of Starch and Elliot (1912) by examining the reliability of the grading by English teachers in a single school district. Ninety high school teachers graded the same student paper following professional development sessions in which they were trained to use NWREL's "6+1 Traits of Writing." These participants had…

  18. Reliability of Grading High School Work in English

    ERIC Educational Resources Information Center

    Brimi, Hunter M.

    2011-01-01

    This research replicates the work of Starch and Elliot (1912) by examining the reliability of the grading by English teachers in a single school district. Ninety high school teachers graded the same student paper following professional development sessions in which they were trained to use NWREL's "6+1 Traits of Writing." These participants had…

  19. Establishment of an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtaining laryngocarcinoma cells with high metastatic potential.

    PubMed

    Chen, L W; Wang, J L; Zhang, L Y; Yang, S M; Li, C S; Yu, N; Zhao W, J D; Zhao, L D; Li, K; Liu, M B; Zhai, S Q

    2013-01-01

    To establish an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtain laryngocarcinoma cells with high metastatic potential, laryngeal squamous cell carcinoma cell line HEP-2 in logarithmic phase were inoculated under the lingual margin mucosa of nude mice. HEP-2 cells metastasized to the cervical lymph nodes were isolated, cultured, and re-inoculated under the lingual margin mucosa of nude mice twice. The tumor formation in the tongue and in the cervical lymph nodes was confirmed by pathological examination. Carcinoma cells' ability of invasion and migration was detected by transwell assay. Human specific Alu sequences were detected by PCR, which indicated that the tumor cells originated from human laryngeal squamous cell carcinoma cell line HEP-2. Finally, an animal model of spontaneous lymph node metastasis of laryngeal squamous cell carcinoma was successfully established. Laryngeal squamous cell carcinoma cells with high metastatic potential to lymph nodes were obtained through repeated inoculations. .

  20. Endoscopic optical diagnosis provides high diagnostic accuracy of esophageal squamous cell carcinoma

    PubMed Central

    2014-01-01

    Background Recent technological advances have stimulated the development of endoscopic optical biopsy technologies. This study compared the accuracy of endoscopic diagnosis using magnifying narrow-band imaging (NBI) and histologic diagnosis of esophageal squamous lesions. Methods Patients at high risk for esophageal squamous cell carcinoma were examined with endoscopy and subsequent biopsy. The lesions diagnosed as cancer on NBI and the lesions diagnosed as cancer on biopsy were resected endoscopically or surgically. Histological diagnoses of resected specimens, the reference standards in this study, were made by a pathologist who was blind to both the endoscopic and biopsy diagnoses. The primary outcome was the accuracy of endoscopic and biopsy diagnosis. A noninferiority trial design with a noninferiority margin of −10% was chosen to investigate the accuracy of endoscopic diagnosis using magnifying NBI. Results Between November 2010 and October 2012, a total of 111 lesions in 85 patients were included in the analysis. The accuracy of endoscopic diagnosis and biopsy diagnosis for all lesions was 91.0% (101/111) and 85.6% (95/111), respectively. The difference in diagnostic accuracy was 5.4% (95% confidence interval: −2.9%–13.7%). The accuracy of endoscopic diagnosis and biopsy diagnosis of invasive cancers was 94.9% (74/78) and 84.6% (66/78), respectively. The difference was 10.3% (95% confidence interval: 1.6%–19.0%) for invasive cancers. The lower bound of the 95% confidence interval was above the prestated −10% in both cases. Conclusion Noninferiority of endoscopic diagnosis by magnifying NBI to histologic diagnosis by biopsy was established in this study (p = 0.0001). Trial registration The study was registered on 9th November 2010 in the University Hospital Medical Network Clinical Trials Registry as number: UMIN000004529. PMID:25108624

  1. Management of high-grade renal injury in children.

    PubMed

    Okur, M H; Arslan, S; Aydogdu, B; Arslan, M S; Goya, C; Zeytun, H; Basuguy, E; Uygun, I; Çigdem, M K; Önen, A; Otcu, S

    2017-02-01

    The management of severe renal trauma is disputable. Herein, we present diagnosis and treatment of patients with high-grade renal injury (grades IV and V). The records of 31 patients with severe renal trauma who were treated between 2009 and 2014 were analyzed retrospectively. All patients' CT results were evaluated by two radiologists and assigned grades of IV or V in accordance with the American Association for the Surgery of Trauma Organ Injury Severity Scale. All hemodynamically stable renal trauma patients were treated conservatively. Patients with renal traumas of grade IV and V were evaluated statistically via the SPSS 15.0 software program. Chi-square and Mann-Whitney U tests were used to evaluate the categorical data. Thirteen (42 %) of 31 patients had grade IV, and 18 (58 %) had grade V renal traumas. Twenty-seven (87 %) of the patients had suffered blunt trauma, and four (13 %) had sustained penetrating injuries. Additional organ injuries were seen in 16 patients (52 %), and 15 (48 %) had no concurrent injuries. Twenty-five patients (89 %) were monitored conservatively, three (10 %) underwent surgery, and three patients with grade V renal trauma and additional organ injuries died. There was no statistically significant difference between the grade IV and grade V groups, except in hemoglobin values and the affected kidney (P = 0.07 and P = 0.02, respectively). Computerized tomography can help to grade renal injury and assess additional organ injuries quickly. Most children with high-grade renal injury can be managed conservatively. However, conservative management of renal traumas relies on a multidisciplinary approach. Additionally, surgical intervention is generally required in the face of hemodynamic instability or other concurrent organ injuries.

  2. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery. ...

  3. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery. ...

  4. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery. ...

  5. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery. ...

  6. 1. Mill exterior, high grade chute partially restored on the ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Mill exterior, high grade chute partially restored on the outside of mill building center of picture. Looking northeast from below bridge. - Kennecott Copper Corporation, Concentration Mill, On Copper River & Northwestern Railroad, Kennicott, Valdez-Cordova Census Area, AK

  7. Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma.

    PubMed

    Zilberg, Catherine; Lee, Matthew Weicai; Yu, Bing; Ashford, Bruce; Kraitsek, Spiridoula; Ranson, Marie; Shannon, Kerwin; Cowley, Mark; Iyer, N Gopalakrishna; Palme, Carsten E; Ch'ng, Sydney; Low, Tsu-Hui Hubert; O'Toole, Sandra; Clark, Jonathan R; Gupta, Ruta

    2017-10-06

    Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalin-fixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer-associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (<45 years). Lower incidences of NOTCH1 mutations were observed compared with that described in metastatic head and neck cutaneous squamous cell carcinoma in the literature. Somatic mutations susceptible to EGFR inhibitors, and other small molecular targeted therapeutics were seen in 60% of cases. This study provides insights into somatic mutations in non-metastatic, high-risk head and neck cutaneous squamous cell carcinoma and identifies potential therapeutic targets. Alterations in FGFR2 and NOTCH1 may have roles in local and distant disease progression.Modern Pathology advance online publication, 6 October 2017; doi:10.1038/modpathol.2017.128.

  8. High-Grading Lunar Samples for Return to Earth

    NASA Technical Reports Server (NTRS)

    Allen, Carlton; Sellar, Glenn; Nunez, Jorge; Winterhalter, Daniel; Farmer, Jack

    2009-01-01

    Astronauts on long-duration lunar missions will need the capability to "high-grade" their samples to select the highest value samples for transport to Earth and to leave others on the Moon. We are supporting studies to defile the "necessary and sufficient" measurements and techniques for highgrading samples at a lunar outpost. A glovebox, dedicated to testing instruments and techniques for high-grading samples, is in operation at the JSC Lunar Experiment Laboratory.

  9. Management of high-risk squamous cell carcinoma of the skin.

    PubMed

    Samarasinghe, Venura; Madan, Vishal; Lear, John T

    2011-05-01

    Cutaneous squamous cell cancer (SCC) is the second most common skin cancer, accounting for one-fifth of all cutaneous malignancies. The majority arise on the head and neck skin, and cumulative UV exposure is thought to be the most likely etiological factor. The majority of deaths from SCC occur in a high-risk subgroup of patients. This high-risk subgroup of patients can be identified as those with tumors greater than 2 cm in diameter; tumor thickness over 4 mm; moderately/poorly differentiated or desmoplastic histological SCC subtype; ear, lip, hand, feet or genital tumor site; presence of perineural or lymphovascular invasion; nodal metastasis at presentation; recurrent SCC; SCC arising from scars or chronic skin disease, for example, chronic ulcers; and SCC arising in immunosuppressed patients. It is important to identify and aggressively treat these patients, as high-risk SCC are associated with a greater mortality and morbidity. This article reviews the diagnosis and management of such high-risk SCC.

  10. Surgical Outcomes of High-Grade Spinal Cord Gliomas

    PubMed Central

    Hida, Kazutoshi; Yano, Syunsuke; Aoyama, Takeshi; Koyanagi, Izumi; Houkin, Kiyohiro

    2015-01-01

    Study Design A retrospective study. Purpose The purpose of this study was to obtain useful information for establishing the guidelines for treating high-grade spinal cord gliomas. Overview of Literature The optimal management of high-grade spinal cord gliomas remains controversial. We report the outcomes of the surgical management of 14 high-grade spinal glioma. Methods We analyzed the outcomes of 14 patients with high-grade spinal cord gliomas who were surgically treated between 1989 and 2012. Survival was charted with the Kaplan-Meier plots and comparisons were made with the log-rank test. Results None of the patients with high-grade spinal cord gliomas underwent total resection. Subtotal resection was performed in two patients, partial resection was performed in nine patients, and open biopsy was performed in three patients. All patients underwent postoperative radiotherapy and six patients further underwent radiation cordotomy. The median survival time for patients with high-grade spinal cord gliomas was 15 months, with a 5-year survival rate of 22.2%. The median survival time for patients with World Health Organization grade III tumors was 25.5 months, whereas the median survival time for patients with glioblastoma multiforme was 12.5 months. Both univariate and multivariate Cox proportional hazards models demonstrated a significant effect only in the group that did not include cervical cord lesion as a factor associated with survival (p=0.04 and 0.03). Conclusions The surgical outcome of patients diagnosed with high-grade spinal cord gliomas remains poor. Notably, only the model which excluded cervical cord lesions as a factor significantly predicted survival. PMID:26713128

  11. Mutations in chromatin machinery and pediatric high-grade glioma

    PubMed Central

    Lulla, Rishi R.; Saratsis, Amanda Muhs; Hashizume, Rintaro

    2016-01-01

    Pediatric central nervous system tumors are the most common solid tumor of childhood. Of these, approximately one-third are gliomas that exhibit diverse biological behaviors in the unique context of the developing nervous system. Although low-grade gliomas predominate and have favorable outcomes, up to 20% of pediatric gliomas are high-grade. These tumors are a major contributor to cancer-related morbidity and mortality in infants, children, and adolescents, with long-term survival rates of only 10 to 15%. The recent discovery of somatic oncogenic mutations affecting chromatin regulation in pediatric high-grade glioma has markedly improved our understanding of disease pathogenesis, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment. We review the current perspective on pediatric high-grade glioma genetics and epigenetics, and discuss the emerging and experimental therapeutics targeting the unique molecular abnormalities present in these deadly childhood brain tumors. PMID:27034984

  12. Low-Grade and High-Grade Mucoepidermoid Carcinoma of the Lung: CT Findings and Clinical Features of 17 Cases.

    PubMed

    Wang, Yiqi Q; Mo, Yunxian X; Li, Sheng; Luo, Rongzhen Z; Mao, Siyue Y; Shen, Jingxian X

    2015-12-01

    The objective of our study was to characterize the CT features and clinical findings of low-grade and high-grade mucoepidermoid carcinoma (MEC) of the lung. The CT findings and clinical information of 17 consecutive patients with primary low-grade (n = 11) or high-grade (n = 6) MEC were analyzed retrospectively. We assessed tumor location, size, contour, margin, density, calcification, obstructive changes, presence of metastasis, and enhancement. In patients with low-grade MEC, tumor location was central in 10 and peripheral in one. In contrast, one and five tumors in patients with high-grade MEC were central and peripheral, respectively. There was a significant difference between central and peripheral locations among tumor grades (p = 0.005). In low-grade MECs, tumor contour was smoothly oval (n = 3) or spheric (n = 4); four were lobular. In five patients with low-grade MEC, tumors had well-defined margins; margins in the other six were poorly defined. Tumor density was homogeneous and heterogeneous in eight and three low-grade tumors, respectively. All six high-grade tumors had heterogeneous density, lobular contours, and poorly defined margins. Enhancement in both low-grade and high-grade tumors was greater than that of chest wall muscles, and low-grade tumors showed greater enhancement (46.90 ± 20.44 HU) than did high-grade tumors (22.50 ± 8.38 HU) (p = 0.015). A markedly enhanced homogeneous central bronchial nodule or mass may suggest low-grade MEC. High-grade MEC tends to be peripheral, to have poorly defined margins, and to be lobular, heterogeneous nodules or masses with less enhancement.

  13. A Comparison of Four Techniques for Producing High-Grade Furniture Core Material From Low-Grade Yellow-Poplar

    Treesearch

    Philip A. Araman

    1978-01-01

    Four Methods of converting low-grade yellow-poplar lumber into high-grade furniture core material (lumber core) were compared. High-grade core material is used in tops, shelves, doors, and drawer fronts and only minor defects are allowed. Three gang-rip first and the conventional crosscut-first manufacturing sequences were evaluated in combination with 1 Common, 2A...

  14. Middle Grades and High Schools Use Effective Strategies to Prepare Students for Challenging High School Studies. High Schools That Work

    ERIC Educational Resources Information Center

    Southern Regional Education Board (SREB), 2011

    2011-01-01

    Middle grades schools have their hands full in working with elementary schools and high schools to improve the likelihood of success for middle grades students--accelerating learning, helping elementary students move seamlessly into the middle grades, preparing middle grades students for rigorous high school courses, changing organization and…

  15. High School Extracurricular Activities & College Grades.

    ERIC Educational Resources Information Center

    Rombokas, Mary; And Others

    Many factors influence the development and socialization of American adolescents including peers, schools, family, and the community. This paper examines how the relationship of extracurricular participation influences academic growth. To determine if selected personal and academic variables during high school currently affect college academic…

  16. Early determination of uterine cervical squamous cell carcinoma radioresponse identifies high- and low-response tumors

    SciTech Connect

    Ohara, Kiyoshi . E-mail: ki-ohara@md.tsukuba.ac.jp; Oki, Akinori; Tanaka, Yumiko Oishi; Onishi, Kayoko; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Satoh, Toyomi; Tsunoda, Hajime; Hata, Masaharu; Sugahara, Shinji; Tokuuye, Koichi; Akine, Yasuyuki; Yoshikawa, Hiroyuki

    2006-03-15

    Purpose: To investigate whether early-assessed radioresponse of tumors corresponds with late-assessed radioresponse, which is associated with local disease control in radiotherapy (RT) for cervical cancer. Methods and Materials: This prospective study included 12 patients with cervical squamous cell carcinoma treated by RT with or without concurrent cisplatin. Tumor volume was estimated by scheduled magnetic resonance imaging before (preRT), 3 to 4 weeks after (early assessment), and 6 to 7 weeks after (late assessment) RT initiation. Radioresponse was assessed with tumor shrinkage curves based on these volumes. Radioresponse for each tumor was calculated as the slope (day{sup -1}) of the shrinkage curve by fitting to an exponential equation. Results: Early-assessed radioresponse ranged from 0.001 to 0.106 day{sup -1} (median, 0.021 day{sup -1}) and late-assessed radioresponse from 0.009 to 0.091 day{sup -1} (median, 0.021 day{sup -1}), with no significant difference between them (p = 0.1191). The early-assessed radioresponse correlated with the late-assessed radioresponse (R {sup 2} = 0.714, p = 0.0005). Conclusions: Correspondence between early- and late-assessed radioresponse in a series of tumors showing a wide range of radioresponse was not particularly close overall. However, early assessment of radioresponsiveness did seem to be useful for characterizing those tumors with high or low radioresponsiveness.

  17. High Proportion of Nuclear Phenotype Identifies Aggressive Cutaneous Squamous Cell Carcinoma.

    PubMed

    Glazer, Evan S; Bartels, Peter H; Liang, Jianming; Prasad, Anil R; Yozwiak, Michael L; Krutzsch, Mary; Clark, Christine; Kha, Stephanie; Bartels, Hubert G; Einspahr, Janine G; Alberts, David S; Krouse, Robert S

    2015-10-01

    To develop a quantitative histopathology algorithm to predict which patients with cutaneous squamous cell carcinoma (cSCC) were likely to experience recurrence or metastases. This retrospective study of cSCC lesions compared patients with aggressive disease (n = 40) and those with nonaggressive disease (n = 35). Based on a previous study using nuclear karyometry, we determined that aggressive lesions had a high proportion of a specific nuclear phenotype. The proportion of those nuclei was used to derive an aggressiveness score for each lesion. The mean age of patients was similar in both groups, as were the locations of index lesions. The mean aggressiveness scorefor cases with aggressive lesions was 0.60 ± 0.21 and was 0.28 ± 0.35 for those with nonaggressive lesions. The overall accuracy in properly characterizing lesions was 72%. The area under the receiver operating characteristic curve was 0.80 ± 0.05. In general, the aggressive nuclear phenotype is represented by elevated levels of chromatin clumps and short linear segments of dark chromatin/intense pixels. These data suggest that discriminant functions may be utilized to distinguish between aggressive and nonaggressive lesions at the time of diagnosis.

  18. Do high-risk human papillomaviruses cause oral cavity squamous cell carcinoma?

    PubMed

    Mirghani, H; Amen, F; Moreau, F; Lacau St Guily, J

    2015-03-01

    High-risk human papillomaviruses (HR-HPV) are an established etiologic factor for a growing number of oropharyngeal cancers. However, their potential role in other upper aerodigestive tract locations is still a matter of debate, particularly in the oral cavity. This is of paramount importance as in the future diagnosis, treatment and follow up in head and neck squamous cell carcinoma may vary according to HPV status. This article reviews the recent published data and highlights some of the pitfalls that have hampered the accurate assessment of HR-HPV oncological role outside the oropharynx. We demonstrate that, in contrast to the oropharynx, only a small fraction of cancers located in the oral cavity seem to be HPV-related even in young non-smoking non-drinking patients. We emphasize several relevant factors to consider in assumed HPV-induced oral cavity cancers and discuss the current theories that explain why HPV-induced cancers arise preferentially in the oropharynx. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Restoration of the normal squamous lining in Barrett's esophagus by argon beam plasma coagulation.

    PubMed

    Byrne, J P; Armstrong, G R; Attwood, S E

    1998-10-01

    Barrett's esophagus is associated with significantly increased risk of development of esophageal adenocarcinoma. Replacing columnar epithelium with the normal squamous lining in this condition offers the possibility of decreasing the risk of degeneration to invasive adenocarcinoma. This study aimed to establish the feasibility of argon beam plasma coagulation (ABPC), in conjunction with control of gastroesophageal reflux, to restore the squamous lining. Thirty patients with Barrett's esophagus (four low-grade dysplasia, three high-grade) were recruited from our surveillance program, and underwent endoscopic ABPC. Twenty-seven patients completed treatment, with macroscopic replacement of their columnar lining by squamous epithelium, histologically confirmed in all 27, and followed up for a median of 9 months (range, 6-18 months). Two patterns of squamous replacement were identified: 70% of patients showed squamous epithelium with no persistent intestinal metaplasia, and in 30% the new squamous epithelium covered areas of underlying intestinal metaplasia. One patient has withdrawn from the study. Two esophageal perforations, with one death, occurred early in the study. ABPC, in conjunction with control of gastroesophageal reflux, allows squamous regrowth in both benign and dysplastic Barrett's esophagus. Despite the theoretical safety advantages of ABPC over techniques such as laser, esophageal perforation may occur with this technique. It is too soon to recommend ABPC for dysplastic or nondysplastic Barrett's because follow-up is too short to show a decreased incidence of and mortality from adenocarcinoma.

  20. Review of high-risk features of cutaneous squamous cell carcinoma and discrepancies between the American Joint Committee on Cancer and NCCN Clinical Practice Guidelines In Oncology.

    PubMed

    Skulsky, Samuel Lamarre; O'Sullivan, Barry; McArdle, Orla; Leader, Mary; Roche, Muireann; Conlon, Peter J; O'Neill, James Paul

    2017-03-01

    Cutaneous squamous cell carcinoma (SCC) is a malignancy that arises from epidermal keratinocytes. Although the majority of cutaneous SCC cases are easily treated without further complication, some behave more aggressively and carry a poor prognosis. These "high-risk" cutaneous SCCs commonly originate in the head and neck and have an increased tendency toward recurrence, local invasion, and distant metastasis. Factors for high-risk cutaneous SCC include large size (>2 cm), a deeply invasive lesion (>2 mm), incomplete excision, high-grade/desmoplastic lesions, perineural invasion (PNI), lymphovascular invasion, immunosuppression, and high-risk anatomic locations. Both the National Comprehensive Cancer Network(®) (NCCN(®) ) and the American Joint Committee on Cancer (AJCC) identify several of these high-risk features of cutaneous SCC. The purpose of this article was to review the high-risk features included in these guidelines, as well as their notable discrepancies and omissions. We also provide a brief overview of current prophylactic measures, surgical options, and adjuvant therapies for high-risk cutaneous SCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 578-594, 2017. © 2016 Wiley Periodicals, Inc.

  1. Hormonal contraceptives and the length of their use are not independent risk factors for high-risk HPV infections or high-grade CIN.

    PubMed

    Longatto-Filho, Adhemar; Hammes, Luciano Serpa; Sarian, Luis Otavio; Roteli-Martins, Cecília; Derchain, Sophie F M; Eržen, Mojca; Branca, Margherita; Tatti, Sílvio; Naud, Paulo; de Matos, Jean Carlos; Gontijo, Renata; Maeda, Marina Y S; Lima, Temístocles; Costa, Silvano; Syrjänen, Stina; Syrjänen, Kari

    2011-01-01

    To evaluate the role of hormonal contraceptives as a risk factor of high-risk human papillomavirus (HR-HPV), cervical intraepithelial lesions (CIN) and cervical cancer in our multi-center population-based LAMS (Latin American Screening) study. A cohort study with >12,000 women from Brazil and Argentina using logistic regression to analyze the covariates of hormonal contraception (HOC - oral, injections, patches, implants, vaginal ring and progesterone intrauterine system) use followed by multivariate modeling for predictors of HR-HPV and CIN2+. HR-HPV infection was a consistent risk factor of high-grade CIN in all three groups of women. The length of HOC use was not significantly related to high-grade squamous intraepithelial lesions (HSIL)+ Pap (p = 0.069), LSIL+ Pap (p = 0.781) or ASCUS+ (p = 0.231). The same was true with the length of HOC use and histology CIN3+ (p = 0.115) and CIN2+ (p = 0.515). Frequently, HOC users have previously shown more HPV-related lesions, as well as lower HPV prevalence if they were current smokers. But HOC use and time of usage were not independent risk factors of either HR-HPV infection or high-grade CIN using multiple logistic regressions. No evidence was found for an association between the use of HOC with an increased risk for HR-HPV infection or high-grade CIN in this cohort. Copyright © 2010 S. Karger AG, Basel.

  2. High Expression of GOLPH3 in Esophageal Squamous Cell Carcinoma Correlates with Poor Prognosis

    PubMed Central

    Zheng, Min; Deng, Jian-Ming; Wang, Ming-Zhi; Lin, Huan-Xin; Chen, Kun; Li, Jun; Yun, Jing-Ping; Luo, Rong-Zhen; Song, Li-Bing

    2012-01-01

    Background Whether the expression of Golgi phosphoprotein 3 (GOLPH3) correlates with esophageal cancer tumorigenesis is currently unclear. The aim of this study was to examine GOLPH3 expression in patients with esophageal squamous cell cancer (ESCC) and explore its clinical significance. Methods Differences in the expression of GOLPH3 at the mRNA and protein level were examined via quantitative reverse transcriptase PCR and western blotting, respectively. GOLPH3 expression levels in ESCC tissue were determined through immunohistochemistry, and were compared in accordance with specific clinicopathological features of the patients and tissue specimens. Factors associated with patient survival were also analyzed. Results A notably higher level of GOLPH3 expression was found in ESCC cell lines and tissues at both mRNA and protein levels. High expression of GOLPH3 in ESCC patients was positively associated with clinical stage, TNM classification, histological differentiation and vital status (all P<0.0001). Expression of GOLPH3 was found to be an independent prognostic factor in ESCC patients. ESCC patients expressing high levels of GOLPH3 exhibited a substantially lower 5-year overall survival than GOLPH3-negative patients. Furthermore, a significant correlation between high GOLPH3 expression and shorter overall survival time was found in different subgroups of ESCC patients stratified by the clinical stage, T classification, and lymph node metastasis. Conclusions Experiments demonstrated potential involvement of GOLPH3 in the development, differentiation, and tumorigenesis of ESCC, and concludes the possibility of its use as a diagnostic and prognostic marker in patients with ESCC. PMID:23056210

  3. Rituximab in high-grade lymphoma.

    PubMed

    Zwick, Carsten; Murawski, Niels; Pfreundschuh, Michael

    2010-04-01

    In 1997, the approval of the anti-CD20 antibody rituximab heralded a new era of combined immunochemotherapy for the treatment of malignant lymphoma. Until then, a combination of cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) had been the standard of treatment for aggressive B-cell lymphoma for more than 25 years. The addition of rituximab led to an impressive improvement of response rates and survival outcomes in patients with follicular and diffuse large B-cell lymphoma (DLBCL) that has been confirmed in several randomized trials. Remaining challenges in the rituximab era are the identification of the optimal chemotherapy partner with respect to synergistic effects, as well as to the lack of interference with its effector mechanisms. Finally, the question of the optimal dosage and schedule of rituximab has to be addressed in well-designed randomized trials. The outcome of patients relapsing after a rituximab-containing induction regimen is dismal even with high-dose therapy and autologous stem cell transplantation (ASCT). For these patients new modalities of second-line therapy are urgently warranted.

  4. Stathmin-1 expression as a complement to p16 helps identify high-grade cervical intraepithelial neoplasia with increased specificity.

    PubMed

    Howitt, Brooke E; Nucci, Marisa R; Drapkin, Ronny; Crum, Christopher P; Hirsch, Michelle S

    2013-01-01

    A fundamental controversy in using biomarkers to diagnose cervical cancer precursors [ie, squamous intraepithelial lesions (SIL)] is their lack of specificity for high-grade SIL [HSIL; cervical intraepithelial neoplasia grade 2/3 (CIN2/3)]. Stathmin-1 (STMN), a microtubule-destabilizing protein important in mitosis, is overexpressed in a variety of malignancies including those from the Müllerian tract and may be associated with poor outcome. However, the use of STMN as a diagnostic marker in cervical SILs has not been explored. A total of 193 cervical samples, including benign cervix and squamous and glandular lesions, were evaluated for STMN, p27 (a known cell cycle regulator inversely expressed with STMN in normal and many neoplastic tissues), p16, and Ki67 expression by immunohistochemical analysis. SILs were independently scored and classified as benign, low-grade SIL (LSIL/CIN1), and HSIL (separated into CIN2 or CIN3) on the basis of a majority diagnosis. Each diagnosis was correlated with biomarker expression independent of hematoxylin and eosin review. STMN was normally expressed in basal cells of the ectocervix and was absent in benign endocervix;"positive" STMN staining was defined as immunoreactivity in at least two thirds of the epithelial thickness. A majority hematoxylin and eosin diagnosis was obtained in 189/193 cases on initial independent review, with squamous epithelia ultimately classified as benign, CIN1, CIN2, and CIN3 in 25, 56, 11, and 16 cases, respectively. STMN was positive in 5/56 (9%) CIN1, 5/11 (45%) CIN2, 14/15 (93%) CIN3, all adenocarcinoma in situ (19/19), and all invasive squamous cell carcinoma (32/32) and adenocarcinoma (34/34) cases. In contrast, 40/56 (71%) CIN1, 11/11 (100%) CIN2, and 15/16 (94%) CIN3 lesions were p16 positive (defined as diffuse block staining in at least one third of the epithelial thickness). One CIN3 was negative for both p16 and STMN. Ki67 and p27 staining was variable in squamous lesions. These results

  5. Successful Nonoperative Management of High-Grade Blunt Renal Injuries

    PubMed Central

    Darwish, Oussama; Dang, Brian; Monda, John J.; Adsul, Prajakta; Syed, Johar; Siddiqui, Sameer A.

    2016-01-01

    Current management of high-grade blunt renal trauma favors a nonoperative approach when possible. We performed a retrospective study of high grade blunt renal injuries at our level I trauma center to determine the indications and success of nonoperative management (NOM). 47 patients with blunt grade IV or V injuries were identified between October 2004 and December 2013. Immediate operative patients (IO) were compared to nonoperatively managed (NOM). Of the 47 patients, 3 (6.4%) were IO and 44 (95.6%) NOM. IO patients had a higher heart rate on admission, 133 versus 100 in NOM (P = 0.01). IO patients had a higher rate of injury to the renal vein or artery (100%) compared to NOM group (18%) (P = 0.01). NOM failed in 3 of 44 patients (6.8%). Two required nonemergent nephrectomy and one required emergent exploration resulting in nephrectomy. Six NOM patients had kidney-related complications (13.6%). The renal salvage rate for the entire cohort was 87.2% and 93.2% for NOM. Nonoperative management for hemodynamically stable patients with high-grade blunt renal trauma is safe with a low risk of complications. Management decisions should consider hemodynamic status and visualization of active renal bleeding as well as injury grade in determining operative management. PMID:28018427

  6. Risk-scoring models for individualized prediction of overall survival in low-grade and high-grade endometrial cancer

    PubMed Central

    AlHilli, Mariam M.; Mariani, Andrea; Bakkum-Gamez, Jamie N.; Dowdy, Sean C.; Weaver, Amy L.; Peethambaram, Preema P.; Keeney, Gary L.; Cliby, William A.; Podratz, Karl C.

    2015-01-01

    Objective Overall survival (OS) in endometrial cancer (EC) is dependent on patient-, disease-, and treatment-specific risk factors. Comprehensive risk-scoring models were developed to estimate OS in low-grade and high-grade EC. Methods Patients undergoing primary surgery for EC from 1999 through 2008 were stratified histologically according to the International Federation of Gynecology and Obstetrics (FIGO) as either (i) low grade: grades 1 and 2 endometrioid EC or (ii) high grade: grade 3, including non-endometrioid EC. Associations between patient-, pathological-, and treatment-specific risk factors and OS starting on postoperative day 30 were assessed using multivariable Cox regression models. Factors independently associated with OS were used to construct nomograms and risk-scoring models. Results Eligible patients (N= 1281) included 925 low-grade and 356 high-grade patients; estimated 5-year OSs were 87.0% and 51.5%, respectively. Among patients alive at last follow-up, median follow-up was 5.0 (low grade) and 4.6 years (high grade), respectively. In low-grade patients, independent factors predictive of compromised OS included age, cardiovascular disease, pulmonary dysfunction, stage, tumor diameter, pelvic lymph node status, and grade 2 or higher 30-day postoperative complications. Among high-grade patients, age, American Society of Anesthesiologists score, stage, lymphovascular space invasion, adjuvant therapy, para-aortic nodal status, and cervical stromal invasion were independent predictors of compromised OS. The two risk-scoring models/nomograms had excellent calibration and discrimination (unbiased c-indices = 0.803 and 0.759). Conclusion Patients with low-grade and high-grade EC can be counseled regarding their predicted OS using the proposed risk-scoring models. This may facilitate institution of personalized treatment algorithms, surveillance strategies, and lifestyle interventions. PMID:24690476

  7. Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

    PubMed Central

    Tan, Guangguo; Wang, Haibo; Yuan, Jianlin; Qin, Weijun; Dong, Xin; Wu, Hong; Meng, Ping

    2017-01-01

    To address the shortcomings of cystoscopy and urine cytology for detecting and grading bladder cancer (BC), ultrahigh performance liquid chromatography (UHPLC) coupled with Q-TOF mass spectrometry in conjunction with univariate and multivariate statistical analyses was employed as an alternative method for the diagnosis of BC. A series of differential serum metabolites were further identified for low-grade(LG) and high-grade(HG) BC patients, suggesting metabolic dysfunction in malignant proliferation, immune escape, differentiation, apoptosis and invasion of cancer cells in BC patients. In total, three serum metabolites including inosine, acetyl-N-formyl-5-methoxykynurenamine and PS(O-18:0/0:0) were selected by binary logistic regression analysis, and receiver operating characteristic (ROC) test based on their combined use for HG BC showed that the area under the curve (AUC) was 0.961 in the discovery set and 0.950 in the validation set when compared to LG BC. Likewise, this composite biomarker panel can also differentiate LG BC from healthy controls with the AUC of 0.993 and 0.991 in the discovery and validation set, respectively. This finding suggested that this composite serum metabolite signature was a promising and less invasive classifier for probing and grading BC, which deserved to be further investigated in larger samples. PMID:28382976

  8. High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity.

    PubMed

    Haffner, Michael C; Laimer, Johannes; Chaux, Alcides; Schäfer, Georg; Obrist, Peter; Brunner, Andrea; Kronberger, Irmgard E; Laimer, Klaus; Gurel, Bora; Koller, Johann-Benedikt; Seifarth, Christof; Zelger, Bettina; Klocker, Helmut; Rasse, Michael; Doppler, Wolfgang; Bander, Neil H

    2012-08-01

    Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer as well as in the neo-vasculature of nonprostatic solid tumors. Here, we determined the expression pattern of PSMA in the vasculature of oral squamous cell carcinoma. Using a previously validated antibody, PSMA staining distribution and cyclooxygenase 2 (COX2) expression status was evaluated in a cohort of patients with squamous cell carcinoma of the oral cavity (n=96) using immunohistochemistry and was correlated with clinicopathological features as well as outcome. Twenty-four (25%) cases showed no detectable PSMA staining, 48 (50%) demonstrated positive immunoreactivity for PSMA in less than 50% of microvessels and 24 (25%) cases showed strong endothelial PSMA expression in more than 50% of tumor-associated microvessels. High endothelial PSMA expression was associated with greatly reduced survival (18.2 vs 77.3 months; P=0.0001) and maintained prognostic significance after adjusting for grade and stage in multivariate analysis (hazard ratio=2.19, P=0.007). Furthermore, we observed a strong association between endothelial PSMA and cancer cell-specific COX2 expression. In conclusion, we provide the first evidence for the prognostic significance of endothelial PSMA expression in oral squamous cell carcinoma and, suggest a potential interaction between arachidonic acid metabolites and endothelial PSMA expression in the tumor neo-vasculature.

  9. Extremely High Tp53 Mutation Load in Esophageal Squamous Cell Carcinoma in Golestan Province, Iran

    PubMed Central

    Abedi-Ardekani, Behnoush; Kamangar, Farin; Sotoudeh, Masoud; Villar, Stephanie; Islami, Farhad; Aghcheli, Karim; Nasrollahzadeh, Dariush; Taghavi, Noushin; Dawsey, Sanford M.; Abnet, Christian C.; Hewitt, Stephen M.; Fahimi, Saman; Saidi, Farrokh; Brennan, Paul; Boffetta, Paolo; Malekzadeh, Reza; Hainaut, Pierre

    2011-01-01

    Background Golestan Province in northeastern Iran has one of the highest incidences of esophageal squamous cell carcinoma (ESCC) in the world with rates over 50 per 100,000 person-years in both sexes. We have analyzed TP53 mutation patterns in tumors from this high-risk geographic area in search of clues to the mutagenic processes involved in causing ESCC. Methodology/Principal Findings Biopsies of 119 confirmed ESCC tumor tissue from subjects enrolled in a case-control study conducted in Golestan Province were analyzed by direct sequencing of TP53 exons 2 through 11. Immunohistochemical staining for p53 was carried out using two monoclonal antibodies, DO7 and 1801. A total of 120 TP53 mutations were detected in 107/119 cases (89.9%), including 11 patients with double or triple mutations. The mutation pattern was heterogeneous with infrequent mutations at common TP53 “hotspots” but frequent transversions potentially attributable to environmental carcinogens forming bulky DNA adducts, including 40% at bases known as site of mutagenesis by polycyclic aromatic hydrocarbons (PAHs). Mutations showed different patterns according to the reported temperature of tea consumption, but no variation was observed in relation to ethnicity, tobacco or opium use, and alcoholic beverage consumption or urban versus rural residence. Conclusion/Significance ESCC tumors in people from Golestan Province show the highest rate of TP53 mutations ever reported in any cancer anywhere. The heterogeneous mutation pattern is highly suggestive of a causative role for multiple environmental carcinogens, including PAHs. The temperature and composition of tea may also influence mutagenesis. PMID:22216294

  10. Interactions Between High- and Low-Risk HPV Types Reduce the Risk of Squamous Cervical Cancer.

    PubMed

    Sundström, Karin; Ploner, Alexander; Arnheim-Dahlström, Lisen; Eloranta, Sandra; Palmgren, Juni; Adami, Hans-Olov; Ylitalo Helm, Nathalie; Sparén, Pär; Dillner, Joakim

    2015-10-01

    The clinical significance of co-infections with high-risk (HR) and low-risk (LR) human papillomavirus (HPV) in the etiology of cervical cancer is debated, as prospective evidence on this issue is limited. However, the question is of increasing relevance in relation to HPV-based cancer prevention. In two population-based nested case-control studies among women participating in cervical screening with baseline normal smears, we collected 4659 smears from women who later developed cancer in situ (CIS; n = 524) or squamous cervical cancer (SCC; n = 378) and individually matched control subjects who remained free of disease during study follow-up. The median follow-up until diagnosis was 6.4 to 7.8 years. All smears were tested for HPV. We used conditional logistic regression models with two-way interaction terms to estimate relative risks (RRs) for CIS and SCC, respectively. All statistical tests were two-sided. Compared with women who were infected with HRHPV only, women who were also infected with LRHPV had a lower risk for SCC (RR = 0.2, 95% confidence interval [CI] = 0.04 to 0.99, P = .049). This interaction was not shown for CIS (RR = 1.1, 95% CI = 0.4 to 3.6). Women who were positive for both HRHPV and LRHPV had, on average, a 4.8 year longer time to diagnosis of SCC than women who were positive for HRHPV only (P = .006). Results were highly robust in sensitivity analyses. Co-infection with LRHPV is associated with a lower risk of future invasive disease and longer time to diagnosis than infection with HRHPV alone. We propose that co-infection with LRHPV interferes with the rate of progression to invasive cervical cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Comparison of subtypes of penile squamous cell carcinoma from high and low incidence geographical regions.

    PubMed

    Chaux, Alcides; Lezcano, Cecilia; Cubilla, Antonio L; Tamboli, Pheroze; Ro, Jae; Ayala, Alberto

    2010-08-01

    There is a worldwide geographical variation in the incidence of penile squamous cell carcinoma (PSCC); some subtypes are HPV-related (warty, basaloid) while others (keratinizing variants) are not. The aims of this study were to compare the distribution of different histological subtypes of PSCC from regions of low (Paraguay, 144 cases) and high (USA, 157 cases) incidence and to identify and compare tumors with and without warty and/or basaloid morphology. The distribution of subtypes in the Paraguayan and the American series was: usual, 49.3 and 46.5%; verrucous, 8.3 and 7.6%; papillary NOS, 7.6 and 5.7%; warty, 6.9 and 8.3%; basaloid, 4.2 and 7.0%; sarcomatoid, 0.7 and 0.6%; adenosquamous, 3.5 and 0.6%; and mixed, 19.4 and 23.6%, respectively. The distribution of mixed PSCC was: warty-basaloid, 50.0 and 59.5%; usual-verrucous, 21.4 and 21.6%; usual-warty, 14.3 and 8.1%; usual-basaloid, 7.1 and 0.0%; usual-papillary, 3.6 and 5.4%; and others, 3.6 and 5.4%, respectively. In conclusion, we found no geographical difference in the incidence of histological subtypes (p = 0.6501), mixed PSCC (p = 0.5937) or HPV-related tumors (p = 0.2505). Geographical variation may be the result of staging variation at clinical presentation or of pathological diagnosis. The identification of similar histological subtypes in both series validates this classification approach for penile cancer. The tendency for typical SCC to mix with verrucous and papillary carcinomas and of the basaloid to preferentially mix with benign condyloma and condylomatous (warty) carcinomas would support the hypothesis of the existence of an etiologically different dual population of penile tumors.

  12. High Intrathoracic Anastomosis with Thoracoscopy Is Safe and Feasible for Treatment of Esophageal Squamous Cell Carcinoma

    PubMed Central

    Jeon, Hyun Woo; Park, Jae Kil; Song, Kyo Young; Sung, Sook Whan

    2016-01-01

    Background Minimally invasive esophagectomy (MIE) has the potential to reduce the morbidity and mortality of esophageal cancer surgery. Esophageal squamous cell carcinoma (ESCC) has a high incidence of earlier lymphatic spread and is usually located more proximal to the incisor than esophageal adenocarcinoma; consequently, the anastomosis should be made more proximal in the thorax or in the neck. We adopted the proximal intrathoracic anastomotic technique using thoracoscopy for mid-to-lower ESCC. Methods From October 2010 to August 2014, fifty-eight consecutive patients underwent MIE for ESCC. After laparoscopic gastric tubing, thoracoscopic esophageal resection and reconstruction were performed using a 28-mm circular stapler following radical mediastinal lymph node dissection. We tried to make an anastomosis at the apex of the chest. Postoperative outcomes, including overall survival and recurrence, were assessed. Results The mean patient age was 64.3±9 years. The mean operative time was 371.8±51.6 minutes, and the duration of the thorax procedure was 254.8±38.3 minutes. The mean number of lymph nodes dissected was 31±11.7. The mean intensive care unit (ICU) stay and hospital stay were 3.5±8.2 hours and 13.6±7.4 days, respectively. The level of anastomosis was 22.3±1.8cm from the incisor. One patient died of uncontrolled sepsis due to necrosis of the gastric graft. Two patients developed small contained leakage. Nine patients exhibited distant metastasis during the follow-up period. Conclusion Thoracoscopic intrathoracic anastomosis at the proximal esophagus is feasible and safe. PMID:27011160

  13. Argon plasma coagulation for superficial esophageal squamous-cell carcinoma in high-risk patients

    PubMed Central

    Tahara, Kumiko; Tanabe, Satoshi; Ishido, Kenji; Higuchi, Katsuhiko; Sasaki, Tohru; Katada, Chikatoshi; Azuma, Mizutomo; Nakatani, Kento; Naruke, Akira; Kim, Myungchul; Koizumi, Wasaburo

    2012-01-01

    AIM: To evaluate the usefulness and safety of argon plasma coagulation (APC) for superficial esophageal squamous-cell carcinoma (SESC) in high-risk patients. METHODS: We studied 17 patients (15 men and 2 women, 21 lesions) with SESC in whom endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and open surgery were contraindicated from March 1999 through February 2009. None of the patients could tolerate prolonged EMR/ESD or open surgery because of severe concomitant disease (e.g., liver cirrhosis, cerebral infarction, or ischemic heart disease) or scar formation after EMR/ESD and chemoradiotherapy. After conventional endoscopy, an iodine stain was sprayed on the esophageal mucosa to determine the lesion margins. The lesion was then ablated by APC. We retrospectively studied the treatment time, number of APC sessions per site, complications, presence or absence of recurrence, and time to recurrence. RESULTS: The median duration of follow-up was 36 mo (range: 6-120 mo). All of the tumors were macroscopically classified as superficial and slightly depressed type (0-IIc). The preoperative depth of invasion was clinical T1a (mucosal cancer) for 19 lesions and clinical T1b (submucosal cancer) for 2. The median treatment time was 15 min (range: 10-36 min). The median number of treatment sessions per site was 2 (range: 1-4). The median hospital stay was 14 d (range: 5-68 d). Among the 17 patients (21 lesions), 2 (9.5%) had recurrence and underwent additional APC with no subsequent evidence of recurrence. There were no treatment-related complications, such as bleeding or perforation. CONCLUSION: APC is considered to be safe and effective for the management of SESC that cannot be resected endoscopically because of underlying disease, as well as for the control of recurrence after EMR and local recurrence after chemoradiotherapy. PMID:23082058

  14. Determinants of Complications and Outcome in High-Risk Squamous Cell Head-and-Neck Cancer Treated With Perioperative High-Dose Rate Brachytherapy (PHDRB)

    SciTech Connect

    Martinez-Monge, Rafael; Pagola Divasson, Maria; Cambeiro, Mauricio; Gaztanaga, Miren; Moreno, Marta; Arbea, Leire; Montesdeoca, Nestor; Alcalde, Juan

    2011-11-15

    Purpose: To determine the impact of a set of patient, tumor, and treatment factors on toxicity and outcome in patients with head-and-neck squamous cell cancer treated with surgical resection and perioperative high-dose rate brachytherapy (PHDRB) alone (single-modality [SM] group) (n = 46) or PHDRB combined with postoperative radiation or chemoradiation (combined-modality [CM] group) (n = 57). Methods and Materials: From 2000 to 2008, 103 patients received PHDRB after complete macroscopic resection. SM patients received 32 or 40 Gy of PHDRB in 8 or 10 twice-daily treatments for R0 and R1 resections. CM patients received 16 or 24 Gy of PHDRB in 4 or 6 twice-daily treatments for R0 and R1 resections, followed by external radiation of 45 Gy in 25 fractions with or without concomitant chemotherapy. Results: Grade {>=}4 complications according to the Radiation Therapy Oncology Group were more frequent in the SM group than in the CM group (p = 0.024). Grade {>=}3 and {>=}4 complications increased with the antecedent of prior irradiation (p = 0.032 and p = 0.006, respectively) and with TV{sub 150} values of 13 mL or greater (p = 0.032 and p = 0.032, respectively). After a median follow-up of 34.8 and 60.8 months for SM and CM patients, respectively, patients with high-risk margins had a 9-year local control rate of 68.0% whereas patients with wider margins had a 9-year local control of 93.7% (p = 0.045). Patients with primary and recurrent tumors had 9-year actuarial locoregional control rates of 81.8% and 54.2%, respectively (p = 0.003). Patients with lymph-vascular space invasion (LVSI)-positive and LVSI-negative tumors had 9-year distant control rates of 62.8% and 81.6%, respectively (p = 0.034). Disease-free survival rates decreased in recurrent cases (p = 0.006) as well as in LVSI-positive patients (p = 0.035). Conclusions: The complications observed are largely attributable to the antecedent of prior irradiation but can possibly be minimized by meticulous mapping and

  15. High School Grades and University Performance: A Case Study

    ERIC Educational Resources Information Center

    Cyrenne, Philippe; Chan, Alan

    2012-01-01

    A critical issue facing a number of colleges and universities is how to allocate first year places to incoming students. The decision to admit students is often based on a number of factors, but a key statistic is a student's high school grades. This paper reports on a case study of the subsequent performance at the University of Winnipeg of high…

  16. Environmental Education for Junior High Grades: A Teacher's Manual.

    ERIC Educational Resources Information Center

    Michigan State Dept. of Natural Resources, Lansing.

    Teaching suggestions for environmental education in junior high school grades are grouped under five general headings: "Geology,""Water Resources,""Soil and Land Use,""Trees, Woodlots, and Forests," and "Wild-life and Fishes." Listed under each heading are attitudes and understandings to develop, topics for discussion, and many suggested…

  17. High School Grades and University Performance: A Case Study

    ERIC Educational Resources Information Center

    Cyrenne, Philippe; Chan, Alan

    2012-01-01

    A critical issue facing a number of colleges and universities is how to allocate first year places to incoming students. The decision to admit students is often based on a number of factors, but a key statistic is a student's high school grades. This paper reports on a case study of the subsequent performance at the University of Winnipeg of high…

  18. High-grade anal intraepithelial neoplasia: Progression to invasive cancer is not a certainty.

    PubMed

    Gautier, Mathilde; Brochard, Charlène; Lion, Annie; Henno, Sébastien; Mallet, Anne Laure; Bodere, Anaïs; Bouguen, Guillaume; Lièvre, Astrid; Siproudhis, Laurent

    2016-07-01

    The incidences of high-grade anal intraepithelial neoplasia (HSIL) and superficially invasive squamous cell carcinomas (SISCCA) related to human papillomavirus (HPV) have increased. These lesions can progress to invasive anal cancer. The aim of the study was to assess the clinical outcome with a special focus on the healing rate. Forty-six consecutive patients (M/F: 35/11; HIV+: 30) with histologically proven HSIL lesions (N=41) or SISCCA (N=5) were enrolled in a follow-up survey. Of the 46 patients, 40 were treated by excision (n=9), electrocoagulation (n=13), topical treatment (n=2) or combined strategies (n=16). After a mean follow-up of 35 (27-43) months, only one patient progressed to an invasive cancer. Regression and healing were observed in 14 (30%) and 15 (33%) patients. The cumulative probabilities of healing were 14%, 49% and 74% after 1, 3 and 5 years. None of the current smokers healed. Heterosexual patients, sexual abstinence, patients older than 44 years old, non-smokers, patients without any past history of condyloma and those with less than 2 high-risk HPVs at baseline were more likely to heal. Progression to invasive cancer is a rare event. Large, prospective cohort studies are needed to plan coherent strategies for both follow-up and treatment. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  19. High-grade neuroendocrine carcinomas display unique cytogenetic aberrations.

    PubMed

    Welborn, Jeanna; Jenks, Helen; Taplett, Janet; Walling, Paula

    2004-11-01

    Neuroendocrine tumors represent a spectrum of tumor types with different biologic and clinical features. The morphologic types include the low-grade typical and atypical carcinoids and the high-grade small cell and large cell neuroendocrine carcinomas (NECs). Cytogenetic descriptions of high-grade NECs are rare. Complete karyotypic descriptions of 34 high-grade NECs are reviewed: 7 extrapulmonary small cell NECs, 3 metastatic NECs of unknown primary, and 24 small cell lung carcinomas (SCLCs). Chromosomal deletions are more frequent than gains and often involve the entire chromosome arm. Typical aberrations are deletions of chromosome 3p, 5q, 10q, and 17p and gains of 1q, 3q, and 5p occurring as isochromosomes. Non-small cell lung cancers (NSCLCs) have different cytogenetic aberrations, but those with a metastatic phenotype display the identical aberrations as SCLC, a tumor known for its metastatic phenotype at onset. A genetic classification of lung cancer that incorporates the pattern of recurrent chromosome aberrations may be a better predictor of clinical outcome than a morphologic classification.

  20. A survival analysis comparing women with ovarian low-grade serous carcinoma to those with high-grade histology.

    PubMed

    Chen, Ming; Jin, Ying; Bi, Yalan; Yin, Jie; Wang, Yongxue; Pan, Lingya

    2014-01-01

    Ovarian low-grade serous carcinoma (LGSC) and high-grade serous carcinoma have distinct molecular profiles, clinical behaviors, and treatment responses. The survival advantage for patients with low-grade carcinoma compared with patients with high-grade histology remains controversial. We retrospectively reviewed the medical charts of 381 patients with ovarian serous carcinoma at Peking Union Medical College Hospital from 2007 to 2010. Patients were classified into two groups according to MD Anderson two-tier system: 35 (9.2%) cases with LGSC and 346 with high-grade serous carcinoma. Patients with low-grade serous ovarian cancer had a significantly younger age at diagnosis (46 versus 56 years, P=0.046), and their median progression-free survival (PFS) and overall survival values were 35.0 and 54.0 months, respectively. A multivariate analysis showed that, for serous ovarian cancer, the histological grade was a significant prognostic factor for PFS but not for overall survival (P=0.022 and P=0.0566, respectively). When stratified by the existence of a residual disease, patients with low-grade disease who underwent cytoreductive surgery without macroscopic residual disease (>1 cm) had a significantly improved median PFS time (36.0 months) compared with that of patients with high-grade carcinoma who received optimal cytoreductive surgery (16.0 months, P=0.017). Conversely, patients with low-grade and high-grade carcinoma who were left with macroscopic residue (>1 cm) experienced a similarly shorter median PFS (10.0 and 13.0 months, respectively, P=0.871). The International Federation of Gynecology and Obstetrics stage and residual disease were significant prognostic factors of low-grade carcinoma, while positive ascites was associated with a worse PFS value. Our data showed that LGSC is a different entity from high-grade carcinoma and that LGSC was associated with improved PFS after optimal cytoreductive surgery but not suboptimal operation.

  1. The Swedish Infant High-grade Reflux Trial - Bladder function.

    PubMed

    Nordenström, J; Sillen, U; Holmdahl, G; Linnér, T; Stokland, E; Sjöström, S

    2017-04-01

    It has been suggested that infants with high-grade vesicoureteral reflux (VUR) have lower urinary tract dysfunction (LUTD) that is characterised by large bladder capacity (BC) and increased post-void residual (PVR). However, most of these infants have normal or small BC in early infancy and develop large capacity during the first year of life. This study aimed to see whether LUTD development during the infant years in children with high-grade VUR could be prevented by early reflux resolution. For early VUR intervention, endoscopic treatment (ET) was used in a randomised trial comprising 77 infants (55 boys) aged <8 months with VUR grade 4-5 (n = 30/n = 47); 39 were randomised to antibiotic prophylaxis and 38 to ET. Voiding cystourethrogram, free voiding observation (FVO) and renal scintigraphy were performed at baseline and after 1 year. Bladder capacity and PVR were obtained from FVO. LUTD was defined as a BC of ≥150% of expected and a PVR of ≥20 ml. There were no differences in bladder function variables seen between the treatment groups, despite significant differences in VUR resolution. Analysing bladder function related to VUR outcome (VUR grade ≤2 vs grade >2), independent of treatment, showed that VUR grade ≤2 was associated with a smaller BC at 1 year (P = 0.050) (a tendency already seen at baseline) and a lower PVR at baseline (P = 0.010). PVR increased from baseline to 1 year (P = 0.037) in children with grade ≤2 VUR (Summary Table). The group with persistent bilateral grade 5 VUR at 1 year had more abnormal bladder variables compared with other study subjects, with a tendency of larger BC (P = 0.057), higher PVR (P = 0.0073) and more LUTD (P = 0.029) at baseline and a larger BC at 1 year (P = 0.016). In explanatory analyses, using logistic regression, a high PVR at baseline was identified as a predictor of VUR grade >2 (P = 0.046), persistent bilateral grade 5 VUR (P = 0.022), recurrent urinary tract infection (P = 0

  2. Phase Ib Study of BKM120 With Cisplatin and XRT in High Risk Locally Advanced Squamous Cell Cancer of Head and Neck

    ClinicalTrials.gov

    2017-05-19

    Carcinoma, Squamous Cell of Head and Neck; HPV Positive Oropharyngeal Squamous Cell Carcinoma; Hypopharyngeal Cancer; Early Invasive Cervical Squamous Cell Carcinoma; Carcinoma of Larynx; Cancer of Nasopharynx

  3. Multiple Human Papillomavirus Infections with High Viral Loads Are Associated with Cervical Lesions but Do Not Differentiate Grades of Cervical Abnormalities

    PubMed Central

    Depuydt, Christophe; Benoy, Ina; Bogers, Johannes; Antoine, Jerome; Arbyn, Marc; Pawlita, Michael

    2013-01-01

    Multiple human papillomavirus (HPV) genotypes often coexist within cervical epithelia and are frequently detected together in smears of different grades of cervical neoplasia. Describing the association between multiple infections and cervical disease is important in generating hypotheses regarding its pathogenesis. We analyzed the prevalence of multiple HPV infections and their attribution to cervical disease in a screening population of 999 consecutive BD SurePath liquid-based cervical cytology samples enriched with atypical squamous cells of undetermined significance (ASCUS) (n = 100), low-grade squamous intraepithelial lesions (LSIL) (n = 100), and high-grade squamous intraepithelial lesions (HSIL) (n = 97). HPV genotyping was performed only on cytology specimens using a broad-spectrum GP5+/6+-PCR/multiplex HPV genotyping (BSGP5+/6+-PCR/MPG) assay that detects and quantifies 51 HPV genotypes and 3 subtypes. Using a recently defined high viral load cutoff, the quantitative data were scored as high or low viral load. In the 36-month follow-up, 79 histologically confirmed cervical intraepithelial neoplasia grade 2 or greater (CIN2+) cases were identified. In the screening population, there was a trend of having more multiple infections at a younger age. Multiple HPV infections were common. Multiple HPV types were most prevalent in LSIL (75.9% of HPV positives), followed by HSIL (65.5%), ASCUS (64.6%), and negative for intraepithelial lesion or malignancy (NILM) (36.8%). On average, 3.2 and 2.5 HPV types were detected per LSIL and HSIL sample, respectively. Multiple HPV types with high viral loads were most prevalent in LSIL (62.6% of high viral load positives), followed by HSIL (51.9%), ASCUS (40.7%), and NILM (19.3%). Patients with multiple high viral loads showed a 4- to 6-fold-higher risk of having cervical precancerous cytological lesions than did patients with single high viral loads. Compared to NILM, multiple infections, especially with multiple high viral

  4. The Relationship of Grade Span in 9th Grade to Math Achievement in High School

    ERIC Educational Resources Information Center

    West, John; Miller, Mary Lou; Myers, Jim; Norton, Timothy

    2015-01-01

    Purpose, Scope, and Method of Study: The purpose of this study was to determine if a correlation exists between grade span for ninth grade and gains in math achievement test scores in 10th grade and 12th grade. A quantitative, longitudinal, correlational research design was employed to investigate the research questions. The population was high…

  5. Endoscopic mucosal resection for superficial carcinoma and high-grade dysplasia of the esophagus.

    PubMed

    Moreira, L F; Kamikawa, Y; Naomoto, Y; Haisa, M; Orita, K

    1995-06-01

    Endoscopic mucosal resection (EMR) is a recently introduced therapeutic method based on the principles of the strip biopsy for resection of flat lesions of the gastrointestinal tract. Eleven asymptomatic patients (nine men, two women) with superficial carcinoma or high-grade dysplasia of the intrathoracic esophagus were treated by EMR during a 6-month period. The patients' mean age was 64 years (range, 49-78). The site of the lesions was the middle third of the esophagus in eight, upper third in two, and lower third in one patient. All patients in this series had a flat (II) type of superficial cancer. The procedure was carried out in all 11 patients without complication. Histopathological examination of the specimens revealed squamous cell carcinoma in nine patients. The remaining two patients were confirmed to have dysplasia only. Free margins measured greater than 5 mm in all cases. No recurrence was detected in a mean follow-up of 8 (5-10) months. For superficial flat lesions, EMR proved to be a safe and curative procedure that provided good quality of life following resection. However, larger trials are needed to confirm these results. Applying EMR to esophageal dysplasia could decrease the incidence of esophageal cancer.

  6. Analysis of DTI-Derived Tensor Metrics in Differential Diagnosis between Low-grade and High-grade Gliomas

    PubMed Central

    Jiang, Liang; Xiao, Chao-Yong; Xu, Quan; Sun, Jun; Chen, Huiyou; Chen, Yu-Chen; Yin, Xindao

    2017-01-01

    Purpose: It is critical and difficult to accurately discriminate between high- and low-grade gliomas preoperatively. This study aimed to ascertain the role of several scalar measures in distinguishing high-grade from low-grade gliomas, especially the axial diffusivity (AD), radial diffusivity (RD), planar tensor (Cp), spherical tensor (Cs), and linear tensor (Cl) derived from diffusion tensor imaging (DTI). Materials and Methods: Fifty-three patients with pathologically confirmed brain gliomas (21 low-grade and 32 high-grade) were included. Contrast-enhanced T1-weighted images and DTI were performed in all patients. The AD, RD, Cp, Cs, and Cl values in the tumor zone, peritumoral edema zone, white matter (WM) adjacent to edema and contralateral normal-appearing white matter (NAWM) were calculated. The DTI parameters and tumor grades were statistically analyzed, and receiver operating characteristic (ROC) curve analysis was also performed. Results: The DTI metrics in the affected hemisphere showed significant differences from those in the NAWM, except for the AD values in the tumor zone and the RD values in WM adjacent to edema in the low-grade groups, as well as the Cp values in WM adjacent to edema in the high-grade groups. AD in the tumor zone as well as Cs and Cl in WM adjacent to edema revealed significant differences between the low- and high-grade gliomas. The areas under the curve (Az) of all three metrics were greater than 0.5 in distinguishing low-grade from high-grade gliomas by ROC curve analysis, and the best DTI metric was Cs in WM adjacent to edema (Az: 0.692). Conclusion: AD in the tumor zone as well as Cs and Cl in WM adjacent to edema will provide additional information to better classify gliomas and can be used as non-invasive reliable biomarkers in glioma grading. PMID:28848428

  7. Correlation of EGFR, pEGFR and p16INK4 expressions and high risk HPV infection in HIV/AIDS-related squamous cell carcinoma of conjunctiva

    PubMed Central

    2014-01-01

    Background Squamous cell carcinoma of conjunctiva has increased tenfold in the era of HIV/AIDS. The disease pattern has also changed in Africa, affecting young persons, with peak age-specific incidence of 30-39 years, similar to that of Kaposi sarcoma, a well known HIV/AIDS defining neoplasm. In addition, the disease has assumed more aggressive clinical course. The contributing role of exposure to high risk HPV in the development of SCCC is still emerging. Objective The present study aimed to investigate if immunohistochemical expressions of EGFR, pEGFR and p16, could predict infection with high risk HPV in HIV-related SCCC. Methods FFPE tissue blocks of fifty-eight cases diagnosed on hematoxylin and eosin with SCCC between 2005-2011, and subsequently confirmed from medical records to be HIV positive at the department of human pathology, UoN/KNH, were used for the study. Immunohistochemistry was performed to assess the expressions of p16INK4A, EGFR and pEGFR. This was followed with semi-nested PCR based detection and sequencing of HPV genotypes. The sequences were compared with the GenBank database, and data analyzed for significant statistical correlations using SPSS 16.0. Ethical approval to conduct the study was obtained from KNH-ERC. Results Out of the fifty-eight cases of SCCC analyzed, twenty-nine (50%) had well differentiated (grade 1), twenty one (36.2%) moderately differentiated (grade 2) while eight (13.8%) had poorly differentiated (grade 3) tumours. Immunohistochemistry assay was done in all the fifty eight studied cases, of which thirty nine cases (67.2%) were positive for p16INK4A staining, forty eight cases (82.8%) for EGFR and fifty one cases (87.9%) showed positivity for p-EGFR. HPV DNA was detected in 4 out of 40 SCCC cases (10%) in which PCR was performed, with HPV16 being the only HPV sub-type detected. Significant statistical association was found between HPV detection and p16INK4 (p=0.000, at 99% C.I) and EGFR (p=0.028, at 95% C.I) expressions

  8. Topical cidofovir to treat high-grade anal intraepithelial neoplasia in HIV-infected patients: a pilot clinical trial.

    PubMed

    Sendagorta, Elena; Bernardino, Jose I; Álvarez-Gallego, Mario; Feíto, Marta; Feltes, Rosa; Beato, Maria J; Pérez-Molina, Jose A; Yllescas, Maria; Díaz-Almirón, Mariana; Arribas, Jose R; González-García, Juan; Herranz, Pedro

    2016-01-02

    To evaluate the efficacy of 1% topical cidofovir cream for the treatment of anal high-grade squamous intraepithelial lesions (HSILs) in HIV-infected individuals. Single-arm, open-label, pilot clinical trial. The study medication was applied intraanally three times per week for 4 weeks. Lesions were assessed with high-resolution anoscopy and biopsy at weeks 12 and 24. The primary endpoint was complete remission (CR) at week 12, defined as clinical and histological remission. We also evaluated partial remission defined as regression to low-grade squamous intraepithelial lesion. We included 17 HIV-infected patients with intraanal HSIL. Median (interquartile range) age was 36 years (28-41), median (interquartile range) CD4 cell count was 545 cells/μl (358-630), and viral load was less than 50  copies/ml in 93.7%. Two patients were lost to follow-up, one of them did not apply treatment. At 12 weeks, in the intention-to-treat population, 10 out of 16 patients [62.5%; 95% confidence interval (CI), 38.2-85.7%] had achieved CR. At 24 weeks, seven of the 10 patients (70%; 95% CI, 47-93%) remained in CR, but two out of 10 patients (20%; 95% CI, 0-40%) presented HSIL. One patient did not attend the visit at 24 weeks. Three patients with persistent HSIL at 12 weeks improved at 24 weeks (partial response in one and CR in two). The mean number of human papillomavirus genotypes decreased from 5.2 to 2.7 at 12 weeks (P = 0.002). Local adverse effects were frequent (81%), although there were no discontinuations because of adverse events. One percent topical cidofovir could be an appropriate alternative therapy in HIV-infected patients with anal HSIL. gov unique identifier: NCT01946009.

  9. OVARIAN LOW-GRADE AND HIGH-GRADE SEROUS CARCINOMA: Pathogenesis, Clinicopathologic and Molecular Biologic Features, and Diagnostic Problems

    PubMed Central

    Vang, Russell; Shih, Ie-Ming; Kurman, Robert J.

    2009-01-01

    Ovarian serous carcinomas have been graded using various systems. Recently, a 2-tier system in which tumors are subdivided into low-grade and high-grade has been proposed. This approach is simplistic, reproducible, and based on biologic evidence indicating that both tumors develop via different pathways. Low-grade serous carcinomas exhibit low-grade nuclei with infrequent mitotic figures. They evolve from adenofibromas or borderline tumors, have frequent mutations of the KRAS, BRAF, or ERBB2 genes, and lack TP53 mutations (Type I pathway). The progression to invasive carcinoma is a slow step-wise process. Low-grade tumors are indolent and have better outcome than high-grade tumors. In contrast, high-grade serous carcinomas have high-grade nuclei and numerous mitotic figures. Identification of a precursor lesion in the ovary has been elusive and therefore the origin of ovarian carcinoma has been described as de novo. More recently, studies have suggested that a proportion appear to originate from intraepithelial carcinoma in the fallopian tube. The development of these tumors is rapid (Type II pathway). The vast majority are characterized by TP53 mutations and lack mutations of KRAS, BRAF, or ERBB2. Although both types of serous carcinomas evolve along different pathways, rare high-grade serous carcinomas seem to arise through the Type I pathway. Immunohistochemical stains for p53, p16, and Ki-67 for distinction of low- from high-grade tumors are of limited value but can be helpful in selected instances. This review provides an update on the pathogenesis and clinicopathologic features of these two types of serous carcinomas and addresses some of the diagnostic problems that are encountered in routine practice. PMID:19700937

  10. Pediatric high-grade glioma: current molecular landscape and therapeutic approaches.

    PubMed

    Braunstein, Steve; Raleigh, David; Bindra, Ranjit; Mueller, Sabine; Haas-Kogan, Daphne

    2017-03-29

    High-grade pediatric central nervous system glial tumors are comprised primarily of anaplastic astrocytomas (AA, WHO grade III) and glioblastomas (GBM, WHO grade IV). High-grade gliomas are most commonly diagnosed in the primary setting in children, but as in adults, they can also arise as a result of transformation of a low-grade malignancy, though with limited frequency in the pediatric population. The molecular genetics of high-grade gliomas in the pediatric population are distinct from their adult counterparts. In contrast to the adult population, high-grade gliomas in children are relatively infrequent, representing less than 20% of cases.

  11. Irradiation of Pediatric High-Grade Spinal Cord Tumors

    SciTech Connect

    Tendulkar, Rahul D.; Pai Panandiker, Atmaram S.; Wu Shengjie; Kun, Larry E.; Broniscer, Alberto; Sanford, Robert A.; Merchant, Thomas E.

    2010-12-01

    Purpose: To report the outcome using radiation therapy (RT) for pediatric patients with high-grade spinal cord tumors. Methods and Materials: A retrospective chart review was conducted that included 17 children with high-grade spinal cord tumors treated with RT at St. Jude Children's Research Hospital between 1981 and 2007. Three patients had gross total resection, 11 had subtotal resection, and 3 underwent biopsy. The tumor diagnosis was glioblastoma multiforme (n = 7), anaplastic astrocytoma (n = 8), or anaplastic oligodendroglioma (n = 2). Seven patients received craniospinal irradiation (34.2-48.6 Gy). The median dose to the primary site was 52.2 Gy (range, 38-66 Gy). Results: The median progression-free and overall survivals were 10.8 and 13.8 months, respectively. Local tumor progression at 12 months (79% vs. 30%, p = 0.02) and median survival (13.1 vs. 27.2 months, p = 0.09) were worse for patients with glioblastoma multiforme compared with anaplastic astrocytoma or oligodendroglioma. The median overall survival was shorter for patients when failure included neuraxis dissemination (n = 8) compared with local failure alone (n = 5), 9.6 vs. 13.8 months, p = 0.08. Three long-term survivors with World Health Organization Grade III tumors were alive with follow-up, ranging from 88-239 months. Conclusions: High-grade spinal cord primary tumors in children have a poor prognosis. The propensity for neuraxis metastases as a component of progression after RT suggests the need for more aggressive therapy.

  12. Treatment of children with high grade glioma with nimotuzumab

    PubMed Central

    Cabanas, Ricardo; Saurez, Giselle; Rios, Martha; Alert, Jose; Reyes, Adnolys; Valdes, Jose; Gonzalez, Maria C.; Pedrayes, Jorge L.; Avila, Melba; Herrera, Raiza; Infante, Mariela; Echevarria, Ernesto; Moreno, Myrna; Luaces, Patricia Lorenzo; Ramos, Tania Crombet

    2013-01-01

    Brain tumors are a major cause of cancer-related mortality in children. Overexpression of epidermal growth factor receptor (EGFR) is detected in pediatric brain tumors and receptor density appears to increase with tumor grading. Nimotuzumab is an IgG1 antibody that targets EGFR. Twenty-three children with high-grade glioma (HGG) were enrolled in an expanded access program in which nimotuzumab was administered alone or with radio-chemotherapy. The mean number of doses was 39. Nimotuzumab was well-tolerated and treatment with the antibody yielded a survival benefit: median survival time was 32.66 mo and the 2-y survival rate was 54.2%. This study demonstrated the feasibility of prolonged administration of nimotuzumab and showed preliminary evidence of clinical benefit in HGG patients with poor prognosis. PMID:23575267

  13. Efficacy of Perfusion Computed Tomography (PCT) in Differentiating High-Grade Gliomas from Low Grade Gliomas, Lymphomas, Metastases and Abscess.

    PubMed

    Karegowda, Lakshmikanth Halegubbi; Kadavigere, Rajagopal; Shenoy, Poonam Mohan; Paruthikunnan, Samir Mustaffa

    2017-05-01

    Tumoural angioneogenesis and its quantification are important in predicting the tumour grade and in the management with respect to the treatment available and to assess the response to treatment and the prognosis. It also plays major role in the growth and spread of tumours. Hence, a need arises for non-invasive in vivo methods to assess tumour angioneogenesis and tumour grade at the time of presentation and for monitoring the response during treatment and follow up. In this regard Perfusion Computed Tomography (PCT) can be easily added into routine CT studies to obtain such information on lesion physiology along with its morphology. Prospective evaluation of the efficacy of PCT in differentiating high grade gliomas from low grade glioma lymphomas, metastases and abscess. Perfusion CT was performed in 68 patients (17 high-grade gliomas, 10 low-grade gliomas, 7 lymphomas, 27 metastases and 7 abscess). Perfusion parameters which include Cerebral Blood Volume (CBV), Cerebral Blood Flow (CBF), Mean Transit Time (MTT) and Time To Peak (TTP) were derived both from the lesion and the normal parenchyma and were Normalized (n) by obtaining the ratio. Statistical analysis for high grade versus low-grade gliomas, high grade gliomas versus lymphomas, metastases and abscess was performed. Difference in the mean nCBV and nCBF in high grade gliomas were statistically significant from low grade gliomas with cut off of > 3.07 for nCBV and > 2.08 for nCBF yielding good sensitivity and specificity. Difference in the mean nCBV and nMTT in the lymphomas were statistically significant from high grade gliomas (p<0.05) with cut off of <3.40 for nCBV and >1.83 for nMTT yielding good sensitivity and specificity. Difference in the mean nCBV and nMTT in the metastases were statistically significant from high grade gliomas (p<0.05) with cut off of >4.95 for nCBV and >1.88 for nMTT yielding a fair sensitivity and specificity. No statistical significant difference seen among the parameters in

  14. Minor Cytological Abnormalities and up to 7-Year Risk for Subsequent High-Grade Lesions by HPV Type

    PubMed Central

    Olsson, Sven-Erik; Dillner, Joakim; Andersson, Sonia

    2015-01-01

    Objective Diagnoses of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are common, but the corresponding risk of disease varies by human papillomavirus (HPV) status, complicating management strategies. Our aim was to estimate the longer-term risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with ASCUS/LSIL by age, HPV status, and genotype(s). Methods A total of 314 women with ASCUS/ LSIL were followed for a median of 3.8 years. Baseline HPV status was determined by reflex testing and women with histologically confirmed CIN2+ were identified through linkage to the Swedish National Quality Register for Cervical Cancer Prevention. Cumulative incidence and hazard ratios were estimated to explore differences between index data and associations with CIN2+. Results In total, 89 women (28.3%) developed CIN2+. High-risk (HR) HPV-positive women developed significantly more CIN2+ than HR-HPV-negative women (cumulative incidence 3.5 years after the index test: 42.2%, 95% CI: 32.5–53.5 for HPV16/18; 36.2%, 95% CI: 28.3–45.4 for other HR-HPV types; and 2.0%, 95% CI: 0.5–7.8 for HR-HPV-negative women; p<0.0001). Conclusion HPV status was of greatest importance in determining the risk of CIN2+. The risk was low among HPV-negative women during the first years of follow-up, suggesting these women could be followed less intensively. HPV16/18-positive women may need intensified follow-up as they showed the highest risk of CIN2+. PMID:26083247

  15. HIGH FREQUENCY ULTRASOUND OF ARMOR-GRADE ALUMINA CERAMICS

    SciTech Connect

    Bottiglieri, S.; Haber, R. A.

    2009-03-03

    Different lots of high density, commercial, armor-grade alumina (Al{sub 2}O{sub 3}) were tested using high frequency ultrasound in order to determine any correlation between measured properties and ballistic performance. C-scan images were taken using a 15 MHz ultrasonic transducer in order to form attenuation coefficient and elastic property maps. These samples were further characterized by using quantitative analysis. The results indicate that attenuation coefficient values appear to have the strongest correlation, of every property measured, to ballistic classifications.

  16. [High-risk human papilloma virus associated oropharynx squamous cell carcinomas: clinical, biological implications and therapeutical perspectives].

    PubMed

    Guihard, S; Jung, A-C; Noël, G

    2012-02-01

    The infection of the head and neck epithelium by high-risk human papillomaviruses (HPV) is a risk factor for cancer onset and development. The incidence of HPV-related head and neck squamous cell carcinoma is currently increasing. These lesions display distinct clinical features. HPV positive patients are often younger and have a smaller history of tobacco smoking and alcohol drinking, but have a history of virus-transmitting sex practices. HPV-related tumours are mainly found in the oropharynx, are more associated to a local lymph node invasion and display a poorly differentiated morphology. Despite these more aggressive features, HPV-positive head and neck squamous cell carcinomas correlate with an improved local control, disease-free and global survival. It is thought that HPV-driven specific biologic abnormalities underlie higher tumour sensitivity to chemotherapeutic drugs and ionizing radiations. The expression of the HPV E6 and E7 oncoproteins induce cell transformation by interfering with cell signalling pathways involved in apoptosis, cell cycle, angiogenesis and induce the overexpression of the CDKN2A gene. Therefore, alternative treatments based on therapies targeting these pathways in combination with radiation dose de-escalation could be proposed to HPV-positive patients, if they are properly and reliably identified.

  17. Reviewing the genetic alterations in high-risk cutaneous squamous cell carcinoma: A search for prognostic markers and therapeutic targets.

    PubMed

    Ashford, Bruce G; Clark, Jonathan; Gupta, Ruta; Iyer, N Gopalakrishna; Yu, Bing; Ranson, Marie

    2017-04-03

    Cutaneous squamous cell carcinoma (SCC) is second only in incidence to basal cell carcinoma (BCC), effecting up to 500 000 people in the United States annually. Metastasis to regional lymph nodes occurs in approximately 5% of cases and imparts significant morbidity. Standard treatment in this group involves a combination of surgery and adjuvant radiation. Currently, there are no clinically useful biomarkers of metastatic potential in primary cutaneous SCC and histological predictors can be unreliable. The high level of mutational burden in normal UV-exposed skin has hampered the search for novel drivers of invasive disease, and indeed metastatic potential. This review outlines the clinical problems in high-risk and metastatic cutaneous SCCs, reviews the known genetic events and molecular mechanisms in high-risk primary cutaneous SCC and metastasis, and identifies avenues for further investigation and potential therapy.

  18. ?Differential Grading Standards among High Schools. ACT Research Report Series, 2004-02

    ERIC Educational Resources Information Center

    Woodruff, David J.; Ziomek, Robert L.

    2004-01-01

    The primary purpose of this study was to investigate differential grading standards among public high schools. This study focused on documenting differential grading standards between 1998 and 2002. Five years were studied to verify that the observed differences in grading standards were not transient. Differences in grading standards among high…

  19. Postoperative Chemoradiotherapy and Cetuximab for High-Risk Squamous Cell Carcinoma of the Head and Neck: Radiation Therapy Oncology Group RTOG-0234

    PubMed Central

    Harari, Paul M.; Harris, Jonathan; Kies, Merrill S.; Myers, Jeffrey N.; Jordan, Richard C.; Gillison, Maura L.; Foote, Robert L.; Machtay, Mitchell; Rotman, Marvin; Khuntia, Deepak; Straube, William; Zhang, Qiang; Ang, Kian

    2014-01-01

    Purpose To report results of a randomized phase II trial (Radiation Therapy Oncology Group RTOG-0234) examining concurrent chemoradiotherapy and cetuximab in the postoperative treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with high-risk pathologic features. Patients and Methods Eligibility required pathologic stage III to IV SCCHN with gross total resection showing positive margins and/or extracapsular nodal extension and/or two or more nodal metastases. Patients were randomly assigned to 60 Gy radiation with cetuximab once per week plus either cisplatin 30 mg/m2 or docetaxel 15 mg/m2 once per week. Results Between April 2004 and December 2006, 238 patients were enrolled. With a median follow-up of 4.4 years, 2-year overall survival (OS) was 69% for the cisplatin arm and 79% for the docetaxel arm; 2-year disease-free survival (DFS) was 57% and 66%, respectively. Patients with p16-positive oropharynx tumors showed markedly improved survival outcome relative to patients with p16-negative oropharynx tumors. Grade 3 to 4 myelosuppression was observed in 28% of patients in the cisplatin arm and 14% in the docetaxel arm; mucositis was observed in 56% and 54%, respectively. DFS in this study was compared with that in the chemoradiotherapy arm of the RTOG-9501 trial (Phase III Intergroup Trial of Surgery Followed by Radiotherapy Versus Radiochemotherapy for Resectable High Risk Squamous Cell Carcinoma of the Head and Neck), which had a hazard ratio of 0.76 for the cisplatin arm versus control (P = .05) and 0.69 for the docetaxel arm versus control (P = .01), reflecting absolute improvement in 2-year DFS of 2.5% and 11.1%, respectively. Conclusion The delivery of postoperative chemoradiotherapy and cetuximab to patients with SCCHN is feasible and tolerated with predictable toxicity. The docetaxel regimen shows favorable outcome with improved DFS and OS relative to historical controls and has commenced formal testing in a phase II/III trial

  20. Radiosurgical boost for primary high-grade gliomas.

    PubMed

    Prisco, Flavio E; Weltman, Eduardo; de Hanriot, Rodrigo M; Brandt, Reynaldo A

    2002-04-01

    The purpose of this study was to retrospectively evaluate the survival of patients with high-grade gliomas treated with external beam radiotherapy with or without radiosurgical boost. From July 1993 to April 1998, 32 patients were selected, 15 of which received radiosurgery. Inclusion criteria were age > 18 years, histological confirmation of high-grade glioma, primary tumor treatment with curative intent, unifocal tumor and supratentorial location. All patients were found to be in classes III-VI, according to the recursive partitioning analysis proposed by the Radiation Therapy Oncology Group. The median interval between radiotherapy and radiosurgery was 5 weeks (range 1-13). Treatment volumes ranged from 2.9 to 70.3 cc (median 15.0 cc). Prescribed radiosurgery doses varied from 8.0 to 12.5 Gy (median 10.0 Gy). Radiosurgery and control groups were well balanced with respect to prognostic factor distributions. Median actuarial survival time in radiosurgery and control groups was 21.4 months and 11.6 months, respectively (p = 0.0254). Among patients with KPS > 80, median survival time was 11.0 months and 53.9 months in the control and radiosurgery groups, respectively (p = 0.0103). Radiosurgery was the single factor correlated with survival on Cox model analysis (p = 0.0362) and was associated with a 2.76 relative reduction in the risk of cancer death (95% confidence interval (CI) 1.07-7.13). Our results suggest that radiosurgery may confer a survival advantage for patients in RPA classes III-VI, especially for those with Karnofsky performance status >80. The definitive role of radiosurgical boost for patients with high-grade gliomas awaits the results of randomized trials.

  1. High-efficiency beam bending using graded photonic crystals.

    PubMed

    Oner, B B; Turduev, M; Kurt, H

    2013-05-15

    We explore beam-bending properties of graded index (GRIN) waveguide with hyperbolic secant profile. The transmission efficiency and bandwidth features are extracted for GRIN photonic crystal (PC) media composed of dielectric rods. Light guiding performance of the GRIN PC medium is analyzed for 90° and 180° waveguide bends. The finite-difference time-domain method is deployed to investigate the performance of the designed GRIN waveguides. By the help of proposed photonic configuration, bending of light is achieved with a high efficiency within a broad bandwidth, which promotes the use of GRIN PC structures for efficient light-bending purposes.

  2. Irradiation and Bevacizumab in High-Grade Glioma Retreatment Settings

    SciTech Connect

    Niyazi, Maximilian; Ganswindt, Ute; Schwarz, Silke Birgit; Kreth, Friedrich-Wilhelm; Tonn, Joerg-Christian; Geisler, Julia; Fougere, Christian la; Ertl, Lorenz; Linn, Jennifer; Siefert, Axel; Belka, Claus

    2012-01-01

    Purpose: Reirradiation is a treatment option for recurrent high-grade glioma with proven but limited effectiveness. Therapies directed against vascular endothelial growth factor have been shown to exert certain efficacy in combination with chemotherapy and have been safely tested in combination with radiotherapy in a small cohort of patients. To study the feasibility of reirradiation combined with bevacizumab treatment, the toxicity and treatment outcomes of this approach were analyzed retrospectively. Patients and Methods: After previous treatment with standard radiotherapy (with or without temozolomide) patients with recurrent malignant glioma received bevacizumab (10 mg/kg intravenous) on Day 1 and Day 15 during radiotherapy. Maintenance therapy was selected based on individual considerations, and mainly bevacizumab-containing regimens were chosen. Patients received 36 Gy in 18 fractions. Results: The data of the medical charts of the 30 patients were analyzed retrospectively. All were irradiated in a single institution and received either bevacizumab (n = 20), no additional substance (n = 7), or temozolomide (n = 3). Reirradiation was tolerated well, regardless of the added drug. In 1 patient treated with bevacizumab, a wound dehiscence occurred. Overall survival was significantly better in patients receiving bevacizumab (p = 0.03, log-rank test). In a multivariate proportional hazards Cox model, bevacizumab, Karnovsky performance status, and World Health Organization grade at relapse turned out to be the most important predictors for overall survival. Conclusion: Reirradiation with bevacizumab is a feasible and effective treatment for patients with recurrent high-grade gliomas. A randomized trial is warranted to finally answer the question whether bevacizumab adds substantial benefit to a radiotherapeutic retreatment setting.

  3. Looking Forward to High School and College: Middle Grade Indicators of Readiness in Chicago Public Schools

    ERIC Educational Resources Information Center

    Allensworth, Elaine M.; Gwynne, Julia A.; Moore, Paul; de la Torre, Marisa

    2014-01-01

    There is a very large population of students who struggle with the transition from the middle grades to high school, raising concerns that high school failures are partially a function of poor middle grade preparation. As a result, middle grade practitioners are grappling with questions about what skills students need to succeed in high school,…

  4. Pre-irradiation chemotherapy for newly diagnosed high grade astrocytoma.

    PubMed

    Mathieu, N Tubiana; Genet, D; Labrousse, F; Bouillet, P; Denes, S Lavau; Martin, J; Labourey, J L; Venat, L; Clavere, P; Moreau, J J

    2004-01-01

    The purpose of this work was to determine the response rate and toxicity of a combination of Carmustine and Cisplatin administered before radiation in patients with newly diagnosed high grade astrocytoma. A good response rate has been published with this association in primary cerebral high grade tumor. This protocol was administered in a homogeneous population of 37 adult patients with measurable tumor on magnetic resonance imaging (MRI) or CT scan. After biopsy or subtotal resection, the patients received BCNU 40 mg/m2/d and CODP 40 mg/m2/d, for 3 days every 28 days for 3 cycles. Evaluation was performed before each cycle. Radiation therapy began 4 weeks after completing the chemotherapy or immediately if there was evidence of tumor progression on chemotherapy. Seven out of 37 (19%) demonstrated tumor regression with a median duration to progression of 11 months. Median survival was 6 months. Myelosuppression was the predominant but manageable toxicity. This work indicated that the first chemotherapy protocol gave poor results in a homogeneous group of patients, with bad prognosis.

  5. Nanoparticle-mediated drug delivery to high-grade gliomas.

    PubMed

    Frosina, Guido

    2016-05-01

    High grade gliomas (HGGs) are fatal brain tumors due to their infiltration capacity and the presence of resistant cell populations. Further, the brain is naturally protected from many exogenous molecules by the brain blood barrier (BBB), which limits or cancels passage of cytotoxic drugs to the tumor sites. In order to cope with the latter problem, nanoparticle (NP)-based carriers are intensively investigated, due to multiple possibilities to drive them across the BBB to the tumor sites and drop cytotoxic molecules there. The current status of research on NP for drug delivery to HGGs has been analyzed. The results indicate gold, lipids and proteins as three main materials featuring NP formulations for HGG treatment. Albeit specific drug targeting to HGG cells may have not been so far significantly improved, NP may help drugs crossing the BBB and enter the brain thus potentially fixing at least one part of the problem. High grade gliomas (HGG) are very aggressive tumours and current therapy remains unsatisfactory. The advance in nanomedicine has allowed the development of novel treatment modalities. In this review article, the authors outlined the current status in using nanoparticle (NP)-based carriers for drug delivery to HGG. This should help readers to understand and develop ideas for further drug carrier designs. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Basaloid squamous cell carcinoma of oral cavity: Report of two cases

    PubMed Central

    Heera, R; Ayswarya, T; Padmakumar, SK; Ismayil, P

    2016-01-01

    Basaloid squamous cell carcinoma (BSCC) is an aggressive, high-grade, variant of squamous cell carcinoma (SCC), which is uncommon in the oral cavity but slightly more common in the oropharynx. We present two cases of BSCC, one arising in the floor of the mouth and the other arising on the lateral border of the tongue. The diagnosis of this subtype of SCC is important owing to its particular behavior, with an aggressive course, a high incidence of local recurrence, regional lymph node metastases and mortality rate. PMID:27721627

  7. Inherited BRCA2 mutation associated with high grade breast cancer.

    PubMed

    Agnarsson, B A; Jonasson, J G; Björnsdottir, I B; Barkardottir, R B; Egilsson, V; Sigurdsson, H

    1998-01-01

    Inheritance is believed to play a major role in 5-10% of breast cancer. The breast cancer susceptibility genes BRCA1 and BRCA2 are estimated to account for more than half of these cases. Recent studies have suggested that breast cancers associated with BRCA1 germline mutations are of higher grade than sporadic cases. The purpose of this investigation was to determine if there are significant pathologic and biologic differences between hereditary BRCA2 related breast carcinomas and non-hereditary breast cancers. Forty cases of hereditary breast cancer from families associated with a specific 999del5 BRCA2 mutation were compared with regard to histologic and biologic factors to an age matched control group. Thirty-four patients (85%) had ductal carcinoma, two had lobular carcinoma, and one patient had medullary carcinoma. Compared to the control group, the BRCA2 tumors had less tubule formation (p = 0.02), more nuclear pleomorphism (p = 0.02), and higher mitotic rates (p = 0.002), and were thus of higher histologic grade (p = 0.003). By flow cytometry the BRCA2 tumors also had significantly higher S-phase fractions than the control tumors (p = 0.02). Significant differences in axillary lymph-node involvement or ploidy status were not detected. According to the results of this study, hereditary breast cancers associated with the 999del5 BRCA2 mutation are high grade tumors with a rapid proliferation rate. Other or additional factors than the defining BRCA2 mutation are involved in determining the tumor type.

  8. Social Science Instructional Guides: High School (Grades 9-12).

    ERIC Educational Resources Information Center

    Hartman, Carl; And Others

    The guide, part of a social science learning continuum from first through twelfth grades, contains outlines for two-semester social studies courses for grades 9-12. Three components comprise each section: time allocations for units, instructional objectives, and a content outline. The Grade 9 course, Cultures of the Non-Western World, contains…

  9. SOCIAL STUDIES CURRICULUM. JUNIOR HIGH SCHOOL, GRADE 9.

    ERIC Educational Resources Information Center

    LIBBER, THEODORE; PENN, JOSEPH E.

    IN GRADE 9, ANCIENT HISTORY IS STUDIED DURING THE FIRST SEMESTER, FOLLOWED BY MEDIEVAL HISTORY THE SECOND SEMESTER. IT IS HOPED THAT MOST STUDENTS WILL CONTINUE THEIR HISTORY STUDY IN THE 10TH GRADE WITH MODERN HISTORY, BASED UPON THE CULTURAL CONCEPTS PRESENTED IN THE 9TH GRADE. GEOGRAPHY AND CIVICS ARE OFFERED AS ONE-SEMESTER ELECTIVES IN 9TH…

  10. Social Science Instructional Guides: High School (Grades 9-12).

    ERIC Educational Resources Information Center

    Hartman, Carl; And Others

    The guide, part of a social science learning continuum from first through twelfth grades, contains outlines for two-semester social studies courses for grades 9-12. Three components comprise each section: time allocations for units, instructional objectives, and a content outline. The Grade 9 course, Cultures of the Non-Western World, contains…

  11. Prevalence of human papillomavirus types in high-grade cervical intraepithelial neoplasia and cancer in Italy.

    PubMed

    Carozzi, Francesca M; Tornesello, Maria L; Burroni, Elena; Loquercio, Giovanna; Carillo, Giuseppe; Angeloni, Claudio; Scalisi, Aurora; Macis, Rosalba; Chini, Francesco; Buonaguro, Franco M; Giorgi Rossi, Paolo

    2010-09-01

    The aim of this multicentric study was to identify human papillomavirus (HPV) type distribution in invasive cervical cancer and high-grade cervical intraepithelial neoplasia 2/3 (CIN2/3) in Italy. Cases were sampled through the electronic databases at the pathology units of eight centers in six regions from central and southern Italy. HPV types were detected from paraffin-embedded tissue samples and cervical specimens through amplification of HPV DNA with GP5+/GP6+ primers, followed by genotyping with reverse line blot (RLB). Untyped HPV-positive samples were sequenced. HPV-negative samples underwent nested PCR, followed by either RLB or sequencing. Finally, the remaining HPV-negative samples were amplified with primers targeting the virus E6 to E7 regions. From 1,162 cases initially selected, 722 samples were further analyzed: 144 CIN2, 385 CIN3, 157 invasive squamous carcinomas, and 36 adenocarcinomas. Samples (6.9%) were HPV negative. The proportion of HPV16/18 was 60.8%, 76.6%, and 78.8% in CIN2, CIN3, and invasive cancers, respectively (P trend = 0.004). There was a significant decreasing trend of HPV16/18 with age in invasive cancers, going from 92% in women <35 years to 73% in women >55 years (P = 0.036). The proportion of coinfections was 16.8%, 15.5%, and 10.0% in CIN2, CIN3, and invasive cancers, respectively (P trend = 0.07). The proportion of invasive cancers caused by HPV16/18 decreases with age at diagnosis. The absolute risk of an invasive cancer due to non-HPV16/18 in women under 35 is extremely low. This finding might prompt us to rise the age at which public HPV screening for vaccinated women should start. (c)2010 AACR.

  12. High-Grade Leiomyosarcoma Arising in a Previously Replanted Limb

    PubMed Central

    Pan, Tiffany J.; Pantanowitz, Liron; Weiss, Kurt R.

    2015-01-01

    Sarcoma development has been associated with genetics, irradiation, viral infections, and immunodeficiency. Reports of sarcomas arising in the setting of prior trauma, as in burn scars or fracture sites, are rare. We report a case of a leiomyosarcoma arising in an arm that had previously been replanted at the level of the elbow joint following traumatic amputation when the patient was eight years old. He presented twenty-four years later with a 10.8 cm mass in the replanted arm located on the volar forearm. The tumor was completely resected and pathology examination showed a high-grade, subfascial spindle cell sarcoma diagnosed as a grade 3 leiomyosarcoma with stage pT2bNxMx. The patient underwent treatment with brachytherapy, reconstruction with a free flap, and subsequently chemotherapy. To the best of our knowledge, this is the first case report of leiomyosarcoma developing in a replanted extremity. Development of leiomyosarcoma in this case could be related to revascularization, scar formation, or chronic injury after replantation. The patient remains healthy without signs of recurrence at three-year follow-up. PMID:26366310

  13. Yoga May Mitigate Decreases in High School Grades

    PubMed Central

    Butzer, Bethany; van Over, Max; Noggle Taylor, Jessica J.; Khalsa, Sat Bir S.

    2015-01-01

    This study involves an exploratory examination of the effects of a 12-week school-based yoga intervention on changes in grade point average (GPA) in 9th and 10th grade students. Participants included 95 high school students who had registered for physical education (PE) in spring 2010. PE class sections were group randomized to receive either a yoga intervention or a PE-as-usual control condition. The yoga intervention took place during the entire third quarter and half of the fourth quarter of the school year, and quarterly GPA was collected via school records at the end of the school year. Results revealed a significant interaction between group and quarter suggesting that GPA differed between the yoga and control groups over time. Post hoc tests revealed that while both groups exhibited a general decline in GPA over the school year, the control group exhibited a significantly greater decline in GPA from quarter 1 to quarter 3 than the yoga group. Both groups showed equivalent declines in GPA in quarter 4 after the yoga intervention had ended. The results suggest that yoga may have a protective effect on academic performance by preventing declines in GPA; however these preventive effects may not persist once yoga practice is discontinued. PMID:26347787

  14. [Occurrence and molecular pathology of high grade gliomas].

    PubMed

    Murnyák, Balázs; Csonka, Tamás; Hegyi, Katalin; Méhes, Gábor; Klekner, Almos; Hortobágyi, Tibor

    2013-09-30

    Glial tumours represent the most frequent type of primary brain cancers. Gliomas are characterized by heterogeneity that makes the diagnosis, histological classification and the choosing of correct therapy more difficult. Despite the advances in developing therapeutic strategies patients with malignant gliomas have a poor prognosis; therefore glial tumours represent one of the most important areas of cancer research. There are no detailed data on the epidemiology of gliomas in Hungary. In the first section of our publication, we analysed the histological diagnosed cases between 2007 and 2011 at the Institute of Pathology, University of Debrecen Medical and Health Science Centre. We analyzed the incidence of 214 high-grade gliomas by tumor grades, gender, age, and the anatomical localization. The majority of cases were glioblastoma (182 cases), and the remaining 32 cases were anaplastic gliomas. The mean age of patients was 57 years (+/- 16.4), and the male:female ratio was 1.1:1. The most frequent area of tumors was the frontal lobe followed by the temporal, parietal and occipital lobe. We include new findings published recently about glioma pathogenesis, molecular pathways, mutant genes and chromosomal regions. We explain briefly the role of selected important genes in glioma genesis and give an update on knowledge provided by modern molecular methods, which could beneficially influence future therapy and the diagnosis of gliomas.

  15. High-grade cytomegalovirus antigenemia after hematopoietic stem cell transplantation.

    PubMed

    Asano-Mori, Y; Oshima, K; Sakata-Yanagimoto, M; Nakagawa, M; Kandabashi, K; Izutsu, K; Hangaishi, A; Motokura, T; Chiba, S; Kurokawa, M; Hirai, H; Kanda, Y

    2005-11-01

    Clinical impact of high-grade (HG) cytomegalovirus (CMV) antigenemia after hematopoietic stem cell transplantation has not been clarified. Therefore, in order to investigate the risk factors and outcome for HG-CMV antigenemia, we retrospectively analyzed the records of 154 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2002 at the University of Tokyo Hospital. Among 107 patients who developed positive CMV antigenemia at any level, 74 received risk-adapted preemptive therapy with ganciclovir (GCV), and 17 of these developed HG-antigenemia defined as > or = 50 positive cells per two slides. The use of systemic corticosteroids at > or = 0.5 mg/kg/day at the initiation of GCV was identified as an independent significant risk factor for HG-antigenemia. Seven of the 17 HG-antigenemia patients developed CMV disease, with a cumulative incidence of 49.5%, which was significantly higher than that in the low-grade antigenemia patients (4%, P<0.001). However, overall survival was almost equivalent in the two groups. In conclusion, the development of HG-antigenemia appeared to depend on the profound immune suppression of the recipient. Although CMV disease frequently developed in HG-antigenemia patients, antiviral therapy could prevent a fatal outcome.

  16. Laryngeal lymphoma: the high and low grades of rare lymphoma involvement sites.

    PubMed

    Azzopardi, Charles Paul; Degaetano, James; Betts, Alexandra; Farrugia, Eric; Magri, Claude; Refalo, Nicholas; Gatt, Alexander; Camilleri, David J

    2014-01-01

    The larynx is an extremely rare site of involvement by lymphomatous disease. We present two cases of isolated laryngeal high-grade and another low-grade lymphoma, together with a literature review of laryngeal lymphoma management.

  17. Re-irradiation alternatives for recurrent high-grade glioma

    PubMed Central

    Dong, Yuanli; Fu, Chengrui; Guan, Hui; Zhang, Tianyi; Zhang, Zicheng; Zhou, Tao; Li, Baosheng

    2016-01-01

    Despite advances in the fields of surgery, chemotherapy and radiotherapy, the prognosis for high-grade glioma (HGG) remains unsatisfactory. The majority of HGG patients experience disease recurrence. To date, no standard treatments have been established for recurrent HGG. Repeat surgery and chemotherapy demonstrate moderate efficacy. As recurrent lesions are usually located within the previously irradiated field, a second course of irradiation was once considered controversial, as it was considered to exhibit unsatisfactory efficacy and radiation-related toxicities. However, an increasing number of studies have indicated that re-irradiation may present an efficacious treatment for recurrent HGG. Re-irradiation may be delivered via conventionally fractionated stereotactic radiotherapy, hypofractionated stereotactic radiation therapy, stereotactic radiosurgery and brachytherapy techniques. In the present review, the current literature regarding re-irradiation treatment for recurrent HGG is summarized with regard to survival outcome and side effects. PMID:27703519

  18. High interstitial fluid pressure promotes tumor cell proliferation and invasion in oral squamous cell carcinoma.

    PubMed

    Yu, Tao; Liu, Kun; Wu, Yingying; Fan, Jinchuan; Chen, Jianchao; Li, Chao; Zhu, Guiquan; Wang, Zhaohui; Li, Longjiang

    2013-11-01

    It has been shown that interstitial fluid pressure (IFP) is elevated in many solid tumors. The elevated IFP in tumors is responsible, at least in part, for the poor blood supply, inadequate delivery of therapeutic agents to solid tumors and poor treatment response in patients. The present study was carried out to examine alterations in malignant phenotypes in oral squamous cell carcinoma cells subjected to conditions mimicking IFP and to identify the relevant molecular mechanisms. We investigated tumor cell proliferation and invasion using SCC-4 and SCC-9 cells subjected to an increased extracellular pressure of 0, 15 and 30 mmHg in vitro. The results revealed that the increased IFP resulted in a marked increase in cancer cell proliferation, survival and invasion in vitro and altered the expression of >1,800 genes involved in invasion and metastasis, the heat shock pathway, the p38 and JNK signaling pathway, apoptosis and the cell growth and differentiation signaling pathway. These results suggest the important potential clinical application of measuring IFP, which can be used as a generic marker of prognosis and response to therapy.

  19. Follow-up practices for high-grade extremity Osteosarcoma.

    PubMed

    Rothermundt, Christian; Seddon, Beatrice M; Dileo, Palma; Strauss, Sandra J; Coleman, Joanne; Briggs, Timothy W; Haile, Sarah R; Whelan, Jeremy S

    2016-05-06

    The optimal conduct of follow-up (FU) of patients with osteosarcoma is uncertain. In the absence of any formal validation of optimal timing and method of surveillance, guidance is provided by oncology societies' recommendations. FU is designed to detect either local recurrence or metastatic disease at a time when early treatment is still possible and might be effective. We performed a retrospective analysis of 101 patients with high-grade extremity osteosarcoma in a single centre. Chest x-ray (CXR) was used as routine surveillance method; however patients with initial lung metastases or previous suspicious findings had computed tomography (CT) scans. With a median FU time of 30.7 months 34 patients relapsed. Relapse-free survival after 5 years was 61% (CI 52%; 73%), late relapses occurred in only two patients between 2 and 5 years of FU. Twenty-five of the 34 relapses were detected at routine FU appointments. All 8 local recurrences were noted clinically. Twenty-two patients had metastases confined to the lungs, either detected on CXR or CT. Thirty-two percent of patients with lung metastases only were salvaged successfully. Routine FU in high-grade osteosarcoma results in clinical detection of local relapse, and detection of lung metastases by CXR at a time when metastatectomy is possible. The optimal time interval for FU appointments is not known, however we recommend more frequent surveillance visits during the two years after treatment. We hypothesize that routine CT scans are not required and propose CXR for detection of lung metastases.

  20. Leaks in nuclear grade high efficiency aerosol filters

    SciTech Connect

    Scripsick, Ronald Clyde

    1994-07-01

    Nuclear grade high efficiency aerosol filters, also known as high efficiency particulate air (HEPA) filters, are commonly used in air cleaning systems for removal of hazardous aerosols. Performance of the filter units is important in assuring health and environmental protection. The filter units are constructed from pleated packs of fiberglass filter media sealed into rigid frames. Results of previous studies on such filter units indicate that their performance may not be completely predicted by ideal performance of the fibrous filter media. In this study, departure from ideal performance is linked to leaks existing in filter units and overall filter unit performance is derived from independent performance of the individual filter unit components. The performance of 14 nuclear grade HEPA filter units (size 1, 25 cfm) with plywood frames was evaluated with a test system that permitted independent determination of penetration as a function of particle size for the whole filter unit, the filter unit frame, and the filter media pack. Tests were performed using a polydisperse aerosol of di-2-ethylhexyl phthalate with a count median diameter of 0.2 {mu}m and geometric standard deviation of 1.6. Flow rate and differential pressure were controlled from 1% to 100% of design values. Particle counts were made upstream and downstream of the filter unit with an optical particle counter (OPC). The OPC provided count information in 28 size channels over the particle diameter range from 0.1 to 0.7 μm. Results provide evidence for a two component leak model of filler unit performance with: (1) external leaks through filter unit frames, and (2) internal leaks through defects in the media and through the seal between the media pack and frame. For the filter units evaluated, these leaks dominate overall filter unit performance over much of the flow rate and particle size ranges tested.

  1. Contribution of Exocervical Biopsy, Endocervical Curettage, and Colposcopic Grading in Diagnosing High-Grade Cervical Intraepithelial Neoplasia.

    PubMed

    Diedrich, Justin Thomas; Felix, Juan C; Lonky, Neal M

    2016-01-01

    To determine the utility of random biopsy and endocervical curettage (ECC) during colposcopy among women who ultimately underwent cervical excisional biopsy. In a retrospective observational study, the charts were reviewed of every patient who underwent cervical excisional procedure performed between June 2010 and August 2011, including the antecedent colposcopic examination and any pathological specimens. A random sample of 15% all pathologic specimens was reviewed. Practice of biopsy, use of ECC, demographic factors, referral cytology results, lesion distribution, and size were assessed for correlation with high-grade cervical intraepithelial neoplasia 2 or worse (CIN 2+). A total of 555 patients were included in our analysis. Of them, 333 (60%) had CIN 2+ on colposcopy or excision. CIN 2+ was most likely in younger women and those referred for high-grade cytology. Among 111 women with no visual lesion seen at colposcopy, 66 underwent ECC alone, 33 had ECC and random biopsy, 9 were referred straight to excision, and 3 underwent random biopsy alone. Of the 99 who underwent ECC, this was consistent with the highest-grade lesion in 68% of cases. Among the 36 with random biopsy, this was consistent with the highest-grade lesion in 72% of cases.At the time of colposcopy, there were 326 who had CIN 2+ diagnosed with satisfactory colposcopy. Biopsy and ECC were performed in 278 cases. In 235 cases, biopsy alone showed CIN 2+; in 43, the biopsy and ECC both showed CIN 2+. In the remaining 48 cases, CIN 2+ was diagnosed with ECC alone. In those ultimately treated with excision, younger women and those whose referral cytology was high-grade both were at higher risk of high-grade histology. Random biopsy and ECC (even among satisfactory colposcopy) were significantly associated with disclosure of high-grade pathology.

  2. Efficiency of immunohistochemical p16 expression and HPV typing in cervical squamous intraepithelial lesion grading and review of the p16 literature.

    PubMed

    Yildiz, Işil Z; Usubütün, Alp; Firat, Pinar; Ayhan, Ali; Küçükali, Türkan

    2007-01-01

    Diagnosing and grading cervical cancer precursors is challenging. This study investigates the presence of HPV infection, the expression of p16, and any correlation between these two findings. H&E-stained slides of cervical loop excision materials diagnosed as LSIL and HSIL were reviewed. An immunohistochemical panel consisting of p16 as well as of all HPV types and HR-HPV types was applied. Staining of p16 was evaluated according to distribution extent and degree of intensity. All HSIL cases and 80% of LSIL cases were positive for p16. In HSIL cases, the staining distribution was as follows: 50% full thickness, 45% basal, and 5% rare. The staining intensity for the same cases was strong in 70%, variable in 20%, and weak in 10% accordingly. In LSIL cases, staining distribution was basal in 58.3% and rare in 41.7%. None of the LSIL cases showed full thickness of p16 positivity. The staining intensity of the same cases was strong in 25%, variable in 16.7%, and weak in 58.3%. Of all cases, 48.6% were positive for screening kit (all HPV types), and 31.4% of all cases were positive for HR-HPV. The distribution of this positivity was 35% for HSIL and 26.6% for LSIL cases. The total HPV-type positivity rate was 48.6%, the distribution being 50% for HSIL and 46.6% for LSIL cases. p16 is a highly sensitive marker for cervical epithelial dysplasia. Strong and full thickness staining of p16 in the cervix epithelium is highly supportive of HSIL, while weak and basal/rare staining favors LSIL. All HPV-positive cases were also p16-positive, but no statistically significant relationship between HPV infection positivity and the intensity and distribution of p16 was found. HPV is not helpful in the grading of SIL, as an unignorable rate of HR-HPV positivity (26.6%) was detected in LSIL group.

  3. High expression of MAGE-A9 is associated with unfavorable survival in esophageal squamous cell carcinoma.

    PubMed

    Qi, Yu; Cao, Ke Xin; Xing, Fu Chen; Zhang, Chun Yang; Huang, Qi; Wu, Kai; Wen, Feng Biao; Zhao, Song; Li, Xin

    2017-09-01

    Melanoma-associated antigens (MAGEs) are a group of well-characterized members of the cancer/testis antigen family, which are expressed in a variety of malignant tumors. MAGE-A9, a subfamily of MAGE-As, has been studied in a number of types of cancer and have been associated with unfavorable survival outcome. However, the expression of MAGE-A9 in human esophageal squamous cell carcinoma (ESCC) and association of MAGE-A9 with the clinicopathological characteristics of ESCC, particularly prognostic characteristics, remains unknown. The present study aimed at determining the expression level of MAGE-A9 and at evaluating its clinical significance in human ESCC. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) analyses were performed to characterize the expression of MAGE-A9 in ESCC tissues. Kaplan-Meier estimator survival and Coxs regression analyses were used to evaluate the prognosis of 103 patients with ESCC. The results of qPCR and IHC analysis revealed that the expression of MAGE-A9 was significantly increased in ESCC tissues, compared with that in healthy tissues. Furthermore, the expression level of MAGE-A9 protein in ESCC was significantly associated with the pathological grade (P=0.008), tumor size (P=0.027) and lymph node metastasis (P=0.009). Multivariate analysis using Coxs regression model identified that the expression level of MAGE-A9 and lymph node metastasis were independent prognostic factors for the overall survival rate of patients with ESCC (P=0.006 and P=0.001, respectively). The results of the present study are, to the best of our knowledge, the first to indicate that MAGE-A9 expression is a valuable prognostic biomarker for ESCC and that it may serve as a targeted therapy in the treatment of ESCC. Increased expression of MAGE-A9 indicated an unfavorable survival outcome in patients with ESCC.

  4. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-05-18

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  5. [Expressions and clinical significance of high mobility group box-1 mRNA and protein in laryngeal squamous cell carcinoma tissues and serum].

    PubMed

    Guo, Ying; Liu, Yong; Tan, Ping-qing; Li, Guo; Su, Zhong-wu; Tian, Yong-quan; Qiu, Yuan-zheng

    2012-06-01

    To investigate the mRNA and protein expressions of high mobility group box-1 (HMGB1) in the tumor tissues and sera of patients with laryngeal squamous cell carcinoma (LSCC) and their clinical significance. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot were used to detected the expressions of HMGB1 mRNA and protein in the tumors and adjacent normal epithelial tissues in 30 patients with LSCC. Serum HMGB1 protein levels in the patients with LSCC and in 10 healthy volunteers were detected with enzyme-linked immunosorbent adsorption experiment (ELISA). RT-PCR demonstrated that the mean relative mRNA expression levels of HMGB1 (HMGB1/GAPDH) in LSCC tissues and in adjacent normal epithelial tissues were 1.25 ± 0.12 and 0.32 ± 0.04, respectively (t = 40.27, P < 0.05). Western blot revealed that the mean relative protein expression levels of HMGB1 (HMGB1/β-actin) were 1.29 ± 0.10 and 0.34 ± 0.03 (t = 49.84, P < 0.05), respectively. Both mRNA and protein expression levels of HMGB1 were associated with T stage, clinical stage, lymph node metastasis status and smoking (all P < 0.05), but no significant correlation with age, alcohol consumption and primary tumor grade and location (all P > 0.05). Mean serum HMGB1 protein levels in patients with LSCC and healthy volunteers were (24.80 ± 14.08) ng/ml and (23.58 ± 14.69) ng/ml (t = 0.37, P > 0.05). Both mRNA and protein expressions of HMGB1 were obviously elevated in LSCC, which were associated closely with T stage, clinical stage and lymph node metastasis.

  6. K14-EGFP-miR-31 transgenic mice have high susceptibility to chemical-induced squamous cell tumorigenesis that is associating with Ku80 repression.

    PubMed

    Tseng, Ssu-Hsueh; Yang, Cheng-Chieh; Yu, En-Hao; Chang, Christine; Lee, Yong-Syu; Liu, Chung-Ji; Chang, Kuo-Wei; Lin, Shu-Chun

    2015-03-15

    Squamous cell carcinoma (SCC) occurring in the head and neck region and the esophagus causes tremendous cancer mortality around the world. miR-31 is among the most eminently upregulated MicroRNAs in SCC, when it occurs in the head and neck region and the esophagus. We established miR-31 transgenic mouse lines, in which miR-31 is under the control of the K14 promoter. 4-nitroquinoline 1-oxide (4NQO) is a mutagen that causes double strand breaks. The transgenic mice exhibited a higher potential for tumor induction than wild-type (Wt) mice of the tongue and esophagus after 4NQO treatment. After 4NQO treatment or irradiation, p-γH2AX expression in squamous epithelium of transgenic mice was increased more than in Wt mice. Exogenous expression of miR-31 was also found to be associated with the higher p-γH2AX expression induced by 4NQO in human oral SCC (OSCC) cell lines. The repair genes PARP1 and Ku80 were validated as new targets of miR-31 in human OSCC cell lines, and were found to be downregulated in the squamous epithelium of the tongue in transgenic mice. However, only the downregulation of Ku80 was essential for maintaining the high level of p-γH2AX induced by 4NQO in OSCC cells. Inverse expression profiles for miR-31 and Ku80 were noted in human OSCC tissue. Our study identifies the high sensitivity of K14-EGFP-miR-31 transgenic mice to chemical carcinogen-induced squamous cell tumorigenesis and shows that this seems to be associated with the downregulation of Ku80 and an impairment of repair activity in squamous cells, which are mediated by miR-31.

  7. Current views and perspectives on classification of squamous intraepithelial lesions of the head and neck.

    PubMed

    Gale, Nina; Zidar, Nina; Poljak, Mario; Cardesa, Antonio

    2014-03-01

    The current state in the field of classifying oral and laryngeal precursor lesions, as proposed in the WHO 2005 Blue Book is not ideal. The results of various inter-observer studies have shown that the currently used grading systems, with different basic concepts and different terminology, cannot continue to be reliably used in the future. The different etiology of cervical and head and neck precursor lesions requires a classification designed to cater to the specificities of the head and neck region. Trying to harmonize different classifications of the oral and laryngeal precursor lesions, we have proposed four crucial steps to set up a unified classification of squamous intraepithelial lesions (SILs): (a) the classification should contain two grades, low-grade and high-grade lesions and, specifically for the larynx, an additional grade-carcinoma in situ (CIS) which must be separated from high-grade laryngeal SILs; (b) the terminology should be unified; our preference is for the term SIL over squamous intraepithelial neoplasia; (c) all leading morphological criteria for low- and high-grade lesions, as well as for CIS, should be clearly defined; (d) agreement between clinicians and pathologists should be achieved on the most appropriate choice of treatment of different grades of SILs in separate head and neck areas.

  8. Molecular profile of head and neck squamous cell carcinomas bearing p16 high phenotype.

    PubMed

    Rampias, T; Pectasides, E; Prasad, M; Sasaki, C; Gouveris, P; Dimou, A; Kountourakis, P; Perisanidis, C; Burtness, B; Zaramboukas, T; Rimm, D; Fountzilas, G; Psyrri, A

    2013-08-01

    We sought to determine biomarker expression differences in head and neck squamous cell cancers (HNSCCs) based on p16/human papillomavirus (HPV) classification. In addition, our aim was to explore how expression of biomarkers is modulated after E6/E7 repression in HPV16⁺ oropharyngeal cancer cells. HPV16⁺ and HPV⁻ HNSCC cells were infected with retroviruses expressing short hairpin RNA targeting HPV16 E6/E7. Components of the epidermal growth factor receptor (EGFR) pathway before and after E6/E7 gene silencing were analyzed by immunoblotting and qRT-PCR. Protein expression of 13 biomarkers was analyzed using AQUA on a tissue microarray (TMA). The HPV16 status was determined using HPV16 in situ hybridization (ISH). In HPV16⁺ cells, E6/E7 silencing was associated with PTEN upregulation and reduction of phosphorylated EGFR. Tumors were classified into four categories based on the HPV and p16 status. HPV⁺/p16⁺ tumors expressed significantly higher levels of E-cadherin (P = 0.003), PTEN (P = 0.004), lower levels of PI3Kp110 and β-catenin (P = 0.07). There was a significant difference in overall survival (OS, P = 0.016) among the four subsets. The median OS was 24.83 months for p16⁻/HPV⁻ patients, 11.63 for p16⁻/HPV⁺ patients and was not reached for p16⁺/HPV⁻ and p16⁺/HPV⁺ groups. Aberrant EGFR signaling contributes to malignant conversion of HPV16⁺ HNSCC cells. These results validate β-catenin as a distinct biomarker in HPV⁺/p16⁺ HNSCC. Wnt signaling inhibitors merit exploration in HPV⁺/p16⁺ HNSCC.

  9. Circulating biomarkers for discrimination between aseptic joint failure, low-grade infection, and high-grade septic failure.

    PubMed

    Ettinger, Max; Calliess, Tilman; Kielstein, Jan T; Sibai, Jasmin; Brückner, Thomas; Lichtinghagen, Ralf; Windhagen, Henning; Lukasz, Alexander

    2015-08-01

    Late-onset chronic (low-grade) periprosthetic joint infections are often accompanied by unspecific symptoms, false-negative cultures or nonspecific low values of serum biomarkers. This may lead to the unintended implantation of a revision prosthesis into an infected surgical site with the risk of short-term failure developing again. Conversely, false diagnosis of joint infection may result in multistage revision procedures, which expose the patient to unnecessary surgical procedures and inappropriate antibiotic treatment. Here, we investigated whether circulating biomarkers can preoperatively distinguish between aseptic prosthesis loosening and low-grade joint infection, and which biomarker combinations are most accurate. Inclusion criteria for the study were indication for revision arthroplasty due to aseptic implant failure, acute high-grade infection, or (suspected) low-grade infection. C-reactive protein (CRP), procalcitonin, tumor necrosis factor α, interleukin 6 (IL-6), interleukin 10, and lipopolysaccharide binding protein were assessed preoperatively in the serum of 98 adult patients. The classification tree method revealed IL-6 and CRP as the most suitable biomarker combination for the discrimination of aseptic loosening vs low-grade joint infection. The combination of IL-6 >5.12 pg/mL and CRP >0.3 mg/dL correctly identified 15 of 16 patients as having low-grade infection (94%) whereas just one patient was aseptic (6%). This is the first comprehensive prospective clinical study to our knowledge investigating the significance of a combined biomarker approach in differentiating between aseptic prosthesis loosening and low-grade joint infection. CRP plus IL-6 seems to be the most helpful combination for preoperative discrimination of aseptic loosening vs low-grade joint infection. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Computer-based image analysis system designed to differentiate between low-grade and high-grade laryngeal cancer cases.

    PubMed

    Ninos, Konstantinos; Kostopoulos, Spiros; Sidiropoulos, Konstantinos; Kalatzis, Ioannis; Glotsos, Dimitris; Athanasiadis, Emmanouil; Ravazoula, Panagiota; Panayiotakis, George; Economou, George; Cavouras, Dionisis

    2013-10-01

    To design a pattern recognition (PR) system for discriminating between low- and high-grade laryngeal cancer cases, employing immunohistochemically stained, for p63 expression, histopathology images. The PR system was designed to assist in the physician's diagnosis for improving patient survival. The material comprised 55 verified cases of laryngeal cancer, 21 of low-grade and 34 of high-grade malignancy. Histopathology images were first processed for automatically segmenting p63 expressed nuclei. Fifty-two features were next extracted from the segmented nuclei, concerning nuclei texture, shape, and physical topology in the image. Those features and the Probabilistic Neural Network classifier were used to design the PR system on the multiprocessors of the Nvidia 580 GTX graphics processing unit (GPU) card using the Compute Unified Device Architecture parallel programming model and C++ programming language. PR system performance in classifying laryngeal cancer cases as low grade and high grade was 85.7% and 94.1%, respectively. The system's overall accuracy was 90.9%, using 7 features, and its estimated accuracy to "unseen" by the system cases was 80%. Optimum system design was feasible after employing parallel processing techniques and GPU technology. The proposed system was structured so as to function in a clinical environment, as a research tool, and with the capability of being redesigned on site when new verified cases are added to its repository.

  11. Discrimination against Students with Foreign Backgrounds: Evidence from Grading in Swedish Public High Schools

    ERIC Educational Resources Information Center

    Hinnerich, Bjorn Tyrefors; Höglin, Erik; Johannesson, Magnus

    2015-01-01

    We rigorously test for discrimination against students with foreign backgrounds in high school grading in Sweden. We analyse a random sample of national tests in the Swedish language graded both non-blindly by the student's own teacher and blindly without any identifying information. The increase in the test score due to non-blind grading is…

  12. Discrimination against Students with Foreign Backgrounds: Evidence from Grading in Swedish Public High Schools

    ERIC Educational Resources Information Center

    Hinnerich, Bjorn Tyrefors; Höglin, Erik; Johannesson, Magnus

    2015-01-01

    We rigorously test for discrimination against students with foreign backgrounds in high school grading in Sweden. We analyse a random sample of national tests in the Swedish language graded both non-blindly by the student's own teacher and blindly without any identifying information. The increase in the test score due to non-blind grading is…

  13. Procarbazine, lomustine and vincristine for recurrent high-grade glioma.

    PubMed

    Parasramka, Saurabh; Talari, Goutham; Rosenfeld, Myrna; Guo, Jing; Villano, John L

    2017-07-26

    Recurrent high-grade glioma (HGG) carries an extremely poor prognosis. There is no current standard of care or guideline-based recommendations. Nitrosourea-based multidrug chemotherapy or PCV - procarbazine, lomustine (CCNU) and vincristine - is one of the treatment options at recurrence. There has been no meta-analysis which looks at the benefits and harms of PCV chemotherapy in adults with recurrent HGG. To assess the effectiveness and safety of procarbazine, lomustine, and vincristine (PCV) chemotherapy with other interventions in adults with recurrent high-grade glioma. To investigate whether predefined subgroups of people benefit more or less from chemotherapy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4, 2017), MEDLINE (1946 to 22 May 2017), and Embase (1980 to 22 May 2017). We searched trial registries including the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch) and the National Institutes of Health (NIH; ClinicalTrials.gov). We searched the reference lists of all identified studies; the electronic table of contents of the Journal of Neuro-Oncology (1983 to 2016) and Neuro-Oncology (1999 to 2016); and conference abstracts from the Society for Neuro-Oncology (SNO) and the American Society of Clinical Oncology (ASCO 2004 to 2016). We also searched unpublished grey literature and other regional databases. There were no language restrictions. Randomised controlled trials (RCTs), quasi-randomised trials (QRCTs), or controlled clinical trials (CCTs) where PCV was used to treat adults with recurrent HGG. Comparison arm included no chemotherapy, other second line chemotherapy or best supportive care. Two review authors extracted the data and undertook a 'Risk of bias' assessment and critical appraisal of the studies. We identified two RCTs meeting our inclusion criteria. The two trials tested different comparisons.One RCT included 35 participants and compared PCV

  14. A Highly Miniaturized Inertial Grade Gyroscope for Space Applications

    NASA Technical Reports Server (NTRS)

    Wiberg, D. V.; Challoner, A. D.; Shcheglov, K.; Hayworth, K.; Bae, S.; Yee, K.; Blaes, B.; DAgostino, S.; Stock, T.

    2001-01-01

    The evolution of inertial grade gyroscopes for space applications represents well over 50 years of technology development and an investment of hundreds of millions of dollars. The workhorse product which represents the current state-of-the art for commercially available high performance devices is the Litton-Hemishperical Resonator Gyro (HRG) Inertial Measurement Unit (IMU). This product has a performance figure of merit of 0.003 deg/hr bias drift, a volume of 567 cubic inches, weighs 19 pounds, draws about 30 watts and costs over $1 million each. Clearly devices of this magnitude are not conducive to the minimized mass, volume, power, and cost constraints of outer planet missions. An approach to breaking these potential barriers is the use of Microelectromechanical Systems (MEMS) based inertial devices. Although substantially reduced in size, mass power and cost, this approach has produced devices in the tactical performance range of greater than 1 deg/hour bias drift. This level of performance satisfies the preponderance of high market volume requirements such as automotive and tactical munitions but does not meet the limited market quantity requirements for the high precision space based market. Because of the very limited size of the space based market, there is little economic incentive for commercial fabricators of tactical grade devices to address the necessary performance improvements. The Jet Propulsion Laboratory (JPL) in conjunction with Boeing Space Systems (BSS) is addressing this void to satisfy our mutual requirements in this area. The project objective to is to achieve 0.01 deg/hr performance in an IMU which is less than 10 cubic inches in volume, weighs less than 0.5 pounds, draws less than 1 watt and is available in volume production for less than $2500. Reductions of this magnitude will be mission enabling capabilities for a variety of anticipated outer planet mission attributes such as autonomous control and docking, formation flying and robotic

  15. Surgical interventions for high grade vulval intraepithelial neoplasia

    PubMed Central

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

    2014-01-01

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

  16. A Highly Miniaturized Inertial Grade Gyroscope for Space Applications

    NASA Technical Reports Server (NTRS)

    Wiberg, D. V.; Challoner, A. D.; Shcheglov, K.; Hayworth, K.; Bae, S.; Yee, K.; Blaes, B.; DAgostino, S.; Stock, T.

    2001-01-01

    The evolution of inertial grade gyroscopes for space applications represents well over 50 years of technology development and an investment of hundreds of millions of dollars. The workhorse product which represents the current state-of-the art for commercially available high performance devices is the Litton-Hemishperical Resonator Gyro (HRG) Inertial Measurement Unit (IMU). This product has a performance figure of merit of 0.003 deg/hr bias drift, a volume of 567 cubic inches, weighs 19 pounds, draws about 30 watts and costs over $1 million each. Clearly devices of this magnitude are not conducive to the minimized mass, volume, power, and cost constraints of outer planet missions. An approach to breaking these potential barriers is the use of Microelectromechanical Systems (MEMS) based inertial devices. Although substantially reduced in size, mass power and cost, this approach has produced devices in the tactical performance range of greater than 1 deg/hour bias drift. This level of performance satisfies the preponderance of high market volume requirements such as automotive and tactical munitions but does not meet the limited market quantity requirements for the high precision space based market. Because of the very limited size of the space based market, there is little economic incentive for commercial fabricators of tactical grade devices to address the necessary performance improvements. The Jet Propulsion Laboratory (JPL) in conjunction with Boeing Space Systems (BSS) is addressing this void to satisfy our mutual requirements in this area. The project objective to is to achieve 0.01 deg/hr performance in an IMU which is less than 10 cubic inches in volume, weighs less than 0.5 pounds, draws less than 1 watt and is available in volume production for less than $2500. Reductions of this magnitude will be mission enabling capabilities for a variety of anticipated outer planet mission attributes such as autonomous control and docking, formation flying and robotic

  17. Claspin as a biomarker of human papillomavirus-related high grade lesions of uterine cervix

    PubMed Central

    2012-01-01

    Background Claspin is a nuclear protein involved in DNA replication and damage response and is a key mediator for the S-phase checkpoint. Claspin expression is significantly high in several human solid tumors. Furthermore, high levels of claspin have been found in cervical cancer cell lines. Nevertheless, no data are available regarding claspin expression in cervical tissues. Methods In order to investigate whether claspin immunoreactivity is related to the lesion severity and High-Risk (HR) HPV infection, we analyzed claspin expression by immunohistochemistry in a series of cervical biopsies which represent the steps occurring during cervical carcinogenesis (normal tissues, Cervical Intraepithelial Neoplasias 1, 2 and 3, Squamous Cell Carcinomas). All patients also had a cervico-vaginal sample for HPV testing, collected immediately before the colposcopy-guided biopsy. The HR-HPV DNA detection was performed by the HR-HPV Hybrid Capture 2 test. HPV genotyping was performed using the Linear Array HPV Genotyping Test. Results Our results evidenced a constant and significant increase of the rate of claspin positivity from the normal tissues to carcinomas (pχ2trend < 0.0001). In fact, the normal tissues displayed either no or faint claspin immunoreactivity, whereas a moderate/high positivity was observed in 16% of the CIN1, 76% of the CIN2, 87.5% of the CIN3 and 93.3% of the cancers. Moreover, we found a statistically significant correlation between claspin expression and HR-HPV infection (pχ2 < 0.0001), irrespective of the genotype. Finally, we demonstrated the feasibility of claspin immunostaining in cervical cytology. Conclusions Our findings indicate that in vivo claspin expression is significantly related to HR-HPV infection and lesion grade both in histological and cytological samples. Therefore, the analysis of claspin expression could be clinically relevant in the diagnosis of HPV-related cervical lesions, in particular when applied to cervico

  18. Significance of a minor high-grade component in a low-grade noninvasive papillary urothelial carcinoma of bladder.

    PubMed

    Reis, Leonardo O; Taheri, Diana; Chaux, Alcides; Guner, Gunes; Mendoza Rodriguez, Maria A; Bivalacqua, Trinity J; Schoenberg, Mark P; Epstein, Jonathan I; Netto, George J

    2016-01-01

    To assess the clinicopathological features and prognostic significance of the presence of 5% or less high-grade component in otherwise low-grade noninvasive bladder urothelial carcinoma, referred to as mixed-grade (MG) urothelial carcinoma, we reviewed all archival cases with such diagnosis between 2005 and 2014. Clinicopathological and outcome parameters were compared to those in our previously reported low- and high-grade noninvasive bladder urothelial carcinoma cohorts (LGUC and HGUC, respectively). The study included 31 MG urothelial carcinomas. Mean patient age was 67.6 years, and mean follow-up was 39.7 months. Intravesical treatment was administered in 15 patients (48.4%). Recurrence occurred in 14 cases (45.2%): 10 as LGUC and 4 as HGUC; there was no stage progression. Mean time to progression was 9 months (5-17 months), and there was no death of disease. MG urothelial carcinoma stage progression and dead of disease rates were comparable to that of LGUC. MG urothelial carcinoma stage progression was significantly lower than that of HGUC, P = .002, using Pearson χ(2) test. MG urothelial carcinoma patients with no intravesical treatment had higher incidence rate of grade progression (25%) compared to LGUC patients (7.9%); however, the difference was not statistically significant. MG urothelial carcinoma had a prognosis closer to "pure" LGUC than "pure" HGUC. Untreated MG urothelial carcinoma may have a higher rate of grade progression than LGUC, although more data are needed before this issue can be definitively addressed. Until such data are available, it is reasonable to keep MG urothelial carcinoma as a distinct grade category with potential management implications.

  19. Anal Squamous Intraepithelial Lesions and HPV Among Young Black Men Who Have Sex with Men.

    PubMed

    Keglovitz, Kristin; Richardson, Andrew D; Lancki, Nicola; Walsh, Tim; Schneider, John A

    2017-02-01

    Limited data are available on anal squamous intraepithelial lesions (ASILs) and anal human papillomavirus (HPV) infection in young, Black populations. The purpose of this study was to examine the prevalence of and relationships between ASILs and high-risk HPV infection in a young (<30 years of age), predominantly Black, men who have sex with men (MSM) population. Results of anal cytology and HPV DNA were gathered for 83 individuals. Forty-two percent of individuals (35) had atypical squamous cells of undetermined significance and 33% (27) had low-grade squamous intraepithelial lesion by cytology. Only 9% tested positive for both high-risk HPV subtypes 16 and 18. Low rates of infection with both HPV types 16 and 18 may provide further evidence that we should continue to vaccinate young, Black MSM against HPV.

  20. Anal Squamous Intraepithelial Lesions and HPV Among Young Black Men Who Have Sex with Men

    PubMed Central

    Keglovitz, Kristin; Lancki, Nicola; Walsh, Tim; Schneider, John A.

    2017-01-01

    Abstract Purpose: Limited data are available on anal squamous intraepithelial lesions (ASILs) and anal human papillomavirus (HPV) infection in young, Black populations. The purpose of this study was to examine the prevalence of and relationships between ASILs and high-risk HPV infection in a young (<30 years of age), predominantly Black, men who have sex with men (MSM) population. Methods: Results of anal cytology and HPV DNA were gathered for 83 individuals. Results: Forty-two percent of individuals (35) had atypical squamous cells of undetermined significance and 33% (27) had low-grade squamous intraepithelial lesion by cytology. Only 9% tested positive for both high-risk HPV subtypes 16 and 18. Conclusion: Low rates of infection with both HPV types 16 and 18 may provide further evidence that we should continue to vaccinate young, Black MSM against HPV. PMID:27673362

  1. Participation and risk of high grade cytological lesions among immigrants and Italian-born women in an organized cervical cancer screening program in Central Italy.

    PubMed

    Visioli, Carmen Beatriz; Crocetti, Emanuele; Zappa, Marco; Iossa, Anna; Andersson, Karin Louise; Bulgaresi, Paolo; Alfieri, Antonia; Amunni, Gianni

    2015-06-01

    Few studies analyzed the risk for high-grade squamous intraepithelial lesions or worse (HSIL+) among immigrants and natives attending organized cervical cancer (CC) screening programs (SP). We evaluated participation and diagnosis of HSIL+ by country of birth with logistic models. Overall 540,779 invitation letters were delivered to target women of Florence SP in three screening rounds (years 2000-2002, 2003-2005, 2006-2008). The probability of attending screening was lower for immigrants than natives, but the difference decreased from 35% (1st round) to 20% (2nd-3rd round) for women born in high migration pressure (HMP) countries. The risk of HSIL+ was double than natives for HMP-born women from countries with high prevalence of human papillomavirus, even adjusting for age and previous history of Pap test. This is an important public health problem due to an increasing proportion over time of immigrant women with a lower attendance and greater risk for CC.

  2. High Vimentin Expression Associated with Lymph Node Metastasis and Predicated a Poor Prognosis in Oral Squamous Cell Carcinoma

    PubMed Central

    Liu, Shuli; Liu, Liu; Ye, Weimin; Ye, Dongxia; Wang, Tong; Guo, Wenzheng; Liao, Yueling; Xu, Dongliang; Song, Hongyong; Zhang, Ling; Zhu, Hanguang; Deng, Jiong; Zhang, Zhiyuan

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is a common public health problem worldwide with poor prognosis, which is largely due to lymph node metastasis and recurrence. Identification of specific molecular markers of OSCC with lymph node metastasis would be very important for early and specific diagnosis. In this study, we screened for the potential prognosis markers via unbiased transcriptomic microarray analysis in paired two OSCC cell lines, a lymph node metastatic HN12 cell line and a low metastatic parental HN4 cell line. The results showed that vimentin, with 87-fold increase of expression, was on the top of all upregulated genes in metastatic HN12 cells compared to non-metastatic HN4 cells. Treatment of non-metastatic HN4 cells with TGF-β1 induced epithelial to mesenchymal transition (EMT), with increased vimentin expression as well as enhanced migration activity. Consistently, knockdown of vimentin via siRNA resulted in suppressed invasion and migration activities of HN12 cells, suggesting an essential role of vimentin in EMT-related functions of OSCC cells. Finally, immunohistochemical (IHC) staining analysis showed that high vimentin expression was strongly associated with high lymph node metastases (p < 0.05), and poor overall survival (p < 0.05) in OSCC patients. Thus, high vimentin expression is strongly associated with increased metastatic potential, and may serve as a prediction marker for poor prognosis in OSCC patients. PMID:27966589

  3. Magnetic fabric and welding processes in high-grade tuffs

    NASA Astrophysics Data System (ADS)

    Pioli, L.; Ort, M.; Lanza, R.; Rosi, M.

    2003-04-01

    The welding fabric of tuffs is generally quantified through two main parameters: porosity and fiamme aspect ratio. However, these parameters are not useful for high-grade ignimbrites that display features indicating extensive rheomorphic flow, partial to complete obliteration of primary vitroclastic textures, and syn-depositional welding rather than load-related compaction. In this case, a 3D-microstructural characterization of the rock fabric is a fundamental proxy for the assessment of the dynamics and duration of welding processes. We have investigated the relations between magnetic fabric and welding textures in a rhyolitic, high-grade ignimbrite from the Sulcis volcanic District (SW Sardinia, Italy). The ignimbrite is characterized by dense welding throughout its preserved thickness and by regular lateral and vertical variations of welding, devitrification and vesiculation facies. Field and structural data indicate that syn-depositional welding and non-particulate (NP) flow were extensive and continuous during the emplacement of the ignimbrite. Paleomagnetic measurements of AMS, NRM, and AIRM of samples from the tuff indicate that the magnetic fabric is strain-sensitive and it is not significantly affected by post-depositional, static processes such as devitrification and vapor-phase alteration; in particular, magnetic susceptibility of the rock and the welding texture correlate well in terms of shape and orientation of the anisotropy ellipsoid. The direction of the K1 axis is indicative of the flow direction in the site of measurement. The anisotropy degree (P) increases with increasing welding and foliation (F) and lineation (L) are directly related to the strain facies. Onset of welding increased the degree of anisotropy and foliation; a non particulate, laminar flow stage further deformed the fabric stretching it along the flow direction and thus increasing L. The intensity of L is strictly related to the duration and the effect of simple shear (laminar

  4. Concurrent thermochemoradiotherapy for brain high-grade glioma

    NASA Astrophysics Data System (ADS)

    Ryabova, A. I.; Novikov, V. A.; Choinzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G.; Baranova, A. V.

    2016-08-01

    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  5. Concurrent thermochemoradiotherapy for brain high-grade glioma

    SciTech Connect

    Ryabova, A. I. Novikov, V. A.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G.; Choinzonov, E. L.; Gribova, O. V.; Baranova, A. V.

    2016-08-02

    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  6. A novel graded bioactive high adhesion implant coating

    NASA Astrophysics Data System (ADS)

    Brohede, Ulrika; Zhao, Shuxi; Lindberg, Fredrik; Mihranyan, Albert; Forsgren, Johan; Strømme, Maria; Engqvist, Håkan

    2009-06-01

    One method to increase the clinical success rate of metal implants is to increase their bone bonding properties, i.e. to develop a bone bioactive surface leading to reduced risks of interfacial problems. Much research has been devoted to modifying the surface of metals to make them become bioactive. Many of the proposed methods include depositing a coating on the implant. However, there is a risk of coating failure due to low substrate adhesion. This paper describes a method to obtain bioactivity combined with a high coating adhesion via a gradient structure of the coating. Gradient coatings were deposited on Ti (grade 5) using reactive magnetron sputtering with increasing oxygen content. To increase the grain size in the coating, all coatings were post annealed at 385 °C. The obtained coating exhibited a gradual transition over 70 nm from crystalline titanium oxide (anatase) at the surface to metallic Ti in the substrate, as shown using cross-section transmission electron microscopy and X-ray photoelectron spectroscopy depth profiling. Using scratch testing, it could be shown that the adhesion to the substrate was well above 1 GPa. The bioactivity of the coating was verified in vitro by the spontaneous formation of hydroxylapatite upon storage in phosphate buffer solution at 37 °C for one week. The described process can be applied to implants irrespective of bulk metal in the base and should introduce the possibility to create safer permanent implants like reconstructive devices, dental, or spinal implants.

  7. Ultra High-Resolution Anterior Segment Optical Coherence Tomography in the Diagnosis and Management of Ocular Surface Squamous Neoplasia

    PubMed Central

    Thomas, Benjamin J.; Galor, Anat; Nanji, Afshan A.; Sayyad, Fouad El; Wang, Jianhua; Dubovy, Sander R.; Joag, Madhura G.; Karp, Carol L.

    2014-01-01

    The development of optical coherence tomography (OCT) technology has helped to usher in a new era of in vivo diagnostic imaging of the eye. The utilization of OCT for imaging of the anterior segment and ocular surface has evolved from time-domain devices to spectral-domain devices with greater penetrance and resolution, providing novel images of anterior segment pathology to assist in diagnosis and management of disease. Ocular surface squamous neoplasia (OSSN) is one such pathology that has proven demonstrable by certain anterior segment OCT machines, specifically the newer devices capable of performing ultra high-resolution OCT (UHR-OCT). Distinctive features of OSSN on high resolution OCT allow for diagnosis and differentiation from other ocular surface pathologies. Subtle findings on these images help to characterize the OSSN lesions beyond what is apparent with the clinical examination, providing guidance for clinical management. The purpose of this review is to examine the published literature on the utilization of UHR-OCT for the diagnosis and management of OSSN, as well as to report novel uses of this technology and potential directions for its future development. PMID:24439046

  8. Fibronectin Modulates Cell Adhesion and Signaling to Promote Single Cell Migration of Highly Invasive Oral Squamous Cell Carcinoma

    PubMed Central

    Ramos, Grasieli de Oliveira; Bernardi, Lisiane; Lauxen, Isabel; Sant’Ana Filho, Manoel; Horwitz, Alan Rick; Lamers, Marcelo Lazzaron

    2016-01-01

    Cell migration is regulated by adhesion to the extracellular matrix (ECM) through integrins and activation of small RhoGTPases, such as RhoA and Rac1, resulting in changes to actomyosin organization. During invasion, epithelial-derived tumor cells switch from laminin-enriched basal membrane to collagen and fibronectin-enriched connective tissue. How this switch affects the tumor migration is still unclear. We tested the hypothesis that ECM dictates the invasiveness of Oral Squamous Cell Carcinoma (OSCC). We analyzed the migratory properties of two OSCC lines, a low invasive cell line with high e-cadherin levels (Linv/HE-cad) or a highly invasive cell line with low e-cadherin levels (Hinv/LE-cad), plated on different ECM components. Compared to laminin, fibronectin induced non-directional collective migration and decreased RhoA activity in Linv/HE-cad OSCC. For Hinv/LE-cad OSCC, fibronectin increased Rac1 activity and induced smaller adhesions, resulting in a fast single cell migration in both 2D and 3D environments. Consistent with these observations, human OSCC biopsies exhibited similar changes in cell-ECM adhesion distribution at the invasive front of the tumor, where cells encounter fibronectin. Our results indicate that ECM composition might induce a switch from collective to single cell migration according to tumor invasiveness due to changes in cell-ECM adhesion and the resulting signaling pathways that alter actomyosin organization. PMID:26978651

  9. High-Performance Slab-on-Grade Foundation Insulation Retrofits

    SciTech Connect

    Goldberg, Louise F.; Mosiman, Garrett E.

    2015-09-01

    A more accurate assessment of slab-on-grade foundation insulation energy savings than traditionally possible is now feasible. This has been enabled by advances in whole building energy simulation with 3-dimensional foundation modelling integration at each time step together with an experimental measurement of the site energy savings of SOG foundation insulation. Ten SOG insulation strategies were evaluated on a test building to identify an optimum retrofit insulation strategy in a zone 6 climate (Minneapolis, MN). The optimum insulation strategy in terms of energy savings and cost effectiveness consisted of two components: (a) R-20 XPS insulation above grade, and, (b) R-20 insulation at grade (comprising an outer layer of R-10 insulation and an interior layer of R-12 poured polyurethane insulation) tapering to R-10 XPS insulation at half the below-grade wall height (the lower half of the stem wall was uninsulated).

  10. Diffuse reflectance spectroscopy can differentiate high grade and low grade prostatic carcinoma.

    PubMed

    Werahera, Priya N; Jasion, Edward A; David Crawford, E; Lucia, M Scott; van Bokhoven, Adrie; Sullivan, Holly T; Kim, Fernando J; Maroni, Paul D; David Port, J; Daily, John W; Rosa, Francisco G La; Werahera, Priya N; Jasion, Edward A; Crawford, E David; Lucia, M Scott; van Bokhoven, Adrie; Sullivan, Holly T; Kim, Fernando J; Maroni, Paul D; Port, J David; Daily, John W; La Rosa, Francisco G; Daily, John W; Van Bokhoven, Adrie; Crawford, E David; Port, J David; Werahera, Priya N; Lucia, M Scott; Sullivan, Holly T; Maroni, Paul D; Jasion, Edward A; La Rosa, Francisco G; Kim, Fernando J

    2016-08-01

    Prostate tumors are graded by the revised Gleason Score (GS) which is the sum of the two predominant Gleason grades present ranging from 6-10. GS 6 cancer exclusively with Gleason grade 3 is designated as low grade (LG) and correlates with better clinical prognosis for patients. GS >7 cancer with at least one of the Gleason grades 4 and 5 is designated as HG indicate worse prognosis for patients. Current transrectal ultrasound guided prostate biopsies often fail to correctly diagnose HG prostate cancer due to sampling errors. Diffuse reflectance spectra (DRS) of biological tissue depend on tissue morphology and architecture. Thus, DRS could potentially differentiate between HG and LG prostatic carcinoma. A 15-gauge optical biopsy needle was prototyped to take prostate biopsies after measuring DRS with a laboratory fluorometer. This needle has an optical sensor that utilizes 8×100 μm optical fibers for tissue excitation and a single 200 μm central optical fiber to measure DRS. Tissue biopsy cores were obtained from 20 surgically excised prostates using this needle after measuring DRS at 5 nm intervals between 500-700 nm wavelengths. Tissue within a measurement window was histopathologically classified as either benign, LG, or HG and correlated with DRS. Partial least square analysis of DRS identified principal components (PC) as potential classifiers. Statistically significant PCs (p<;0.05) were tested for their ability to classify biopsy tissue using support vector machine and leave-one-out cross validation method. There were 29 HG and 49 LG cancers among 187 biopsy cores included in the study. Study results show 76% sensitivity, 80% specificity, 93% negative predictive value, and 50% positive predictive value for HG versus benign, and 76%, 73%, 84%, and 63%, for HG versus LG prostate tissue classification. DRS failed to diagnose 7/29 (24%) HG cancers. This study demonstrated that an optical biopsy needle guided by DRS has sufficient accuracy to differentiate HG

  11. HPV-related squamous neoplasia of the lower anogenital tract: an update and review of recent guidelines.

    PubMed

    Maniar, Kruti P; Nayar, Ritu

    2014-09-01

    Squamous cell carcinomas of the lower anogenital tract that are related to human papillomavirus (HPV) infection represent a significant disease burden worldwide. The diagnosis and management of their noninvasive precursors has been the subject of extensive study and debate over several decades, accompanied by an evolving understanding of HPV biology. Recent new consensus recommendations for the pathologic diagnosis of these precursor lesions were published in 2012, the result of the Lower Anogenital Squamous Terminology project cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Most salient among the new guidelines are the recommendation to switch to a 2-tiered nomenclature (high-grade squamous intraepithelial lesion and low-grade squamous intraepithelial lesion) rather than the traditional 3-tiered "intraepithelial neoplasia" terminology, and the recommendation to expand use of the immunohistochemical marker p16 to distinguish between low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion/intraepithelial neoplasia 2. The goals of the project were to align diagnostic terminology with our knowledge of HPV biology, increase reproducibility, consolidate diverse systems of nomenclature, and ultimately better determine a patient's true cancer risk. The clinical guidelines for screening and management of cervical intraepithelial neoplasia have also been recently updated, most notably with a lengthening of screening intervals. In this review, we focus on the new guidelines put forth for pathologic diagnosis of HPV-related anogenital neoplasia, with discussion of the evidence behind them and their potential implications. We also provide an update on relevant biomarkers, clinical recommendations, and the newest developments relating to cervical neoplasia.

  12. Squamous-cell Carcinoma of the Anus and Anal Canal: An Analysis of 55 Cases

    PubMed Central

    Gabriel, W. B.

    1941-01-01

    The analysis is of 55 cases admitted into St. Mark's Hospital from 1922 to 1940. The incidence was 3.35% of all cases of cancer of the rectum, anal canal and anus admitted during this period. Sex distribution—27 males and 28 females. The average age (61.7 years) is higher than that of columnar-cell carcinoma of the rectum (57.4 years). Histology.—The cases have been graded into three grades of malignancy—low grade, medium grade, and high grade. Low grade squamous carcinoma is twice as frequent in men as in women, and generally originates at the anal margin. Medium grade squamous carcinoma is equally distributed between men and women; it may arise at the anus or in the anal canal. High grade squamous carcinoma is much more common in the female sex and is almost entirely limited to the anal canal. Quadrant affected—about one-third of the anal margin growths and one-half of the anal canal growths were situated anteriorly. Differential diagnosis from simple papilloma, simple ulcer, chronic inflammation, tuberculous ulcer, tuberculide, primary chancre, amœbic ulcer, basal-cell carcinoma, columnar-cell carcinoma. Biopsy and grading essential before treatment is decided upon. The results of treatment in the three grades of malignancy are described. The best results were obtained in the early low-grade cases treated by interstitial radium needling. In the medium and high grades only three five-year survivals can be reported and these followed excision of the rectum. The management of the inguinal glands is discussed and the importance of a very close post-operative supervision emphasized. Squamous carcinoma of the anal canal may cause lymphatic metastases in the superior hæmorrhoidal glands; there have been four such cases in this series. Diathermy perineal excision is indicated in these cases. ImagesFig. 1Fig. 2Fig. 3Fig. 5Fig. 6aFig. 6bFig. 7Fig. 1Fig. 2Fig. 3Fig. 4 PMID:19992316

  13. The significance of marked nuclear atypia in grade 1 cervical intraepithelial neoplasia.

    PubMed

    Fadare, Oluwole; Rodriguez, Rosemarie

    2009-10-01

    Approximately 10% to 15% of cases of grade 1 cervical intraepithelial neoplasia are found to have progressed to a high-grade squamous intraepithelial lesion or higher at follow-up, and there are presently no reliable morphological predictors of this subset. It has recently been reported that cases of grade 1 cervical intraepithelial neoplasia that display marked nuclear atypia (defined as cases with at least 5 epithelial cells with nuclear enlargement of at least 5 times the size of an intermediate cell, and/or multinucleation of at least 5 nuclei.) have a substantially higher rate of high-grade squamous intraepithelial lesion on short-term follow-up and may, therefore, require more aggressive initial management. We report herein our experience with a cohort of such cases. After a review of consecutive cervical biopsies, 352 cases with grade 1 cervical intraepithelial neoplasia were classified into group 1 (grade 1 cervical intraepithelial neoplasia with marked atypia, n = 31) and group 2 (grade 1 cervical intraepithelial neoplasia without marked atypia, n = 321). The average follow-up rates for groups 1 and 2 were 93.55% (29/31) and 90.65% (291/321), respectively. Average follow-up durations were 14.3 and 17.9 months, respectively. The follow-up high-grade squamous intraepithelial lesion rate of the cases with marked atypia was 10.34%, as compared with 11.68% for cases without marked atypia. The follow-up interpretive frequency (in cytologic samples) of "low-grade squamous intraepithelial lesion" was significantly higher in group 1(19/29 versus 114/291, P = .009). However, no significant differences were identified between groups 1 and 2 regarding the interpretive frequencies of either high-grade squamous intraepithelial lesion (3/29 versus 34/291, P = 1) or "negative for intraepithelial lesion or malignancy" (6/29 versus 56/291, P = .8) in follow-up cytologic samples. In subsets of both groups in which high-risk human papillomavirus testing was performed in the

  14. New Perspectives on the Correlation of SAT Scores, High School Grades, and Socioeconomic Factors

    ERIC Educational Resources Information Center

    Zwick, Rebecca; Greif Green, Jennifer

    2007-01-01

    In studies of the SAT, correlations of SAT scores, high school grades, and socioeconomic factors (SES) are usually obtained using a university as the unit of analysis. This approach obscures an important structural aspect of the data: The high school grades received by a given institution come from a large number of high schools, all of which have…

  15. DAP1 high expression increases risk of lymph node metastases in squamous cell carcinoma of the oral cavity.

    PubMed

    Santos, M; Maia, L L; Silva, C V M; Peterle, G T; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-09-08

    Death-associated protein 1 (DAP1) is a member of the DAP family. Its expression is associated with cell growth and normal death of the neoplastic cells, regulated by the mammalian target of the rapamycin protein. Activated DAP1 negatively regulates autophagy, which has been associated with the development and progression of several diseases, such as cancer, and with prognosis and survival of diverse tumor types. Therefore, in this study we analyzed DAP1 expression in 54 oral squamous cell carcinoma tumor samples and in 20 non-tumoral margins by immunohistochemistry. The results showed that DAP1 is more frequently expressed in tumor tissues compared with marginal non-tumoral cells. Additionally, high DAP1 expression is associated with a 4-fold increase in the risk of lymph node metastases. Our results suggest that the DAP1 protein can be used as a potential marker of lymph node metastases predisposition, helping define the best therapy for each patient to minimize risk of developing metastases.

  16. Differential mRNA expression profiling of oral squamous cell carcinoma by high-throughput RNA sequencing

    PubMed Central

    Ge, Liangyu; Liu, Siyu; Xie, Long; Sang, Lei; Ma, Changyan; Li, Hongwei

    2015-01-01

    Abstract Differentially expressed genes are thought to regulate the development and progression of oral squamous cell carcinomas (OSCC). The purpose of this study was to screen differentially expressed mRNAs in OSCC and matched paraneoplastic normal tissues, and to explore the intrinsic mechanism of OSCC development and progression. We obtained the differentially expressed mRNA expression profiles in 10 pairs of fresh-frozen OSCC tissue specimens and matched paraneoplastic normal tissue specimens by high-throughput RNA sequencing. By using Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, the functional significance of the differentially expressed genes were analyzed. We identified 1,120 significantly up-regulated mRNAs and 178 significantly down-regulated mRNAs in OSCC, compared to normal tissue. The differentially expressed mRNAs were involved in 20 biological processes and 68 signal pathways. Compared to adjacent normal tissue, the expression of MAGEA11 was up-regulated; TCHH was down-regulated. These findings were verified by real-time PCR. These differentially expressed mRNAs may function as oncogenes or tumor suppressors in the development and progression of OSCC. This study provides novel insights into OSCC. However, further work is needed to determine if these differentially expressed mRNAs have potential roles as diagnostic biomarkers and candidate therapeutic targets for OSCC. PMID:26273018

  17. High Prevalence of Discordant HPV and p16 Oropharynx Squamous Cell Carcinomas in an African American Cohort

    PubMed Central

    Liu, Jeffrey C.; Parajuli, Shobha; Blackman, Elizabeth; Gibbs, Denise; Ellis, Ashley; Hull, Anna; Beck, J Robert; Giri, Veda; Iherjirka, Patrick; Khurana, Jasvir S.; Ragin, Camille R

    2015-01-01

    Background Most studies on Human Papilloma Virus associated oropharynx squamous cell carcinoma (HPV OPSCC) have been performed in whites. Our study examined the incidence of HPV in an African American (AA) OPSCC cohort and its survival. Methods AA OPSCC patients in a combined tumor registry were identified. HPV16 testing was performed by PCR from DNA extracted from tumor blocks. p16 staining was performed using standard immunohistochemistry. Results 44 patients were identified for analysis. 73% of tumors were HPV positive. Only 39% of HPV+ patients were also p16+. Survival between all three tumor types, HPV+/p16, HPV+/p16+,and HPV−/p16− patients was significantly different. (p=0.03). HPV/p16 status was significant on univariate and multivariate analysis. Conclusions HPV OPSCC is strongly present in this AA cohort. Two-thirds of HPV positive patients were p16 negative. Greater study is needed to explain the high p16 negativity amongst this HPV+ OPSCC AA cohort. PMID:25962720

  18. Opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of Iran.

    PubMed

    Nasrollahzadeh, D; Kamangar, F; Aghcheli, K; Sotoudeh, M; Islami, F; Abnet, C C; Shakeri, R; Pourshams, A; Marjani, H A; Nouraie, M; Khatibian, M; Semnani, S; Ye, W; Boffetta, P; Dawsey, S M; Malekzadeh, R

    2008-06-03

    The very high incidence of oesophageal squamous cell carcinoma (ESCC) in Golestan Province in northeastern Iran was suggested by studies in the 1970s as partly due to opium use, which is not uncommon in this area, but based on limited numbers. From December 2003 to June 2007, we administered a validated structured questionnaire to 300 ESCC cases and 571 controls, matched on neighbourhood of residence, age (+/-2 years), and sex. We used conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for potential confounders. Compared with those who used neither tobacco nor opium, risk of ESCC was increased in those who used tobacco only (OR, 95% CI: 1.70, 1.05-2.73), in those who used opium only (2.12, 1.21-3.74), and in those who used both tobacco and opium (2.35, 1.50-3.67). All forms of tobacco use (cigarettes, hookah, and nass) were associated with higher ESCC risk. Similarly, use of both crude opium and other forms of opium were associated with higher risk. Alcohol consumption was seen in only 2% of the cases and 2% of the controls, and was not associated with ESCC risk.

  19. Opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of Iran

    PubMed Central

    Nasrollahzadeh, D; Kamangar, F; Aghcheli, K; Sotoudeh, M; Islami, F; Abnet, C C; Shakeri, R; Pourshams, A; Marjani, H A; Nouraie, M; Khatibian, M; Semnani, S; Ye, W; Boffetta, P; Dawsey, S M; Malekzadeh, R

    2008-01-01

    The very high incidence of oesophageal squamous cell carcinoma (ESCC) in Golestan Province in northeastern Iran was suggested by studies in the 1970s as partly due to opium use, which is not uncommon in this area, but based on limited numbers. From December 2003 to June 2007, we administered a validated structured questionnaire to 300 ESCC cases and 571 controls, matched on neighbourhood of residence, age (±2 years), and sex. We used conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for potential confounders. Compared with those who used neither tobacco nor opium, risk of ESCC was increased in those who used tobacco only (OR, 95% CI: 1.70, 1.05–2.73), in those who used opium only (2.12, 1.21–3.74), and in those who used both tobacco and opium (2.35, 1.50–3.67). All forms of tobacco use (cigarettes, hookah, and nass) were associated with higher ESCC risk. Similarly, use of both crude opium and other forms of opium were associated with higher risk. Alcohol consumption was seen in only 2% of the cases and 2% of the controls, and was not associated with ESCC risk. PMID:18475303

  20. Distribution and attribution of high-risk human papillomavirus genotypes in cervical precancerous lesions in China.

    PubMed

    Wang, Wenpeng; An, Jusheng; Song, Yan; Wang, Minjie; Huang, Manni; Wu, Lingying

    2017-07-01

    While human papillomavirus vaccine was recently approved by China Food and Drug Administration, mapping of high-risk human papillomavirus distribution and attribution in cervical precancerous lesions in China becomes critical in development of a high-risk human papillomavirus-based cervical cancer screening and prevention strategy. In total, 1016 patients with cervical precancerous lesions diagnosed in the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively, including 111 patients with low-grade squamous intraepithelial lesions and 905 patients with high-grade squamous intraepithelial lesions. HPV16, 58, 52, 33, and 31 were the most common high-risk human papillomavirus genotypes in order of decreasing frequency among high-risk human papillomavirus-positive high-grade squamous intraepithelial lesions; this differed from the high-risk human papillomavirus distribution in low-grade squamous intraepithelial lesions (HPV16, 52, 39, 56, and 58). The distribution of high-risk human papillomavirus genotypes in single-type infections for high-grade squamous intraepithelial lesions (HPV16, 58, 33, and 52) was similar to that in multiple-type infections (HPV16, 58, 52, and 33). By contrast, a more diverse distribution spectrum of high-risk human papillomavirus genotypes for low-grade squamous intraepithelial lesions was observed between single-type (HPV16, 52, 39, and 56) and multiple-type infection (HPV52, 68, 58, 59, 39 and 56). A previously published method was adopted to calculate the fractional proportion of individual high-risk human papillomavirus genotypes in multiple infections. For this proportional attribution, HPV16 (48.9%), 58 (10.0%), 33 (5.5%), and 52 (5.5%) were the most frequent among all high-grade squamous intraepithelial lesions, whereas HPV16 (13.2%), 52 (11.6%), 39 (9.5%), and 56 (7.6%) were the most frequent among all low-grade squamous intraepithelial lesions. Differences in high-risk human

  1. Effect of the treatment with β-glucan in women with cervical cytologic report of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (L-SIL).

    PubMed

    Laccetta, G; Carrone, A; Burratti, M; Mancino, P

    2015-04-01

    The aim of this study was to evaluate the effect of β-glucan in women with ASCUS or L-SIL, as detected by cervical cytologic screening. A total of 356 women with ASCUS or L-SIL were enrolled and divided into two groups: 1) 176 patients, treated with topical β-glucan; and 2) 180 patients who were only followed-up. The treatment consisted of two cycles of topical β-glucan applied once a day for 20 consecutive days and treatment separated by ten days. The effect of β-glucan was evaluated comparing Pap cytology results and colposcopic findings between treated patients and controls after 6 and 12 months of follow-up. After 6 months from enrollment, 63.1% (111/176) of patients treated with β-glucan had a negative Pap smear versus 45% (81/180) of controls (P<0.001), and 43.4% (36/83) of treated patients versus 18.2% (14/77) of controls experienced the disappearance of colposcopic lesions (P=0.001). At the end of the 12-month follow up, 83.5% (147/176) of treated patients versus 60% (108/180) of controls had a negative Pap smear (P<0.001), and 55.4% (46/83) of treated patients versus 24.7% (19/77) of controls experienced the disappearance of colposcopic lesions (P<0.001). No side effects were observed in treated patients. β-glucan increases the spontaneous regression rate of low-grade cytologic abnormalities as well as cervical findings.

  2. Extensive Regional Metastasis of High-Grade Mucoepidermoid Carcinoma of an Unknown Primary Tumor.

    PubMed

    Ghazali, Naseem; Flashburg, Alyssa; Ord, Robert A

    2017-04-01

    Mucoepidermoid carcinoma (MEC) is the most common salivary carcinoma. It arises most frequently in the major salivary glands, but can also arise in minor glands or intraosseous sites. MEC of an unknown primary occurs very rarely. The present report documents only the third case reported in medical studies. A 66-year-old man with previous carcinoma in situ (CIS) of the left posterior oral tongue that had been excised in 2004 and again in 2010 presented with a hard lymph node, 3 × 2 cm at level II of the right neck in July 2015. Positron emission tomography-computed tomography (PET-CT) revealed multiple, bilateral cervical lymphadenopathy, with no primary site identified. Fine needle aspiration biopsy and cytologic examination from the right neck was positive for malignancy, suggestive of metastatic squamous cell carcinoma. Panendoscopy and biopsy revealed CIS at the tongue bases and tonsils bilaterally (p16-negative). The patient's case was presented to a tumor board, and definitive concurrent cispl.atin-based chemoradiation was recommended for TisN2cM0, stage IVA oropharyngeal CIS, which was completed in November 2015. PET-CT in January 2015 showed complex interval changes, with some areas demonstrating improvement (ie, no uptake in the left neck) and worsening in others (ie, increased metabolic activity in the right neck), suggestive of residual disease. Repeat PET-CT in March 2016 showed increased nodal involvement and increasing standardized uptake value. Bilateral modified radical neck dissection was undertaken, and histologic examination showed high-grade MEC in 51 of 61 lymph nodes with extracapsular spread and soft tissue involvement. The patient died in May 2016 at 2 months after surgery. Metastatic MEC of an unknown primary is a diagnostic challenge. PET-CT might not be the most reliable diagnostic investigation to identify the primary or metastatic foci, such as was demonstrated in the present case. Copyright © 2016 American Association of Oral and

  3. Nimotuzumab in combination with radiotherapy in high grade glioma patients

    PubMed Central

    Solomon, Maria Teresa; Miranda, Nederlay; Jorrín, Eugenia; Chon, Ivonne; Marinello, Jorge Juan; Alert, José; Lorenzo-Luaces, Patricia; Crombet, Tania

    2014-01-01

    Nimotuzumab, a humanized antibody targeting epidermal growth factor receptor, has potent anti-proliferative, anti-angiogenic, and pro-apoptotic effects in vitro and in vivo. It also reduces the number of radio-resistant CD133+ glioma stem cells. The antibody has been extensively evaluated in patients with advanced head and neck, glioma, lung, esophageal, pancreatic, and gastric cancer. In this single institution experience, 35 patients with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) were treated with irradiation and 200 mg doses of nimotuzumab. The first 6 doses were administered weekly, together with radiotherapy, and then treatment continued every 21 days until 1 year. The median number of doses was 12, and the median cumulative dose was thus 2400 mg of nimotuzumab. The most frequent treatment-related toxicities were increase in liver function tests, fever, nausea, anorexia, asthenia, dizziness, and tremors. These adverse reactions were classified as mild and moderate. The median survival time was 12.4 mo or 27.0 mo for patients with GBM or AA patients, respectively, who received curative-intent radiotherapy in combination with the antibody. The survival time of a matched population treated at the same hospital with irradiation alone was decreased (median 8.0 and 12.2 mo for GBM and AA patients, respectively) compared with that of the patients who received nimotuzumab and curative-intent radiotherapy. We have thus confirmed that nimotuzumab is a very well-tolerated drug, lacking cumulative toxicity after maintenance doses. This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients. PMID:24521695

  4. Novel Oncogenic PDGFRA Mutations in Pediatric High-Grade Gliomas

    PubMed Central

    Paugh, Barbara S.; Zhu, Xiaoyan; Qu, Chunxu; Endersby, Raelene; Diaz, Alexander K.; Zhang, Junyuan; Bax, Dorine A.; Carvalho, Diana; Reis, Rui M.; Onar-Thomas, Arzu; Broniscer, Alberto; Wetmore, Cynthia; Zhang, Jinghui; Jones, Chris; Ellison, David W.; Baker, Suzanne J.

    2013-01-01

    The outcome for children with high-grade gliomas (HGG) remains dismal, with a two-year survival rate of only 10–30%. Diffuse intrinsic pontine glioma (DIPG) comprise a subset of HGG that arise in brainstem almost exclusively in children. Genome-wide analyses of copy number imbalances previously showed that platelet derived growth factor receptor alpha (PDGFRA) is the most frequent target of focal amplification in pediatric HGGs, including DIPGs. To determine whether PDGFRA is also targeted by more subtle mutations missed by copy number analysis, we sequenced all PDGFRA coding exons from a cohort of pediatric HGGs. Somatic activating mutations were identified in 14.4% (13/90) of non-brainstem pediatric HGGs and 4.7% (2/43) of DIPGs, including missense mutations and in-frame deletions and insertions not previously described. 40% of tumors with mutation showed concurrent amplification, while 60% carried heterozygous mutations. Six different mutations impacting different domains all resulted in ligand-independent receptor activation that was blocked by small molecule inhibitors of PDGFR. Expression of mutants in p53-null primary mouse astrocytes conferred a proliferative advantage in vitro, and generated HGGs in vivo with complete penetrance when implanted into brain. The gene expression signatures of these murine HGGs reflected the spectrum of human diffuse HGGs. PDGFRA intragenic deletion of exons 8 and 9 were previously shown in adult HGG, but were not detected in 83 non-brainstem pediatric HGG and 57 DIPGs. Thus, a distinct spectrum of mutations confers constitutive receptor activation and oncogenic activity to PDGFRα in childhood HGG. PMID:23970477

  5. Low-Cost High Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial

    PubMed Central

    Polydorides, Alexandros D.; Dawsey, Sanford M.; Cui, Junsheng; Xue, Liyan; Zhang, Fan; Quang, Timothy; Pierce, Mark C.; Shin, Dongsuk; Schwarz, Richard A.; Bhutani, Manoop S.; Lee, Michelle; Parikh, Neil; Hur, Chin; Xu, Weiran; Moshier, Erin; Godbold, James; Mitcham, Josephine; Hudson, Courtney

    2015-01-01

    Background and Aims Esophageal squamous cell neoplasia (ESCN) has high mortality due to late detection. In high risk regions such as China, screening is performed by Lugol's chromoendoscopy (LCE). LCE has low specificity resulting in unnecessary tissue biopsy with subsequent increase in procedure cost and risk. The purpose of this study is to evaluate the accuracy of a novel, low-cost high resolution microendoscope (HRME) as an adjunct to LCE. Methods In this prospective trial, 147 consecutive high-risk patients were enrolled from two US and two Chinese tertiary centers. Three expert and four novice endoscopists performed white light endoscopy followed by LCE and HRME. All optical images were compared to gold standard of histopathology. Results Using a per biopsy analysis, sensitivity of LCE vs. LCE + HRME was 96% vs. 91% (p=0.0832), specificity 48% vs. 88% (p<0.001), PPV 22% vs 45% (p<0.0001), NPV 98% vs. 98% (p=0.3551), and overall accuracy 57% vs. 90% (p<0.001). Using a per patient analysis, sensitivity of LCE vs. LCE + HRME was 100% vs. 95% (p=0.16), specificity 29% vs. 79% (p<0.001), PPV 32% vs. 60%, 100% vs. 98%, and accuracy 47% vs. 83% (p<0.001). With use of HRME, 136 biopsies (60%; 95% CI: 53-66%) could have been spared, and 55 patients (48%; 95% CI: 38-57%) spared any biopsy. Conclusion In this trial, HRME improved the accuracy of LCE for ESCN screening and surveillance. HRME may be a cost-effective “optical” biopsy adjunct to LCE, potentially reducing unnecessary biopsy and facilitating real-time decision-making in globally underserved regions; ClinicalTrials.gov, NCT 01384708. PMID:25980753

  6. Establishment of a highly metastatic buccal squamous cell carcinoma cell line from a Sprague-Dawley Rat.

    PubMed

    Qin, Xing; Yan, Ming; Zhang, Jianjun; Xu, Qin; Lv, Zhongjing; Chen, Wantao

    2016-02-01

    The incidence of buccal squamous cell carcinoma (buccal SCC) is considered to be the second highest out of all oral cancers, but the unsatisfactory in vivo tumorigenicity and metastatic potential of the widely used cell lines have greatly delayed studies on the mechanisms of tumor progression. This study aimed to establish a highly metastatic buccal SCC cell line, which may serve a useful tool in buccal SCC research. Buccal SCC was induced by 4-nitroquinoline-1-oxide (4NQO) in Sprague-Dawley rats. The cancer samples were collected, and the tumor cells were purified in vitro. A highly aggressive cell line termed "Rca-B" was established by an invasion assay. Its proliferative ability, cell cycle distribution, baseline level of apoptosis, carcinogenicity and metastatic behavior in nude mice were investigated. To date, Rca-B cells have been stably cultured in vitro for more than 180 passages. These cells were polygonal or spindle-shaped, grew adhesively, and exhibited a stable epithelial phenotype as characterized by positive expression of cytokeratin. The population doubling time was 25.09 h. Cells in S-phase of the cell cycle accounted for 31.17% of the total number of cells, and the baseline level of apoptosis was 8.52%. The in vitro migration and invasion assays revealed highly aggressive features of Rca-B cells. In addition, the rate of xenograft formation was 100%, and the incidence of experimental lung metastasis was 81.8% in immunodeficient nude mice. The Rca-B cell line was established as a highly metastatic rat buccal SCC cell line, and its in-depth characterization, which includes malignant behaviors, allows for a wealth of functional studies on the molecular mechanisms of buccal SCC progression and targeted therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Predictors of nephrectomy in high grade blunt renal trauma patients treated primarily with conservative intent.

    PubMed

    Prasad, Narla Hari; Devraj, Rahul; Chandriah, G Ram; Sagar, S Vidya; Reddy, Ch Ram; Murthy, Pisapati Venkata Lakshmi Narsimha

    2014-04-01

    There is no consensus on the optimal management of high grade renal trauma. Delayed surgery increases the likelihood of secondary hemorrhage and persistent urinary extravasation, whereas immediate surgery results in high renal loss. Hence, the present study was undertaken to evaluate the predictors of nephrectomy and outcome of high Grade (III-V) renal injury, treated primarily with conservative intent. The records of 55 patients who were admitted to our institute with varying degrees of blunt renal trauma from January 2005 to December 2012 were retrospectively reviewed. Grade III-V renal injury was defined as high grade blunt renal trauma and was present in 44 patients. The factors analyzed to predict emergency intervention were demographic profile, grade of injury, degree of hemodynamic instability, requirement of blood transfusion, need for intervention, mode of intervention, and duration of intensive care unit stay. Rest of the 40 patients with high grade injury (grade 3 and 4)did not require emergency intervention and underwent a trail of conservative management. 7 of the 40 patients with high grade renal injury (grade 3 and 4), who were managed conservatively experienced complications requiring procedural intervention and three required a delayed nephrectomy. Presence of grade V injuries with hemodynamic instability and requirement of more than 10 packed cell units for resuscitation were predictors of nephrectomy. Predictors of complications were urinary extravasation and hemodynamic instability at presentation. Majority of the high grade renal injuries can be successfully managed conservatively. Grade V injuries and the need for more packed cell transfusions during resuscitation predict the need for emergency intervention.

  8. Patients with high c-MYC-expressing squamous cell carcinomas of the tongue show better survival than those with low- and medium-expressing tumours.

    PubMed

    Strindlund, Klas; Troiano, Giuseppe; Sgaramella, Nicola; Coates, Philip J; Gu, Xiaolian; Boldrup, Linda; Califano, Luigi; Fahraeus, Robin; Muzio, Lorenzo Lo; Ardito, Fatima; Colella, Giuseppe; Tartaro, Gianpaolo; Franco, Renato; Norberg-Spaak, Lena; Saadat, Mohammad; Nylander, Karin

    2017-04-10

    c-MYC is a potent oncoprotein with roles in a wide range of cellular processes such as differentiation, apoptosis and growth control. Deregulation of the MYC gene is commonly seen in human tumours resulting in overexpression of the protein. Here we studied expression of c-MYC in correlation to clinical outcome in patients with primary squamous cell carcinoma of the mobile tongue. Immunohistochemistry was used to identify c-MYC in a group of 104 tongue squamous cell carcinomas with an antibody directed against the N-terminal part of the protein. Staining was evaluated by multiplying the percentage of c-MYC-expressing cells with staining intensity, giving a quick score for each tumour. All 104 tumours expressed c-MYC at varying levels. Quantitation according to per cent of positive cells and staining intensity revealed that most (15/21; 71%) high-expressing tumours were seen in males. Within the group of high c-MYC-expressing tumours, the majority were alive 2 and 5 years after treatment. The present findings show that expression of c-MYC has prognostic value in squamous cell carcinoma of the tongue, and could be useful in choice of therapy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Junior High School English 1 and 2, Grade 9.

    ERIC Educational Resources Information Center

    Burbank Unified School District, CA.

    Designed for ninth grade English teachers, this curriculum guide contains (1) a course description; (2) educational goals; (3) teaching perspective; (4) a set of general principles; (5) a list of questions that teachers ask, along with answers; (6) an overview; and (7) directions for writing as a process, higher level thinking skills, how to…

  10. Occupational Exploration at Ontario Junior High School: 8th Grade.

    ERIC Educational Resources Information Center

    Bates, Gene; And Others

    The document contains 47 activities for Grade 8. The contents include the following areas: questionnaires; work vocabularies; employment seeking procedures--employment ads, application forms, resumes, job interviews, and resume preparation advice; a 24-page unit presenting occupational information in relation to career choice and job application…

  11. Occupational Exploration at Ontario Junior High School: 9th Grade.

    ERIC Educational Resources Information Center

    Bates, Gene; And Others

    The document contains 56 activities for Grade 9. The contents include the following areas: questions about the future; job seeking activities and guidelines; career games; a personal interest check list; unit guides for courses in World of Work (55 pages), and Career Educational Planning (40 pages) which include objectives, activities, evaluation,…

  12. Occupational Exploration at Ontario Junior High School: 8th Grade.

    ERIC Educational Resources Information Center

    Bates, Gene; And Others

    The document contains 47 activities for Grade 8. The contents include the following areas: questionnaires; work vocabularies; employment seeking procedures--employment ads, application forms, resumes, job interviews, and resume preparation advice; a 24-page unit presenting occupational information in relation to career choice and job application…

  13. Occupational Exploration at Ontario Junior High School: 7th Grade.

    ERIC Educational Resources Information Center

    Bates, Gene; And Others

    The document contains 47 activities for Grade 7. The contents include the following areas: vocabulary; a large variety of inventory and other forms focusing especially on self awareness, self evaluation, and value clarification; a 44-page unit guide for a course called Know Yourself, which includes objectives, activities, evaluation, and…

  14. Occupational Exploration at Ontario Junior High School: 9th Grade.

    ERIC Educational Resources Information Center

    Bates, Gene; And Others

    The document contains 56 activities for Grade 9. The contents include the following areas: questions about the future; job seeking activities and guidelines; career games; a personal interest check list; unit guides for courses in World of Work (55 pages), and Career Educational Planning (40 pages) which include objectives, activities, evaluation,…

  15. Junior High School English 1 and 2, Grade 9.

    ERIC Educational Resources Information Center

    Burbank Unified School District, CA.

    Designed for ninth grade English teachers, this curriculum guide contains (1) a course description; (2) educational goals; (3) teaching perspective; (4) a set of general principles; (5) a list of questions that teachers ask, along with answers; (6) an overview; and (7) directions for writing as a process, higher level thinking skills, how to…

  16. Examining Teacher-Assigned Math Grades as Predictors for High-Stakes Testing

    ERIC Educational Resources Information Center

    Denson, Bettina Coley

    2013-01-01

    This study sought to determine whether a relationship existed between teacher-assigned classroom grades and high-stakes test scores. The study examined teacher-assigned math grades in correlation to the student scores on the Florida Comprehensive Assessment test (FCAT) in a selected Florida high school. It also sought to determine the relationship…

  17. [Vasculogenic mimicry in tongue squamous cell carcinoma].

    PubMed

    Zhang, Xiaogen; Liu, Chundong; Luo, Luqiao; Cai, Xiaohui

    2013-04-01

    To investigate the presence of vasculogenic mimicry (VM) in tongue squamous cell carcinoma and explore its clinical significance. Forty-two surgical specimens of tongue squamous cell carcinoma were examined for the presence of VM using HE staining and double staining of CD34 and PAS. Of the 42 specimens, 18 (42.86%) showed the presence of VM. VM was not correlated with the patients' age or gender, but with lymph node metastasis and the grade of tumor differentiation. Compared with tumors without VM, the tumors with VM had a significantly higher rate of lymph node metastasis (P<0.05) and a lower grade of differentiation (P<0.05). VM can be present in tongue squamous cell carcinoma, and the poorly differentiated tumors contain more VM, which is associated with a greater likeliness of lymph node metastasis and a poorer prognosis.

  18. High PD-L1 Expression Correlates with Metastasis and Poor Prognosis in Oral Squamous Cell Carcinoma.

    PubMed

    Lin, Yueh-Min; Sung, Wen-Wei; Hsieh, Ming-Ju; Tsai, Shih-Chen; Lai, Hung-Wen; Yang, Shu-Mei; Shen, Ko-Hong; Chen, Mu-Kuan; Lee, Huei; Yeh, Kun-Tu; Chen, Chih-Jung

    2015-01-01

    PD-L1 has been widely demonstrated to contribute to failed antitumor immunity. Blockade of PD-L1 with monoclonal antibody could modulate the tumor immune environment to augment immunotherapy. PD-L1 expression is also detected in several types of cancer and is associated with poor prognosis. However, the prognostic role of PD-L1 in oral squamous cell carcinoma (OSCC) is still controversial. Our aim was to determine the role of PD-L1 in the prognosis of OSCC patients to identify its potential therapeutic relevance. PD-L1 immunoreactivity was analyzed by immunohistochemistry in 305 cancer specimens from primary OSCC patients. The medium follow-up time after surgery was 3.8 years (range from 0.1 to 11.1 years). The prognostic value of PD-L1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. Higher PD-L1 expression is more likely in tumor tissues of female than male OSCC patients (P = 0.0062). Patients with distant metastasis also had high PD-L1 expression (P = 0.0103). Multivariate analysis identified high PD-L1 expression as an independent risk factor in males and smokers (males: hazard ratio = 1.556, P = 0.0077; smokers: hazard ratio = 2.058, P = 0.0004). We suggest that PD-L1 expression, determined by IHC staining, could be an independent prognostic marker for OSCC patients who are male or who have a smoking habit.

  19. Different spectral hounsfield unit curve and high-energy virtual monochromatic image characteristics of squamous cell carcinoma compared with nonossified thyroid cartilage.

    PubMed

    Forghani, R; Levental, M; Gupta, R; Lam, S; Dadfar, N; Curtin, H D

    2015-06-01

    The attenuation of normal nonossified thyroid cartilage can be similar to that of head and neck squamous cell carcinoma on CT. We compared dual-energy CT spectral Hounsfield unit attenuation characteristics of nonossified thyroid cartilage with that of squamous cell carcinoma to determine the optimal virtual monochromatic image reconstruction energy levels for distinguishing tumor from normal nonossified thyroid cartilage. Dual-energy CT scans from 30 patients with histopathology-proved squamous cell carcinoma at different primary sites (laryngeal and nonlaryngeal) and 10 healthy patients were evaluated. Patients were scanned with a 64-section single-source scanner with fast-kilovolt (peak) switching, and scans were reconstructed at different virtual monochromatic energy levels ranging from 40 to 140 keV. Spectral attenuation curves of tumor and nonossified thyroid cartilage were quantitatively evaluated and compared. Any part of the tumor invading the cartilage, when present, was excluded from ROI analysis to avoid cross-contamination from areas where there could be a mixture of cartilage and invading tumor. Normal nonossified thyroid cartilage had a characteristic, predictable spectral attenuation curve that was different from that of tumors. The greatest difference in attenuation of nonossified cartilage compared with tumor was on virtual monochromatic images of ≥95 keV (P < .0001), with sharp contrast between the relatively high attenuation of nonossified cartilage compared with that of tumor. Head and neck squamous cell carcinoma has significantly different attenuation on virtual monochromatic images of ≥95 keV, compared with nonossified thyroid cartilage. © 2015 by American Journal of Neuroradiology.

  20. Differential LINE-1 Hypomethylation of Gastric Low-Grade Dysplasia from High Grade Dysplasia and Intramucosal Cancer

    PubMed Central

    Lee, Jeong Rok; Chung, Woo Chul; Kim, Jin Dong; Lee, Kang Moon; Paik, Chang Nyol; Jung, Sung Hoon; Jung, Ji Han; Lee, Yun Kyung

    2011-01-01

    Background/Aims Gastric epithelial dysplasia is considered a precancerous lesion with a variable clinical course. There is disagreement, however, regarding histology-based diagnoses, which has led to confusion in choosing a therapeutic plan. New objective markers are needed to determine which lesions progress to true malignancy. We measured LINE-1 methylation levels, which have been reported to strongly correlate with the global methylation level in gastric epithelial dysplasia and intramucosal cancer. Methods A total of 145 tissue samples were analyzed by two histopathologists. All tissues were excised by therapeutic endoscopic mucosal resection and paired with adjacent normal tissue samples. A modified long interspersed nucleotide elements-combined bisulfite restriction analysis (COBRA-LINE-1) method was used. Results Gastric epithelial dysplasia and intramucosal cancer tissues had significantly lower levels of LINE-1 methylation than adjacent normal gastric tissues. High-grade dysplasia and intramucosal cancer were distinguishable from low-grade dysplasia based on LINE-1 methylation levels. Furthermore, the distinction could be determined with high sensitivity and specificity, as shown by the receiver operating characteristic (ROC) curve (AUC, 0.82; 95% confidence interval, 0.74 to 0.88). Conclusions LINE-1 methylation levels may provide a diagnostic tool for identifying high-grade dysplasia and intramucosal cancer. PMID:21814593

  1. Bilateral Basaloid Squamous Cell Carcinoma of the Parotid Gland: A Case Report and Review of the Literature

    PubMed Central

    Rivero, Alexander; Tang, Christopher G; Rasgon, Barry M

    2017-01-01

    Introduction: We describe the first known case of bilateral basaloid squamous cell carcinoma of the parotid gland, and we review existing literature. Case Presentation: A previously healthy, 70-year-old white man presented with a 2-cm enlarging mass in the tail of the right parotid gland. Magnetic resonance imaging and computed tomography showed ipsilateral pathologic adenopathy. Results of fine-needle aspiration revealed a high-grade malignancy with squamous features. The patient underwent a right total parotidectomy and modified radical neck dissection. Final pathologic findings revealed a basaloid squamous cell carcinoma. Four years after the initial resection, the patient presented with an enlarging left parotid mass. Findings of fine-needle aspiration and imaging were similar to those 4 years earlier. The patient received a left total parotidectomy and modified radical neck dissection. Postoperative radiation therapy was performed after each surgical intervention. He remains disease free at 4-year follow-up after the second mass was resected. Discussion: Squamous cell carcinoma with basaloid features is a rare and aggressive type of squamous cell carcinoma. To our knowledge, this is the first case report of bilateral parotid basaloid squamous cell carcinoma. PMID:28333602

  2. Changes in gene expression of neo-squamous mucosa after endoscopic treatment for dysplastic Barrett’s esophagus and intramucosal adenocarcinoma

    PubMed Central

    Levert-Mignon, Angelique; Bourke, Michael J; Lord, Sarah J; Taylor, Andrew C; Wettstein, Antony R; Edwards, Melanie; Botelho, Natalia K; Sonson, Rebecca; Jayasekera, Chatura; Fisher, Oliver M; Thomas, Melissa L; Macrae, Finlay; Hussey, Damian J; Watson, David I

    2016-01-01

    Background Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett’s esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD). Objective The purpose of this study was to investigate the molecular effects of endotherapy. Methods mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals. Results Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes. Conclusion Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more “normal” profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy. PMID:28405317

  3. High-grade sarcomatous overgrowth in solitary fibrous tumors: a clinicopathologic study of 10 cases.

    PubMed

    Collini, Paola; Negri, Tiziana; Barisella, Marta; Palassini, Elena; Tarantino, Eva; Pastorino, Ugo; Gronchi, Alessandro; Stacchiotti, Silvia; Pilotti, Silvana

    2012-08-01

    We describe 10 solitary fibrous tumors (SFT) with high-grade malignant overgrowth, all of which showed the presence of a synchronous or previous classic SFT/malignant SFT (MSFT) component. Seven were "dedifferentiated," with an abrupt transition from a classic SFT/MSFT to a high-grade component consisting of a nondistinctive high-grade sarcoma in 4 cases and divergent differentiation in 3. The nondistinctive high-grade component consisted of epithelioid and/or spindle cells often associated with overt pleomorphism or small round cell sarcomas. The divergent differentiation featured a rhabdomyosarcoma in 2 cases and an osteosarcoma in 1. Three cases (tentatively called "evolved") showed a gradual transition from classic SFT/MSFT to a nondistinctive high-grade sarcoma or presented features of high-grade sarcoma at the time of metastasis (assessed by fine-needle aspiration cytology) without any component suggesting a diagnosis of classic SFT/MSFT. The high-grade component showed loss of CD34 expression in half of the dedifferentiated SFTs and all of the dedifferentiated SFTs with divergent differentiation, whereas Ki-67 was markedly increased in all of the evaluable cases and paralleled the tumor grade. In 4 cases, the expression and phosphorylation status of key factors that control transcription and protein synthesis were also investigated. Both S6 and 4E-BP1 showed low activation in the low-grade MSFT and a high level of activation in the high-grade component. Seven of the 10 patients died of their disease during follow-up, with a median overall survival of 73 months (range, 5 to 288 mo). The median time to distant metastasis was 156 months after the initial diagnosis, and median overall survival from the first signs of metastasis was 8 months.

  4. Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma variants: An update with special reference to HPV-related carcinomas

    PubMed Central

    2014-01-01

    Accurate identification of the microscopic risk factors of oral and oropharyngeal (OP) squamous cell carcinomas (SCC) and their morphologic variants is of at most importance, as these generally determine treatment modalities, prognosis and overall patient outcome. The great majority of oral and oropharyngeal squamous cell carcinomas are microscopically described as kerartinizing squamous cell carcinoma (KSCC). They bear certain resemblance to keratinizing stratified squamous epithelium. Tobacco habits and excessive consumption of alcoholic beverages have been considered to be the main etiologic agents in these carcinomas. The tumors occurred in older patients more commonly affected the oral tongue and floor of the mouth with well established morphologic risk factors including tumor grade, pattern of invasion and perineural involvement. Within the last 30 years however, the advent and expanding prevalence of high risk human papillomavirus (HPV) as an important etiologic agent for head and neck squamous cell carcinoma, particularly in the OP, has resulted in a significant change in the established morphologic criteria for risk assessment. The majority of HPV relate carcinomas of the OP are nonkeratinizing squamous cell carcinoma (NKSCC). These tumors are found to be more responsive to treatment with a favorable patient outcome and good prognosis. Consequently, alterations in treatment protocols aimed at de-escalation are currently being evaluated. More recently, other morphologic variants that are HPV positive are reported with increasing frequency in the OP and other head and neck sites. As a result, several clinical and pathologic questions have emerged. Importantly, whether the virus is biologically active in these tumors and involved in their pathogenesis, and second, what are the clinical implications with regard to patient management and outcome in the HPV-related variants. Examples of HPV-related squamous cell carcinoma variants that will be addressed here are

  5. YWHAE Rearrangement in a Purely Conventional Low-grade Endometrial Stromal Sarcoma that Transformed Over Time to High-grade Sarcoma: Importance of Molecular Testing.

    PubMed

    Aisagbonhi, Omonigho; Harrison, Beth; Zhao, Liena; Osgood, Rebecca; Chebib, Ivan; Oliva, Esther

    2017-08-31

    Low and high-grade endometrial stromal sarcomas (ESS) can be distinguished on a morphologic basis. Low-grade ESS is composed of oval cells that resemble normal proliferative-phase endometrial stroma, while the well-known high-grade ESS is composed of round cells growing in nests separated by delicate sinusoidal vasculature. Recurrent JAZF1 rearrangements have been reported to be most frequent in low-grade stromal sarcomas (up to 60%), while YWHAE rearrangements are characteristic of high-grade ESS. Herein, we report a case of a 45-yr-old woman with stage IA typical low-grade ESS who developed multiple abdominopelvic recurrences and lung metastases 15 mo after her primary tumor was resected. The unusual morphology (without high-grade areas) as well as the aggressive behavior of the tumor prompted molecular testing which showed YWHAE rearrangement in her abdominopelvic recurrence and her primary tumor. Five years after her primary tumor was resected, she developed scalp metastases with a typical morphology of a high-grade ESS associated with t(10;17) and died of her disease. Our case highlights the potential value of molecular testing in all low-grade ESS at time of initial diagnosis to stratify patients at higher risk for developing high-grade ESS with the goal of offering closer follow-up for early detection and treatment if transformation occurs.

  6. High Performance Slab-on-Grade Foundation Insulation Retrofits

    SciTech Connect

    Goldberg, Louise F.; Mosiman, Garrett E.

    2015-09-01

    ?A more accurate assessment of SOG foundation insulation energy savings than traditionally possible is now feasible. This has been enabled by advances in whole building energy simulation with 3-dimensional foundation modelling integration at each time step together with an experimental measurement of the site energy savings of SOG foundation insulation. Ten SOG insulation strategies were evaluated on a test building to identify an optimum retrofit insulation strategy in a zone 6 climate (Minneapolis, MN). The optimum insulation strategy in terms of energy savings and cost effectiveness consisted of two components: (a) R-20 XPS insulation above grade, and, (b) R-20 insulation at grade (comprising an outer layer of R-10 insulation and an interior layer of R-12 poured polyurethane insulation) tapering to R-10 XPS insulation at half the below-grade wall height (the lower half of the stem wall was uninsulated). The optimum insulation strategy was applied to single and multi-family residential buildings in climate zone 4 - 7. The highest site energy savings of 5% was realized for a single family home in Duluth, MN, and the lowest savings of 1.4 % for a 4-unit townhouse in Richmond, VA. SOG foundation insulation retrofit simple paybacks ranged from 18 to 47 years. There are other benefits of SOG foundation insulation resulting from the increase in the slab surface temperatures. These include increased occupant thermal comfort, and a decrease in slab surface condensation particularly around the slab perimeter.

  7. High expression of Naa10p associates with lymph node metastasis and predicts favorable prognosis of oral squamous cell carcinoma.

    PubMed

    Zeng, Yan; Zheng, Jun; Zhao, Juan; Jia, Pei-Rong; Yang, Yang; Yang, Guo-Jun; Ma, Jing-Feng; Gu, Yong-Qing; Xu, Jiang

    2016-05-01

    N-a-Acetyltransferase 10 protein (Naa10p) is a potential prognostic biomarker and a modulator of several types of cancer. Despite the efforts to elucidate the relationship between Naa10p expression and clinical prognosis, little is known about its expression and role in human oral squamous cell carcinoma (OSCC). In this study, we firstly detected the mRNA and protein levels of Naa10p in 10 paired OSCC tissue samples and found Naa10p was frequently overexpressed in the tumor tissues of patients with OSCC. Further detection by immunohistochemistry was used to examine Naa10p expression in 124 OSCC tumor specimens by tissue microarray (TMA), and a relative high level of Naa10p protein expression was found in 98 out of 124 cases (79.03 %). Additional analyses illustrated that Naa10p expression inversely correlated with clinical stage (p = 0.047), degree of lymph node status (p = 0.020), differentiation (p = 0.022), and recurrence (p = 0.016) of patients with OSCC. The survival analysis showed that patients with Naa10p-positive expression had a better prognosis for disease-free survival (DFS) or overall survival (OS) than those with Naa10p-negative expression (p = 0.003 for both). Furthermore, we assessed the effect of Naa10p knockdown on motility of oral cancer cells in vitro, and the results showed that Naa10p inhibit cell wound healing, migration, and invasion. In summary, our study illustrated that the expression of Naa10p had a potential value for predicting the progression of OSCC and prognosis of OSCC patients.

  8. Secondhand Smoking and the Risk of Esophageal Squamous Cell Carcinoma in a High Incidence Region, Kashmir, India

    PubMed Central

    Rafiq, Rumaisa; Shah, Idrees Ayoub; Bhat, Gulzar Ahmad; Lone, Mohd Maqbool; Islami, Farhad; Boffetta, Paolo; Dar, Nazir Ahmad

    2016-01-01

    Abstract Studies have associated secondhand smoking (SHS) with cancers of the lung, larynx, and pharynx. Only a few studies have examined the association between SHS and esophageal squamous cell carcinoma (ESCC) and the findings are inconclusive. We aimed to investigate the association between SHS and risk of ESCC in a case-control study in Kashmir, where the incidence of ESCC is high. We recruited 703 histopathologically confirmed ESCC cases and 1664 hospital-based controls individually matched to the cases for age, sex, and district of residence. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using conditional logistic regression models. Among never-tobacco users, the ORs for the association between SHS and ESCC risk were above unity with ever exposure to SHS (OR = 1.32; 95% CI, 0.43–4.02) and exposure to SHS for >14 h/wk (median value) (OR = 2.69; 95% CI, 0.75–20.65). In the analysis of data from all participants, the OR (95% CI) for the association between SHS and ESCC was (OR = 1.02; 95% CI, 0.53–1.93) for SHS ≤14 h/wk and (OR = 1.91; 95% CI, 0.75–4.89) for SHS >14 h/wk in the models adjusted for tobacco use and several other potential confounding factors. We found an indication of increased risk of ESCC associated with exposure to SHS. Studies with larger numbers of SHS-exposed never tobacco users are required to further examine this association. PMID:26735535

  9. Role of high resolution optical coherence tomography in diagnosing ocular surface squamous neoplasia with coexisting ocular surface diseases.

    PubMed

    Atallah, Marwan; Joag, Madhura; Galor, Anat; Amescua, Guillermo; Nanji, Afshan; Wang, Jianhua; Perez, Victor L; Dubovy, Sander; Karp, Carol L

    2017-10-01

    Coexistence of an ocular surface disease can mask the typical features of ocular surface squamous neoplasia (OSSN). The purpose of this study was to evaluate high resolution optical coherence tomography (HR-OCT) as an adjunct in the detection and differentiation of OSSN within coexisting ocular surface pathologies. Retrospective study of 16 patients with ocular surface disease and lesions suspicious for OSSN that were evaluated with HR-OCT. HR-OCT images of the lesions were taken to look for evidence of OSSN. Biopsies were performed in all cases, and the HR-OCT findings were compared to the histological results. Of the 16 patients with OSSN and a coexisting ocular surface disease, 12 were found to have OSSN by HR-OCT and all were subsequently confirmed by biopsy. Two patients had OSSN with rosacea, one with pingueculum, two within pterygia, one with Salzmann' nodular degeneration, six with limbal stem cell deficiency (LSCD)/scarring. In all 12 cases HR-OCT images revealed classical findings of hyper-reflective, thickened epithelium and an abrupt transition from normal to abnormal epithelium. OSSN was ruled out by HR-OCT in four cases (2 Salzmann's, 1 mucous membrane pemphigoid, and 1 LSCD). Negative findings were confirmed by biopsy. HR-OCT was used to follow resolution of the OSSN in positive cases, and it detected recurrence in 1 case. While histopathology is the gold standard in the diagnosis of OSSN, HR-OCT can be used to noninvasively detect the presence of OSSN in patients with coexisting ocular conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Prevalence of high-risk human papillomavirus in an inner-city population with atypical squamous cells of undetermined significance.

    PubMed

    Allen, Gretchen L; Klobocista, Merieme M; Sugarman, Shannon; Gravel, Katie; Feldman, Deborah; Schnatz, Peter F

    2009-04-01

    To compare the prevalence of high-risk human papillomavirus (HPV) in patients with atypical squamous cells of undetermined significance (ASCUS) cytology in an inner-city clinic and a private office population to determine if HPV screening is useful in either group before colposcopy. After an institutional review board approval at Hartford Hospital, we reviewed the charts of patients with ASCUS cytology and high-risk HPV DNA who were seen at the Community Health Services, Inc. in Hartford, CT (clinic patients), between January 1, 2000, and July 1, 2004, and at a private practice site in Hartford, CT (private patients), between January 1, 2004, and December 31, 2004. All charts were reviewed for demographic information, history of sexually transmitted diseases, tobacco, alcohol, and other drug use. A power analysis indicated that 32 patients would be needed in each group for a p <.05 with 80% confidence. A total of 257 patient's charts were reviewed: 79 clinic charts and 178 private office charts. Three patients were eliminated due to a lack of HPV testing. High-risk HPV was identified in 94.9% of the clinic patients and 45.5% of the private patients. The populations were statistically different with regard to history of chlamydia (26.6% of clinic patients and 6.2% of private office patients; p <.0001), gonorrhea (11.4% clinic patients and 1.1% of private patients; p =.0005), and trichomonas (7.6% of clinic patients and 0% of private office patients; p =.0007). The prevalence of herpes simplex virus in clinic patients was 2.5%, whereas it was present in 6.2% of private patients (p =.35). Tobacco use was significantly higher in clinic patients (31.6% of clinic patients and 15.2% of private patients; p =.009). In our study, 94.9% of the women in the clinic population with an ASCUS cytology had high-risk HPV compared with a rate of 45.5% in the private patients studied. Because most clinic patients with ASCUS have high-risk HPV, it is reasonable to defer reflex testing

  11. High-grade internal rectal prolapse: Does it explain so-called "idiopathic" faecal incontinence?

    PubMed

    Bloemendaal, A L A; Buchs, N C; Prapasrivorakul, S; Cunningham, C; Jones, O M; Hompes, R; Lindsey, I

    2016-01-01

    Faecal incontinence is a multifactorial disorder, with multiple treatment options. The role of internal rectal prolapse in the aetiology of faecal incontinence is debated. Recent data has shown the importance of high-grade internal rectal prolapse in case of faecal incontinence. We aimed to determine the incidence and relevance of internal rectal prolapse in patients with faecal incontinence without an anal sphincter defect. Patient data, collected in a prospective pelvic floor database, were assessed. All females with moderate to severe pure faecal incontinence, without obstructed defecation and sphincter muscle defects, were included. Data on defecation proctography, anorectal physiology and incontinence scores were analysed. Of 2082 females in the database, 174 fitted the inclusion criteria. High-grade internal rectal prolapse was found in 49% of patients and was associated predominantly with urge faecal incontinence. Passive faecal incontinence was more common in low-grade compared to high-grade internal rectal prolapse patients. Maximum resting pressure was lower in older patients and in patients with high-grade compared to low-grade internal rectal prolapse. Internal rectal prolapse grade was not significantly correlated with faecal incontinence severity score. High-grade internal rectal prolapse is common in female patients suffering particularly urge faecal incontinence, without anal sphincter lesions. Defecation proctography should be routine in the work up of faecal incontinence. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  12. High-dose radiation therapy alone by moderate hypofractionation for patients with thoracic esophageal squamous cell carcinoma.

    PubMed

    Oh, Dongryul; Noh, Jae Myoung; Nam, Heerim; Lee, Hyebin; Kim, Tae Gyu; Ahn, Yong Chan

    2016-08-01

    We conducted retrospective analyses to investigate the clinical outcome of thoracic esophageal cancer patients who were treated with high-dose radiation therapy (RT) alone by moderate hypofractionation due to medical unfitness or refusal to receive either surgery or chemo-radiotherapy.Between May 2003 and April 2013, 70 patients were treated with high-dose RT alone with curative aim. The planned total RT dose was 60 Gy in daily 3.0 Gy per fraction. We evaluated the survival outcome, toxicities, and prognostic factors affecting patients' survival.At the time of analysis, 32 patients experienced disease progression. The 2-year overall survival (OS), cancer-specific survival (CSS) and local control (LC) rates were 52.1%, 57.8%, and 68.2%, respectively. Among them, 25 patients had superficial (cT1a-b) esophageal cancers, and the 2-year OS, CSS, and LC rates were 80.0%, 87.3%, and 81.6%, respectively. Multivariate analysis revealed that cT disease (P < 0.001) and tumor location (P = 0.022) were the significant factors for OS. The incidence of grade 3 or higher toxicities were 9.9%, including grade 3 esophagitis (2 patients, 2.8%) and grade 4 or 5 trachea-esophageal fistula (5 patients, 7.1%).High-dose RT alone by moderate hypofractionation had led to reasonable clinical outcomes at acceptable toxicity risk in thoracic esophageal cancer patients who are medically unfit or refuse surgery or chemotherapy, especially for the patients having superficial lesion.

  13. High-dose radiation therapy alone by moderate hypofractionation for patients with thoracic esophageal squamous cell carcinoma

    PubMed Central

    Oh, Dongryul; Noh, Jae Myoung; Nam, Heerim; Lee, Hyebin; Kim, Tae Gyu; Ahn, Yong Chan

    2016-01-01

    Abstract We conducted retrospective analyses to investigate the clinical outcome of thoracic esophageal cancer patients who were treated with high-dose radiation therapy (RT) alone by moderate hypofractionation due to medical unfitness or refusal to receive either surgery or chemo-radiotherapy. Between May 2003 and April 2013, 70 patients were treated with high-dose RT alone with curative aim. The planned total RT dose was 60 Gy in daily 3.0 Gy per fraction. We evaluated the survival outcome, toxicities, and prognostic factors affecting patients’ survival. At the time of analysis, 32 patients experienced disease progression. The 2-year overall survival (OS), cancer-specific survival (CSS) and local control (LC) rates were 52.1%, 57.8%, and 68.2%, respectively. Among them, 25 patients had superficial (cT1a-b) esophageal cancers, and the 2-year OS, CSS, and LC rates were 80.0%, 87.3%, and 81.6%, respectively. Multivariate analysis revealed that cT disease (P < 0.001) and tumor location (P = 0.022) were the significant factors for OS. The incidence of grade 3 or higher toxicities were 9.9%, including grade 3 esophagitis (2 patients, 2.8%) and grade 4 or 5 trachea-esophageal fistula (5 patients, 7.1%). High-dose RT alone by moderate hypofractionation had led to reasonable clinical outcomes at acceptable toxicity risk in thoracic esophageal cancer patients who are medically unfit or refuse surgery or chemotherapy, especially for the patients having superficial lesion. PMID:27537591

  14. Feasibility of Transoral Robotic-Assisted High Resolution Microendoscopic Imaging of Oropharyngeal Squamous Cell Carcinoma

    PubMed Central

    Patsias, Alexis; Giraldez-Rodriguez, Laureano A.; Polydorides, Alexandros D.; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila; Quang, Timothy; Sikora, Andrew G.; Miles, Brett A.

    2015-01-01

    Background Transoral robotic-assisted oncologic surgery of the head and neck offers promising functional results. Nonetheless, the efficacy of oncologic surgery remains critically dependent on obtaining negative margins. We aimed to integrate a miniaturized high resolution fiberoptic microendoscope (HRME), which provides real time histological assessment, with the da Vinci robotic system (Intuitive Surgical Inc., Sunnyvale, CA). Methods Three patients undergoing transoral robotic surgery were prospectively enrolled. Optical imaging of the oropharynx was performed intraoperatively with the robotic-assisted HRME. Results All patients underwent the procedure successfully with no complications. The HRME was successfully integrated with the Da Vinci Robotic system. Several sites of the oropharynx and associated malignancy were imaged, which correlated with the standard histopathological analysis. Conclusions Transoral robotic-assisted high resolution microendoscopic imaging of the oropharynx is a safe and technically feasible approach, providing a real time histological assessment and may serve as a valuable aid in oncologic surgery. PMID:25327825

  15. Expression profile of skin papillomas with high cancer risk displays a unique genetic signature that clusters with squamous cell carcinomas and predicts risk for malignant conversion.

    PubMed

    Darwiche, N; Ryscavage, A; Perez-Lorenzo, R; Wright, L; Bae, D-S; Hennings, H; Yuspa, S H; Glick, A B

    2007-10-18

    Chemical induction of squamous tumors in the mouse skin induces multiple benign papillomas: high-frequency terminally benign low-risk papillomas and low-frequency high-risk papillomas, the putative precursor lesions to squamous cell carcinoma (SCC). We have compared the gene expression profile of twenty different early low- and high-risk papillomas with normal skin and SCC. Unsupervised clustering of 514 differentially expressed genes (P<0.001) showed that 9/10 high-risk papillomas clustered with SCC, while 1/10 clustered with low-risk papillomas, and this correlated with keratin markers of tumor progression. Prediction analysis for microarrays (PAM) identified 87 genes that distinguished the two papilloma classes, and a majority of these had a similar expression pattern in both high-risk papillomas and SCC. Additional classifier algorithms generated a gene list that correctly classified unknown benign tumors as low- or high-risk concordant with promotion protocol and keratin profiling. Reduced expression of immune function genes characterized the high-risk papillomas and SCC. Immunohistochemistry confirmed reduced T-cell number in high-risk papillomas, suggesting that reduced adaptive immunity defines papillomas that progress to SCC. These results demonstrate that murine premalignant lesions can be segregated into subgroups by gene expression patterns that correlate with risk for malignant conversion, and suggest a paradigm for generating diagnostic biomarkers for human premalignant lesions with unknown individual risk for malignant conversion.

  16. A Comparison of High School Student Interests across Three Grade and Ability Levels.

    ERIC Educational Resources Information Center

    Gill, Newell T.

    1980-01-01

    Students (Grades 9-11) in two Florida metropolitan high schools rated their interest in 28 topics, such as travel, popular music, religion, the opposite sex, war, and politics. Interests were analyzed by sex, grade, and ability track in English (Honors, Average, Basic). Findings, especially those on romantic interests, are discussed. (SJL)

  17. High School Grade Inflation from 1991 to 2003. Research Report Series 2004-04

    ERIC Educational Resources Information Center

    Woodruff, David J.; Ziomek, Robert L.

    2004-01-01

    This report presents the results of a study investigating inflation in high school grade point average (HSGPA). Inflation was measured by comparing HSGPA to ACT Assessment (ACT) scores over the years 1991 to 2003. The results indicate the presence of grade inflation over the 13 years. That is, HSGPAs increased without a concomitant increase in…

  18. Exploring High-Achieving Sixth Grade Students' Erroneous Answers and Misconceptions on the Angle Concept

    ERIC Educational Resources Information Center

    Bütüner, Suphi Önder; Filiz, Mehmet

    2017-01-01

    The aim of this research was to investigate high achievers' erroneous answers and misconceptions on the angle concept. The participants consisted of 233 grade 6 students drawn from eight classes in two well-established elementary schools of Trabzon, Turkey. All the participants were considered to be current achievers in mathematics, graded 4 or 5…

  19. Double Jeopardy: How Third-Grade Reading Skills and Poverty Influence High School Graduation

    ERIC Educational Resources Information Center

    Hernandez, Donald J.

    2011-01-01

    Educators and researchers have long recognized the importance of mastering reading by the end of third grade. Students who fail to reach this critical milestone often falter in the later grades and drop out before earning a high school diploma. This study relies on a unique national database of 3,975 students born between 1979 and 1989. The…

  20. Perris Valley Junior High School's Language Processing for Grades 7-10.

    ERIC Educational Resources Information Center

    Zemmels, Elizabeth

    An ongoing, interdisciplinary reading program for students in grades 7-10 in Perris Union High School District (California) is described. Initiated in 1979 as a result of low reading scores, the program divides all incoming seventh grade students into homogeneous groups. In the first 6 weeks of school these new groups meet once a day for 50…

  1. Improved Middle Grades Schools for Improved High School Readiness: Ten Best Practices in the Middle Grades

    ERIC Educational Resources Information Center

    Bottoms, Gene; Timberlake, Allison

    2012-01-01

    In 2009, the Southern Regional Education Board (SREB) Committee to Improve High School Graduation Rates and Achievement, led by then-Governor Sonny Perdue of Georgia, released a report of 10 key recommendations for ensuring more students graduate from high school, and they graduate ready for college and careers. Among these 10 recommendations was…

  2. Improved Middle Grades Schools for Improved High School Readiness: Ten Best Practices in the Middle Grades

    ERIC Educational Resources Information Center

    Bottoms, Gene; Timberlake, Allison

    2012-01-01

    In 2009, the Southern Regional Education Board (SREB) Committee to Improve High School Graduation Rates and Achievement, led by then-Governor Sonny Perdue of Georgia, released a report of 10 key recommendations for ensuring more students graduate from high school, and they graduate ready for college and careers. Among these 10 recommendations was…

  3. Feasibility of transoral robotic-assisted high-resolution microendoscopic imaging of oropharyngeal squamous cell carcinoma.

    PubMed

    Patsias, Alexis; Giraldez-Rodriguez, Laureano; Polydorides, Alexandros D; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila; Quang, Timothy; Sikora, Andrew G; Miles, Brett

    2015-08-01

    Transoral robotic-assisted oncologic surgery of the head and neck offers promising functional results. Nonetheless, the efficacy of oncologic surgery remains critically dependent on obtaining negative margins. We aimed to integrate a miniaturized high-resolution fiber-optic microendoscope (HRME), which provides real-time histological assessment, with the da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA). Three patients undergoing transoral robotic surgery (TORS) were prospectively enrolled in this study. Optical imaging of the oropharynx was performed intraoperatively with the robotic-assisted HRME. All patients underwent the procedure successfully with no complications. The HRME was successfully integrated with the da Vinci robotic system. Several sites of the oropharynx and associated malignancy were imaged, which correlated with the standard histopathological analysis. Transoral robotic-assisted HRME imaging of the oropharynx is a safe and technically feasible approach, providing a real-time histological assessment and may serve as a valuable aid in oncologic surgery. © 2015 Wiley Periodicals, Inc.

  4. Genomic Integration of High-Risk HPV Alters Gene Expression in Oropharyngeal Squamous Cell Carcinoma.

    PubMed

    Walline, Heather M; Komarck, Christine M; McHugh, Jonathan B; Bellile, Emily L; Brenner, J Chad; Prince, Mark E; McKean, Erin L; Chepeha, Douglas B; Wolf, Gregory T; Worden, Francis P; Bradford, Carol R; Carey, Thomas E

    2016-10-01

    High-risk HPV (hrHPV) is the leading etiologic factor in oropharyngeal cancer. HPV-positive oropharyngeal tumors generally respond well to therapy, with complete recovery in approximately 80% of patients. However, it remains unclear why some patients are nonresponsive to treatment, with 20% of patients recurring within 5 years. In this study, viral factors were examined for possible clues to differences in tumor behavior. Oropharynx tumors that responded well to therapy were compared with those that persisted and recurred. Viral oncogene alternate transcripts were assessed, and cellular sites of viral integration were mapped and sequenced. Effects of integration on gene expression were assessed by transcript analysis at the integration sites. All of the tumors demonstrated active viral oncogenesis, indicated by expression of HPV E6 and E7 oncogenes and alternate E6 splicing. In the responsive tumors, HPV integration occurred exclusively in intergenic chromosome regions, except for one tumor with viral integration into TP63. Each recurrent tumor exhibited complex HPV integration patterns into cancer-associated genes, including TNFRSF13B, SCN2A, SH2B1, UBE2V2, SMOC1, NFIA, and SEMA6D Disrupted cellular transcripts were identified in the region of integration in four of the seven affected genes.

  5. High relative density of lymphatic vessels predicts poor survival in tongue squamous cell carcinoma.

    PubMed

    Seppälä, Miia; Pohjola, Konsta; Laranne, Jussi; Rautiainen, Markus; Huhtala, Heini; Renkonen, Risto; Lemström, Karl; Paavonen, Timo; Toppila-Salmi, Sanna

    2016-12-01

    Tongue cancer has a poor prognosis due to its early metastasis via lymphatic vessels. The present study aimed at evaluating lymphatic vessel density, relative density of lymphatic vessel, and diameter of lymphatic vessels and its predictive role in tongue cancer. Paraffin-embedded tongue and lymph node specimens (n = 113) were stained immunohistochemically with a polyclonal antibody von Willebrand factor, recognizing blood and lymphatic endothelium and with a monoclonal antibody podoplanin, recognizing lymphatic endothelium. The relative density of lymphatic vessels was counted by dividing the mean number of lymphatic vessels per microscopic field (podoplanin) by the mean number of all vessels (vWf) per microscopic field. The high relative density of lymphatic vessels (≥80 %) was associated with poor prognosis in tongue cancer. The relative density of lymphatic vessels predicted poor prognosis in the group of primary tumor size T1-T2 and in the group of non-metastatic cancer. The lymphatic vessel density and diameter of lymphatic vessels were not associated with tongue cancer survival. The relative density of lymphatic vessels might have clinically relevant prognostic impact. Further studies with increased number of patients are needed.

  6. Morphological and immunohistochemical re-evaluation of tumors initially diagnosed as ovarian endometrioid carcinoma with emphasis on high-grade tumors

    PubMed Central

    Lim, Diana; Murali, Rajmohan; Murray, Melissa P.; Veras, Emmanuela; Park, Kay J.; Soslow, Robert A.

    2016-01-01

    Aims Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Methods Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): i) squamous metaplasia; ii) endometriosis; iii) adenofibromatous background; and iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Results Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years and 75% of patients were younger than 60 years. 92% presented with disease confined to the pelvis and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high-grade (grade 3 out of 3). 80% of cases had at least 1 CEF and 59% had at least 2 CEFs. 11% overexpressed p16, 0% overexpressed p53 and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were re-classified as serous carcinoma (OSC). The median patient age was 54.5 years and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one-half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular

  7. High glucose uptake unexpectedly is accompanied by high levels of the mitochondrial β-F1-ATPase subunit in head and neck squamous cell carcinoma

    PubMed Central

    Preuss, Simon F.; Schiffer, Theresa; Schilder, Sarah; Guntinas-Lichius, Orlando; Schmidt, Matthias; Klussmann, Jens P.; Wiesner, Rudolf J.

    2015-01-01

    A hallmark of solid tumors is the consumption of large amounts of glucose and production of lactate, also known as Warburg-like metabolism. This metabolic phenotype is typical for aggressive tumor growth, and can be visualized by 18F-fluorodeoxyglucose (18F-FDG) uptake detected by positron emission tomography (PET). High 18F-FDG uptake inversely correlates with survival and goes along with reduced expression of the catalytic beta-subunit of the H+-ATP synthase (β-F1-ATPase) in several tumor entities analyzed so far. For this study we characterized a series of 15 head and neck squamous cell carcinoma (HNSCC) by (i) determining 18F-FDG-uptake; (ii) quantitative expression analysis of β-F1-ATPase (Complex V), NDUF-S1 (Complex I) and COX1 (Complex IV) of the mitochondrial electron transport chain (ETC), as well as Hsp60 (mitochondrial mass) and GAPDH (glycolysis) in tumor cells; (iii) sequencing of the mtDNA of representative tumor samples. Whereas high 18F-FDG-uptake also correlates with poor prognosis in HNSCC, it surprisingly is accompanied by high levels of β-F1-ATPase, but not by any of the other analyzed proteins. In conclusion, we here describe a completely new phenotype of metabolic adaptation possibly enabling those tumors with highest levels of β-F1-ATPase to rapidly proliferate even in hypoxic zones, which are typical for HNSCC. PMID:26452026

  8. Serous versus high-grade endometrioid endometrial carcinoma: immunohistochemistry of RFP is not useful for differentiation.

    PubMed

    Ussakli, Cigdem; Usubutun, Alp; Dincer, Nazmiye; Dolgun, Anil; Bülbül, Diilek; Isikdogan, Zuhal; Haberal, Nihan; Ozen, Ozlem; Tezel, Gaye Guler

    2016-01-01

    We evaluated the immunohistochemical expression of ret finger protein (RFP) along with conventional immunohistochemical markers in endometrioid and serous carcinomas of the endometrium. A total of 124 endometrial carcinoma cases (24 grade 1 endometrioid, 60 grade 3 endometrioid, 40 serous) were retrieved from pathology archives. Tissue microarrays were constructed. The expression of RFP, WT1, ER, PR, p53 and p16 was examined immunohistochemically. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve,  statistic for interobserver reproducibility, Kruskal-Wallis test, Mann-Whitney U test and Fisher's exact tests were performed for statistical analyses. The mean RFP score was 1.54 in grade 1 endometrioid, 4.31 in grade 3 endometrioid, and 6.31 in serous carcinomas (p < 0.001). Overall, RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). p16 and p53 staining patterns were able to differentiate between high-grade endometrioid and serous carcinoma (p < 0.001). ER, PR and WT-1 did not reach statistical significance for subtyping. The  values of the general agreement between the observers were 0.737 and 0.727 for endometrioid and serous carcinomas respectively (p < 0.001). Diffuse p53 and p16 staining provides the most sensitive and specific immunomarkers for differentiating high-grade endometrioid and serous carcinomas.

  9. Salivary gland hybrid tumour revisited: could they represent high-grade transformation in a low-grade neoplasm?

    PubMed

    Hellquist, Henrik; Skalova, Alena; Azadeh, Bahram

    2016-12-01

    Salivary gland hybrid tumour, first described in 1996, is a very rare neoplasm for which exact morphological criteria have not been universally agreed upon. In contrast, the concept of high-grade transformation (HGT) in salivary neoplasms has been widely accepted during the last decade, and the number of reported cases is rapidly increasing. A review of the literature revealed 38 cases of hybrid tumour reported in 22 publications. During approximately the same time period, well over 100 cases of HGT in salivary neoplasms have been reported. There are important histological similarities between hybrid tumours and salivary tumours with HGT. In the latter, containing one tumour component of low-grade malignancy and the other of high grade, the two tumour components are not entirely separated and appear to originate in the same area. Virtually, all cases reported as hybrid tumour had no clear lines of demarcation between the two tumour types. We are inclined to suggest that most of the 38 cases of hybrid tumours described in the literature would today better be called tumour with HGT rather than hybrid tumour. The relative proportion of the two components may vary, and the high-grade component is sometimes very small, which emphasises the importance of very generous sampling of the surgical specimen. The molecular genetic mechanisms responsible for HGT, including what used to be called hybrid tumour, remain largely unknown. Abnormalities of a few genes (including p53, C-MYC, cyclin D1, HER-2/neu) have been documented. As insufficient data exist on gene abnormalities in these lesions, conclusions as to whether or not they have a common origin and which mechanisms are involved in transformation cannot be drawn. Due to the small number of cases reported, many of which lack follow-up details; indicators of prognosis of hybrid tumours are not available, but their behaviour seems to be similar to that of tumours with HGT, i.e. an accelerated aggressive course. HGT of

  10. Obesity Increases the Risk for High-grade Prostate Cancer: Results from the REDUCE study

    PubMed Central

    Vidal, Adriana C.; Howard, Lauren E.; Moreira, Daniel M.; Castro-Santamaria, Ramiro; Andriole, Gerald L.; Freedland, Stephen J.

    2014-01-01

    Background Studies suggest obesity is associated with lower risk of prostate cancer (PC) but more aggressive cancers. As obesity lowers PSA levels, these observations may be influenced by detection bias. We examined the association between obesity and risk of low- and high-grade PC in REDUCE, where biopsies were largely independent of PSA. Methods The REDUCE study tested dutasteride for PC risk reduction in men with a PSA of 2.5–10.0 ng/mL and a negative biopsy. Study participants included 6,729 men who underwent at least one on-study biopsy. The association between baseline body mass index (BMI <25 kg/m2-normal weight; 25–29.9 kg/m2-overweight; ≥30 kg/m2-obese) and risk of high-grade (Gleason ≥7) or low-grade PC (Gleason <7) vs. no PC was examined using multinomial logistic regression. Results Overall, 1,739 men (27%) were normal weight, 3,384 (53%) overweight, and 1,304 (20%) were obese. Obesity was associated with lower risk of low-grade PC in both univariable (OR 0.74, p=0.001) and multivariable analyses (OR 0.79, p=0.01). In univariable analysis, obesity was not associated with high-grade PC (OR 1.08, p=0.50). However, in multivariable analysis, obesity was associated with increased risk of high-grade PC (OR 1.28, p=0.042). The current analysis was not able to address how obesity may influence prostate cancer progression. Conclusions Obesity is associated with decreased risk of low-grade and increased risk of high-grade PC. These data provide further support to the hypothesis that obesity is associated with aggressive PC. Impact Obesity is linked with aggressive PC. Avoiding obesity may prevent the risk of developing high-grade PC. PMID:25261967

  11. Overexpression of TELO2 decreases survival in human high-grade gliomas

    PubMed Central

    Feng, Shao-Wei; Chen, Ying; Tsai, Wen-Chiuan; Chiou, Hsin-Ying Clair; Wu, Sheng-Tang; Huang, Li-Chun; Lin, Chin; Hsieh, Chih-Chuan; Yang, Yun-Ju; Hueng, Dueng-Yuan

    2016-01-01

    High-grade gliomas are characterized with poor prognosis. To improve the clinical outcome, biomarker is urgently needed for distinguishing oncotarget in high-grade gliomas. Telomere maintenance 2 (TELO2) regulates S-phase checkpoint in cell cycle, and is involved in DNA repair. However, the role of TELO2 in survival outcome of high-grade gliomas is still not yet clarified. This study aims to investigate the correlation between TELO2 mRNA expression and survival outcome of patients with high-grade gliomas. Based on bioinformatics study, we found that Kaplan-Meier analysis demonstrated shorter survival in patients with higher TELO2 mRNA levels than in those with lower TELO2 expression (median survival, 59 vs. 113 weeks, p=0.0017, by log-rank test, hazard ratio: 0.3505, 95% CI: 01824.-0.6735). TELO2 mRNA expression significantly higher in World Health Organization (WHO) grade IV than in non-tumor control (p=2.85 × 10−9). Moreover, TELO2 level was greater in WHO grade III than in non-tumor controls (p= 0.017) human gliomas. We further validated TELO2 mRNA expression and protein levels by using quantitative RT-PCR, Western blot, and immunohistochemical (IHC) stain of tissue microarray. Consistently, the TELO2 mRNA and protein expression were significantly elevated in human glioma cells in comparison with normal brain control. Additionally, IHC staining showed higher TELO2 immunostain score in high-grade gliomas than in low-grade gliomas, or normal brain control. Taken together, human high-grade gliomas increase TELO2 mRNA expression, and overexpression of TELO2 mRNA expression correlates with shorter survival outcome, supporting that TELO2 is an oncotarget in human gliomas. PMID:27329594

  12. Overexpression of TELO2 decreases survival in human high-grade gliomas.

    PubMed

    Feng, Shao-Wei; Chen, Ying; Tsai, Wen-Chiuan; Chiou, Hsin-Ying Clair; Wu, Sheng-Tang; Huang, Li-Chun; Lin, Chin; Hsieh, Chih-Chuan; Yang, Yun-Ju; Hueng, Dueng-Yuan

    2016-07-19

    High-grade gliomas are characterized with poor prognosis. To improve the clinical outcome, biomarker is urgently needed for distinguishing oncotarget in high-grade gliomas. Telomere maintenance 2 (TELO2) regulates S-phase checkpoint in cell cycle, and is involved in DNA repair. However, the role of TELO2 in survival outcome of high-grade gliomas is still not yet clarified. This study aims to investigate the correlation between TELO2 mRNA expression and survival outcome of patients with high-grade gliomas. Based on bioinformatics study, we found that Kaplan-Meier analysis demonstrated shorter survival in patients with higher TELO2 mRNA levels than in those with lower TELO2 expression (median survival, 59 vs. 113 weeks, p=0.0017, by log-rank test, hazard ratio: 0.3505, 95% CI: 01824.-0.6735). TELO2 mRNA expression significantly higher in World Health Organization (WHO) grade IV than in non-tumor control (p=2.85 x 10-9). Moreover, TELO2 level was greater in WHO grade III than in non-tumor controls (p= 0.017) human gliomas. We further validated TELO2 mRNA expression and protein levels by using quantitative RT-PCR, Western blot, and immunohistochemical (IHC) stain of tissue microarray. Consistently, the TELO2 mRNA and protein expression were significantly elevated in human glioma cells in comparison with normal brain control. Additionally, IHC staining showed higher TELO2 immunostain score in high-grade gliomas than in low-grade gliomas, or normal brain control. Taken together, human high-grade gliomas increase TELO2 mRNA expression, and overexpression of TELO2 mRNA expression correlates with shorter survival outcome, supporting that TELO2 is an oncotarget in human gliomas.

  13. Armodafinil in Reducing Cancer-Related Fatigue in Patients With High Grade Glioma | Division of Cancer Prevention

    Cancer.gov

    This randomized phase III trial studies armodafinil to see how well it works in reducing cancer-related fatigue in patients with high grade glioma. Armodafinil may help relieve fatigue in patients with high grade glioma. |

  14. View looking northwest toward HIghGrade Ore Bin and Concentrate Bin ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View looking northwest toward HIgh-Grade Ore Bin and Concentrate Bin - Kennecott Copper Corporation, Concentration Mill, On Copper River & Northwestern Railroad, Kennicott, Valdez-Cordova Census Area, AK

  15. How do we manage high-grade T1 bladder cancer? Conservative or aggressive therapy?

    PubMed Central

    Kim, Seon-Kyu; Kim, Wun-Jae

    2016-01-01

    High-grade T1 bladder cancer has a poor prognosis due to a higher incidence of recurrence and progression than other nonmuscle invasive bladder cancer; thus patients with high-grade T1 have to be carefully monitored and managed. If patients are diagnosed with high-grade T1 at initial transurethral resection (TUR), a second TUR is strongly recommended regardless of whether muscle layer is present in the specimen because of the possibility of understating due to incomplete resection. Since high-grade T1 disease shows diverse clinical courses, individual approaches are recommended for treatment. In cases with low risk of progression, cystectomy could represent overtreatment and deteriorate quality of life irreversibly, while, in those with high risk, bacillus Calmette-Guérin (BCG) therapy may worsen survival by delaying definitive therapy. Therefore, a strategy for predicting prognosis based on the risk of progression is needed for managing high-grade T1 disease. Molecular risk classifiers predicting the risk of progression and response to BCG may help identify the optimal management of high-grade T1 disease for each individual. PMID:27326407

  16. High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

    PubMed

    Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

    2015-01-01

    Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

  17. Endoscopic Ultrasound Does Not Accurately Stage Early Adenocarcinoma or High-Grade Dysplasia of the Esophagus

    DTIC Science & Technology

    2010-01-01

    MeSH search terms: " endoscopic ultrasound," "Barrett’s esophagus ," "adeno· carcinoma," "Barrett’s esophagus and high grade dyspla.c;ia...adenocarcinoma of the esophagus ; EMR, endoscopic mucosal resection; EUS, endoscopic ul- trasound; HGD, high-grade dysplasia. <D 2010 by the AGA Institute... esophagus and early adenocarcinoma found EUS examination to have perfecr accuracy for differentiating Tl CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol

  18. Novel Diffusion-Weighted MRI for High-Grade Prostate Cancer Detection

    DTIC Science & Technology

    2016-10-01

    1 1 AWARD NUMBER: W81XWH-15-1-0346 TITLE: Novel Diffusion-Weighted MRI for High-Grade Prostate Cancer Detection PRINCIPAL INVESTIGATOR...2016 4. TITLE AND SUBTITLE Novel Diffusion-Weighted MRI for High-Grade Prostate Cancer Detection 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1...therapy, and reduce biopsies needed on surveillance of indolent disease. 15. SUBJECT TERMS FROC, Prostate Cancer, MRI , Diffusion 16. SECURITY

  19. High-risk human papillomavirus DNA test: could it be useful in low-grade cervical lesion triage? Five-year follow-up.

    PubMed

    Saccardi, Carlo; Gizzo, Salvatore; Noventa, Marco; Anis, Omar; Di Gangi, Stefania; Patrelli, Tito Silvio; D'Antona, Donato; Nardelli, Giovanni Battista

    2014-02-01

    We conducted a retrospective, observational study in order to evaluate the role of high-risk human papillomavirus (hrHPV)-DNA test in patients with first diagnosis of low-grade squamous intraepithelial lesions (L-SILs).Patients were divided into group A, annual Papanicolaou test and hrHPV-DNA tests (167 patients) and group B, immediate colposcopy, followed by annual papanicolaou test and hrHPV-DNA tests (164 patients). We assessed sensitivity, specificity, negative predictive value (NPV), positive predictive value, positive-negative likelihood ratio of hrHPV-DNA test, and 5-year relative risk of cervical intraepithelial neoplasia grade 2 in hrHPV-DNA+. Colposcopy is still considered the best choice for women with L-SIL and hrHPV-DNA+ test. High sensitivity and NPV of hrHPV-DNA test permit to use it in the follow-up of L-SIL with a HPV-negative status, without necessity of referring to colposcopy.

  20. Non-operative management versus operative management in high-grade blunt hepatic injury.

    PubMed

    Cirocchi, Roberto; Trastulli, Stefano; Pressi, Eleonora; Farinella, Eriberto; Avenia, Stefano; Morales Uribe, Carlos Hernando; Botero, Ana Maria; Barrera, Luis M

    2015-08-24

    Surgery used to be the treatment of choice in cases of blunt hepatic injury, but this approach gradually changed over the last two decades as increasing non-operative management (NOM) of splenic injury led to its use for hepatic injury. The improvement in critical care monitoring and computed tomographic scanning, as well as the more frequent use of interventional radiology techniques, has helped to bring about this change to non-operative management. Liver trauma ranges from a small capsular tear, without parenchymal laceration, to massive parenchymal injury with major hepatic vein/retrohepatic vena cava lesions. In 1994, the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma (AAST) revised the Hepatic Injury Scale to have a range from grade I to VI. Minor injuries (grade I or II) are the most frequent liver injuries (80% to 90% of all cases); severe injuries are grade III-V lesions; grade VI lesions are frequently incompatible with survival. In the medical literature, the majority of patients who have undergone NOM have low-grade liver injuries. The safety of NOM in high-grade liver lesions, AAST grade IV and V, remains a subject of debate as a high incidence of liver and collateral extra-abdominal complications are still described. To assess the effects of non-operative management compared to operative management in high-grade (grade III-V) blunt hepatic injury. The search for studies was run on 14 April 2014. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (Ovid), PubMed, ISI WOS (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), clinical trials registries, conference proceedings, and we screened reference lists. All randomised trials that compare non-operative management versus operative management in high-grade blunt hepatic injury. Two authors independently

  1. Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats

    PubMed Central

    Kalinich, John F.; Emond, Christy A.; Dalton, Thomas K.; Mog, Steven R.; Coleman, Gary D.; Kordell, Jessica E.; Miller, Alexandra C.; McClain, David E.

    2005-01-01

    Continuing concern regarding the potential health and environmental effects of depleted uranium and lead has resulted in many countries adding tungsten alloy (WA)-based munitions to their battlefield arsenals as replacements for these metals. Because the alloys used in many munitions are relatively recent additions to the list of militarily relevant metals, very little is known about the health effects of these metals after internalization as embedded shrapnel. Previous work in this laboratory developed a rodent model system that mimicked shrapnel loads seen in wounded personnel from the 1991 Persian Gulf War. In the present study, we used that system and male F344 rats, implanted intramuscularly with pellets (1 mm × 2 mm cylinders) of weapons-grade WA, to simulate shrapnel wounds. Rats were implanted with 4 (low dose) or 20 pellets (high dose) of WA. Tantalum (20 pellets) and nickel (20 pellets) served as negative and positive controls, respectively. The high-dose WA-implanted rats (n = 46) developed extremely aggressive tumors surrounding the pellets within 4–5 months after implantation. The low-dose WA-implanted rats (n = 46) and nickel-implanted rats (n = 36) also developed tumors surrounding the pellets but at a slower rate. Rats implanted with tantalum (n = 46), an inert control metal, did not develop tumors. Tumor yield was 100% in both the low- and high-dose WA groups. The tumors, characterized as high-grade pleomorphic rhabdomyosarcomas by histopathology and immunohistochemical examination, rapidly metastasized to the lung and necessitated euthanasia of the animal. Significant hematologic changes, indicative of polycythemia, were also observed in the high-dose WA-implanted rats. These changes were apparent as early as 1 month postimplantation in the high-dose WA rats, well before any overt signs of tumor development. These results point out the need for further studies investigating the health effects of tungsten and tungsten-based alloys. PMID:15929896

  2. Ninth Grade Physics: A Necessity for High School Science Programs

    ERIC Educational Resources Information Center

    Wilt, John R.

    2005-01-01

    The traditional order in which science courses are taught in U.S. high schools is biology, chemistry, physics. The physics course usually is regarded as very difficult because it requires both high-level mathematical skills and high-level thinking skills; it is taught in the final year of high school to provide time for students to develop the…

  3. Differential proteomics analysis of low- and high-grade of astrocytoma using iTRAQ quantification

    PubMed Central

    Ren, Tong; Lin, Shide; Wang, Zhongfeng; Shang, Aijia

    2016-01-01

    Astrocytoma is one of the most common types of brain tumor, which is histologically and clinically classified into four grades (I–IV): I (pilocytic astrocytoma), II (diffuse astrocytoma), III (anaplastic astrocytoma), and IV (glioblastoma multiforme). A higher grade astrocytoma represents a worse prognosis and is more aggressive. In this study, we compared the differential proteome profile of astrocytoma from grades I to IV. The protein samples from clinical specimens of grades I, II, III, and IV astrocytoma were analyzed by two-dimensional liquid chromatography–tandem mass spectrometry and isobaric tags for relative and absolute quantitation and quantification. A total of 2,190 proteins were identified. Compared to grade I astrocytoma, 173 (12.4%), 304 (14%), and 462 (21.2%) proteins were aberrantly expressed in grades II, III, and IV, respectively. By bioinformatics analysis, the cell proliferation, invasion, and angiogenesis-related pathways increase from low- to high-grade of astrocytoma. Five differentially expressed proteins were validated by Western blot. Within them, matrix metalloproteinase-9 and metalloproteinase inhibitor 1 were upregulated in glioblastoma multiforme group; whereas fibulin-2 and -5 were downregulated in grade II/III/IV astrocytoma, and the negative expression was significantly associated with advanced clinical stage. Functional analysis showed that both fibulin-2 and -5 may exert an antitumor effect by inhibiting cell proliferation, in vitro migration/invasion in glioma cells. New molecular biomarkers are likely to be used for accurate classification of astrocytoma and likely to be the target for drug development. PMID:27713642

  4. Semiconductor Seeded Nanorods with Graded Composition Exhibiting High Quantum-Yield, High Polarization, and Minimal Blinking.

    PubMed

    Hadar, Ido; Philbin, John P; Panfil, Yossef E; Neyshtadt, Shany; Lieberman, Itai; Eshet, Hagai; Lazar, Sorin; Rabani, Eran; Banin, Uri

    2017-04-12

    Seeded semiconductor nanorods represent a unique family of quantum confined materials that manifest characteristics of mixed dimensionality. They show polarized emission with high quantum yield and fluorescence switching under an electric field, features that are desirable for use in display technologies and other optical applications. So far, their robust synthesis has been limited mainly to CdSe/CdS heterostructures, thereby constraining the spectral tunability to the red region of the visible spectrum. Herein we present a novel synthesis of CdSe/Cd1-xZnxS seeded nanorods with a radially graded composition that show bright and highly polarized green emission with minimal intermittency, as confirmed by ensemble and single nanorods optical measurements. Atomistic pseudopotential simulations elucidate the importance of the Zn atoms within the nanorod structure, in particular the effect of the graded composition. Thus, the controlled addition of Zn influences and improves the nanorods' optoelectronic performance by providing an additional handle to manipulate the degree confinement beyond the common size control approach. These nanorods may be utilized in applications that require the generation of a full, rich spectrum such as energy-efficient displays and lighting.

  5. Thallium-201 imaging and estimation of residual high grade astrocytoma

    SciTech Connect

    Stafford-Schuck, K.; Mountz, J.M.; McKeever, P.; Taren, J.; Beierwaltes, W.H.

    1987-09-01

    Thallium-201 brain imaging was performed on five patients as a method to differentiate persistent and/or recurrent viable Grades III and IV astrocytoma tissue from necrosis or post-therapy changes. Planar images of the head and heart were obtained in order to calculate the ratio of tumor counts to cardiac counts. The heart was chosen as the internal reference organ, as thallium uptake dynamics are reproducible under ordinary circumstances. The numerical estimation of thallium uptake in the brain tumor, expressed in terms of the tumor/cardiac index, correlated well with the clinical course in all five patients. By visual inspection, the initial computed tomographic (CT) and thallium images suggested that the tumors were approximately the same size. Follow-up thallium images were discordant with follow-up CT images. Computed tomography, in general, appeared to depict image alterations suggesting more extensive regrowth of tumor than the actual clinical status or thallium brain scans demonstrated. Histologic examination best correlated with thallium images. In one patient's course of imaging they were able to detect tumor recurrence, by means of thallium imaging, 4 months prior to its appearance on CT. When performed serially, the tumor/cardiac index may provide an estimate of residual tumor burden, which can help distinguish tumor recurrence from changes secondary to therapy.

  6. Detection of High Grade Prostate Cancer among PLCO Participants Using a Prespecified 4-Kallikrein Marker Panel.

    PubMed

    Kim, Eric H; Andriole, Gerald L; Crawford, E David; Sjoberg, Daniel D; Assel, Melissa; Vickers, Andrew J; Lilja, Hans

    2017-04-01

    We assessed the performance of a 4-kallikrein panel with and without microseminoprotein-β to predict high grade (Gleason 7+/Gleason Grade Group 2+) prostate cancer on biopsy in a multiethnic cohort from PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial). Levels of free, intact, total prostate specific antigen, human kallikrein-2 and microseminoprotein-β were measured while blinded to outcomes in cryopreserved serum from men in the intervention arm of PLCO. Marker levels of 946 men, of whom 100 were African American, were incorporated into a prespecified statistical model to predict high grade prostate cancer on biopsy. The detection of high grade prostate cancer in 94 men (10%) was enhanced by the 4-kallikrein panel with an AUC of 0.79 compared to 0.73 for PCPTRC (Prostate Cancer Prevention Trial Risk Calculator), representing a 0.060 increase (95% CI 0.032-0.088, p <0.01). Additionally, the AUC increased from 0.79 to 0.81 when microseminoprotein-β was added to the 4-kallikrein panel. In African American men, the 4-kallikrein panel model also enhanced high grade prostate cancer detection over that of prostate specific antigen (AUC 0.80 vs 0.67). As an illustration of clinical implications, using 1 cutoff point for biopsy (6% risk of high grade prostate cancer) with the 4-kallikrein panel model would have eliminated unnecessary biopsies in 420 per 1,000 men (42%) while detecting high grade prostate cancer in 83 of 93 (88%). In a multiethnic United States population, the 4-kallikrein panel demonstrated improved risk discrimination for high grade prostate cancer over conventional clinical variables (age, prostate specific antigen and digital rectal examination) as well as PCPTRC. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  7. Human Papillomavirus Genotype Distribution among Thai Women with High-Grade Cervical Intraepithelial Lesions and Invasive Cervical Cancer: a Literature Review.

    PubMed

    Kietpeerakool, Chumnan; Kleebkaow, Pilaiwan; Srisomboon, Jatupol

    2015-01-01

    Infection with high-risk human papillomavirus (HR-HPV) is an essential cause of cervical cancer. Because of substantial geographical variation in the HPV genotype distribution, data regarding HPV type-specific prevalence for a particular country are mandatory for providing baseline information to estimate effectiveness of currently implemented HPV-based cervical cancer prevention. Accordingly, this review was conducted to evaluate the HR-HPV genotype distribution among Thai women with precancerous cervical lesions i.e. cervical intraepithelial neoplasia grade 2-3 (CIN 2-3), adenocarcinoma in situ (AIS), and invasive cervical cancer by reviewing the available literature. The prevalence of HR-HPV infection among Thai women with CIN 2-3 ranged from 64.8% to 90.1% and the three most common genotypes were HPV 16 (38.5%), HPV 58 (20.0%), and HPV 18 (5.5%). There were high squamous cell carcinoma/CIN 2-3 prevalence ratios in women with CIN 2-3 infected with HPV 33 and HPV 58 (1.40 and 1.38, respectively), emphasizing the importance of these subtypes in the risk of progression to invasive cancer among Thai women. Data regarding the prevalence and genotype distribution of HR-HPV in Thai women with AIS remain unavailable. Interesting findings about the distribution of HPV genotype in cervical cancer among Thai women include: (1) a relatively high prevalence of HPV 52 and HPV 58 in invasive squamous cell carcinoma; (2) the prevalence of HPV 18-related adenocarcinoma is almost double thepreviously reported prevalence, and (3) 75% of neuroendocrine carcinomas are HPV18-positive when taking into account both single and multiple infections.

  8. The utility of endocervical curettage: does routine ECC at the time of colposcopy for low-grade cytologic abnormalities improve diagnosis of high-grade disease?

    PubMed

    Rose, Joseph D; Byun, Sharon Y; Sims, Shireen Madani; Davis, John D

    2012-06-01

    To determine the use of endocervical curettage at the time of colposcopy for low-grade cytologic abnormalities. We conducted a retrospective chart review of women with low-grade Papanicolaou smears who had undergone satisfactory colposcopic examinations with identifiable lesions. We evaluated results during a 2-year period thereafter to determine whether endocervical curettage increased the diagnosis of high-grade dysplasia. The study group consisted of 374 patients. Of these patients, 16 had endocervical curettages suggestive of high-grade dysplasia. Of these 16 patients, 4 did not have concomitant high-grade dysplasia identified on ectocervical biopsy. Therefore, 93 to 94 endocervical curettages needed to be performed to detect 1 case of high-grade dysplasia that would not have been identified otherwise. Routine endocervical curettage at the time of satisfactory colposcopy for low-grade cytologic abnormalities with a visible lesion does not significantly improve the diagnosis of high-grade dysplasia. Copyright © 2012 Mosby, Inc. All rights reserved.

  9. Pre-vaccination prevalence of infections with 25 non-high-risk human papillomavirus types among 1,000 Slovenian women in cervical cancer screening.

    PubMed

    Učakar, Veronika; Poljak, Mario; Oštrbenk, Anja; Klavs, Irena

    2014-10-01

    Cervical infections with non-high-risk human papillomavirus (non-HR-HPV) types have been associated with genital warts and a fraction of atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. The pre-vaccination prevalence of cervical infections with 25 non-HR-HPV types has been estimated, regardless of and without the coexistence of infection with HR-HPV types among Slovenian women 20-64 years old in cervical cancer screening, overall and according to age and cytology result. One thousand cervical specimens selected randomly from 4,455 specimens collected in 2010 in the Slovenian HPV prevalence survey were tested with Linear Array HPV Genotyping Test. Prevalence of cervical infections with any of the 25 non-HR-HPV types was 10.0% (95% CI: 8.1-11.9%) and with exclusively non-HR-HPV types 4.5% (95% CI: 3.2-5.8%). Prevalence of infections with any non-HR-HPV types among women with normal cytology was 8.8%, with atypical squamous cells of undetermined significance 30.4%, with low-grade squamous intraepithelial lesions 60.0%, and with high-grade squamous intraepithelial lesions 7.7%. Non-HR-HPV types without coexisting HR-HPV types were found in 4.0% of women with normal cytology, 26.1% with atypical squamous cells of undetermined significance, 6.7% with low-grade squamous intraepithelial lesions, and none with high-grade squamous intraepithelial lesion. Non-HR-HPV type cervical infections without coexisting HR-HPV infections were common among Slovenian women in cervical cancer screening with atypical squamous cells of undetermined significance, while rare in those with low-grade squamous intraepithelial lesions or worse. J. Med. Virol. 86: 1772-1779, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

  10. [Prevalence of epithelial squamous cell abnormalities and associated factors in women of a rural town of Colombia].

    PubMed

    Grisales, Hugo; Vanegas, Angela Patricia; Gaviria, Angela M; Castaño, Jorge; Mora, Martín Alonso; Borrero, Mauricio; Rojas, Carlos; Arbeláez, María Patricia; Sánchez, Gloria I

    2008-06-01

    In spite of implementation of cytology-based cervical cancer screening in Colombia, mortality rates remain stable. The description of factors associated to cervical pre-neoplasic lesions is needed to establish strategies for mortality prevention. The prevalence of epithelial squamous cell abnormalities was determined to explore the association of cytology abnormalities with described risk factors. This population-based, cross-sectional study included 739 women randomly selected by age. A validated face-to-face questionnaire and conventional cervical cytology were used to collect the information. To establish the association between cervical abnormalities and some qualitative variables, the independent chi squared test was used. We also calculated prevalence ratio with their 95% confidence intervals. A logistic regression model was used to explore variables that potentially explain cytology abnormalities. The prevalence of squamous cell abnormality was 15.8%. Among women with abnormal cytology, 10% presented atypical squamous cells of undetermined significance, 3.9% low grade squamous intra-epithelial lesion and 1.9% high grade squamous intra-epithelial lesion. The adjusted logistical regression analysis showed that history of sexual transmitted disease, two or more sexual partners during entire life and previous abnormal cytology were associated with cytology abnormalities. The relation of epithelial squamous cell abnormalities with sexual behavior history reflexes the link between human papiloma virus infection and cervical cancer pre-neoplasic lesions. The frequency of use and knowledge about the purpose of cytology were factors that suggested other diagnostic limitations such as quality of cervical cytology or barriers to access health care. These latter factors may be the underlying basis for the high cervical cancer mortality rates.

  11. Natural Antibodies to Human Papillomavirus 16 and Recurrence of Vulvar High-Grade Intraepithelial Neoplasia (VIN3).

    PubMed

    Madeleine, Margaret M; Johnson, Lisa G; Doody, David R; Tipton, Elaine R; Carter, Joseph J; Galloway, Denise A

    2016-07-01

    Approximately 30% of women treated for squamous high-grade intraepithelial neoplasia (VIN3), often associated with human papillomavirus (HPV), have recurrent disease. In this study, we assess predictors of recurrence that may provide targets for early prevention or treatment. Women with VIN3 who participated in a previous population-based case-control study with blood and tumor samples completed a follow-up telephone interview an average of 5 years after initial diagnosis. The risk of recurrence was determined by proportional hazards modeling. Women with VIN3 in the follow-up study (n = 65) were similar to women with VIN3 in the parent study (n = 215) with regard to age at primary diagnosis, level of current cigarette smoking (>60%), and lifetime number of partners. We found that 22 (33.8%) of 65 participants had a vulvar recurrence and that 73.4% recurred within 3 years of treatment. Recurrences occurred more often among women with common warts in the decade before diagnosis (hazard ratio [HR] = 2.5, 95% CI = 1.1-5.8) and among those with a previous anogenital cancer (HR = 2.7, 95% CI = 1.2-6.3). Interestingly, recurrence was less frequent among women who mounted a natural antibody response to HPV16 (HR = 0.4, 95% CI = 0.2-0.9). These data provide strong preliminary evidence that VIN3 recurrence was less frequent among those with HPV16 antibodies. Vaccination with the currently licensed HPV vaccine as part of adjunctive therapy for VIN3 would increase antibody response and may decrease risk of recurrence. Randomized controlled trials are needed to determine whether HPV vaccination is effective against VIN3 recurrence.

  12. Weekly chemotherapy with radiation versus high-dose cisplatin with radiation as organ preservation for patients with HPV-positive and HPV-negative locally advanced squamous cell carcinoma of the oropharynx.

    PubMed

    Dobrosotskaya, Irina Y; Bellile, Emily; Spector, Matthew E; Kumar, Bhavna; Feng, Felix; Eisbruch, Avraham; Wolf, Gregory T; Prince, Mark E P; Moyer, Jeffrey S; Teknos, Theodoros; Chepeha, Douglas B; Walline, Heather M; McHugh, Jonathan B; Cordell, Kitrina G; Ward, P Daniel; Byrd, Serena; Maxwell, Jessica H; Urba, Susan; Bradford, Carol R; Carey, Thomas E; Worden, Francis P

    2014-05-01

    Optimal treatment for locally advanced squamous cell carcinoma of the oropharynx (SCCOP) is not well defined. Here we retrospectively compare survival and toxicities from 2 different organ preservation protocols. The matched dataset consisted of 35 patients from each trial matched for age, stage, smoking, and tumor human papillomavirus (HPV) status. Patients in the University of Michigan Cancer Center (UMCC) trial 9921 were treated with induction chemotherapy (IC) followed by high-dose cisplatin and radiation in responders or surgery in nonresponders. Patients in the UMCC trial 0221 were treated with weekly carboplatin and paclitaxel and radiation. Survival was comparable for both studies and did not differ significantly across each trial after stratifying by HPV status. Grade 3 and 4 toxicities were more frequent in UMCC 9921. At 6 months posttreatment, gastrostomy tube (G-tube) dependence was not statistically different. These data suggest that survival outcomes in patients with locally advanced SCCOP are not compromised with weekly chemotherapy and radiation therapy, and such treatment is generally more tolerable. Copyright © 2013 Wiley Periodicals, Inc.

  13. Grades--Scores--Predictions: A Study of the Efficiency of High School Grades and American College Test Scores in Predicting Academic Achievement at Montgomery College.

    ERIC Educational Resources Information Center

    Gell, Robert L.; Bleil, David F.

    This report analyzes the relationship between high school grades, American College Test (ACT) scores, and first-semester college grades. Based on the Standard Research Service of the ACT program, 1,379 students in the fall 1969 freshman class of Montgomery College (Maryland) were studied. Measures of academic background used ACT scores in English,…

  14. Cytology and Human Papillomavirus Testing 6 to 12 Months after ASCUS or LSIL Cytology in Organized Screening To Predict High-Grade Cervical Neoplasia between Screening Rounds

    PubMed Central

    Sjøborg, Katrine D.; Nygård, Mari; Røysland, Kjetil; Campbell, Suzanne; Alfsen, G. Cecilie; Jonassen, Christine M.

    2012-01-01

    We carried out a prospective study comparing the performance of human papillomavirus (HPV) E6/E7 mRNA (PreTect HPV-Proofer; NorChip, Klokkarstua, Norway) and DNA (Amplicor HPV test; Roche Diagnostics, Basel, Switzerland) triage testing of women 6 to 12 months after atypical-squamous-cells-of-undetermined-significance (ASCUS) or low-grade-squamous-intraepithelial-lesion (LSIL) cytology in organized screening to predict high-grade cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) between screening rounds. Between January 2005 and April 2008, 692 study women with screening-detected ASCUS/LSIL cytology 6 to 12 months earlier returned for HPV mRNA and DNA testing and repeat cytology. The median follow-up time was 3 years, using existing health care facilities. Follow-up test results were available for 625 women. Of the 145 CIN2+ cases detected during the study period, 95 (65.5%) were HPV mRNA positive 6 to 12 months after screening-detected ASCUS/LSIL, 44 (30.4%) were HPV mRNA negative, and 6 (4.1%) were invalid. The corresponding HPV DNA results were 139 (95.9%), 5 (3.4%), and 1 (0.7%), respectively. The cumulative incidences of CIN2+ 3 years after a negative HPV mRNA and DNA test were 10.3% (95% confidence interval [CI], 7.2 to 13.3%) and 1.8% (95% CI, 0.0 to 3.6%), respectively. The cumulative incidences of CIN2+ 3 years after positive HPV mRNA and DNA tests were 52.8% (95% CI, 40.1 to 60.1%) and 41.3% (95% CI, 35.5 to 46.6%), respectively. In conclusion, both positive HPV mRNA and DNA test results have a high enough long-term prediction of CIN2+ risk to consider referral to colposcopy as good practice when performed in delayed triage of women with ASCUS/LSIL cytology. In addition, the low CIN2+ risk among women with a negative Amplicor HPV test in our study confirms its safe use in a clinical setting. PMID:22518869

  15. High expression of ALDH1 and SOX2 diffuse staining pattern of oral squamous cell carcinomas correlates to lymph node metastasis.

    PubMed

    Michifuri, Yoshitaka; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Miyazaki, Akihiro; Kobayashi, Junichi; Sasaki, Takanori; Fujino, Jyunki; Asanuma, Hiroko; Tamura, Yasuaki; Nakamori, Kenji; Hasegawa, Tadashi; Hiratsuka, Hiroyoshi; Sato, Noriyuki

    2012-10-01

    One of the major factors involved in the prognosis of oral squamous cell carcinoma (OSCC) patients is metastasis. Recent progress in cancer stem-like cell/cancer-initiating cell (CSC/CIC) research indicates that CSCs are related to metastasis. Aldehyde dehydrogenase 1 - (ALDH1) and SRY-related HMG-box gene 2 (SOX2) have recently been shown to be putative CSC markers for several human malignancies. The aim of this study was to determine the association of ALDH1 and SOX2 expression in oral squamous cell carcinoma (OSCC) with lymph node metastasis. Immunohistochemical staining of ALDH1, SOX2 and Ki67 was performed in 80 OSCC tissues. High expression rates of ALDH1 (2%-40%) were found to be related to lymph node metastasis (P = 0.0017). Interestingly, we found that SOX2 staining could be classified into two patterns: (i) peripheral staining pattern; and (ii) diffuse staining pattern. The diffuse staining pattern showed a significant correlation with lymph node metastasis (P < 0.001). No correlation was found between Ki67 staining and lymph node metastasis (P = 0.4724). The ALDH1 positive staining rates in metastatic lymph nodes were higher than that in corresponding primary OSCC tissues. These results indicate that high expression rates of ALDH1 and SOX2 diffuse staining patterns might be novel prediction markers for OSCC lymph node metastasis.

  16. Correlation of p16INK4a immunoexpression and human papillomavirus (HPV) detected by in-situ hybridization in cervical squamous neoplasia.

    PubMed

    Cheah, P L; Koh, C C; Nazarina, A R; Teoh, K H; Looi, L M

    2016-04-01

    Persistence and eventual integration of high-risk HPV (hrHPV) into the cervical cell is crucial to the progression of cervical neoplasia and it would be beneficial to morphologically identify this transformation in routine surgical pathology practice. Increased p16(INK4a) (p16) expression is a downstream event following HPV E7 binding to pRB. A study was conducted to assess the correlation between hrHPV detection using a commercial in-situ hybridization assay (Ventana INFORM HPV ISH) and p16 immunoexpression (CINtec Histology Kit) in cervical squamous intraepithelial lesions and squamous carcinoma. 27 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSIL), 21 high-grade squamous intraepithelial lesions (HSIL) and 51 squamous carcinoma (SCC) were interrogated. hrHPV was significantly more frequent in HSIL (76.2%) and SCC (88.2%) compared to LSIL(37.0%). p16 expression was similarly more frequent in HSIL (95.2%) and SCC (90.2%) compared to LSIL(3.7%). That the rates of hrHPV when compared with p16 expression were almost equivalent in HSIL and SCC while p16 was expressed in only 1 of the 10 LSIL with hrHPV, are expected considering the likelihood that transformation has occurred in HSIL and SCC but does not occur in majority of LSIL.

  17. [High-grade pressure sores in frail older high-risk persons. A retrospective postmortem case-control-study].

    PubMed

    Von Renteln-Kruse, W; Krause, T; Anders, J; Kühl, M; Heinemann, A; Püschel, K

    2004-04-01

    Some old persons at risk do develop, but others, at comparable risk, do not develop high-grade pressure sores. To evaluate potentially different risk factors, we performed a post mortem case-control study in old persons who developed high-grade pressure sores within six months until 14 days before death. Consecutive cases with pressure sores grade >/=3 and potential controls at comparably high risk for pressure sores were examined before cremation. After written informed consent had been obtained by the next relatives, all available nursing and medical records of the deceased were thoroughly evaluated. Cases and controls were matched according to age, gender, immobility, and cachexia.A total of 100 cases with 71 pressure sores grade 3 and 29 pressure sores grade 4 were compared to 100 controls with 27 pressure sores grade high degree of disablement and immobility, in particular, are risk factors for high-grade pressure sores in frail older high-risk persons. Sedative drug effects and impaired patient compliance with preventive and therapeutic measures may also be associated with the development of high-grade pressure sores in old persons at high risk.

  18. Poor interobserver reproducibility in the diagnosis of high-grade endometrial carcinoma.

    PubMed

    Gilks, C Blake; Oliva, Esther; Soslow, Robert A

    2013-06-01

    Patients with high-grade subtypes of endometrial carcinoma (grade 3 endometrioid, serous, clear cell, or carcinosarcoma) have a relatively poor prognosis. The specific subtype may be used to guide patient management, but there is little information on the reproducibility of subtype diagnosis in cases of high-grade endometrial carcinoma. Fifty-six cases diagnosed as a high-grade subtype of endometrial carcinoma were identified from the pathology archives of Vancouver General Hospital. All slides for each case were reviewed independently by 3 pathologists, who diagnosed the specific tumor subtype(s) and assigned the percentage of each subtype for mixed tumors. Agreement between observers was categorized as follows: major disagreement: (A) no consensus for low-grade endometrioid versus high-grade carcinoma (any subtype), or (B) no consensus with respect to the predominant high-grade subtype present; minor disagreement: consensus was reached about the cell type of the predominant component of a mixed tumor, but there was disagreement about the subtype of the minor component. A tissue microarray was constructed from these cases and immunostained for p16, ER, PR, PTEN, and p53. In 35 of 56 (62.5%) cases, there was agreement between all 3 reviewers regarding the subtype diagnosis of the exclusive (in pure tumors) or predominant (in mixed tumors) high-grade component. Of these cases, there was a minor disagreement (ie, disagreement about the minor high-grade component subtype in a mixed tumor) in 4 cases (4/56, 7.1%). In 20 of 56 (35.8%) cases there was a major disagreement; in 17 (30.4%) of these cases there was no consensus about the major subtype diagnosis, whereas in 3 (5.4%) cases there was disagreement about whether a component of high-grade endometrial carcinoma was present. In the final case, all 3 reviewers diagnosed the case as low-grade endometrioid carcinoma, disagreeing with the original diagnosis of high-grade carcinoma. The most frequent areas of

  19. Renal ultrasound and DMSA screening for high-grade vesicoureteral reflux.

    PubMed

    Wongbencharat, Kunruedi; Tongpenyai, Yothi; Na-Rungsri, Kunyalak

    2016-03-01

    Selection of the appropriate radiologic investigation in a child after first febrile urinary tract infection (UTI) remains a contentious issue. This report investigated the effectiveness of renal bladder ultrasound (RBUS) and late 6 month dimercaptosuccinic acid (DMSA) renal scan in the detection of high-grade vesicoureteral reflux (VUR) after first febrile UTI in infants aged <1 year. A total of 387 infants aged <1 year with first febrile UTI who completed diagnostic follow up consisting of RBUS, voiding cystourethrogram (VCUG) and late 6 month DMSA scan were enrolled in the study. The effectiveness of RBUS and DMSA scan in the detection of high-grade VUR, including cost and benefit were assessed. Abnormal RBUS was identified in 95 infants (24.5%). VUR was identified on VCUG in 79 (20.4%), of whom eight (2.1%) had high-grade VUR (grade IV-V). Abnormal renal parenchyma was identified on late 6 month DMSA scan in 22 infants (5.7%). The sensitivity of abnormal RBUS and of late 6 month DMSA scan in the prediction of high-grade VUR was 50% and 87.5%, and the proportion of infants who avoided unnecessary VCUG was 75.5% and 94.3%, respectively. Fifty percent of high-grade VUR was not identified on RBUS screening after first febrile UTI. Although late 6 month DMSA scan had higher sensitivity in the detection of high-grade VUR, with the added benefit of detection of renal scars, the practical application of this method was limited due to its high cost, radiation exposure and the associated delay in decision making. © 2015 Japan Pediatric Society.

  20. Blood Magnesium, and the Interaction with Calcium, on the Risk of High-Grade Prostate Cancer

    PubMed Central

    Motley, Saundra S.; Smith, Joseph A.; Concepcion, Raoul; Barocas, Daniel; Byerly, Susan

    2011-01-01

    Background Ionized calcium (Ca) and magnesium (Mg) compete as essential messengers to regulate cell proliferation and inflammation. We hypothesized that inadequate Mg levels, perhaps relative to Ca levels (e.g. a high Ca/Mg ratio) are associated with greater prostate cancer risk. Study Design In this biomarker sub-study of the Nashville Men's Health Study (NMHS), we included 494 NMHS participants, consisting of 98 high-grade (Gleason≥7) and 100 low-grade cancer cases, 133 prostate intraepithelial neoplasia (PIN) cases, and 163 controls without cancer or PIN at biopsy. Linear and logistic regression were used to determine associations between blood Ca, Mg, and the Ca/Mg ratio across controls and case groups while adjusting for potential confounding factors. Results Serum Mg levels were significantly lower, while the Ca/Mg ratio was significantly higher, among high-grade cases vs. controls (p = 0.04, p = 0.01, respectively). Elevated Mg was significantly associated with a lower risk of high-grade prostate cancer (OR = 0.26 (0.09, 0.85)). An elevated Ca/Mg ratio was also associated with an increased risk of high-grade prostate cancer (OR = 2.81 (1.24, 6.36) adjusted for serum Ca and Mg). In contrast, blood Ca levels were not significantly associated with prostate cancer or PIN.Mg, Ca, or Ca/Mg levels were not associated with low-grade cancer, PIN, PSA levels, prostate volume, or BPH treatment. Conclusion Low blood Mg levels and a high Ca/Mg ratio were significantly associated with high-grade prostate cancer. These findings suggest Mg affects prostate cancer risk perhaps through interacting with Ca. PMID:21541018

  1. A Quantitative Comparative Analysis of Ninth Grade Academies and Graduation Rates in Texas High Schools

    ERIC Educational Resources Information Center

    Lyons, Guy Kevin

    2014-01-01

    Students face many challenges in the transition to high school. From pressures of high-stakes testing for graduation to transitioning to the high school environment, many diversions can delay or even stop a student's path to graduation. Ninth-grade students are at a pivotal point in their educational careers, and a successful transition to high…

  2. Effect of High-Grade Disease on Outcomes of Surgically Treated Colon Cancer.

    PubMed

    Amri, Ramzi; Bordeianou, Liliana G; Berger, David L

    2016-04-01

    Tumor grade is one of the cardinal pathological characteristics of colon cancer. Despite a large body of evidence on disease grade in general, the exact impact of high-grade disease in the context of the simplified high/low-grade dichotomy that is based on glandular formation rate has yet to be quantified. Patients with sporadic colon cancer treated surgically at our center (2004-2011) were included in an institutional review board-approved database. We measured the rates of distant and nodal disease spread in baseline pathology and the multivariable hazard radio (mHR) of recurrence and overall- and disease-specific mortality. Among 922 patients with specified tumor grade in baseline surgical pathology, 175 (19.0 %) had high-grade disease. These patients were at far higher risk of lymph node metastasis (63.8 vs. 39.6 %; P < 0.001) and metastatic presentation (31.4 vs. 15.8 %; P < 0.001). These baseline differences also led to significantly worse outcomes, including disease recurrence (17.1 vs. 10.6 %; mHR = 1.83; P = 0.026), overall mortality (57.7 vs. 33.3 %; mHR = 1.65; P < 0.001), and colon cancer-specific mortality (39.4 vs. 16.9 %; mHR = 1.57; P = 0.004). Most significantly, in stage II patients (n = 294), those with high-grade disease (16.0 %) had an mHR of 2.84 (P < 0.001) for mortality. High-grade disease on baseline surgical pathology is associated with a considerably higher rate of nodal and distant metastasis in colon cancer. As a result, the colon cancer-related mortality doubles for patients with high-grade disease. These findings were independent of baseline staging and confirm that the high-/low-grade tumor dichotomy is an important prognostic factor greatly influencing colon cancer outcomes across stages.

  3. Utility of the Roche Cobas 4800 for detection of high-risk human papillomavirus in formalin-fixed paraffin-embedded oropharyngeal squamous cell carcinoma.

    PubMed

    Pettus, Jason R; Wilson, Terri L; Steinmetz, Heather B; Lefferts, Joel A; Tafe, Laura J

    2017-02-01

    Clinical laboratories are expected to reliably identify human papilloma virus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) for prognostic and potential therapeutic applications. In addition to surrogate p16 immunohistochemistry (IHC) testing, DNA-based HPV-specific testing strategies are widely utilized. Recognizing the efficiency of the Roche Cobas 4800 platform for testing gynecological cytology specimens for high-risk HPV, we elected to evaluate the potential utility of this platform for testing formalin-fixed paraffin-embedded (FFPE) OPSCC tissue. Using the Roche Linear Array assay for comparison, we tested twenty-eight samples (16 primary OPSCC, 2 lymph node metastases from primary OPSCC, 1 oral tongue carcinoma, 3 benign squamous papillomas, and 3 non-oropharyngeal carcinoma tissues). Excluding two invalid results, the Roche Cobas 4800 testing resulted in excellent inter-assay concordance (25/26, 96.2%) and 100% concordance for HPV-16/HPV-18 positive samples. This data suggests that the Roche Cobas 4800 platform may be a cost-effective method for testing OPSCC FFPE tissues in a clinical molecular pathology laboratory setting. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Atypical squamous cells of undetermined significance: Bethesda classification and association with Human Papillomavirus.

    PubMed

    Barcelos, Ana Cristina Macêdo; Michelin, Márcia Antoniazi; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2011-01-01

    To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed. Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031). ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN.

  5. An Investigation of the Relationship Between Retention in First Grade and Performance on High Stakes Tests in 3 Grade.

    PubMed

    Hughes, Jan N; Chen, Qi; Thoemmes, Felix; Kwok, Oi-Man

    2010-05-19

    The association between grade retention in first grade and passing the third grade state accountability tests, the Texas Assessment of Knowledge and Skills (TAKS) reading and math, was investigated in a sample of 769 students who were recruited into the study when they were in first grade. Of these 769 students, 165 were retained in first grade and 604 were promoted. Using propensity matching, we created five imputed datasets (average N=321) in which promoted and retained students were matched on 67 comprehensive covariates. Using GEE models, we obtained the association between retention and passing the 3(rd) grade TAKS reading and math tests. The positive association between retention and math scores was significant while the association was marginally significant for reading scores.

  6. An Investigation of the Relationship Between Retention in First Grade and Performance on High Stakes Tests in 3rd Grade

    PubMed Central

    Hughes, Jan N.; Chen, Qi; Thoemmes, Felix; Kwok, Oi-man

    2010-01-01

    The association between grade retention in first grade and passing the third grade state accountability tests, the Texas Assessment of Knowledge and Skills (TAKS) reading and math, was investigated in a sample of 769 students who were recruited into the study when they were in first grade. Of these 769 students, 165 were retained in first grade and 604 were promoted. Using propensity matching, we created five imputed datasets (average N=321) in which promoted and retained students were matched on 67 comprehensive covariates. Using GEE models, we obtained the association between retention and passing the 3rd grade TAKS reading and math tests. The positive association between retention and math scores was significant while the association was marginally significant for reading scores. PMID:20628547

  7. Lymph node metastasis in lower lip squamous cell carcinoma in relation to tumour size, histologic variables and p27Kip1 protein expression.

    PubMed

    Rodolico, Vito; Barresi, Elisa; Di Lorenzo, Roberto; Leonardi, Vincenza; Napoli, Pietro; Rappa, Francesca; Di Bernardo, Cristofaro

    2004-01-01

    We studied a consecutive series of 95 patients undergoing radical surgical resection of lower lip squamous cell carcinoma (LLSCC) to assess the correlation between lymph node status and several prognostic variables, such as sex and age, tumour size, histologic grading, maximal microscopic tumour thickness, perineural infiltration and p27Kip1 protein status, to see which of these might be predictive of the development of lymph node metastases. Statistical analysis demonstrated a significant association between node status and tumour size, histological grading, maximal thickness, perineural invasion and p27Kip1 protein expression; additionally to node metastasis, low p27Kip1 protein expression was significant correlated with high microscopic thickness. These results indicate that lower lip squamous cell carcinomas of >2 cm, with G3-G4 histological grading, maximal thickness of >6 mm, perineural invasion and low p27Kip1 protein expression (LI<19.7%) are at high risk for the development of lymph node metastases.

  8. Protein and mRNA levels of YKL-40 in high-grade glioma.

    PubMed

    Kazakova, M H; Staneva, D N; Koev, I G; Staikov, D G; Mateva, N; Timonov, P T; Miloshev, G A; Sarafian, V S

    2014-01-01

    Malignant gliomas are the most common type of primary malignant brain tumours, characterized by extreme proliferation and aggressive invasion. There is evidence for over-expression of the YKL40 gene in high-grade gliomas. The high serum levels of the glycoprotein are associated with poor prognosis of various inflammatory and tumour processes. We investigated the YKL40 mRNA level and protein expression in the tumour site and in the serum of high-grade glioma patients. The YKL-40 expression in 36 patients with glial tumours (astrocytoma grade III, glioblastoma) and 33 age-matched healthy persons was measured by gene analysis, immunohistochemistry and ELISA. YKL-40 serum levels in high-grade glioma patients compared to healthy subjects were significantly increased (P ≤ 0.05). A wide range of variability in YKL40 mRNA expression was found. YKL-40 staining in situ was more abundant in glioblastoma tissue than in anaplastic astrocytoma, with the lowest level in normal brain tissue. Our gene analysis revealed that in general, YKL40 mRNA in glioma patients was over-expressed versus normal brain. A significant correlation between YKL40 transcript and protein levels was observed (P ≤ 0.05). It could be speculated that the YKL-40 protein might contribute to glioblastomas' specific biological characteristics that distinguish them from grade III gliomas. A complex investigation of YKL40 expression was performed at the molecular and cellular levels in human high-grade gliomas. Serum YKL-40 concentrations increased with tumour grade and correlated positively with transcript rate, being the highest in glioblastoma. We provide evidence for a relationship between YKL40 expression and the malignancy of glial tumours.

  9. The Role of Adjuvant Treatment in Patients with High-Grade Meningioma.

    PubMed

    Cho, Minjae; Joo, Jin-Deok; Kim, In Ah; Han, Jung Ho; Oh, Chang Wan; Kim, Chae-Yong

    2017-09-01

    To investigate the efficacy of adjuvant treatment in patients with high-grade meningioma. A retrospective analysis was performed for patients with high-grade meningioma, World Health Organization grade 2 or 3, in a single center between 2003 and 2014. The patients were reviewed according to age at diagnosis, sex, the location of meningioma, degree of tumor resection, histological features, and type of adjuvant treatment. These factors were analyzed by Firth logistic regression analyses. Fifty-three patients with high-grade meningioma were enrolled. Thirty-four patients received adjuvant treatment; conventional radiotherapy or radiosurgery. Clinical follow-up ranged from 13-113 months with a median follow-up of 35.5 months. Gross total removal (GTR), Simpson grade 1 or 2, was achieved in 29 patients and, among them, 13 patients received adjuvant treatment. In the other 24 patients with non-GTR, conventional adjuvant radiotherapy and radiosurgery were performed in 11 and 10 patients, respectively. The other 3 patients did not receive any adjuvant treatment. Radiation-related complications did not occur. Of the 53 patients, 19 patients had suffered from recurrence. The recurrence rate in the adjuvant treatment group was 23.5% (8 out of 34). On the other hand, the rate for the non-adjuvant treatment group was 57.9% (11 out of 19) (odds ratio [OR]=0.208, p=0.017). In the GTR group, the recurrence rate was 7.5% (1 out of 13) for patients with adjuvant treatment and 50% (8 out of 16) for patients without adjuvant treatment (OR=0.121, p=0.04). Adjuvant treatment appears to be safe and effective, and could lead to a lower recurrence rate in high-grade meningioma, regardless of the extent of removal. Our results might be used as a reference for making decisions when planning adjuvant treatments for patients with high-grade meningioma after surgery.

  10. IDH mutations as an early and consistent marker in low-grade astrocytomas WHO grade II and their consecutive secondary high-grade gliomas.

    PubMed

    Juratli, Tareq A; Kirsch, Matthias; Robel, Katja; Soucek, Silke; Geiger, Kathrin; von Kummer, Rüdiger; Schackert, Gabriele; Krex, Dietmar

    2012-07-01

    This study investigated the prognostic and predictive significance of IDH1 and IDH2 mutations in low-grade astrocytomas (LGA). The presence and consistency of IDH mutations during the progression of LGA to secondary high-grade gliomas (sHGG) were detected. Samples of patients with LGA and sHGG were investigated. The genomic regions around IDH1 codon 132 and IDH2 codon 172 were PCR amplified and directly sequenced. Furthermore, the MGMT promoter status was provided using the methylation-specific PCR. Our population comprised 71 patients with a total of 45 pairs of LGA and their consecutive sHGG. Median follow-up was 9.6 years. IDH mutations were found in 36/45 LGA (80%) and their sHGG without changes in the mutation status. A total of 71 patients with LGA were analyzed according to clinical and molecular tumor-related factors: 56/71 patients (78.8%) had an IDH mutation without significant influence on the progression-free or overall survival (OS), and 22/71 (31%) of the patients received postoperative radiotherapy (RT) after diagnosis of LGA. Patients with early RT but without IDH mutations had the shortest survival. Our study shows that IDH mutation status is stable during the progression course of LGA to sHGG. The presence of IDH mutations fails to demonstrate a significant influence on survival in the multivariate analysis of LGA patients. Early RT appears to be beneficial only LGA patients with IDH-mutations.

  11. Deubiquitinase USP9X deubiquitinates β-catenin and promotes high grade glioma cell growth

    PubMed Central

    Wang, Zhihao; Yang, Chunxu; Ouyang, Wen; Zhou, Fuxiang; Zhou, Yunfeng; Xie, Conghua

    2016-01-01

    β-catenin is a crucial signal transduction molecule in the Wnt/β-catenin signal pathway, and increased β-catenin expression has consistently been found in high grade gliomas. However, the mechanisms responsible for β-catenin overexpression have remained elusive. Here we show that the deubiquitinase USP9X stabilizes β-catenin and thereby promotes high grade glioma cell growth. USP9X binds β-catenin and removes the Lys 48-linked polyubiquitin chains that normally mark β-catenin for proteasomal degradation. Increased USP9X expression correlates with increased β-catenin protein in high grade glioma tissues. Moreover, patients with high grade glioma overexpressing USP9X have a poor prognosis. Knockdown of USP9X suppresses cell proliferation, inhibits G1/S phase conversion, and induces apoptosis in U251 and A172 cells. Interestingly, c-Myc and cyclinD1, which are important downstream target genes in the Wnt/β-catenin signal pathway, also show decreased expression in cells with siRNA-mediated down-regulation of USP9X. Down-regulation of USP9X also consistently inhibits the tumorigenicity of primary glioma cells in vivo. In summary, these results indicate that USP9X stabilizes β-catenin and activates Wnt/β-catenin signal pathway to promote glioma cell proliferation and survival. USP9X could also potentially be a novel therapeutic target for high grade gliomas. PMID:27783990

  12. p16 overexpression in high-grade neuroendocrine carcinomas of the head and neck: potential diagnostic pitfall with HPV-related carcinomas.

    PubMed

    Alos, Llucia; Hakim, Sofia; Larque, Ana-Belen; de la Oliva, Jorge; Rodriguez-Carunchio, Leonardo; Caballero, Miguel; Nadal, Alfons; Marti, Carles; Guimera, Nuria; Fernandez-Figueras, Maria-Teresa; Quint, Wim; Ordi, Jaume

    2016-09-01

    High-grade neuroendocrine carcinomas (HGNECs) of the head and neck have the morphological appearance of undifferentiated carcinomas and could be histologically similar to human papillomavirus (HPV)-associated non-keratinizing squamous cell carcinomas of the head and neck. The aim of the study is to characterize histologically, immunohistochemically, and virologically these unusual neoplasms. Nineteen HGNECs of the head and neck (1 oropharyngeal, 5 sinonasal, 7 of the larynx, and 6 of the parotid gland) were reviewed and analyzed with a immunohistochemical panel, with special emphasis on cell cycle proteins. The tumors were tested for HPV by in situ hybridization (GenPoint HPV, Dako) and PCR (SPF10-DEIA-LiPA25). Merkel cell polyomavirus was studied using the antibody CM2B4. Fifteen HGNEC were of small cell and 4 of large cell type. Most of the tumors (14/19, 73.7 %), including all the pure small cell carcinomas, showed a strong and diffuse positive staining for p16. Eleven of them (78.5 %) had Rb loss and a low or absent cyclin D1 expression. All cases were negative for HPV and polyomavirus. Most patients were smokers, diagnosed at advanced stages of the disease, and had a poor outcome, with a 5-year survival of 18 %. In conclusion, HGNECs of the head and neck are infrequently related to HPV infection, but usually show strong, diffuse positive p16 immunostaining due to Rb pathway dysregulation. Awareness of this immunohistochemical pattern of expression may avoid a potential diagnostic pitfall with HPV-associated non-keratinizing squamous cell carcinomas, which have a better prognosis.

  13. Research and development of intelligent controller for high-grade sanitary ware

    NASA Astrophysics Data System (ADS)

    Bao, Kongjun; Shen, Qingping

    2013-03-01

    With the social and economic development and people's living standards improve, more and more emphasis on modern society, people improve the quality of family life, the use of intelligent controller applications in high-grade sanitary ware physiotherapy students. Analysis of high-grade sanitary ware physiotherapy common functions pointed out in the production and use of the possible risks, proposed implementation of the system hardware and matching, given the system software implementation process. High-grade sanitary ware physiotherapy intelligent controller not only to achieve elegant and beautiful, simple, physical therapy, water power, deodorant, multi-function, intelligent control, to meet the consumers, the high-end sanitary ware market, strong demand, Accelerate the enterprise product Upgrade and improve the competitiveness of enterprises.

  14. High-grade optical polydimethylsiloxane for microfluidic applications.

    PubMed

    Lovchik, Robert Dean; Wolf, Heiko; Delamarche, Emmanuel

    2011-12-01

    Commercially available polydimethylsiloxane (PDMS) elastomers, such as Sylgard 184® are widely used in soft lithography and for microfluidic applications. These PDMS elastomers contain fillers to enhance their mechanical stability. The reinforcing fillers, often sub-micrometer small SiO(2) particles, tend to aggregate, swell with water, and thereby become cognoscible in a way that can strongly interfere with the visualization of micro-scale events taking place next to PDMS structures. As PDMS microfluidics are often used for studying cells and micro-/nanoparticles and for creating/handling nanodroplets, it has become highly desirable to employ a PDMS having high optical quality and that allows microscopy observation without artifacts. Here, we present a PDMS formulation that is free of fillers and has sufficiently low viscosity to perform a filtration step of the mixed prepolymers before curing. By molding a bi-layer microfluidic network (MFN), composed of a thin filler-free PDMS layer and a thicker Sylgard 184® backing layer, PDMS MFNs featuring both high optical quality and mechanical stability, can be fabricated.

  15. Contrast-Enhanced Ultrasound Differentiation Between Low and High-Grade Bladder Urothelial Carcinoma and Correlation With Tumor Microvessel Density.

    PubMed

    Guo, Suping; Xu, Pan; Zhou, Aiyun; Wang, Gongxian; Chen, Weimin; Mei, Jinhong; Xiao, Fan; Liu, Juan; Zhang, Cheng

    2017-05-27

    Time-intensity curves (TICs) of contrast-enhanced ultrasound (CEUS) were analyzed retrospectively to differentiate between low-grade and high-grade bladder urothelial carcinoma, and to investigate correlation with tumor microvessel density (MVD). The data of 105 patients with pathologically confirmed bladder urothelial carcinoma (55 low-grade and 50 high-grade) were reviewed. Lesions were examined before surgery using conventional ultrasound and CEUS with TIC analysis. The TIC parameters time from peak to one-half the signal intensity (TPH) and the corresponding descending slope (DS) of the low-grade and high-grade groups were compared, and receiver operating characteristic curves constructed. The MVDs of the resectioned tissue specimens were quantified via immunohistochemistry for CD34. Based on conventional ultrasound, the low-grade and high-grade groups were similar in tumor shape, number, topography, internal echo, height, width, and vascularity. The TPH of the high-grade group was significantly longer than that of the low-grade group, and the DS was lower. The cutoff points of TPH and DS for differentiating low-grade and high-grade bladder urothelial carcinoma were 48.06 seconds and 0.15 dB/seconds, respectively (area under the receiver operating characteristic curve = 0.79 for both). The mean MVDs per high-power field of the low-grade and high-grade groups were 41.39 16.65 and 51.03 20.16, respectively (P = .009). The TPH correlated linearly with MVD (P < .01), as did the DS (P < .01). Contrast-enhanced ultrasound can be used to differentiate low from high-grade bladder urothelial carcinoma. The TIC parameters of CEUS reflect the MVD of bladder urothelial tumors and may be helpful for evaluating tumor angiogenesis, with implications for clinical diagnosis, treatment, and prognosis. © 2017 by the American Institute of Ultrasound in Medicine.

  16. Chronic esophagitis evolving to verrucous squamous cell carcinoma: possible role of exogenous chemical carcinogens.

    PubMed

    Kavin, H; Yaremko, L; Valaitis, J; Chowdhury, L

    1996-03-01

    A patient exposed to aerosolized lye and ingested kerosene was followed up for 16 years with chronic esophagitis before developing verrucous esophageal squamous carcinoma. The aim of this study was to elucidate the pathogenesis of the carcinoma. Multiple biopsy specimens were graded according to the severity of esophagitis and dysplasia. Molecular biological techniques and immunocytological assay were used to look for human papillomavirus infection, p53 mutations, loss of heterozygosity for TP53 and chromosome 8 markers, and ras mutations. Morphological features of the chronic esophagitis in this patient were similar to the precancerous lesions from high-risk areas for esophageal squamous cancer and the precancerous lesions induced in rats by N-methyl-N-nitrosoaniline. Gastroesophageal acid reflux and human papillomavirus infection were ruled out. No loss of heterozygosity of p53 or for chromosome 8 markers was found. Mutations of the ras oncogene were not identified. By immunocytological assay overexpression of p53 was identified only in the invasive portion of the carcinoma. In this patient, verrucous squamous carcinoma evolved from chronic esophagitis, squamous papillary hyperplasia, and dysplasia. Although exogenous carcinogens may have been important, they probably did not act by causing loss of heterozygosity or ras mutations. p53 overexpression occurred late.

  17. Differentiation of high-grade and low-grade diffuse gliomas by intravoxel incoherent motion MR imaging

    PubMed Central

    Togao, Osamu; Hiwatashi, Akio; Yamashita, Koji; Kikuchi, Kazufumi; Mizoguchi, Masahiro; Yoshimoto, Koji; Suzuki, Satoshi O.; Iwaki, Toru; Obara, Makoto; Van Cauteren, Marc; Honda, Hiroshi

    2016-01-01

    Background Our aim was to assess the diagnostic performance of intravoxel incoherent motion (IVIM) MR imaging for differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs). Methods Forty-five patients with diffuse glioma (age 50.9 ± 20.4 y; 26 males, 19 females) were assessed with IVIM imaging using 13 b-values (0–1000 s/mm2) at 3T. The perfusion fraction (f), true diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were calculated by fitting the bi-exponential model. The apparent diffusion coefficient (ADC) was obtained with 2 b-values (0 and 1000 s/mm2). Relative cerebral blood volume was measured by the dynamic susceptibility contrast method. Two observers independently measured D, ADC, D*, and f, and these measurements were compared between the LGG group (n = 16) and the HGG group (n = 29). Results Both D (1.26 ± 0.37 mm2/s in LGG, 0.94 ± 0.19 mm2/s in HGG; P < .001) and ADC (1.28 ± 0.35 mm2/s in LGG, 1.03 ± 0.19 mm2/s in HGG; P < .01) were lower in the HGG group. D was lower than ADC in the LGG (P < .05) and HGG groups (P < .0001). D* was not different between the groups. The f-values were significantly larger in HGG (17.5 ± 6.3%) than in LGG (5.8 ± 3.8%; P < .0001) and correlated with relative cerebral blood volume (r = 0.85; P < .0001). Receiver operating characteristic analyses showed areas under curve of 0.95 with f, 0.78 with D, 0.73 with ADC, and 0.60 with D*. Conclusion IVIM imaging is useful in differentiating HGGs from LGGs. PMID:26243792

  18. Field experimental observations of highly graded sediment plumes.

    PubMed

    Jensen, Jacob Hjelmager; Saremi, Sina; Jimenez, Carlos; Hadjioannou, Louis

    2015-06-15

    A field experiment in the waters off the south-eastern coast of Cyprus was carried out to study near-field formation of sediment plumes from dumping. Different loads of sediment were poured into calm and limpid waters one at the time from just above the sea surface. The associated plumes, gravitating towards the seafloor, were filmed simultaneously by four divers situated at different depths in the water column, and facing the plume at different angles. The processes were captured using GoPro-Hero-series cameras. The high-quality underwater footage from near-surface, mid-depth and near-bed positions gives unique insight into the dynamics of the descending plume and near-field dispersion processes, and enables good understanding of flow and sediment transport processes involved from-release-to-deposition of the load in a non-scaled environment. The high resolution images and footages are available through the link provided herein. Observations support the development of a detailed multi-fractional sediment plume model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. IDH1 status is significantly different between high-grade thalamic and superficial gliomas.

    PubMed

    Zuo, Mingrong; Li, Mao; Chen, Ni; Yu, Tianping; Kong, Bing; Liang, Ruofei; Wang, Xiang; Mao, Qing; Liu, Yanhui

    2017-08-23

    While major progress has been made in diagnosis and treatment of gliomas based on molecules, molecular features of thalamic glioma have rarely been reported till now. IDH1 mutation is important for prognosis of gliomas and represents a distinctive category of glioma. We intended to survey specific molecular abnormalities in high-grade thalamic gliomas (WHO III-IV). We collected data of 50 and 93 newly diagnosed high-grade thalamic and superficial glioma patients respectively and conducted a comparative analysis of molecular characteristics between them. We analyzed expressions of molecules as follow: IDH1/2, P53, Ki-67, ATRX, PTEN, MMP9 and MGMT by Immunohistochemistry (IHC). Direct gene sequencing was performed to test the IDH1(R 132H) mutation. We found a significant difference of IDH1 mutation between those high-grade gliomas, with 92% (46/50) of the thalamic tumors and 71% (66/93) of the superficial gliomas showing IDH1 wild-type (p= 0.004). It also showed that IDH1 mutation in superficial glioblastomas 18.6% (13/70) occurred more than thalamic glioblastomas 2.6% (1/39) (p= 0.017). As to high-grade superficial gliomas, there were 26 patients with IDH1 mutation, which contained 7, 13, and 6 high, moderate and low Ki-67 expression gliomas, respectively. The IDH1 wild-type group (62 patients), was composed of 29, 30, and 3 high, moderate and low Ki-67 expression gliomas, respectively. There was a significant distinction between the IDH1 mutation and Ki-67 expressions (p= 0.024). We also noted that the occurrence of low Ki-67 expressions 23.1% (6/26) in IDH1 mutation group was outnumbered than IDH1 wild-type group 4.8% (3/62) (p= 0.018). In addition, we found PTEN negative correlated with MMP9 negative in thalamic high-grade gliomas, whereas no such difference was found in superficial gliomas (p= 0.016). The rare occurrence of IDH1 mutant high-grade thalamic gliomas strongly suggested that the high-grade thalamic glioma is another distinct tumor entity as compared

  20. Closer to the Finish Line? Compulsory Attendance, Grade Attainment, and High School Graduation

    ERIC Educational Resources Information Center

    Moussa, Wael S.

    2017-01-01

    High school graduation rates are a central policy topic in the United States and have been shown to be stagnant for the past three decades. Using student-level administrative data from New York City Public Schools, I examine the impact of compulsory school attendance on high school graduation rates and grade attainment, focusing the analysis on…

  1. The Impact of the Non-Graded, Multi-Selective English Curriculum on High School Students.

    ERIC Educational Resources Information Center

    Gage, Thomas Evans

    Studies involving different populations were involved in this four-part evaluation of the impact of non-graded, multi-selective English on high school students. Study A involved students who consistently scored high or low in percentile gain in the four ability groups, to ascertain any pattern of courses selected, sequences of courses attended,…

  2. Closer to the Finish Line? Compulsory Attendance, Grade Attainment, and High School Graduation

    ERIC Educational Resources Information Center

    Moussa, Wael S.

    2017-01-01

    High school graduation rates are a central policy topic in the United States and have been shown to be stagnant for the past three decades. Using student-level administrative data from New York City Public Schools, I examine the impact of compulsory school attendance on high school graduation rates and grade attainment, focusing the analysis on…

  3. Relationship between First-Grade Marks and the High School Dropout Problem.

    ERIC Educational Resources Information Center

    Simner, Marvin L.; Barnes, Michael J.

    1991-01-01

    Reviewed academic records for students who attended public school, completing secondary education between 1982 and 1986. Students who experienced most difficulty in mastering first grade reading and arithmetic had much higher probability of leaving high school without graduating and of experiencing serious academic problems while in high school…

  4. Small Classes in the Early Grades, Academic Achievement, and Graduating From High School

    ERIC Educational Resources Information Center

    Finn, Jeremy D.; Gerber, Susan B.; Boyd-Zaharias, Jayne

    2005-01-01

    This investigation addressed 3 questions about the long-term effects of early school experiences: (a) Is participation in small classes in the early grades (K-3) related to high school graduation? (b) Is academic achievement in K-3 related to high school graduation? (c) If class size is related to graduation, is the relationship explained by the…

  5. Obesity increases the risk for high-grade prostate cancer: results from the REDUCE study.

    PubMed

    Vidal, Adriana C; Howard, Lauren E; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

    2014-12-01

    Studies suggest that obesity is associated with lower risk of prostate cancer but more aggressive cancers. As obesity lowers PSA levels, these observations may be influenced by detection bias. We examined the association between obesity and risk of low- and high-grade prostate cancer in REDUCE, in which biopsies were largely independent of PSA. The REDUCE study tested dutasteride for prostate cancer risk reduction in men with a PSA of 2.5 to 10.0 ng/mL and a negative biopsy. Study participants included 6,729 men who underwent at least one on-study biopsy. The association between baseline body mass index (BMI <25 kg/m(2) normal weight; 25-29.9 kg/m(2) overweight; and ≥30 kg/m(2) obese) and risk of high-grade (Gleason ≥7) or low-grade prostate cancer (Gleason <7) versus no prostate cancer was examined using multinomial logistic regression. Overall, 1,739 men (27%) were normal weight, 3,384 (53%) overweight, and 1,304 (20%) were obese. Obesity was associated with lower risk of low-grade prostate cancer in both univariable (OR, 0.74; P = 0.001) and multivariable analyses (OR, 0.79; P = 0.01). In univariable analysis, obesity was not associated with high-grade prostate cancer (OR, 1.08; P = 0.50). However, in multivariable analysis, obesity was associated with increased risk of high-grade prostate cancer (OR, 1.28; P = 0.042). This analysis was not able to address how obesity may influence prostate cancer progression. Obesity is associated with decreased risk of low-grade and increased risk of high-grade prostate cancer. These data provide further support to the hypothesis that obesity is associated with aggressive prostate cancer. Obesity is linked with aggressive prostate cancer. Avoiding obesity may prevent the risk of developing high-grade prostate cancer. ©2014 American Association for Cancer Research.

  6. Oral undifferentiated high-grade pleomorphic sarcoma: report of a case.

    PubMed

    Alfredo, Edson; de Pádua, Joubert Magalhães; Vicentini, Eduardo Luis; Marchesan, Melissa Andreia; Comelli Lia, Raphael Carlos; da Cruz Perez, Danyel Elias; Silva-Sousa, Yara Teresinha Corrêa

    2008-01-01

    The current World Health Organization classification considers the existence of an undifferentiated unclassifiable category of pleomorphic sarcomas, defined as a group of pleomorphic high-grade sarcomas. Undifferentiated high-grade pleomorphic sarcoma represents about 5% of all soft tissue sarcomas in adults and occurs more commonly in the extremities. In the oral cavity, undifferentiated pleomorphic sarcoma is extremely rare. We report a case of undifferentiated high-grade pleomorphic sarcoma located in the floor of the mouth in a man 56 years old. Microscopically, spindle-shaped cells with accented pleomorphism arranged in a storiform pattern, several bizarre giant cells, and frequent atypical mitoses were observed. The tumor cells were positive only for vimentin, with focal positivity for CD68. The patient was treated by surgery and postoperative radiation therapy, and after 25 months, no recurrence was observed.

  7. The Minimum Grading Controversy: Results of a Quantitative Study of Seven Years of Grading Data from an Urban High School

    ERIC Educational Resources Information Center

    Carey, Theodore; Carifio, James

    2012-01-01

    In an effort to reduce failure and drop-out rates, schools have been implementing minimum grading. One form involves raising catastrophically low student quarter grades to a predetermined minimum--typically a 50. Proponents argue it gives struggling students a reasonable chance to recover from failure. Critics contend the practice induces grade…

  8. Prospective Assessment of Patterns of Failure After High-Precision Definitive (Chemo)Radiation in Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Gupta, Tejpal

    2011-06-01

    Purpose: To prospectively analyze patterns of failure in patients with head-and-neck squamous cell carcinoma treated with definitive high-precision radiotherapy with a focus on location of failure relative to target volume coverage. Methods and Materials: Sixty patients treated with three-dimensional conformal radiotherapy or intensity-modulated radiation therapy were included. Locoregional failure volume was defined on the planning data set at relapse, and dose received was analyzed by use of dose-volume histograms. Results: Thirteen patients were deemed to have had locoregional failures, of which two did not have any viable tumor on salvage neck dissection, leaving eleven patients with proven persistent or recurrent locoregional disease. Of these, 9 patients had in-field failure, 1 marginal failure, and 1 both in-field and marginal failures. Overall, only 2 of 11 patients (18%) with relapse had any marginal failure. Of the 20 sites of locoregional failure, 15 (75%) were in-field and 5 (25%) marginal. Distant metastases were detected in 3 patients, whereas a second new primary developed in 3 others. With a median follow-up of 26 months (interquartile range, 18-31 months) for surviving patients, the 3-year local control, locoregional control, disease-free survival, and overall survival rates were 75.3%, 74%, 67.2%, and 60.5%, respectively. Conclusions: Locoregional relapse remains the predominant pattern of failure in head-and-neck squamous cell carcinoma treated with high-precision definitive radiotherapy with the majority of failures occurring 'in-field' within the high-dose volume. Marginal failures can occur, particularly in the vicinity of the spared parotid gland. The therapeutic index of high-precision conformal radiotherapy is largely dependent on adequate selection and delineation of target volumes and organs at risk.

  9. Detection of high-grade atypia nuclei in breast cancer imaging

    NASA Astrophysics Data System (ADS)

    Noël, Henri; Roux, Ludovic; Lu, Shijian; Boudier, Thomas

    2015-03-01

    Along with mitotic count, nuclear pleomorphism or nuclear atypia is an important criterion for the grading of breast cancer in histopathology. Though some works have been done in mitosis detection (ICPR 2012,1 MICCAI 2013,2 and ICPR 2014), not much work has been dedicated to automated nuclear atypia grading, especially the most difficult task of detection of grade 3 nuclei. We propose the use of Convolutional Neural Networks for the automated detection of cell nuclei, using images from the three grades of breast cancer for training. The images were obtained from ICPR contests. Additional manual annotation was performed to classify pixels into five classes: stroma, nuclei, lymphocytes, mitosis and fat. At total of 3,000 thumbnail images of 101 × 101 pixels were used for training. By dividing this training set in an 80/20 ratio we could obtain good training results (around 90%). We tested our CNN on images of the three grades which were not in the training set. High grades nuclei were correctly classified. We then thresholded the classification map and performed basic analysis to keep only rounded objects. Our results show that mostly all atypical nuclei were correctly detected.

  10. Quantitative genome-wide methylation analysis of high-grade non-muscle invasive bladder cancer

    PubMed Central

    Kitchen, Mark O.; Bryan, Richard T.; Emes, Richard D.; Glossop, John R.; Luscombe, Christopher; Cheng, K. K.; Zeegers, Maurice P.; James, Nicholas D.; Devall, Adam J.; Mein, Charles A.; Gommersall, Lyndon; Fryer, Anthony A.; Farrell, William E.

    2016-01-01

    ABSTRACT High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a clinically unpredictable disease with greater risks of recurrence and progression relative to their low-intermediate-grade counterparts. The molecular events, including those affecting the epigenome, that characterize this disease entity in the context of tumor development, recurrence, and progression, are incompletely understood. We therefore interrogated genome-wide DNA methylation using HumanMethylation450 BeadChip arrays in 21 primary HG-NMIBC tumors relative to normal bladder controls. Using strict inclusion-exclusion criteria we identified 1,057 hypermethylated CpGs within gene promoter-associated CpG islands, representing 256 genes. We validated the array data by bisulphite pyrosequencing and examined 25 array-identified candidate genes in an independent cohort of 30 HG-NMIBC and 18 low-intermediate-grade NMIBC. These analyses revealed significantly higher methylation frequencies in high-grade tumors relative to low-intermediate-grade tumors for the ATP5G2, IRX1 and VAX2 genes (P<0.05), and similarly significant increases in mean levels of methylation in high-grade tumors for the ATP5G2, VAX2, INSRR, PRDM14, VSX1, TFAP2b, PRRX1, and HIST1H4F genes (P<0.05). Although inappropriate promoter methylation was not invariantly associated with reduced transcript expression, a significant association was apparent for the ARHGEF4, PON3, STAT5a, and VAX2 gene transcripts (P<0.05). Herein, we present the first genome-wide DNA methylation analysis in a unique HG-NMIBC cohort, showing extensive and discrete methylation changes relative to normal bladder and low-intermediate-grade tumors. The genes we identified hold significant potential as targets for novel therapeutic intervention either alone, or in combination, with more conventional therapeutic options in the treatment of this clinically unpredictable disease. PMID:26929985

  11. Energy and Economics for the Senior High Grades. Unit III. Lessons and Activities for the Senior High Grades.

    ERIC Educational Resources Information Center

    Backler, Alan

    Twelve energy lessons developed for use by senior high school students are presented. These lessons are designed to help students become more aware of the energy choices that they must make in the present and for the future and to understand that the costs of maintaining a specific standard of living and thriving national economy can be controlled…

  12. Oncocytoma-Like Renal Tumor With Transformation Toward High-Grade Oncocytic Carcinoma

    PubMed Central

    Sirintrapun, Sahussapont J.; Geisinger, Kim R.; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L.; Ghazalpour, Anatole; Bender, Ryan P.; Gatalica, Zoran

    2014-01-01

    Abstract Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt–Hogg–Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the

  13. Detection Rate of High-Grade Cervical Neoplasia and Cost-Effectiveness of High-Risk Human Papillomavirus Genotyping with Reflex Liquid-based Cytology in Cervical Cancer Screening.

    PubMed

    Tay, Sun Kuie; Lin, Lynette Eo; Goh, Ronald Ch

    2017-07-01

    This study aimed to determine the prevalence of cervical intraepithelial neoplasia grade 3 or worse (≥CIN3) and cost-effectiveness of human papillomavirus (HPV) genotyping with reflex liquid-based cytology (LBC) for cervical cancer screening in Singapore. Women who were ≥25 years old and undertook co-testing with LBC and HPV-genotyping (Cobas-4800, Roche, USA) for HPV-16, HPV-18 and 12 high-risk HPV types in a single institution were studied retrospectively. A single cervical smear in ThinPrep® PreservCyt® solution (Hologic, USA) was separated for tests in independent cytology and molecular pathology laboratories. The results were reviewed by a designated gynaecologist according to institutional clinical management protocols. Those who tested positive for HPV-16 and/or HPV-18 (regardless of cytology results), cytology showing low-grade squamous intraepithelial lesions (LSIL) or high-grade SIL (HSIL), or atypical squamous cells of undetermined significance (ASCUS) with positive 12 high-risk HPV types were referred for colposcopy. Colposcopy was performed by experienced colposcopists. Cervical biopsy, either directed punch biopsies or excisional biopsy, was determined by a colposcopist. The diagnosis of ≥CIN3 was reviewed by a gynaecologic pathologist. Cost-effectiveness of HPV-based screening in terms of disease and financial burden was analysed using epidemiological, clinical and financial input data from Singapore. Of 1866 women studied, 167 (8.9%) had abnormal cytology (≥ASCUS) and 171 (9.2%) tested positive for high-risk HPV. Twenty-three CIN were detected. Three of the 10 ≥CIN3 cases had negative cytology but positive HPV-16. Compared to cytology, HPV genotyping detected more ≥CIN3 (OR: 1.43). HPV+16/18 genotyping with reflex LBC was superior in terms of cost-effectiveness to LBC with reflex HPV, both for disease detection rate and cost per case of ≥CIN2 detected. Compared to cytology, HPV+16/18 genotyping with reflex LBC detected more ≥CIN3

  14. ADVANCES IN IMAGING TECHNOLOGIES IN THE EVALUATION OF HIGH-GRADE BLADDER CANCER

    PubMed Central

    Zlatev, Dimitar V.; Altobelli, Emanuela; Liao, Joseph C.

    2015-01-01

    Bladder cancer is a heterogeneous disease that ranges from low-grade variant with an indolent course, to high-grade subtype with a recurrent, progressive, and potentially lethal outcome. Accurate assessment for individualized treatment depends critically on the diagnostic accuracy of white light cystoscopy. Despite its central role, white light cystoscopy has several well-documented shortcomings including difficult flat lesion detection, imprecise tumor delineation that limits complete resection, differentiation between inflammation and malignancy, and grade and stage determination. As the limitations of white light cystoscopy contribute to the risk of cancer persistence, recurrence, and progression, there is a need for improved visualization of flat, multifocal, high-grade, and muscle-invasive lesions. Optical imaging technologies have emerged as an adjunct to white light cystoscopy with the goal to guide more effective treatment by improving cancer detection and patient stratification on the basis of grade and stage. Photodynamic diagnosis and narrow band imaging are macroscopic imaging modalities similar to white light cystoscopy, but provide additional contrast enhancement of bladder tumors and have been shown to improve detection rates. Confocal laser endomicroscopy and optical coherence tomography are microscopic imaging technologies that enable real-time high resolution, subsurface tissue characterization with spatial resolutions similar to histology. Molecular imaging offers the potential for the combination of optical imaging technologies with cancer-specific molecular agents to improve the specificity of disease detection. PMID:25882557

  15. 5α-reductase Inhibitors and Risk of High-grade or Lethal Prostate Cancer

    PubMed Central

    Preston, Mark A.; Wilson, Kathryn; Markt, Sarah C.; Ge, Rongbin; Morash, Christopher; Stampfer, Meir J.; Loda, Massimo F.; Giovannucci, Edward; Mucci, Lorelei A.; Olumi, Aria F.

    2014-01-01

    Importance 5α-reductase inhibitors (5ARIs) are widely used for benign prostatic hyperplasia despite controversy regarding potential risk of high-grade prostate cancer with use. Furthermore, the effect of 5ARIs on progression and prostate cancer death remains unclear. Objective To determine the association between 5ARI use and development of high-grade or lethal prostate cancer. Design, Setting, and Participants Prospective observational study of 38,058 men followed for prostate cancer diagnosis and outcomes between 1996–2010 in the Health Professionals Follow-up Study. Exposure Use of 5ARIs between 1996–2010. Main Outcome Measures Cox proportional hazards models were used to estimate risk of prostate cancer diagnosis or development of lethal disease with 5ARI use, adjusting for possible confounders including prostate specific antigen testing. Results During 448,803 person-years of follow-up, we ascertained 3681 incident prostate cancer cases. Of these, 289 were lethal (metastatic or fatal), 456 were high-grade (Gleason 8–10), 1238 were Gleason grade 7, and 1600 were low-grade (Gleason 2–6). A total of 2878 (7.6%) men reported use of 5ARIs between 1996 and 2010. After adjusting for confounders, men who reported ever using 5ARIs over the study period had a reduced risk of overall prostate cancer (HR 0.77; 95% CI, 0.65–0.91). 5ARI users had a reduced risk of Gleason 7 (HR 0.67; 95% CI, 0.49–0.91) and low-grade (Gleason 2–6) prostate cancer (HR 0.74; 95% CI, 0.57–0.95). 5ARI use was not associated with risk of high-grade (Gleason 8–10, HR 0.97; 95% CI, 0.64–1.46) or lethal disease (HR 0.99; 95% CI, 0.58–1.69). Increased duration of use was associated with significantly lower risk of overall prostate cancer (HR for 1 year of additional use 0.95; 95% CI, 0.92–0.99), localized (HR 0.95; 95% CI, 0.90–1.00), and low-grade disease (HR 0.92; 95% CI, 0.85–0.99). There was no association for lethal, high-grade, or grade 7 disease. Conclusions and

  16. [Raman spectral characteristics of oral squamous cell carcinoma, epithelial dysplasia and normal mucosa].

    PubMed

    Xue, Lili; Li, Yi; Cai, Qiaoling; Sun, Pei; Luo, Xianyang; Yan, Bing

    2015-01-01

    To investigate the Raman spectral characteristics of oral squamous cell carcinoma, high-grade epithelial dysplasia and normal mucosa. Fifty- six fresh samples of oral carcinoma, 50 of high-grade epithelial dysplasia and 32 of normal mucosa were collected. The i-Raman spectrometer with an optical fiber tube was applied to acquire Raman spectrum. The diagnostic model established by principle component analysis (PCA) and discriminant function analysis (DFA) was used to analyze and classify the spectra of different samples. There were significant differences among the Raman spectra of these samples. Compared with the spectra of normal mucosa, the spectra of oral carcinoma and dysplasia showed strong peaks which were contributed to nucleic acids, proteins and lipids. The diagnostic models established by PCA-DFA could successfully classify these Raman spectra of different samples with a high accuracy of 96.4% (133/138). The model was evaluated by 'Leave one out' cross-validation and reached a high accuracy of 92.8% (128/138). The proliferation and metabolism of oral squamous cell carcinoma and epithelial high-grade dysplasia are more active than normal mucosa. The diagnostic models established by PCA-DFA can classify these Raman spectra of different samples with a high accuracy.

  17. Significance of signet ring cells in high-grade mucinous adenocarcinoma of the peritoneum from appendiceal origin☆,☆☆

    PubMed Central

    Sirintrapun, S. Joseph; Blackham, Aaron U.; Russell, Greg; Votanopoulos, Konstantinos; Stewart, John H.; Shen, Perry; Levine, Edward A.; Geisinger, Kim R.; Bergman, Simon

    2014-01-01

    Summary Significance of signet ring cells in mucinous adenocarcinoma of the peritoneum from appendiceal origin has never been specifically studied. We retrospectively reviewed cases of mucinous adenocarcinoma of the peritoneum from appendiceal origin (n = 55) and collected clinical follow-up data. Signet ring cells were identified in 29 of 55 cases. No low-grade mucinous adenocarcinoma case (n = 11) had signet ring cells, whereas 29 of 44 high-grade mucinous adenocarcinoma cases did. Cases of high-grade mucinous adenocarcinoma were subdivided into 3 groups: (1) high-grade mucinous adenocarcinoma without signet ring cells (n = 15), (2) high-grade mucinous adenocarcinoma with signet ring cells only within mucin pools (n = 20), and (3) high-grade mucinous adenocarcinoma with signet ring cells invading tissue (n = 9). Overall survival (OS) and progression-free survival were subsequently evaluated. Five-year OS for cases of high-grade mucinous adenocarcinoma without signet ring cells and high-grade mucinous adenocarcinoma with signet ring cells within mucin pools were similar at 31.8% (SE, 14.4%) and 35.8% (SE, 13.9%), respectively. A significant survival difference was seen for cases of high-grade mucinous adenocarcinoma with signet ring cells invading tissue with a median OS of 0.5 years versus 2.9 and 2.4 years (P = .04 and P = .03), respectively, for cases of high-grade mucinous adenocarcinoma without signet ring cells and high-grade mucinous adenocarcinoma with signet ring cells within mucin pools. Finding signet ring cells floating in extracellular mucin pools made no prognostic difference when compared with cases of high-grade mucinous adenocarcinoma without signet ring cells. In contrast, high-grade mucinous adenocarcinoma with signet ring cells invading tissue was significant for worse survival, and thus, we propose reporting signet ring cell tissue invasion particularly when extensive. PMID:24814804

  18. Significance of signet ring cells in high-grade mucinous adenocarcinoma of the peritoneum from appendiceal origin.

    PubMed

    Sirintrapun, S Joseph; Blackham, Aaron U; Russell, Greg; Votanopoulos, Konstantinos; Stewart, John H; Shen, Perry; Levine, Edward A; Geisinger, Kim R; Bergman, Simon

    2014-08-01

    Significance of signet ring cells in mucinous adenocarcinoma of the peritoneum from appendiceal origin has never been specifically studied. We retrospectively reviewed cases of mucinous adenocarcinoma of the peritoneum from appendiceal origin (n = 55) and collected clinical follow-up data. Signet ring cells were identified in 29 of 55 cases. No low-grade mucinous adenocarcinoma case (n = 11) had signet ring cells, whereas 29 of 44 high-grade mucinous adenocarcinoma cases did. Cases of high-grade mucinous adenocarcinoma were subdivided into 3 groups: (1) high-grade mucinous adenocarcinoma without signet ring cells (n = 15), (2) high-grade mucinous adenocarcinoma with signet ring cells only within mucin pools (n = 20), and (3) high-grade mucinous adenocarcinoma with signet ring cells invading tissue (n = 9). Overall survival (OS) and progression-free survival were subsequently evaluated. Five-year OS for cases of high-grade mucinous adenocarcinoma without signet ring cells and high-grade mucinous adenocarcinoma with signet ring cells within mucin pools were similar at 31.8% (SE, 14.4%) and 35.8% (SE, 13.9%), respectively. A significant survival difference was seen for cases of high-grade mucinous adenocarcinoma with signet ring cells invading tissue with a median OS of 0.5 years versus 2.9 and 2.4 years (P = .04 and P = .03), respectively, for cases of high-grade mucinous adenocarcinoma without signet ring cells and high-grade mucinous adenocarcinoma with signet ring cells within mucin pools. Finding signet ring cells floating in extracellular mucin pools made no prognostic difference when compared with cases of high-grade mucinous adenocarcinoma without signet ring cells. In contrast, high-grade mucinous adenocarcinoma with signet ring cells invading tissue was significant for worse survival, and thus, we propose reporting signet ring cell tissue invasion particularly when extensive. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Yield of Cytology Surveillance After High-Grade Vulvar Intraepithelial Neoplasia or Cancer.

    PubMed

    Kuroki, Lindsay M; Frolova, Antonina I; Wu, Ningying; Liu, Jingxia; Powell, Matthew; Thaker, Premal H; Massad, L Stewart

    2017-07-01

    The aim of the study was to estimate the risk of high-grade cervical and vaginal intraepithelial neoplasia (CIN/VAIN 2+) and cancer among women treated surgically for high-grade vulvar intraepithelial neoplasia (HGVIN) and vulvar cancer. We performed a retrospective cohort study of women who underwent surgery for HGVIN/vulvar cancer between 2006 and 2010. Univariate and multivariate analyses using stepwise selection were used to identify correlates of abnormal cytology after treatment for VIN and vulvar cancer. Among 191 women under surveillance for a median of 3.7 years who underwent treatment for HGVIN/vulvar cancer, primary vulvar lesions included VIN 2 (10, 5%), VIN 3 (102, 53%), and carcinoma (79, 41%). During follow-up, 71 (37%) had abnormal cytology, including 47 (25%) low grade, 23 (12%) high grade, and 1 (0.5%) carcinoma. Subsequent risk for VAIN 2+ was 11% (6/57) after previous hysterectomy and 8% for CIN 2+ (10/124) with intact cervix. Overall risk for CIN 3+ was 5%. Correlates of high-grade cytology after treatment for HGVIN/vulvar cancer included nonwhite race (odds ratio [OR] = 3.3, 95% CI = 1.50-7.36), immunodeficiency (OR = 4.2, 95% CI = 1.76-9.94), and previous abnormal cytology (OR = 2.7, 95% CI = 1.29-5.78). Stepwise multivariate analysis revealed immunosuppression as the only significant correlate of high-grade cytology after vulvar treatment (adjusted OR = 3.7, 95% CI = 1.26-10.83). Women with HGVIN/cancer should have cervical/vaginal cytology before vulvar surgery. Those with a negative cervical or vaginal cytology result should undergo cytology testing at 1- to 3-year intervals, based on the threshold for CIN 3+ set forth by the American Society for Colposcopy and Cervical Pathology.

  20. Stereotactic Radiosurgery for Pediatric High-Grade Brain Arteriovenous Malformations: Our Experience and Review of Literature.

    PubMed

    Patibandla, Mohana Rao; Ding, Dale; Xu, Zhiyuan; Sheehan, Jason P

    2017-06-01

    Although high-grade AVMs pose a particularly high lifetime hemorrhage risk to pediatric patients (age <18 years), little is known about the treatment outcomes. Therefore, the aim of this retrospective cohort study was to evaluate the outcomes after single-session stereotactic radiosurgery (SRS) for pediatric high-grade AVMs. We reviewed baseline and treatment outcomes data from pediatric patients aged less than 18 years with Spetzler-Martin grade IV AVMs treated with SRS in a single session at our institution. The study cohort comprised 28 pediatric patients with Spetzler-Martin grade IV AVMs, with a mean age of 12.1 years. Statistical analyses were performed to determine predictors of obliteration and compare the outcomes of patients with versus without previous AVM hemorrhage. The mean nidus volume, radiosurgical margin dose, and follow-up duration were 5.9 cm(3), 19.4 Gy, and 116 months, respectively. The actuarial obliteration rates at 3, 5, 7, and 10 years were 11%, 19%, 29%, and 35%, respectively. Older age was significantly associated with obliteration in the univariate Cox proportional regression analysis (P = 0.01). During the latency period before obliteration, the annual post-SRS hemorrhage rate was 3.2%. Symptomatic and permanent radiation-induced changes were detected in 7.1% and 3.5%, respectively. A favorable outcome was achieved in 35.7%, and it was more frequently achieved for those with ruptured AVMs (P = 0.0484). The efficacy of single-session SRS for the treatment of high-grade AVMs in the pediatric population is limited, particularly for those with unruptured nidi. Multimodal therapies should be considered in the management of selected pediatric high-grade AVMs. However, further prospective analyses are warranted to define the optimal management strategy for these challenging vascular malformations. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Prognostic and predictive markers in recurrent high grade glioma; results from the BR12 randomised trial.

    PubMed

    Collins, Vincent Peter; Ichimura, Koichi; Di, Ying; Pearson, Danita; Chan, Ray; Thompson, Lindsay C; Gabe, Rhian; Brada, Michael; Stenning, Sally P

    2014-06-20

    We evaluated the prognostic and predictive value of a range of molecular changes in the setting of a randomised trial comparing standard PCV (procarbazine, CCNU (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) and vincristine) chemotherapy with the standard temozolomide (TMZ) 5-day (200 mg/m2/day) schedule and a 21-day (100 mg/m2/day) schedule in chemo-naïve, high-grade glioma (non-oligodendroglial tumours; WHO (World Health Organisation) grades III and IV) patients at first progression following radiotherapy.354 samples (79.2%) from the first operation of the 447 randomised patients provided enough tumour DNA for some or all parts of the study. Genome-wide array comparative genomic hybridisation (aCGH), mutation analysis of IDH1/2 and TP53 and methylation analyses of the MGMT CpG-island was done.84% of grade III tumours and 17% of grade IV had IDH1 or IDH2 mutations that conferred a better prognosis in both; MGMT methylation (defined as average value across 16 CpGs ≥ 10%) occurred in 75% of tumours and was also associated with improved survival. Both were of independent prognostic value after accounting for clinical factors and tumour grade. None of the molecular changes investigated gave clear evidence of a predictive benefit of TMZ over PCV or 21-day TMZ over 5-day TMZ although power was limited and a role for MGMT methylation could not be ruled out. Loss of 1p and 19q was seen in only 4 patients although hemizygous loss of 1p36 occurred in 20%.The findings support reports that IDH1/2 mutations and MGMT methylation can be used in addition to tumour grade and clinical factors to predict survival in patients with recurrent high grade gliomas when treated with any of the therapy regimes used.

  2. Risk score predicts high-grade prostate cancer in DNA-methylation positive, histopathologically negative biopsies.

    PubMed

    Van Neste, Leander; Partin, Alan W; Stewart, Grant D; Epstein, Jonathan I; Harrison, David J; Van Criekinge, Wim

    2016-09-01

    Prostate cancer (PCa) diagnosis is challenging because efforts for effective, timely treatment of men with significant cancer typically result in over-diagnosis and repeat biopsies. The presence or absence of epigenetic aberrations, more specifically DNA-methylation of GSTP1, RASSF1, and APC in histopathologically negative prostate core biopsies has resulted in an increased negative predictive value (NPV) of ∼90% and thus could lead to a reduction of unnecessary repeat biopsies. Here, it is investigated whether, in methylation-positive men, DNA-methylation intensities could help to identify those men harboring high-grade (Gleason score ≥7) PCa, resulting in an improved positive predictive value. Two cohorts, consisting of men with histopathologically negative index biopsies, followed by a positive or negative repeat biopsy, were combined. EpiScore, a methylation intensity algorithm was developed in methylation-positive men, using area under the curve of the receiver operating characteristic as metric for performance. Next, a risk score was developed combining EpiScore with traditional clinical risk factors to further improve the identification of high-grade (Gleason Score ≥7) cancer. Compared to other risk factors, detection of DNA-methylation in histopathologically negative biopsies was the most significant and important predictor of high-grade cancer, resulting in a NPV of 96%. In methylation-positive men, EpiScore was significantly higher for those with high-grade cancer detected upon repeat biopsy, compared to those with either no or low-grade cancer. The risk score resulted in further improvement of patient risk stratification and was a significantly better predictor compared to currently used metrics as PSA and the prostate cancer prevention trial (PCPT) risk calculator (RC). A decision curve analysis indicated strong clinical utility for the risk score as decision-making tool for repeat biopsy. Low DNA-methylation levels in PCa-negative biopsies led

  3. Identifying patients at risk for high-grade intra-abdominal hypertension following trauma laparotomy.

    PubMed

    Strang, Steven G; Van Imhoff, Diederik L; Van Lieshout, Esther M M; D'Amours, Scott K; Van Waes, Oscar J F

    2015-05-01

    Abdominal Compartment Syndrome (ACS) is an uncommon but deleterious complication after trauma laparotomy. Early recognition of patients at risk of developing ACS is crucial for their outcome. The aim of this study was to compare the characteristics of patients who developed high-grade intra-abdominal hypertension (IAH) (i.e., grade III or IV; intra-abdominal pressure, IAP >20 mm Hg) following an injury-related laparotomy versus those who did not (i.e., IAP ≤20 mm Hg). A retrospective analysis of consecutive trauma patients admitted to a level 1 trauma centre in Australia between January 1, 1995 and January 31, 2010 was performed. A comparison was made between characteristics of patients who developed high-grade IAH following trauma laparotomy versus those who did not. A total of 567 patients (median age 31 years) were included in this study. Of these patients 10.2% (58/567) developed high-grade IAH of which 51.7% (30/58) developed ACS. Patients with high-grade IAH were older (p<0.001), had a higher Injury Severity Score (p<0.001), larger base deficit (p<0.001) and lower temperature at admission (p=0.011). In the first 24h of admission, patients with high-grade IAH received larger volumes of crystalloids (p<0.001), larger volumes of colloids (p<0.001) and more units of packed red blood cells (p<0.001). Following surgery prolonged prothrombin (p<0.001) and partial thromboplastin times (p<0.001) were seen. The patients with high-grade IAH suffered higher mortality rates (25.9% (15/58) vs. 12.2% (62/509); p=0.012). Of all patients who underwent a trauma laparotomy, 10.2% developed high-grade IAH, which increases the risk of mortality. Patients with acidosis, coagulopathy, and hypothermia were especially at risk. In these patients, the abdomen should be left open until adequate resuscitation has been achieved, allowing for definitive surgery. This is a level III retrospective study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Histologic variation in high grade oral epithelial dysplasia when associated with high-risk human papillomavirus.

    PubMed

    Khanal, Sujita; Trainor, Patrick J; Zahin, Maryam; Ghim, Shin-Je; Joh, Joongho; Rai, Shesh N; Jenson, Alfred Bennett; Shumway, Brian S

    2017-05-01

    Reported cytologic alterations associated with high-risk human papillomavirus (HR-HPV) in oral epithelial dysplasia (HPV-OED) need further characterization. Archival cases of high-grade oral epithelial dysplasia (hgOED) (N = 38) were assigned a cytologic score (CS) based on the average number of mitotic, karyorrhectic, and apoptotic cells per high-power field. Three groups were then generated on the basis of increasing CS: Focal (group 1, N = 14), Intermediate (group 2, N = 12), and Diffuse (group 3, N = 12). Polymerase chain reaction-based HPV genotyping and p16 immunohistochemistry were performed. HR-HPV was found significantly more in group 3 (83.3%) compared with groups 1 and 2 (group 1&2; 42.9% and 41.7%, respectively; P = .047). HPV16 predominated in HR-HPV-positive cases (90.5%). By location, the tongue or the floor of mouth was associated with all groups (P = .04). Increasing CS was associated with a slightly younger age (P = .04) and increased expression of p16 (P = .005). CS and p16 expression were not sensitive but were highly specific predictors for HR-HPV presence. Based on limited follow-up information, HPV-OED does not differ in clinical aggressiveness compared with conventional OED. Increased CS in hgOED is strongly associated with HR-HPV (mostly HPV16) and p16 expression. CS and p16 expression are specific predictors of HR-HPV presence. Further molecular study and long-term follow-up of HPV-OED are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Utility of peripheral blood flow cytometry in differentiating low grade versus high grade myelodysplastic syndromes (MDS) and in the evaluation of cytopenias.

    PubMed

    Rashidi, Hooman H; Xu, Xiangdong; Wang, Huan-You; Shafi, Nelofar Q; Rameshkumar, Karuna; Messer, Karen; Smith, Brian R; Rose, Michal G

    2012-01-01

    The diagnostic utility of flow cytometry in the evaluation of cytopenias and in the differential diagnosis of low-grade versus high-grade myelodysplastic syndrome (MDS) is not widely appreciated. In this report, we measured granulocyte CD10/control fluorescence ratio in 29 patients with MDS & chronic myelomonocytic leukemia (CMML) using peripheral blood (PB) flow cytometry (FC). We found a lower ratio in high-grade MDS and CMML (mean ratio of 2.2 ± 0.7) vs. low-grade MDS (3.65 ± 0.9) and 16 cytopenic controls without MDS (3.67 ± 0.65; p<0.001). The sensitivity and specificity of CD10 ratio <3 for the group that included the high risk MDS and CMML patients were 87.5% and 100%, respectively. Our data suggests that FC of PB may be helpful in the work-up of patients with cytopenias and in the differential diagnosis of low-grade vs. high-grade MDS.

  6. Extrusion granulation and high shear granulation of different grades of lactose and highly dosed drugs: a comparative study.

    PubMed

    Keleb, E I; Vermeire, A; Vervaet, C; Remon, Jean Paul

    2004-07-01

    Formulations containing different lactose grades, paracetamol, and cimetidine were granulated by extrusion granulation and high shear granulation. Granules were evaluated for yield, friability, and compressibility. Tablets were prepared from those granules and evaluated for tensile strength, friability, disintegration time, and dissolution. The different lactose grades had an important effect on the extrusion granulation process. Particle size and morphology affected powder feeding and power consumption, but had only a minor influence on the granule and tablet properties obtained by extrusion granulation. In contrast, the lactose grades had a major influence on the granule properties obtained by high shear granulation. Addition of polyvinylpyrrolidone (PVP) was required to process pure paracetamol and cimetidine by high shear granulation, whereas it was feasible to granulate these drugs without PVP by extrusion granulation. Granules prepared by extrusion granulation exhibited a higher yield and a lower friability than those produced by high shear granulation. Paracetamol and cimetidine tablets compressed from granules prepared by extrusion granulation showed a higher tensile strength, lower friability, and lower disintegration time than those prepared from granules produced by high shear granulation. Paracetamol tablets obtained via extrusion granulation exhibited faster dissolution than those obtained via high shear granulation. For all lactose grades studied, extrusion granulation resulted in superior granule and tablet properties in comparison with those obtained by high shear granulation. These results indicate that extrusion granulation is more efficient than high shear granulation.

  7. Clinical studies of combined photodynamic therapy using 5-fluorouracil and methyl-aminolevulinate in patients at high risk for squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Lohser, Sara; Tellez, Alejandra; Wene, Lauren; Ishak, Rim; Anand, Sanjay

    2013-03-01

    Photodynamic therapy (PDT) using aminolevulinic acid or its methyl ester, methyl-aminolevulinate (MAL), is an increasingly recognized approach for treating squamous neoplasia of the skin. Advantages of MAL-PDT include its ability to cover broad diseased areas (field treatment), and to do multiple sessions with little-to-no risk of scarring or mutagenesis. MAL-PDT is especially valuable in certain populations at high risk for skin cancer, including Caucasian patients with extensive solar damage, and organ transplant recipients (OTR) who take immunosuppressive drugs to prevent graft rejection. The latter group has a 65-200 fold increased risk of developing squamous cell carcinoma (SCC), a major cause of mortality. Therapeutic options for those patients, other than frequent surgeries, are very limited. Topical 5-Fluorouracil (5-FU), frequently prescribed in normal patients for pre-SCC of the skin, is only minimally effective in the OTR group. MAL-PDT, however, has ~40% efficacy for pre-SCC in OTR patients. Based upon our preclinical studies in mouse tumor models, which showed that preconditioning with 5-FU can drive higher accumulation of target protoporphyins (PpIX), we proposed a rational combination regimen of 5-FU and MAL-PDT in humans. A clinical trial was designed to test the hypothesis that a combination of 5-FU followed by MAL-PDT will elevate PpIX levels and achieve better clinical outcomes in high-risk OTR patients. Primary endpoints include PpIX levels and biochemical markers (p53) measured noninvasively and in skin biopsies. Lesion clearance and recurrence (via photographs and clinical exam) are secondary endpoints. Ongoing results of this clinical trial are presented.

  8. Verrucous carcinomas of the head and neck, including those with associated squamous cell carcinoma, lack transcriptionally active high-risk human papillomavirus.

    PubMed

    Patel, Kalyani R; Chernock, Rebecca D; Zhang, Tian R; Wang, Xiaowei; El-Mofty, Samir K; Lewis, James S

    2013-11-01

    Most oropharyngeal squamous cell carcinomas (SCC) and histologic variants harbor transcriptionally active human papillomavirus (HPV). While HPV DNA can be found in many non-oropharyngeal head and neck carcinomas, transcriptionally active HPV is rare. Verrucous carcinoma is a variant with bland cytology, warty appearance, locally destructive growth, and lack of metastasis when lacking a frankly invasive carcinoma component. Studies have shown variable rates of HPV DNA and p16 protein expression in such tumors but still have not clearly addressed if the virus has biological activity or clinical relevance in the positive cases. Department files were searched for verrucous neoplasms, including pure verrucous carcinoma, verrucous carcinoma with dysplasia or minimal invasion, and SCC arising in verrucous carcinoma (ie, having a major component of frankly invasive carcinoma). p16 immunohistochemistry, HPV DNA polymerase chain reaction (PCR) and E6/E7 mRNA reverse transcription PCR for high-risk HPV types were performed. Of the 49 cases, 6 (12.2%) showed strong (>50%) staining for p16. HPV DNA was detected in 7/49 (14.3%) cases, but only one case was positive for both p16, and HPV DNA. A total of 36 cases yielded sufficient RNA for RT-PCR (18 verrucous carcinomas, 13 atypical verrucous carcinomas, and 5 SCC arising in verrucous carcinoma). All 36 were negative, including the four p16-positive and three HPV DNA-positive tumors tested. Although a minority of verrucous carcinoma lesions are p16 and HPV DNA positive, transcriptionally active high-risk HPV is uniformly absent. These findings argue that verrucous carcinoma and its related squamous cell carcinomas are not HPV-driven tumors. © 2013.

  9. High Expression of KIF20A Is Associated with Poor Overall Survival and Tumor Progression in Early-Stage Cervical Squamous Cell Carcinoma

    PubMed Central

    Gu, Haifeng; Li, Min; Liu, Zhimin; Feng, Yanling; Zheng, Nianzhen; Xie, Chuanmiao; Zhang, Yanna

    2016-01-01

    Background The kinesin family member 20a (KIF20A) protein has been implicated in the development and progression of many human cancers; however, its precise function and role in cervical cancer remain largely unclear. This study aimed to investigate the expression profile and prognostic value of KIF20A in patients with early-stage cervical squamous cell carcinoma. Methods We examined the mRNA and protein levels of KIF20A in eight cervical cancer cell lines and eight paired cervical cancer samples, compared with normal cervical epithelial cells and adjacent normal cervical tissues, respectively. Immunohistochemistry was performed to detect the expression of KIF20A in paraffin-embedded specimens from 169 early-stage cervical squamous cell carcinoma patients. Statistical analyses were applied to analyze the association between KIF20A expression and clinical variables, as well with patient survival. Results The mRNA and protein expression levels of KIF20A were significantly elevated in cervical cancer cell lines and lesions compared with normal cells and corresponding normal tissues (P < 0.05). Immunohistochemistry analysis in 169 cervical cancer cases revealed that increased KIF20A expression was strongly associated with human papillomavirus (HPV) infection (P = 0.008), clinical stage (P = 0.001), tumor recurrence (P = 0.016), vital status (P < 0.001), the property of the surgical margin (P = 0.032), the lymphovascular space involvement (P = 0.014), and pelvic lymph node metastasis (P = 0.001). The overall survival and disease-free survival of patients with high levels of KIF20A expression were significantly poorer than those with low KIF20A expression. KIF20A was an independent survival prognostic factor, as evidenced by univariate and multivariate analysis. Conclusions Our results illustrate that elevated KIF20A expression correlates with HPV infection, clinical stage, tumor recurrence, lymphovascular space involvement, pelvic lymph node metastasis, and poor outcome

  10. Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.

    PubMed

    Otto, Benjamin; Gruner, Katharina; Heinlein, Christina; Wegwitz, Florian; Nollau, Peter; Ylstra, Bauke; Pantel, Klaus; Schumacher, Udo; Baumbusch, Lars O; Martin-Subero, José Ignacio; Siebert, Reiner; Wagener, Christoph; Streichert, Thomas; Deppert, Wolfgang; Tolstonog, Genrich V

    2013-03-15

    Mammary carcinomas developing in SV40 transgenic WAP-T mice arise in two distinct histological phenotypes: as differentiated low-grade and undifferentiated high-grade tumors. We integrated different types of information such as histological grading, analysis of aCGH-based gene copy number and gene expression profiling to provide a comprehensive molecular description of mammary tumors in WAP-T mice. Applying a novel procedure for the correlation of gene copy number with gene expression on a global scale, we observed in tumor samples a global coherence between genotype and transcription. This coherence can be interpreted as a matched transcriptional regulation inherited from the cells of tumor origin and determined by the activity of cancer driver genes. Despite common recurrent genomic aberrations, e.g. gain of chr. 15 in most WAP-T tumors, loss of chr. 19 frequently occurs only in low-grade tumors. These tumors show features of "basal-like" epithelial differentiation, particularly expression of keratin 14. The high-grade tumors are clearly separated from the low-grade tumors by strong expression of the Met gene and by coexpression of epithelial (e.g. keratin 18) and mesenchymal (e.g. vimentin) markers. In high-grade tumors, the expression of the nonmutated Met protein is associated with Met-locus amplification and Met activity. The role of Met as a cancer driver gene is supported by the contribution of active Met signaling to motility and growth of mammary tumor-derived cells. Finally, we discuss the independent origin of low- and high-grade tumors from distinct cells of tumor origin, possibly luminal progenitors, distinguished by Met gene expression and Met signaling. Copyright © 2012 UICC.

  11. Supporting Young Adolescents' Middle-to-High-School Transition by Creating a Ninth Grade Community of Care: Implications for Middle Grades Educators

    ERIC Educational Resources Information Center

    Ellerbrock, Cheryl R.; Kiefer, Sarah M.

    2014-01-01

    The middle-to-high-school transition and the first year of high school are critical periods in students' lives. According to the Southern Regional Education Board (SREB), "The passage of students from the middle grades to high school is the most difficult transition point in education" (2002, p. 24). Although there are many different…

  12. Supporting Young Adolescents' Middle-to-High-School Transition by Creating a Ninth Grade Community of Care: Implications for Middle Grades Educators

    ERIC Educational Resources Information Center

    Ellerbrock, Cheryl R.; Kiefer, Sarah M.

    2014-01-01

    The middle-to-high-school transition and the first year of high school are critical periods in students' lives. According to the Southern Regional Education Board (SREB), "The passage of students from the middle grades to high school is the most difficult transition point in education" (2002, p. 24). Although there are many different…

  13. Can diffusion-weighted magnetic resonance imaging of clear cell renal carcinoma predict low from high nuclear grade tumors.

    PubMed

    Parada Villavicencio, Carolina; Mc Carthy, Robert J; Miller, Frank H

    2017-04-01

    To assess the diagnostic performance of the apparent diffusion coefficient (ADC) in predicting the Fuhrman nuclear grading of clear cell renal cell carcinomas (ccRCC). A total of 129 patients who underwent partial and radical nephrectomies with pathology-proven ccRCC were retrospectively evaluated. Histopathological characteristics and nuclear grades were analyzed. In addition, conventional magnetic resonance imaging (MRI) features were assessed in consensus by two radiologists to discriminate nuclear grading. ADC values were obtained from a region of interest (ROI) measurement in the ADC maps calculated from diffusion-weighted imaging (DWI) using b values of 50, 500, and 800 s/mm(2). The threshold values for predicting and differentiating low-grade cancers (Fuhrman I-II) from high grade (Fuhrman III-IV) was obtained using binary logistic regression. The ADC cut-off value for differentiating low- and high-grade tumors was determined using classification analysis. Significant associations (P < 0.001) were found between nuclear grading, conventional MR features, and DWI. Hemorrhage, necrosis, perirenal fat invasion, enhancement homogeneity, and cystic component were identified as independent predictors of tumor grade. High-grade ccRCC had significantly lower mean ADC values compared to low-grade tumors. An ADC cut-off value of 1.6 × 10(-3) mm(2)/s had an optimal predictive percentage of 65.5% for low-grade tumors above this threshold and 81% for high-grade ccRCC below this threshold. Overall predictive accuracy was 70.5%. The addition of ADC values to a model based on MRI conventional features demonstrates increased sensitivity and high specificity improving the distinguishing accuracy between both high-grade and low-grade ccRCC.

  14. A Multi-Institutional Experience in Pediatric High-Grade Glioma

    PubMed Central

    Walston, Steve; Hamstra, Daniel A.; Oh, Kevin; Woods, Gary; Guiou, Michael; Olshefski, Randal S.; Chakravarti, Arnab; Williams, Terence M.

    2015-01-01

    Introduction: Pediatric high-grade gliomas are rare tumors with poor outcomes and incompletely defined management. We conducted a multi-institutional retrospective study to evaluate association of clinical, pathologic, and treatment characteristics with outcomes. Materials and methods: Fifty-one patients treated from 1984 to 2008 at the Ohio State University or University of Michigan were included. Histologic subgroups were compared. Log-rank and stepwise Cox proportional hazard modeling were used to analyze progression-free survival (PFS) and overall survival (OS) within the whole group, grade III subgroup, grade IV subgroup, and sub-total resection/biopsy subgroup. Results: Median OS was 27.6 months. Grade III histology, complete tumor resection, and cerebral tumor location correlated with improved PFS and OS. Temozolomide use and chemotherapy after radiotherapy or chemoradiation (CRT) were associated with better PFS while seizure at presentation was associated with better OS. In multivariate analysis, complete resection and chemotherapy following radiotherapy or CRT were independent predictors for improved PFS and OS. For grade III and IV subgroups, complete resection was associated with improved OS (grade III) and seizure presentation was associated with improved OS (grade IV). In the incompletely resection subgroup, temozolomide use and concurrent CRT independently correlated with improved PFS, while higher radiation dose (≥59.4 Gy) and adjuvant chemotherapy were independently associated with improved OS. Discussion: Total resection and receiving chemotherapy adjuvant to radiation or CRT are most closely associated with improved PFS and OS. For higher risk incompletely resected patients, temozolomide use and treatment intensification with concurrent CRT, adjuvant chemotherapy, and higher radiation dose were associated with improved outcomes. PMID:25741472

  15. Widespread chromosomal abnormalities in high-grade ductal carcinoma in situ of the breast. Comparative genomic hybridization study of pure high-grade DCIS.

    PubMed

    Moore, E; Magee, H; Coyne, J; Gorey, T; Dervan, P A

    1999-03-01

    For a variety of technical reasons it is rarely possible to study cytogenetic abnormalities in ductal carcinoma in situ (DCIS) using traditional techniques. However, by combining molecular biology and computerized image analysis it is possible to carry out cytogenetic analyses on formalin-fixed, paraffin-embedded tissue, using comparative genomic hybridization (CGH). The purpose of this study was to identify the prevalence of chromosomal amplifications and deletions in high-grade DCIS and to look specifically for unique or consistent abnormalities in this pre-invasive cancer. Twenty-three cases of asymptomatic, non-palpable, screen-detected, high-grade DCIS were examined using CGH on tumour cells obtained from histology slides. All cases showed chromosomal abnormalities. A wide variety of amplifications and deletions were spread across the genome. The most frequent changes were gains of chromosomes 17 (13 of 23), 16p (13 of 23), and 20q (9 of 23) and amplifications of 11q13 (22 of 23), 12q 24.1-24.2 (12 of 23), 6p21.3 (11 of 23), and 1q31-qter (6 of 23). The most frequent deletions were on 13q 21.3-q33 (7 of 23), 9p21 (4 of 23), and 6q16.1 (4 of 23). These findings indicate that high-grade DCIS is, from a cytogenetic viewpoint, an advanced lesion. There was no absolutely consistent finding in every case, but amplification of 11q13 was found in 22 of the 23 cases. The precise significance of this is unknown at present. This region of chromosome 11q harbours a number of known oncogenes, including cyclin D1 andINT2. It is likely that many of these findings are the result of accumulated chromosomal abnormalities, reflecting an unstable genome in established malignancy.

  16. High BAX/BCL2 mRNA ratio predicts favorable prognosis in laryngeal squamous cell carcinoma, particularly in patients with negative lymph nodes at the time of diagnosis.

    PubMed

    Giotakis, Aris I; Kontos, Christos K; Manolopoulos, Leonidas D; Sismanis, Aristides; Konstadoulakis, Manousos M; Scorilas, Andreas

    2016-08-01

    Laryngeal squamous cell carcinoma (LSCC), a common type of head and neck cancer, is associated with high rates of metastasis and recurrence. Therefore, accurate prognostic stratification of LSCC patients based on molecular prognostic tumor biomarkers would definitely lead to a better clinical management of this malignancy. The aim of this study was the investigation of the potential combinatorial prognostic value of BCL2 and BAX mRNA expression in LSCC. Total RNA was isolated from 105 cancerous laryngeal tissue specimens obtained from patients having undergone surgical treatment for primary LSCC. After cDNA preparation, a low-cost, in-house developed, sensitive and accurate real-time quantitative PCR (qPCR) methodology was applied for the quantification of BCL2 and BAX mRNA levels. Then, we carried out a biostatistical analysis to assess the prognostic value of the BAX/BCL2 mRNA expression ratio. High BAX/BCL2 mRNA expression constitutes a favorable prognosticator in LSCC, predicting significantly longer disease-free survival (P=0.011) and overall survival (P=0.014) of patients. More importantly, the significant prognostic value of the BAX/BCL2 mRNA expression appeared to be independent of the histological grade and size of the malignant laryngeal tumor as well as TNM stage, as revealed by the multivariate bootstrap Cox regression analysis. Kaplan-Meier survival analysis demonstrated also that the BAX/BCL2 ratio can stratify node-negative (N0) LSCC patients into two subgroups with significantly different DFS and OS (P=0.021 and P=0.009, respectively). The BAX/BCL2 mRNA ratio is a putative molecular tissue biomarker in CLL and hence deserves further validation in larger cohorts of LSCC patients. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  17. Separation of Nitration By-Products in Commercial-Grade Trinitro-Toluene by High Performance Liquid Chromatography.

    DTIC Science & Technology

    1982-06-01

    MRL-TN-464 SEPARATION OF NITRATION BY-PRODUCTS IN COMMERCIAL-GRADE TITR-TOLUENE BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY Peter J. Sanders ABSTRACT...UNCLASSIFIED TITLE SEPARATION OF NITRATION BY-PRODUCTS IN COMMERCIAL-GRADE TRXNITRO-TOLUENE BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY AUTHOR(S...PRODUCTS IN COMMERCIAL-GRADE TRINITRO-TOLUENE BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY 16 INTRODUCTION Fbr some time, a need has existed for the

  18. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer.

    PubMed

    Moran-Jones, Kim; Gloss, Brian S; Murali, Rajmohan; Chang, David K; Colvin, Emily K; Jones, Marc D; Yuen, Samuel; Howell, Viive M; Brown, Laura M; Wong, Carol W; Spong, Suzanne M; Scarlett, Christopher J; Hacker, Neville F; Ghosh, Sue; Mok, Samuel C; Birrer, Michael J; Samimi, Goli

    2015-12-29

    Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer.

  19. Group Art Therapy with Eighth-Grade Students Transitioning to High School

    ERIC Educational Resources Information Center

    Spier, Erin

    2010-01-01

    This study examined the effectiveness of a group art therapy intervention within a school setting to increase coping skills and decrease disruptive behaviors in a group of 6 eighth-grade students at risk for making a poor transition to high school. The mixed-method AB single-case experiment measured each individual's changes in behavior and coping…

  20. High School Grade Inflation from 2004 to 2011. ACT Research Report Series, 2013 (3)

    ERIC Educational Resources Information Center

    Zhang, Qian; Sanchez, Edgar I.

    2013-01-01

    This study explores inflation in high school grade point average (HSGPA), defined as trend over time in the conditional average of HSGPA, given ACT® Composite score. The time period considered is 2004 to 2011. Using hierarchical linear modeling, the study updates a previous analysis of Woodruff and Ziomek (2004). The study also investigates…

  1. Connecting Entrance and Departure: The Transition to Ninth Grade and High School Dropout

    ERIC Educational Resources Information Center

    Neild, Ruth Curran; Stoner-Eby, Scott; Furstenberg, Frank

    2008-01-01

    Recent reports have demonstrated that the United States has a dropout crisis of alarming proportions. In some large-city school systems, more than 50% of students leave high school without a diploma. A large proportion of these dropouts have not accumulated enough credits to be promoted beyond ninth grade. Using survey and student record data for…

  2. Low- and High-Achieving Sixth-Grade Students' Access to Participation during Mathematics Discourse

    ERIC Educational Resources Information Center

    Lack, Brian; Swars, Susan Lee; Meyers, Barbara

    2014-01-01

    A descriptive, holistic, multiple-case methodology was applied to examine the nature of participation in discourse of two low- and two high-achieving grade 6 students while solving mathematical tasks in a standards-based classroom. Data collected via classroom observations and student interviews were analyzed through a multiple-cycle coding…

  3. "Career Education" Junior High School Style: "Semester Course" for Seventh Grade.

    ERIC Educational Resources Information Center

    Alpine School District, American Fork, UT.

    The curriculum guide is a product of the Alpine School District (American Fork, Utah) program to integrate career education concepts into the curriculum of all junior high schools in the district. The guide offers teacher-developed materials designed to help seventh grade students become aware of the dignity of work and to explore the world of…

  4. Accelerated Mathematics and High-Ability Students' Math Achievement in Grades Three and Four

    ERIC Educational Resources Information Center

    Stanley, Ashley M.

    2011-01-01

    The purpose of this study was to explore the relationship between the use of a computer-managed integrated learning system entitled Accelerated Math (AM) as a supplement to traditional mathematics instruction on achievement as measured by TerraNova achievement tests of third and fourth grade high-ability students. Gender, socioeconomic status, and…

  5. Examining the Accuracy of Self-Reported High School Grade Point Average

    ERIC Educational Resources Information Center

    Shaw, Emily J.; Mattern, Krista D.

    2010-01-01

    [Slides] presented at AERA in Denver, CO in April 2010. This study examined the relationship between students' self-reported high school grade point average (HSGPA) from the SAT Questionnaire and their HSGPA provided by the colleges and universities they attend. The purpose of this research was to offer updated information on the relatedness of…

  6. Managing the Transition to Ninth Grade in a Comprehensive Urban High School. Snapshot

    ERIC Educational Resources Information Center

    Smith, Thomas J.

    2007-01-01

    This "snapshot" illustrates how one school is managing to make a positive difference for ninth graders. It describes the Ninth Grade Success Academy, a school-within-a-school at Thomas A. Edison High School in Philadelphia, Pennsylvania, which has a number of features specifically designed to help ninth-graders make successful…

  7. 40 CFR 246.200-2 - Recommended procedures: High-grade paper recovery from smaller offices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... offices. The recovery of high-grade paper generated by office facilities of less than 100 office workers... paper recovery from smaller offices. 246.200-2 Section 246.200-2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE SEPARATION FOR MATERIALS RECOVERY GUIDELINES...

  8. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer

    PubMed Central

    Moran-Jones, Kim; Gloss, Brian S.; Murali, Rajmohan; Chang, David K.; Colvin, Emily K.; Jones, Marc D.; Yuen, Samuel; Howell, Viive M.; Brown, Laura M.; Wong, Carol W.; Spong, Suzanne M.; Scarlett, Christopher J.; Hacker, Neville F.; Ghosh, Sue; Mok, Samuel C.; Birrer, Michael J.; Samimi, Goli

    2015-01-01

    Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer. PMID:26575166

  9. Tracking Structural Development through Data Modelling in Highly Able Grade 1 Students

    ERIC Educational Resources Information Center

    Mulligan, Joanne; Hodge, Kerry; Mitchelmore, Mike; English, Lyn

    2013-01-01

    A 3-year longitudinal study "Transforming Children's Mathematical and Scientific Development" integrates, through data modelling, a pedagogical approach focused on mathematical patterns and structural relationships with learning in science. As part of this study, a purposive sample of 21 highly able Grade 1 students was engaged in an…

  10. The Impact of High-Speed Internet Connectivity at Home on Eighth-Grade Student Achievement

    ERIC Educational Resources Information Center

    Kingston, Kent J.

    2013-01-01

    In the fall of 2008 Westside Community Schools - District 66, in Omaha, Nebraska implemented a one-to-one notebook computer take home model for all eighth-grade students. The purpose of this study was to determine the effect of a required yearlong one-to-one notebook computer program supported by high-speed Internet connectivity at school on (a)…

  11. Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology.

    PubMed

    Damrauer, Jeffrey S; Hoadley, Katherine A; Chism, David D; Fan, Cheng; Tiganelli, Christopher J; Wobker, Sara E; Yeh, Jen Jen; Milowsky, Matthew I; Iyer, Gopa; Parker, Joel S; Kim, William Y

    2014-02-25

    We sought to define whether there are intrinsic molecular subtypes of high-grade bladder cancer. Consensus clustering performed on gene expression data from a meta-dataset of high-grade, muscle-invasive bladder tumors identified two intrinsic, molecular subsets of high-grade bladder cancer, termed "luminal" and "basal-like," which have characteristics of different stages of urothelial differentiation, reflect the luminal and basal-like molecular subtypes of breast cancer, and have clinically meaningful differences in outcome. A gene set predictor, bladder cancer analysis of subtypes by gene expression (BASE47) was defined by prediction analysis of microarrays (PAM) and accurately classifies the subtypes. Our data demonstrate that there are at least two molecularly and clinically distinct subtypes of high-grade bladder cancer and validate the BASE47 as a subtype predictor. Future studies exploring the predictive value of the BASE47 subtypes for standard of care bladder cancer therapies, as well as novel subtype-specific therapies, will be of interest.

  12. Life in the Fast Lane: Effects of Early Grade Acceleration on High School and College Outcomes

    ERIC Educational Resources Information Center

    McClarty, Katie Larsen

    2015-01-01

    Research has repeatedly demonstrated the positive effects of acceleration for gifted and talented students. This study expands the literature by not only evaluating the impact of early grade skipping on high school and college outcomes but also examining the role of postacceleration opportunities on subsequent performance. Using a representative…

  13. Accelerated Mathematics and High-Ability Students' Math Achievement in Grades Three and Four

    ERIC Educational Resources Information Center

    Stanley, Ashley M.

    2011-01-01

    The purpose of this study was to explore the relationship between the use of a computer-managed integrated learning system entitled Accelerated Math (AM) as a supplement to traditional mathematics instruction on achievement as measured by TerraNova achievement tests of third and fourth grade high-ability students. Gender, socioeconomic status, and…

  14. Life in the Fast Lane: Effects of Early Grade Acceleration on High School and College Outcomes

    ERIC Educational Resources Information Center

    McClarty, Katie Larsen

    2015-01-01

    Research has repeatedly demonstrated the positive effects of acceleration for gifted and talented students. This study expands the literature by not only evaluating the impact of early grade skipping on high school and college outcomes but also examining the role of postacceleration opportunities on subsequent performance. Using a representative…

  15. Characterizing a Highly Accomplished Teacher's Noticing of Third-Grade Students' Mathematical Thinking

    ERIC Educational Resources Information Center

    Taylan, Rukiye Didem

    2017-01-01

    This study investigated a highly accomplished third-grade teacher's noticing of students' mathematical thinking as she taught multiplication and division. Through an innovative method, which allowed for documenting in-the-moment teacher noticing, the author was able to explore teacher noticing and reflective practices in the context of classroom…

  16. The Impact of High-Speed Internet Connectivity at Home on Eighth-Grade Student Achievement

    ERIC Educational Resources Information Center

    Kingston, Kent J.

    2013-01-01

    In the fall of 2008 Westside Community Schools - District 66, in Omaha, Nebraska implemented a one-to-one notebook computer take home model for all eighth-grade students. The purpose of this study was to determine the effect of a required yearlong one-to-one notebook computer program supported by high-speed Internet connectivity at school on (a)…

  17. [High-grade prostatic intraepithelial neoplasia: state-of-the-art].

    PubMed

    Allina, D O; Andreeva, Iu Iu; Zavalishina, L E; Kekeeva, T V; Frank, G A

    2015-01-01

    According to current views, high-grade prostatic intraepithelial neoplasia is the most likely precursor of prostate adenocarcinoma. This review gives the latest data of genetic, proteomic, and morphological analyses of this neoplasia and touches upon the probems that might arise when searching for new markers for differential diagnosis and prognosis estimation.

  18. Radiomic analysis of soft tissues sarcomas can distinguish intermediate from high-grade lesions.

    PubMed

    Corino, Valentina D A; Montin, Eros; Messina, Antonella; Casali, Paolo G; Gronchi, Alessandro; Marchianò, Alfonso; Mainardi, Luca T

    2017-06-27

    To assess the feasibility of grading soft tissue sarcomas (STSs) using MRI features (radiomics). MRI (echo planar SE, 1.5T) from 19 patients with STSs and a known histological grading, were retrospectively analyzed. The apparent diffusion coefficient (ADC) maps, obtained by diffusion-weighted imaging acquisitions, were analyzed through 65 radiomic features, intensity-based (first order statistics, FOS) and texture (gray level co-occurrence matrix, GLCM; and gray level run length matrix, GLRLM) features. Feature selection (sequential forward floating search) and classification (k-nearest neighbor classifier) were performed to distinguish intermediate- from high-grade STSs. Classification was performed using the three different sub-groups of features separately as well as all the features together. The entire dataset was divided in three subsets: the training, validation and test set, containing, respectively, 60, 30, and 10% of the data. Intermediate-grade lesions had a higher and less disperse ADC values compared with high-grade ones: most of FOS related to intensity are higher for the intermediate-grade STSs, while FOS related to signal variability were higher in the high grade (e.g., the feature variance is 2.6*10(5)  ± 0.9*10(5) versus 3.3*10(5)  ± 1.6*10(5) , P = 0.3). The GLCM features related to entropy and dissimilarity were higher in the high-grade. When performing classification, the best accuracy is obtained with a maximum of three features for each subgroup, FOS features being those leading to the best classification (validation set: FOS accuracy 0.90 ± 0.11, area under the curve [AUC] 0.85 ± 0.16; test set: FOS accuracy 0.88 ± 0.25, AUC 0.87 ± 0.34). Good accuracy and AUC could be obtained using only few Radiomic features, belonging to the FOS class. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017. © 2017 International Society for Magnetic Resonance in Medicine.

  19. High throughput interrogation of somatic mutations in high grade serous cancer of the ovary.

    PubMed

    Matulonis, Ursula A; Hirsch, Michelle; Palescandolo, Emanuele; Kim, Eejung; Liu, Joyce; van Hummelen, Paul; MacConaill, Laura; Drapkin, Ronny; Hahn, William C

    2011-01-01

    Epithelial ovarian cancer is the most lethal of all gynecologic malignancies, and high grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. The objective of this study was to determine the frequency and types of point somatic mutations in HGSC using a mutation detection protocol called OncoMap that employs mass spectrometric-based genotyping technology. The Center for Cancer Genome Discovery (CCGD) Program at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection protocol, termed OncoMap has been expanded to detect more than 1000 mutations in 112 oncogenes in formalin-fixed paraffin-embedded (FFPE) tissue samples. We performed OncoMap on a set of 203 FFPE advanced staged HGSC specimens. We isolated genomic DNA from these samples, and after a battery of quality assurance tests, ran each of these samples on the OncoMap v3 platform. 56% (113/203) tumor samples harbored candidate mutations. Sixty-five samples had single mutations (32%) while the remaining samples had ≥ 2 mutations (24%). 196 candidate mutation calls were made in 50 genes. The most common somatic oncogene mutations were found in EGFR, KRAS, PDGRFα, KIT, and PIK3CA. Other mutations found in additional genes were found at lower frequencies (<3%). Sequenom analysis using OncoMap on DNA extracted from FFPE ovarian cancer samples is feasible and leads to the detection of potentially druggable mutations. Screening HGSC for somatic mutations in oncogenes may lead to additional therapies for this patient population.

  20. GRADE in Systematic Reviews of Acupuncture for Stroke Rehabilitation: Recommendations based on High-Quality Evidence

    PubMed Central

    Xin, Zhang; Xue-Ting, Liu; De-Ying, Kang

    2015-01-01

    Systematic reviews (SRs) of randomized controlled trials (RCTs) have demonstrated acupuncture’s effectiveness in stroke rehabilitation. The current study reviews the quality of evidence in SRs of acupuncture in stroke rehabilitation, and rates the strength of recommendation for its use based on this evidence using the GRADE (grading of recommendations, assessment, development and evaluations) approach. A comprehensive literature search was performed using multiple databases (e.g., Medline, Embase) with advanced search strategies. Two authors independently selected articles, collected data, and assessed the methodological quality of each identified SR according to AMSTAR (a measurement tool to assess systematic reviews) and OQAQ (Oxman and Guyatt’s overview quality assessment questionnaire). Outcomes related to stroke rehabilitation were evaluated. SRs of high methodological quality (AMSTAR score ≥9 and OQAQ score ≥7) were graded using GRADE. Ultimately, acupuncture yields benefits in stroke rehabilitation (neurological function improvement: RR = 1.34; swallowing improvement: RR = 1.61, 1.49, 1.07; disability: SMD = 0.49 or 0.07). Poor evidentiary quality and insufficient information about harm led to weak recommendations. In conclusion, acupuncture may improve stroke rehabilitation, as the GRADE approach indicated a weak recommendation for acupuncture’s usage in this context. PMID:26560971

  1. Age and HPV type as risk factors for HPV persistence after loop excision in patients with high grade cervical lesions: an observational study.

    PubMed

    Pirtea, Laurențiu; Grigoraş, Dorin; Matusz, Petru; Pirtea, Marilena; Moleriu, Lavinia; Tudor, Anca; Ilina, Răzvan; Secoşan, Cristina; Horhat, Florin; Mazilu, Octavian

    2016-10-06

    Persistent infections with high risk human papillomaviruses (HR-HPV) cause virtually all cervical cancers. An observational study was conducted aiming to estimate the rate of HPV infection persistence after LEEP in patients with high grade squamous intraepithelial lesions (HSIL). Moreover, the study investigated if persistence is age related. For this reason a total of 110 patients were included between January 2010 and June 2015. At 6 months after LEEP the overall HPV infection persistence rate was 40.9 %, at 12 months 20 % and at 18 months 11.8 %. Type 16 showed the highest persistence rate: 27.3 % at 6 months, 12.7 % at 12 months and 10 % at 18 months after LEEP. The persistence for HPV type 16 at 6 months after LEEP was significantly higher in the group > =36.5 years old compared to the persistence rate in the group <36.5 years old (p = 0.0027, RR = 2.75, 95 %ϵ(1.34; 5.64)) (see Table 3). LEEP does not completely eradicate HPV infection. HPV persistence rate after LEEP is higher in infections with type 16 and in women older than 36.5 years.

  2. Cancer stem cell, cytokeratins and epithelial to mesenchymal transition markers expression in oral squamous cell carcinoma derived from ortothopic xenoimplantation of CD44(high) cells.

    PubMed

    de Andrade, Nathália Paiva; Rodrigues, Maria Fernanda Setúbal Destro; Rodini, Camila Oliveira; Nunes, Fabio Daumas

    2017-03-01

    Oral squamous cell carcinoma (OSCC) is the most prevalent neoplasia of oral cavity worldwide and prognosis remains unchanged in decades. Recently, different authors reported that head and neck squamous cell carcinomas have a subpopulation of tumor initiating cells that apparently correspond to cancer stem cells (CSC) and are also responsible for tumor growth and metastasis. The purpose of the present study was to investigate the microscopic and phenotypic characteristics of OSCC tumors induced after orthotopic xenoimplantation of SCC9(WT) cell line and CSC-enriched subpopulation isolated from SCC9 cell line based on high expression of the putative CSC marker CD44. Different numbers of FACS-sorted SCC9 CD44(high) and CD44(low) cells as well as SCC9(WT) (wild type) were transplanted into the tongue of BALB/C nude (NOD/SCID) mice to evaluate their tumorigenic potential. Sixty days post-induction, tumors were morphologically characterized and immunostained for CSC markers (CD44, Nanog and Bmi-1), epithelial-mesenchymal transition (Snail, Slug) and epithelial differentiating cell markers (cytokeratins 4, 13, 15, 17 and 19), as well as E-cadherin and β-catenin. The data presented here shows that SCC9 CD44(high) cells have higher ability to form tumors than SCC9 CD44(low) cells, even when significantly lower numbers of SCC9 CD44(high) cells were transplanted. Immunoassessment of tumors derived from SCC9 CD44(high) cells revealed high expression of cytokeratin CK19, β-catenin, E-cadherin and CD44, and negative or low expression of CK17, CK4, CK15, CK13, Nanog, Bmi-1, Snail and Slug. While tumors derived from SCC9(WT) showed high expression of CK17, CK19, CD44, Nanog, Bmi-1, Snail and Slug, and negative or low expression of CK4, CK15, CK13, β-catenin and E-cadherin. Thus, SCC9 CD44(high) cells were highly tumorigenic, capable of originating heterogeneous tumors and these tumors have a immunohistochemical profile different from those formed by the wild type cell line.

  3. Preparation of High-Grade Titania Slag from Ilmenite-Bearing High Ca and Mg by Vacuum Smelting Method

    NASA Astrophysics Data System (ADS)

    Zhang, Kai; Lv, Xuewei; Huang, Run; Song, Bing; Xi, Fei

    2014-06-01

    Ilmenite produced from the Panxi area in China has high impurities such as Ca and Mg. High-grade titanium (Ti) slag can be obtained by the electric arc furnace process, a traditional method of treating ilmenite. Thus, Ti slag prepared from the Panxi ilmenite contains high CaO and MgO, exceeding 5 pct of the slag content. This high CaO and MgO content confers considerable difficulty in producing titania (TiO2) white using fluidizing chlorination. In this study, a new process named vacuum separation was found to produce high-grade TiO2 materials. The effects of separation temperature and time on the TiO2 grade were studied. The high-grade TiO2 slag, which has 93 pct TiO2, <0.1 pct MgO, <1.2 pct SiO2, and <0.5 pct CaO, can be produced at 1823 K (1550 °C) in 45 minutes through the proposed method.

  4. High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications.

    PubMed

    Grand, Bertrand; Cazes, Aurélie; Mordant, Pierre; Foucault, Christophe; Dujon, Antoine; Guillevin, Elizabeth Fabre; Barthes, Françoise Le Pimpec; Riquet, Marc

    2013-09-01

    Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China.

    PubMed

    Chen, Xingdong; Winckler, Björn; Lu, Ming; Cheng, Hongwei; Yuan, Ziyu; Yang, Yajun; Jin, Li; Ye, Weimin

    2015-01-01

    Poor oral health has been linked with an increased risk of esophageal squamous cell carcinoma (ESCC). We investigated whether alteration of oral microbiota is associated with ESCC risk. Fasting saliva samples were collected from 87 incident and histopathologicallly diagnosed ESCC cases, 63 subjects with dysplasia and 85 healthy controls. All subjects were also interviewed with a questionnaire. V3-V4 region of 16S rRNA was amplified and sequenced by 454-pyrosequencing platform. Carriage of each genus was compared by means of multivariate-adjusted odds ratios derived from logistic regression model. Relative abundance was compared using Metastats method. Beta diversity was estimated using Unifrac and weighted Unifrac distances. Principal coordinate analysis (PCoA) was applied to ordinate dissimilarity matrices. Multinomial logistic regression was used to compare the coordinates between different groups. ESCC subjects had an overall decreased microbial diversity compared to control and dysplasia subjects (P<0.001). Decreased carriage of genera Lautropia, Bulleidia, Catonella, Corynebacterium, Moryella, Peptococcus and Cardiobacterium were found in ESCC subjects compared to non-ESCC subjects. Multinomial logistic regression analyses on PCoA coordinates also revealed that ESCC subjects had significantly different levels for several coordinates compared to non-ESCC subjects. In conclusion, we observed a correlation between altered salivary bacterial microbiota and ESCC risk. The results of our study on the saliva microbiome are of particular interest as it reflects the shift in microbial communities. Further studies are warranted to verify this finding, and if being verified, to explore the underlying mechanisms.

  6. High Level of Plasma EGFL6 Is Associated with Clinicopathological Characteristics in Patients with Oral Squamous Cell Carcinoma

    PubMed Central

    Chuang, Chun-Yi; Chen, Mu-Kuan; Hsieh, Ming-Ju; Yeh, Chia-Ming; Lin, Chiao-Wen; Yang, Wei-En; Yang, Shun-Fa; Chou, Ying-Erh

    2017-01-01

    EGF-like domain 6 (EGFL6), a member of the epidermal growth factor (EGF) repeat protein superfamily, is a secreted protein that promotes endothelial cell migration and angiogenesis. The current study investigated the association between the clinicopathological characteristics and plasma level of EGFL6 in patients with oral squamous cell carcinoma (OSCC). We measured the plasma EGFL6 levels of 392 OSCC patients by using a commercial enzyme-linked immunosorbent assay. We also analyzed EGFL6 mRNA levels of 328 OSCC patients from The Cancer Genome Atlas (TCGA) dataset. The results showed that plasma EGFL6 levels were significantly higher in patients with OSCC than in healthy controls (p < 0.001). Similar results were observed for the TCGA bioinformatics database. Moreover, plasma EGFL6 levels were significantly higher in the patients with advanced T status (p = 0.002), distant metastasis (p = 0.001), and higher TNM stage (p=0.033). In conclusion, our results suggest that plasma level of EGFL6 may be useful to assess disease progression, and especially advanced T status and higher TNM stage in patients with OSCC. PMID:28539817

  7. High Level of Plasma EGFL6 Is Associated with Clinicopathological Characteristics in Patients with Oral Squamous Cell Carcinoma.

    PubMed

    Chuang, Chun-Yi; Chen, Mu-Kuan; Hsieh, Ming-Ju; Yeh, Chia-Ming; Lin, Chiao-Wen; Yang, Wei-En; Yang, Shun-Fa; Chou, Ying-Erh

    2017-01-01

    EGF-like domain 6 (EGFL6), a member of the epidermal growth factor (EGF) repeat protein superfamily, is a secreted protein that promotes endothelial cell migration and angiogenesis. The current study investigated the association between the clinicopathological characteristics and plasma level of EGFL6 in patients with oral squamous cell carcinoma (OSCC). We measured the plasma EGFL6 levels of 392 OSCC patients by using a commercial enzyme-linked immunosorbent assay. We also analyzed EGFL6 mRNA levels of 328 OSCC patients from The Cancer Genome Atlas (TCGA) dataset. The results showed that plasma EGFL6 levels were significantly higher in patients with OSCC than in healthy controls (p < 0.001). Similar results were observed for the TCGA bioinformatics database. Moreover, plasma EGFL6 levels were significantly higher in the patients with advanced T status (p = 0.002), distant metastasis (p = 0.001), and higher TNM stage (p=0.033). In conclusion, our results suggest that plasma level of EGFL6 may be useful to assess disease progression, and especially advanced T status and higher TNM stage in patients with OSCC.

  8. Identification of high-risk human papillomavirus (hrHPV)-associated genes in early stage cervical squamous cell carcinomas.

    PubMed

    Hu, Y; Liu, Y; Liu, C-B; Ling, Z-Q

    2011-01-01

    This retrospective study investigated gene expression in tumour samples from 38 patients with early stage human papillomavirus (HPV)-associated cervical squamous cell carcinoma (CSCC). The patients were divided into two groups based on the presence of viral markers of HPV16 or HPV18 infection. Gene expression profiles of tumour samples and the corresponding normal cervical epithelium were analysed using cDNA microarrays. Several genes showed differential expression between the two groups of HPV-infected CSCC patients, although seven genes showed similar changes in both groups. The four genes encoding cyclin-dependent kinase inhibitor 2A, matrix metallopeptidase 9, laminin γ-1, and epidermal growth factor receptor were up-regulated, and the three genes encoding transforming growth factor β receptor 1, interleukin-1α and insulin-like growth factor-binding protein 6 were down-regulated, in both HPV16(+) and HPV18(+) CSCC. These proteins are involved in cell proliferation, cell structure and cell attachment, so their expression might be involved in the mechanism of HPV-induced carcino genesis. A clearer understanding of HPV type-specific gene expression might aid diagnosis and treatment.

  9. CEUS in the differentiation between low and high-grade bladder carcinoma

    PubMed Central

    Drudi, F.M.; Di Leo, N.; Malpassini, F.; Antonini, F.; Corongiu, E.; Iori, F.

    2012-01-01

    Introduction Bladder cancer ranks 4th overall in the number of newly diagnosed cancers and 10th in causes of cancer deaths. More than 90% of all cases of bladder cancer are transitional cell carcinoma (TCC). The goal of this study is to confirm the usefulness of low mechanical index contrast-enhanced ultrasonography (CEUS), also in association with time–intensity curves, in the differentiation between high- and low-grade bladder malignant lesions. Materials and methods From February 2006 to February 2012 we recruited 144 patients. All patients underwent grayscale ultrasonography (US), color-Doppler ultrasonography (CDUS) and contrast-enhanced ultrasonography (CEUS). Subsequently all patients underwent cystoscopy and TURB. Results Histological diagnoses were: 88 high-grade carcinomas (61.1%), and 56 low-grade carcinomas (38.9%). Sensitivity and specificity of CDUS were 87.5% (126/144) and 60%, respectively. Sensitivity and specificity of CEUS were 90.9% and 85.7%, respectively. Sensitivity and specificity of TIC were 91.6% (132/144) and 85.7%, respectively. Discussion and conclusions CEUS is a reliable noninvasive method for differentiating low- and high-grade bladder carcinomas since it provides typical enhancement patterns as well as specific contrast-sonographic perfusion curves. PMID:23730389

  10. Declining rates of high-grade cervical lesions in young women in Connecticut, 2008-2011.

    PubMed

    Niccolai, Linda M; Julian, Pamela J; Meek, James I; McBride, Vanessa; Hadler, James L; Sosa, Lynn E

    2013-08-01

    Vaccines that prevent infection with human papillomavirus (HPV) types 16 and 18 that are known to cause cervical cancer have been available in the United States since 2006. High-grade cervical lesions are important for monitoring early vaccine impact because they are strong surrogates for cancer yet can develop within years after infection as opposed to decades. Trends in high-grade cervical lesions including cervical intraepithelial neoplasia grades 2, 2/3, and 3 and adenocarcinoma in situ among women ages 21 to 39 years old were examined using a statewide surveillance registry in Connecticut from 2008 to 2011. During this time period, HPV vaccine initiation increased among adolescent females from 45% to 61%. Analyses were stratified by age, according to census tract measures of proportion of population Black, Hispanic, living in poverty, and by urban/nonurban counties. The annual rate per 100,000 females ages 21 to 24 years declined from 834 in 2008 to 688 in 2011 (P(trend) < 0.001). No significant declines were observed among women ages 25 to 39 years. Significant declining trends also occurred in census tracts with lower proportions of the population being Black, Hispanic, or living below the federal poverty level. Declines in high-grade cervical lesions have occurred among young women during 2008 to 2011. This is the first report of declines in cervical neoplasia in the United States since HPV vaccines became available. Continued surveillance is needed to measure vaccine impact and monitor health disparities.

  11. ERBB2 mutations associated with solid variant of high-grade invasive lobular breast carcinomas

    PubMed Central

    Bidard, François-Clément; Vacher, Sophie; Schnitzler, Anne; Chemlali, Walid; Trémoulet, Laurence; Fuhrmann, Laetitia; Cottu, Paul; Rouzier, Roman; Bièche, Ivan; Vincent-Salomon, Anne

    2016-01-01

    ERBB2 and ERBB3 somatic gain-of-function mutations, which may be targeted by anti-ERBB2 therapies, were reported by high-throughput sequencing studies in 1% and 2% of invasive breast cancers respectively. Our study aims to determine ERBB2 and ERBB3 mutations frequencies in grade 3 and/or ERBB2-positive invasive lobular breast carcinomas (ILC). All the 529 ILC surgically-excised registered at Institut Curie in the years 2005 to 2008 were reviewed. Thirty-nine grade 3 ERBB2-negative ILC and 16 ERBB2-positive ILC were retrieved and subjected to Sanger sequencing of the ERBB2 and ERBB3 activation mutation hotspots (ERBB2: exons 8, 17, 19, 20, 21; ERBB3: exons 3, 6, 7, 8). Among the 39 grade 3 ERBB2-negative ILC, six tumors were found to have at least one detectable ERBB2 activating mutation (incidence rate: 15%, 95%CI [4%-27%]). No ERBB2 mutation was found among the 16 ERBB2-positive ILC. No ERBB3 mutation was found in any of the 55 ILC. ERBB2 mutations were statistically associated with solid ILC features (p=0.01). Survival analyses showed no significant prognostic impact of ERBB2 mutations. Our study demonstrates that high grade ERBB2-negative ILC display a high frequency of ERBB2 mutations, and should be subjected to systematic genetic screening. PMID:27602491

  12. Prognostic impact of metallothionein on oral squamous cell carcinoma.

    PubMed

    Cardoso, Sérgio V; Barbosa, Hugo M; Candellori, Ignez M; Loyola, Adriano M; Aguiar, Maria Cássia F

    2002-08-01

    Metallothionein (MT), a low-molecular-weight protein with high cysteine content, seems to be related to neoplastic resistance to oncologic treatment and therefore has been studied as a prognostic factor for a variety of human malignant tumors. MT overexpression in neoplasms of ectodermal origin is usually associated with a poor prognosis. MT expression was evaluated in 60 samples of oral squamous cell carcinoma by immunohistochemistry to study its prognostic influence on oral cancer. Possible associations of MT immunoexpression were also investigated with respect to clinical stage (TNM), histological grading, and proliferation index (Ki-67) of the lesions. No significant statistical correlation was observed among these variables. The impact on overall survival was assessed by uni and multivariate statistical tests. Mean MT labeling index was 60%. High MT labeling indexes (over 76%) predicted shorter survival in univariate statistical analysis. In multivariate analysis, MT labeling index and clinical stage were independent prognostic factors. MT overexpression in oral squamous cell carcinoma seems to be related to a worse prognosis for patients.

  13. GLUT-1 Expression in Cutaneous Basal and Squamous Cell Carcinomas.

    PubMed

    Abdou, Asmaa Gaber; Eldien, Marwa Mohammad Serag; Elsakka, Daliah

    2015-09-01

    Glucose uptake is a key regulating step in glucose metabolism and is mediated by facilitative glucose transporters (GLUTs), and GLUT-1 is the predominant glucose transporter in many types of human cells. Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent the most common skin cancer in Egypt. The present study aimed at evaluation of the pattern and distribution of GLUT-1 in cutaneous BCC (16 cases) and SCC (16 cases) by means of immunohistochemistry. GLUT-1 was expressed in all SCC (100%) and in 62.5% of BCC. Membranous pattern of GLUT-1 was seen in 62.5% of SCC and 31.25% of BCC. Positivity (P = .02) and percentage (P = .000) of GLUT-1 expression were in favor of SCC in comparison to BCC. The high percentage of GLUT-1 expression was associated with high grade in SCC (P = .03). The immunoreactivity for GLUT-1 was more in the periphery of malignant nests of SCC while it was more in the center of BCC nests. GLUT-1 is overexpressed in cutaneous non-melanoma skin cancer. Its expression in SCC is related to differentiation status, and its expression in BCC is intimately associated with squamous metaplastic areas.

  14. The "flowerpot" sign: inference of poor renal function in high grade vesicoureteral reflux by calyceal orientation.

    PubMed

    Martin, Aaron D; Gupta, Kavita; Swords, Kelly A; Belman, A Barry; Majd, Massoud; Rushton, H Gil; Pohl, Hans G

    2015-02-01

    Modern radiographic advances have allowed for detailed and accurate imaging of not only urologic anatomy but also urologic function. The art of observational inference of subtle anatomic features and function from a static radiograph is being traded for new, more precise, and more expensive modalities. While the superiority of these methods cannot be denied, the total information provided in simpler tests should not be ignored. The relationship between high grade vesicoureteral reflux with the dilated calyces arranged cephalad to a dilated funnel-shaped renal pelvis on VCUG and reduced differential renal function has not been previously described, but has been anecdotally designated a "flowerpot" sign by our clinicians. We hypothesize that the appearance of a "flowerpot" kidney as described herein is an indicator of poor renal function in the setting of high grade VUR. IRB approval was obtained and 315 patients were identified from system-wide VCUG reports from 2004-2012 with diagnosed "high grade" or "severe" vesicoureteral reflux. Inclusion into the study required grade IV or V VUR on initial VCUG and an initial radionuclide study for determination of differential function. Patients with a solitary kidney, posterior urethral valve, multicystic dysplastic kidney, renal ectopia, or duplex collecting systems were excluded. Grade of reflux, angle of the inferior-superior calyceal axis relative to the lumbar spine, and differential uptake were recorded along with presence of the new "flowerpot" sign. Variables were analyzed using the Mann-Whitney U test to determine statistical significance. Fifty seven patients met inclusion criteria with 11 being designated as "flowerpot" kidneys. These "flowerpot" kidneys could be objectively differentiated from other kidneys with grade IV and/or grade V VUR both by inferior-superior calyceal axis (median angle, 52° [37-66] vs. 13° [2-37], respectively p < 0.001) and by differential renal uptake (median, 23% [5-49] vs. 45% [15

  15. Use of the HPV MLPA assay in cervical cytology for the prediction of high grade lesions.

    PubMed

    Litjens, Rogier J N T M; Theelen, Wendy; van de Pas, Yvonne; Ossel, Jessica; Reijans, Martin; Simons, Guus; Speel, Ernst-Jan M; Slangen, Brigitte F M; Ramaekers, Frans C S; Kruitwagen, Roy F P M; Hopman, Anton H N

    2013-08-01

    Current screening methods for uterine cervical cancer such as Papanicolaou smears and/or high risk human Papillomavirus (HR-HPV) detection have a high negative predictive value but a low positive predictive value for the presence of high grade cervical lesions. Therefore, new parameters are needed to reduce the rate of unnecessary referrals for colposcopy. The predictive value of the HPV multiplex ligation-dependent probe amplification (MLPA) assay, which can assess simultaneously HPV16/18 viral load and viral integration, was evaluated. The assay was applied to 170 cervical cytological samples, and the results were correlated with the matching histological follow-up. The GP5+/6+ assay and qPCR were used as a control for HR-HPV typing. The MLPA assay classified a higher percentage of cases as high-risk (high-viral load and/or viral integration) with higher grades of dysplasia. There was a high correlation between the HPV MLPA assay and qPCR for viral load and HPV genotyping, and between the MLPA assay and the GP5+/6+ assay for HPV genotyping. The sensitivity and specificity of the HPV MLPA assay for the detection of high-grade lesions were 44% and 93%, respectively. This study demonstrates that the HPV MLPA assay can reliably detect HPV 16/18, viral load, and viral integration in cytological samples. Also, high-risk classification correlated well with the presence of high-grade dysplasia. However, for the implementation of the MLPA assay into clinical practice, additional HR-HPV types need to be included to increase the sensitivity of the assay, and thereby increase its negative predictive value.

  16. Feasibility of Using Bevacizumab With Radiation Therapy and Temozolomide in Newly Diagnosed High-Grade Glioma

    SciTech Connect

    Narayana, Ashwatha Golfinos, John G.; Fischer, Ingeborg; Raza, Shahzad; Kelly, Patrick M.D.; Parker, Erik; Knopp, Edmond A.; Medabalmi, Praveen; Zagzag, David; Eagan, Patricia; Gruber, Michael L.

    2008-10-01

    Introduction: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. Methods and Materials: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m{sup 2}. Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m{sup 2} for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. Results: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. Conclusion: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely.

  17. Liver stiffness measurement predicts high-grade post-hepatectomy liver failure: A prospective cohort study.

    PubMed

    Chong, Charing Ching-Ning; Wong, Grace Lai-Hung; Chan, Anthony Wing-Hung; Wong, Vincent Wai-Sun; Fong, Anthony Kwong-Wai; Cheung, Yue-Sun; Wong, John; Lee, Kit-Fai; Chan, Stephen L; Lai, Paul Bo-San; Chan, Henry Lik-Yuen

    2017-02-01

    Liver stiffness measurement using transient elastography appears to be an excellent tool for detection of liver fibrosis and cirrhosis with high accuracy. The aim of this study is to evaluate the efficacy of preoperative liver stiffness measurement in predicting post-hepatectomy liver failure. A prospective cohort study of all consecutive patients undergoing hepatectomy for hepatocellular carcinoma from February 2010 to August 2014 was studied. All patients received detailed preoperative assessments including liver stiffness measurement. The primary outcome was post-hepatectomy liver failure according to the International Study Group of Liver Surgery definition. A total of 255 patients were included. Liver stiffness measurement showed significant correlation with grade B or C post-hepatectomy liver failure. (P = 0.003) Using the cutoff at 12 kPa, liver stiffness measurement had a sensitivity of 52.4% and specificity of 73.3% in predication of high-grade (grade B or C) post-hepatectomy liver failure. Liver stiffness measurement > 12 kPa was also an independent prognostic factor for both high-grade post-hepatectomy liver failure and major postoperative complications by multivariate analysis. The diagnostic accuracy was better in patients without right lobe tumor with an area under the receiver operating characteristic of 0.83 compared with an area under the receiver operating characteristic of only 0.62 in patients with right lobe tumor. Liver stiffness measurement using Fibroscan is good to predict high-grade post-hepatectomy liver failure especially in patients without right lobe tumor. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  18. Prognostic value of endocervical sampling following loop excision of high grade intraepithelial neoplasia.

    PubMed

    Cui, Yiwen; Sangi-Haghpeykar, Haleh; Patsner, Bruce; Bump, Jennifer M M; Williams-Brown, Marian Y; Binder, Gary L; Masand, Ramya P; Anderson, Matthew L

    2017-03-01

    To assess the role of additional biopsies performed with loop electrosurgical excisional procedure (LEEP) in predicting the likelihood of persistent high grade intraepithelial neoplasia. Clinicopathologic data were abstracted from women who underwent excision of high grade intraepithelial lesions between 2001 and 2014. Persistent disease was defined as uninterrupted high grade intraepithelial neoplasia, whereas recurrent disease was defined as disease diagnosed ≥1year after treatment with intervening normal evaluation. Chi-square and Fisher's exact tests were used to examine associations between demographic and histologic parameters and clinical outcomes. A total of 606 women underwent LEEP for high grade intraepithelial neoplasia (HSIL), of whom, 178 (29%) were additionally evaluated by endocervical curettage, 80 (13%), top hat and 99 (16%), both procedures. With mean follow-up of 1.9±1.5years, persistent disease was identified in 87 women (14%) while recurrent disease was diagnosed in 20 (3%). After adjusting for age, HIV status and histologic grade of disease, the presence of disease at the endocervical margin (aOR=2.2, 95% CL 1.8-5.5, p<0.0001), with endocervical curettage (aOR=2.39, 95% CL 1.2-9.9, p=0.025) or on top hat (aOR=4.0, 95% CL 1.1-16.2, p=0.04) correlated with the likelihood of persistent but not recurrent disease. Only endocervical margin status remained predictive (p=0.03) of outcome after controlling for pre-procedure likelihood of endocervical disease. Sensitivity of endocervical margin status for persistent disease was 56.9% with specificity of 72.2%. Positive predictive value (PPV) was 24.9% and negative predictive value (NPV) 90.9%. Despite frequent use of additional procedures to sample the endocervix, these strategies do not improve the ability of endocervical margin status to predict persistent or recurrent dysplasia. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Highly Transparent Compositionally Graded Buffers for New Metamorphic Multijunction Solar Cell Designs

    DOE PAGES

    Schulte, Kevin L.; France, Ryan M.; Geisz, John F.

    2016-11-11

    The development of compositionally graded buffer layers (CGBs) with enhanced transparency would enable novel five and six junction solar cells, with efficiencies approaching 50% under high concentration. Here, we demonstrate highly transparent grades between the GaAs and InP lattice constants on both A- and B-miscut GaAs substrates, employing AlxGayIn1-x-yAs and highly Se-doped Burstein-Moss (BM) shifted GaxIn 1-xP. Transparency to >810 and >890 nm wavelengths is demonstrated with BM-shifted GaxIn1-xP on B-miscut substrates and AlxGayIn1-x-yAs/GaxIn1-xP(Se) combined grades on A-miscut substrates, respectively. 0.74 eV GaInAs solar cells grown on these transparent CGBs exhibit Woc = 0.41 V at mA/ cm2, performance comparablemore » with the state-of-the-art GaxIn1-xP grade employed in the four-junction-inverted metamorphic multijunction (IMM) cell. A GaAs/0.74cV GaInAs tandem cell was grown with a transparent BM-shifted GaxIn1-xP CGB to verify the CGB performance in a multijunction device structure. Quantum efficiency measurements indicate that the CGB is completely transparent to photons below the GaAs bandedge, validating its use in 4-6 junction IMM devices with a single-graded buffer. Furthermore, this tandem represents a highly efficient two-junction band gap combination, achieving 29.6% ± 1.2% efficiency under the AM1.5 global spectrum, demonstrating how the additional transparency enables new device structures.« less

  20. Highly Transparent Compositionally Graded Buffers for New Metamorphic Multijunction Solar Cell Designs

    SciTech Connect

    Schulte, Kevin L.; France, Ryan M.; Geisz, John F.

    2017-01-01

    The development of compositionally graded buffer layers (CGBs) with enhanced transparency would enable novel five and six junction solar cells, with efficiencies approaching 50% under high concentration. We demonstrate highly transparent grades between the GaAs and InP lattice constants on both A- and B-miscut GaAs substrates, employing AlxGayIn1-x-yAs and highly Se-doped Burstein-Moss (BM) shifted GaxIn 1-xP. Transparency to >810 and >890 nm wavelengths is demonstrated with BM-shifted GaxIn1-xP on B-miscut substrates and AlxGayIn1-x-yAs/GaxIn1-xP(Se) combined grades on A-miscut substrates, respectively. 0.74 eV GaInAs solar cells grown on these transparent CGBs exhibit Woc = 0.41 V at mA/ cm2, performance comparable with the state-of-the-art GaxIn1-xP grade employed in the four-junction-inverted metamorphic multijunction (IMM) cell. A GaAs/0.74cV GaInAs tandem cell was grown with a transparent BM-shifted GaxIn1-xP CGB to verify the CGB performance in a multijunction device structure. Quantum efficiency measurements indicate that the CGB is completely transparent to photons below the GaAs bandedge, validating its use in 4-6 junction IMM devices with a single-graded buffer. This tandem represents a highly efficient two-junction band gap combination, achieving 29.6% +/- 1.2% efficiency under the AM1.5 global spectrum, demonstrating how the additional transparency enables new device structures.

  1. Early hepatocellular carcinoma with high-grade atypia in small vaguely nodular lesions.

    PubMed

    Ojima, Hidenori; Masugi, Yohei; Tsujikawa, Hanako; Emoto, Katsura; Fujii-Nishimura, Yoko; Hatano, Mami; Kawaida, Miho; Itano, Osamu; Kitagawa, Yuko; Sakamoto, Michiie

    2016-04-01

    Multistep hepatocarcinogenesis progresses from dysplastic nodules to early hepatocellular carcinoma (eHCC) and to advanced HCC. The aim of the present study was to investigate the detailed histopathological features of eHCC. We investigated 66 small vaguely nodular lesions resected from 40 patients. The degree of cellular and structural atypia and stromal invasion were assessed. The immunohistochemical expression of HCC-related markers adenylate cyclase-associated protein 2 (CAP2), heat shock protein 70 (HSP70), Bmi-1, CD34 and h-caldesmon were evaluated. Of the 66 nodules, 10 were diagnosed as low-grade dysplastic nodules (LGDN), 10 as high-grade dysplastic nodules (HGDN) and 46 as eHCC. Among the 46 eHCC, 18 nodules (39.1%) showed marked stromal invasion and/or the presence of the scirrhous component and were subclassified as high-grade eHCC (HGeHCC). The remaining 28 eHCC, which lacked these features, were subclassified as low-grade eHCC (LGeHCC) and were examined further. HGeHCC showed high levels of cellular and structural atypia and large tumor size. The immunohistochemical expression of CAP2 and the area of sinusoidal vascularization showed increases from LGDN to HGeHCC. The density of arterial tumor vessels was high in HGeHCC compared with other nodule types. Cluster analysis of these parameters subclassified 65 nodules into HGeHCC-dominant, LGeHCC and HGDN-dominant, and LGDN-dominant groups. These results indicate the increased malignant potential of HGeHCC and suggest that it is already a transitional stage to advanced HCC. We consider that our grading classification system may be valuable for considering treatment strategies for eHCC around 2 cm in diameter.

  2. HER2 over-expressing high grade endometrial cancer expresses high levels of p95HER2 variant

    PubMed Central

    Growdon, Whitfield B.; Groeneweg, Jolijn; Byron, Virginia; DiGloria, Celeste; Borger, Darrell R.; Tambouret, Rosemary; Foster, Rosemary; Chenna, Ahmed; Sperinde, Jeff; Winslow, John; Rueda, Bo R.

    2015-01-01

    Background Subsets of high grade endometrial cancer (EnCa) over-express HER2 (ERBB2), yet clinical trials have failed to demonstrate any anti-tumor activity utilizing trastuzumab, an approved platform for HER2 positive breast cancer (BrCa). A truncated p95HER2 variant lacking the trastuzumab binding site may confer resistance. The objective of this investigation was to characterize the expression of the p95HER2 truncated variant in EnCa. Materials and Methods With institutional approval, 86 high grade EnCa tumors were identified with tumor specimens from surgeries performed between 2000-2011. Clinical data were collected and all specimens underwent tumor genotyping, HER2 immunohistochemistry (IHC, HercepTest®), HER2 fluorescent in situ hybridization (FISH), along with total HER2 (H2T) and p95HER2 assessment with VeraTag® testing. Regression models were used to compare a cohort of 86 breast tumors selected for equivalent HER2 protein expression. Results We identified 44 high grade endometrioid and 42 uterine serous carcinomas (USC). IHC identified high HER2 expression (2+ or 3+) in 59% of the tumors. HER2 gene amplification was observed in 16 tumors (12 USC, 4 endometrioid). Both HER2 gene amplification and protein expression correlated with H2T values. High p95HER2 expression above 2.8 RF/mm2 was observed in 53% (n = 54) with significant correlation with H2T levels. When matched to a cohort of 107 breast tumors based on HercepTest HER2 expression, high grade EnCa presented with higher p95 levels (p < 0.001). Conclusions: These data demonstrate that compared to BrCa, high grade EnCa expresses higher levels of p95HER2 possibly providing rationale for the trastuzumab resistance observed in EnCa. PMID:25602714

  3. A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas

    ClinicalTrials.gov

    2015-03-02

    Adult Anaplastic Astrocytoma; Recurrent Grade III Glioma; Recurrent Grade IV Glioma; Adult Anaplastic Oligodendroglioma; Adult Brain Tumor; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Adult Anaplastic Oligoastrocytoma; Recurrent High Grade Glioma

  4. [Tubeless superimposed high frequency jet ventilation in high grade laryngeal stenoses].

    PubMed

    Aloy, A; Kimla, T; Schragl, E; Donner, A; Grasl, M

    1994-08-01

    Massive stenosis of the larynx may present a potentially life-threatening situation for the patient, requiring immediate measures to ensure a patient's airway. The aim of this prospective study was to evaluate potential benefits of Superimposed High Frequency Jet Ventilation (SHFJV) in patients requiring microlaryngeal surgery due to massive stenosis of the larynx. 23 patients (age range 1.5 to 90 years) with laryngeal stenosis grade 2 and 3 according to the Cotton scale were ventilated using SHFJV. The duration of the SHFJV was 12 to 116 minutes. SHFJV was performed using a Bronchotron Respirator via a jet-laryngoscope. Arterial blood gases demonstrated paO2 between 71 and 295 mmHg and paCO2 of 28 to 81 mmHg. The mean FiO2 applied was 61.75 +/- 19.26. The airway pressure was measured at the tip of the jet-laryngoscope and was between 6 and 15 mmHg, and PEEP was 1 to 5 mmHg. In 13 patients a CO2 laser was utilised during surgery. In all patients SHFJV was performed without problems. Since the ventilation is delivered above any possible stenosis the danger of barotrauma is minimised. The surgeon obtains optimal visibility of the larynx and is not obstructed in the surgical procedure. SHFJV enables both the surgeon and the anesthetist to perform their respective duties and therefore increases the safety of the patient in the management of such a difficult problem as massive stenosis of the larynx.

  5. Radiofrequency ablation for early oesophageal squamous neoplasia: Outcomes form United Kingdom registry

    PubMed Central

    Haidry, Rehan J; Butt, Mohammed A; Dunn, Jason; Banks, Matthew; Gupta, Abhinav; Smart, Howard; Bhandari, Pradeep; Smith, Lesley Ann; Willert, Robert; Fullarton, Grant; John, Morris; Di Pietro, Massimo; Penman, Ian; Novelli, Marco; Lovat, Laurence B

    2013-01-01

    AIM: To report outcomes on patients undergoing radiofrequency ablation (RFA) for early oesophageal squamous neoplasia from a National Registry. METHODS: A Prospective cohort study from 8 tertiary referral centres in the United Kingdom. Patients with squamous high grade dysplasia (HGD) and early squamous cell carcinoma (ESCC) confined to the mucosa were treated. Visible lesions were removed by endoscopic mucosal resection (EMR) before RFA. Following initial RFA treatment, patients were followed up 3 monthly. Residual flat dysplasia was treated with RFA until complete reversal dysplasia (CR-D) was achieved or progression to invasive Squamous cell cancer defined as infiltration into the submucosa layer or beyond. The main outcome measures were CR-D at 12 mo from start of treatment, long term durability, progression to cancer and adverse events. RESULTS: Twenty patients with squamous HGD/ESCC completed treatment protocol. Five patients (25%) had EMR before starting RFA treatment. CR-D was 50% at 12 mo with a median of 1 RFA treatment, mean 1.5 (range 1-3). Two further patients achieved CR-D with repeat RFA after this time. Eighty per cent with CR-D remain dysplasia free at latest biopsy, with median follow up 24 mo (IQR 17-54). Six of 20 patients (30%) progressed to invasive cancer at 1 year. Four patients (20%) required endoscopic dilatations for symptomatic structuring after treatment. Two of these patients have required serial dilatations thereafter for symptomatic dysphagia with a median of 4 dilatations per patient. The other 2 patients required only a single dilatation to achieve an adequate symptomatic response. One patient developed cancer during follow up after end of treatment protocol. CONCLUSION: The role of RFA in these patients remains unclear. In our series 50% patients responded at 12 mo. These figures are lower than limited published data. PMID:24106401

  6. Advances in the management of cutaneous squamous cell carcinoma

    PubMed Central

    Parikh, Sonal A.

    2014-01-01

    Cutaneous squamous cell carcinoma is one of the most common non-melanoma skin cancers worldwide. While most cutaneous squamous cell carcinomas are easily managed, there is a high-risk subset of tumors that can cause severe morbidity and mortality. Tumor characteristics as well as patient characteristics contribute to the classification of cutaneous squamous cell carcinomas as low-risk vs. high-risk. Advances in the treatment of cutaneous squamous cell carcinomas largely relate to the management of this high-risk subset. Surgical and non-surgical management options, including newer targeted molecular therapies, will be discussed here. Larger, multicenter studies are needed to determine the exact significance of individual risk factors with respect to aggressive clinical behavior and the risks of metastasis and death, as well as the role of surgical and adjuvant therapies in patients with high-risk cutaneous squamous cell carcinomas. PMID:25165569

  7. High success rate with new modified endoscopic treatment for high-grade VUR: A pilot study with preliminary report.

    PubMed

    Asgari, S A; Asl, A S; Safarinejad, M R; Ghanaei, M M

    2016-04-01

    Despite the benefits of the minimally invasive endoscopic treatment for vesicoureteral reflux (VUR) it has a major drawback which is low success rate in high grade VUR. For overcoming this problem, we introduce a new modified technique of endoscopic treatment called periureteral injection technique (PIT). In a prospective study a total of 37 ureters in 19 boys and 14 girls were treated, including 3 bilateral cases. Of 37 units, 30 (81.1%) had grade IV and 7 (18.9%) had grade V primary VUR (18 right, 13 left and 3 bilateral units). Subureteral injection of Vantris(®) was done at the 5-o'clock and 7-o'clock positions in which the direction of injecting needles were almost parallel. Pre- and post-operative evaluation included urinalysis, urinary tract ultrasonography, voiding cystourethrography (VCUG), dimercaptosuccinic acid scan and urodynamic studies. The median age was 38 months (range 8-125). At 6 months follow up period confirmed with VCUG, the VUR has been disappeared in 34 (91.8%) units and 3 units [2 (5.4%) grade II and 1 (2.7%) had grade III)] had downgraded VUR. Complications included early fever due to urinary tract infection in 1 children, transient dysuria in 2 patients and low back pain in one patient (Summary Table). The success rate of PIT for treatment of high grade VUR is high. However, further studies with more patients and longer follow up periods are needed to draw final conclusion. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  8. 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

  9. High Anxiety: Addressing Family Issues in the Transition of Students with Disabilities from Middle Grades to High School

    ERIC Educational Resources Information Center

    Brigham, Nancy; Aguilar, Cynthia M.

    2011-01-01

    This article documents the development of a protocol that addresses the anxieties and tensions felt by the families of students with disabilities when they face the daunting transition from middle grades to high school. The tool grew out of a study of schools that form meaningful partnerships with diverse families of students with disabilities,…

  10. Facets and determinants of quality of life in patients with recurrent high grade glioma.

    PubMed

    Giovagnoli, A R; Silvani, A; Colombo, E; Boiardi, A

    2005-04-01

    To assess patients with recurrent high grade brain glioma with the aim of evaluating facets of quality of life (QOL) and their association with mood, cognition, and physical performance. Ninety four glioma patients (four groups with different duration of glioma recurrence) were compared with 24 patients with other chronic neurological diseases and 48 healthy subjects. The Functional Living Index-Cancer (FLIC) provided QOL self evaluations, and standardised scales and neuropsychological tests assessed physical performance, mood, and cognition. In glioma patients, factor analysis of the FLIC items documented five domains: Psychological well being, Role/sociability, Inner experience of disease, Isolation/sharing, and Nausea. Higher FLIC total scores were related to better cognition, physical performances, and mood, and lower grading; poorer Psychological well being and worse Inner experience of disease to depressed mood; minor Role/sociability to worse cognitive and physical performances and higher grading; worse Nausea to longer disease duration. Compared with healthy subjects, all glioma groups were cognitively impaired and more anxious, and two groups with short duration of recurrence were also more depressed. Patients with chronic neurological diseases showed worse mood and cognitive abilities compared with healthy subjects, but performed attention tests better than glioma patients. Glioma and chronic disease patients showed similar FLIC scores and autonomy. These results show that QOL of recurrent high grade glioma patients is multifaceted and determined by multiple factors. Disease severity does not necessarily eliminate the possibility of expressing personal feelings and opinions which could provide criteria for clinical decision making and psychological support.

  11. Low- and high-grade bladder cancer determination via human serum-based metabolomics approach.

    PubMed

    Bansal, Navneeta; Gupta, Ashish; Mitash, Nilay; Shakya, Prashant Singh; Mandhani, Anil; Mahdi, Abbas Ali; Sankhwar, Satya Narain; Mandal, Sudhir Kumar

    2013-12-06

    To address the shortcomings of urine cytology and cystoscopy for probing and grading urinary bladder cancer (BC), we applied (1)H nuclear magnetic resonance (NMR) spectroscopy as a surrogate method for the identification of BC. This study includes 99 serum samples comprising low-grade (LG; n = 36) and high-grade (HG; n = 31) BC as well as healthy controls (HC; n = 32). (1)H NMR-derived serum data were analyzed using orthogonal partial least-squares discriminant analysis (OPLS-DA). OPLS-DA-derived model validity was confirmed using an internal and external cross-validation. Internal validation was performed using the initial samples (n = 99) data set. External validation was performed on a new batch of suspected BC patients (n = 106) through a double-blind study. Receiver operating characteristic (ROC) curve analysis was also performed. OPLS-DA-derived serum metabolomics (six biomarkers, ROC; 0.99) were able to discriminate 95% of BC cases with 96% sensitivity and 94% specificity when compared to HC. Likewise (three biomarkers, ROC; 0.99), 98% of cases of LG were able to differentiate from HG with 97% sensitivity and 99% specificity. External validation reveals comparable results to the internal validation. (1)H NMR-based serum metabolic screening appears to be a promising and less invasive approach for probing and grading BC in contrast to the highly invasive and painful cystoscopic approach for BC detection.

  12. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia

    PubMed Central

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-01-01

    Abstract Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized. A case–control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted. After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24–2.81) and women (adjusted OR = 2.72, 95% CI = 1.44–5.16). The 2 highest BMI categories (27.5–29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5–29.9: adjusted OR = 1.78, 95% CI = 1.02–3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27–5.08) and women (BMI = 27.5–29.9: adjusted OR = 2.88, 95% CI = 1.27–6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36–5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25–3.14) and women (adjusted OR = 2.88, 95% CI = 1.43–5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25–2.69) in women. Increased BMI was associated with an increased risk

  13. Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China

    PubMed Central

    Chen, Xingdong; Winckler, Björn; Lu, Ming; Cheng, Hongwei; Yuan, Ziyu; Yang, Yajun; Jin, Li; Ye, Weimin

    2015-01-01

    Poor oral health has been linked with an increased risk of esophageal squamous cell carcinoma (ESCC). We investigated whether alteration of oral microbiota is associated with ESCC risk. Fasting saliva samples were collected from 87 incident and histopathologicallly diagnosed ESCC cases, 63 subjects with dysplasia and 85 healthy controls. All subjects were also interviewed with a questionnaire. V3–V4 region of 16S rRNA was amplified and sequenced by 454-pyrosequencing platform. Carriage of each genus was compared by means of multivariate-adjusted odds ratios derived from logistic regression model. Relative abundance was compared using Metastats method. Beta diversity was estimated using Unifrac and weighted Unifrac distances. Principal coordinate analysis (PCoA) was applied to ordinate dissimilarity matrices. Multinomial logistic regression was used to compare the coordinates between different groups. ESCC subjects had an overall decreased microbial diversity compared to control and dysplasia subjects (P<0.001). Decreased carriage of genera Lautropia, Bulleidia, Catonella, Corynebacterium, Moryella, Peptococcus and Cardiobacterium were found in ESCC subjects compared to non-ESCC subjects. Multinomial logistic regression analyses on PCoA coordinates also revealed that ESCC subjects had significantly different levels for several coordinates compared to non-ESCC subjects. In conclusion, we observed a correlation between altered salivary bacterial microbiota and ESCC risk. The results of our study on the saliva microbiome are of particular interest as it reflects the shift in microbial communities. Further studies are warranted to verify this finding, and if being verified, to explore the underlying mechanisms. PMID:26641451

  14. Evaluating Nuclear Membrane Irregularity for the Classification of Cervical Squamous Epithelial Cells

    PubMed Central

    Tang, Jing Rui; Mat Isa, Nor Ashidi; Ch’ng, Ewe Seng

    2016-01-01

    Pap test involves searching of morphological changes in cervical squamous epithelial cells by pathologists or cytotechnologists to identify potential cancerous cells in the cervix. Nuclear membrane irregularity is one of the morphological changes of malignancy. This paper proposes two novel techniques for the evaluation of nuclear membrane irregularity. The first technique, namely, penalty-driven smoothing analysis, introduces different penalty values for nuclear membrane contour with different degrees of irregularity. The second technique, which can be subdivided into mean- or median-type residual-based analysis, computes the number of points of nuclear membrane contour that deviates from the mean or median of the nuclear membrane contour. Performance of the proposed techniques was compared to three state-of-the-art techniques, namely, radial asymmetric, shape factor, and rim di