Al Barbarawi, Mohamed; Odat, Ziad; Alheis, Mwaffaq; Qudsieh, Suhair; Qudsieh, Tareq
Neoplastic cervical spine lesions are seen infrequently by the spinal surgeon. The surgical management of these tumors, particularly with associated neurovascular compromise, is challenging in terms of achieving proper resection and spinal stabilization and ensuring no subsequent recurrence or failure of fixation. In this report we highlight some of the problems encountered in the surgical management of tumors involving the cervical spine with techniques applied for gross total resection of the tumor without compromising the vertebral arteries. Ten patients with neoplastic cervical spine lesions were managed in our study. The common cardinal presentation was neck and arm pain with progressive cervical radiculo-myelopathy. All patients had plain X-rays, computer tomography scans, and magnetic resonance imaging of the cervical spine. Digital subtraction or magnetic resonance angiograms were performed on both vertebral arteries when the pathology was found to be in proximity to the vertebral artery. When a tumor blush with feeders was evident, endovascular embolization to minimize intraoperative bleeding was also considered. A single approach or a combined anterior cervical approach for corpectomy and cage-with-plate fixation and posterior decompression for resection of the rest of the tumor with spinal fixation was then accomplished as indicated. All cases made a good neurological recovery and had no neural or vascular complications. On the long-term follow-up of the survivors there was no local recurrence or surgical failure. Only three patients died: two from the primary malignancy and one from pulmonary embolism. This report documents a safe and reliable way to deal with neoplastic cervical spine lesions in proximity to vertebral arteries with preservation of both arteries. PMID:21577335
Arafa, Mohammad; Boniver, Jacques; Delvenne, Philippe
The aim of this study was to evaluate the usefulness of a panel of biomarkers in the characterization of human papillomavirus (HPV)-induced cervical lesions. Management of these lesions depends on their histologic confirmation. Misinterpretation especially for benign mimics results in a significant diagnostic disagreement. For these reasons, a continuous effort is still needed to discover surrogate markers, which could support the final diagnosis. Archival biopsies of normal ectocervical and endocervical tissues, squamous metaplasia, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma, adenocarcinoma in situ, and adenocarcinoma were retrieved to perform a tissue microarray (TMA). A panel of markers was tested on the TMA obtained slides by in situ hybridization (HPV DNA) and immunohistochemistry (p16, involucrin, Ki-67, and HPV L1 proteins). The sensitivity to detect high-risk HPV DNA increased with lesion's severity. In situ hybridization signals suggesting integrated viral physical status predominated in CIN II/III, squamous cell carcinoma, and glandular (pre) neoplastic lesions. The p16 and Ki-67 protein expression increased from CIN I to CIN III and to infiltrative lesions. Involucrin positivity was better appreciated in well-differentiated diagnostic entities (ectocervix, mature metaplasia, and CIN I). HPV L1 antibody detected the viral capsid protein in a low proportion of CIN I and II. In conclusion, using a panel of cervical biomarkers improves the final reporting of various HPV-induced epithelial lesions. Carefully constructed TMA with single spots of 1-mm diameter are powerful tools, which have a high reliability in representing full tissue sections.
el-All, Howayda S Abd; Refaat, Amany; Dandash, Khadiga
Data from Egyptian studies provide widely varying estimates on the prevalence of pre-malignant and malignant cervical abnormalities and human papilloma virus (HPVs) infection. To define the prevalence and risk factors of pre-invasive and invasive cervical cancer (cacx), a community based full-scale cross sectional, household survey including 5453 women aged between 35 and 60 years was conducted. The study period was between February 2000 and December 2002. Initially, conventional Papanicolaou (Pap) smears were evaluated using the Bethesda system (TBS), followed by colposcopic guided biopsy (CGB) for all epithelial abnormalities (EA). In a third step, HPV was tested on all EA by in-situ hybridization (ISH) using first the broad spectrum HPV probe recognizing HPVs 6, 11, 16, 18, 30, 31, 35, 45, 51 and 52 followed by subtyping with probes 6/11, 16/18 and 31/33. Lastly, unequivocal cases were immunostained for herpes simplex type-2 (HSV-2), cytomegalovirus (CMV), and human immunodeficiency virus (HIV). EA representing 7.8% (424/5453), were categorized into atypical squamous cell of undetermined significance (ASCUS) (34.4%), atypical glandular cell of undetermined significance (AGCUS) (15.3%), combined ASCUS and AGCUS (3.1%), low grade squamous intraepithelial lesions (SIL) (41.0%), high grade SIL (5.2%) and invasive lesions (1%). CGB of EA (n = 281) showed non neoplastic lesions (12.8%), atypical squamous metaplasia (ASM) (19.2%), cervical intraepithelial neoplasia I (CIN) (44.4%), CIN II (4.4%), CINIII (2.8%), endocervical lesions (5.2%), combined squamous and endocervical lesions (10.0%), invasive squamous cell carcinoma (SCC) (0.02%) and extranodal marginal zone B cell lymphoma (MZBCL) (0.02%). The overall predictive value of cytology was 87% while the predictive value for high grade lesions was 80%. On histological basis, HPVs were present in 94.3% of squamous lesions while it was difficult to be identified in endocervical ones. ISH revealed positivity for pan HPV
Prata, Thiago Theodoro Martins; Bonin, Camila Mareti; Ferreira, Alda Maria Teixeira; Padovani, Cacilda Tezelli Junqueira; Fernandes, Carlos Eurico dos Santos; Machado, Ana Paula; Tozetti, Inês Aparecida
A specific immune response to human papillomavirus (HPV) in the cervical microenvironment plays a key role in eradicating infection and eliminating mutated cells. However, high-risk HPVs modulate immune cells to create an immunosuppressive microenvironment, and induce these immune cells to produce interleukin 10 (IL-10). This production of IL-10, in conjunction with HPV infection, contributes to the appearance of cervical neoplastic lesions. We sought to characterize the IL-10-producing cellular phenotype, and investigate the influence of host and HPV factors upon the induction of an immunosuppressive microenvironment. Immunohistochemical analysis demonstrated an increase in IL-10 production by keratinocytes, macrophages and Langerhans cells in high-grade cervical lesions and cervical cancer. This increase was more pronounced in patients older than 30 years, and was also correlated with high viral load, and infection with a single HPV type, particularly high-risk HPVs. Our results indicate the existence of a highly immunosuppressive microenvironment composed of different IL-10-producing cellular phenotypes in cervical cancer samples, and samples classified as high-grade cervical lesions (cervical intraepithelial neoplasia stages II and III). The immunosuppressive microenvironment that developed for these different cellular phenotypes favours viral persistence and neoplastic progression. PMID:26059395
Prata, Thiago Theodoro Martins; Bonin, Camila Mareti; Ferreira, Alda Maria Teixeira; Padovani, Cacilda Tezelli Junqueira; Fernandes, Carlos Eurico dos Santos; Machado, Ana Paula; Tozetti, Inês Aparecida
A specific immune response to human papillomavirus (HPV) in the cervical microenvironment plays a key role in eradicating infection and eliminating mutated cells. However, high-risk HPVs modulate immune cells to create an immunosuppressive microenvironment, and induce these immune cells to produce interleukin 10 (IL-10). This production of IL-10, in conjunction with HPV infection, contributes to the appearance of cervical neoplastic lesions. We sought to characterize the IL-10-producing cellular phenotype, and investigate the influence of host and HPV factors upon the induction of an immunosuppressive microenvironment. Immunohistochemical analysis demonstrated an increase in IL-10 production by keratinocytes, macrophages and Langerhans cells in high-grade cervical lesions and cervical cancer. This increase was more pronounced in patients older than 30 years, and was also correlated with high viral load, and infection with a single HPV type, particularly high-risk HPVs. Our results indicate the existence of a highly immunosuppressive microenvironment composed of different IL-10-producing cellular phenotypes in cervical cancer samples, and samples classified as high-grade cervical lesions (cervical intraepithelial neoplasia stages II and III). The immunosuppressive microenvironment that developed for these different cellular phenotypes favours viral persistence and neoplastic progression. © 2015 John Wiley & Sons Ltd.
Galamb, Ádám; Benczik, Márta; Zinner, Balázs; Vígh, Eszter; Baghy, Kornélia; Jeney, Csaba; Kiss, András; Lendvai, Gábor; Sobel, Gábor
Data discussed in recent reviews demonstrated that dysregulation of microRNA (miRNA) expression profiles occurs during cervical carcinogenesis and characteristic up- or downregulation of certain miRNAs might be used as biomarkers. The majority of altered miRNAs, however were found to be inconsistent upon comparison with cancerous and normal cervical epithelia in the discussed studies due to several reasons. The results obtained in this present review suggest the need for further investigations on miRNAs on larger sample sizes in order to indicate sensitivity and specificity by means of well defined, "unified" methods. In addition, obtaining further data on the clinical course and outcome of patients in comparison to the dysregulation of miRNA expression profile could turn miRNAs into prognostic and/or progression markers. Inhibition of overexpressed miRNAs, as suggested by some authors, might even serve as target for cancer therapy.
Background Tuberculous spondylitis is one of the commonest forms of skeletal tuberculosis in developing countries like India causing significant morbidity due to compression of spinal cord and adjacent nerve roots. Diagnosis and intervention at early stage can prevent permanent damage such as spinal deformity and neurological deficits. Aim The purpose of this study was to demonstrate atypical MRI features in cases of tubercular spondylitis resembling neoplastic lesions and to stress that tuberculous spondylitis should be one of the differential diagnoses in any spinal pathology especially in developing countries. Materials and Methods This was a prospective study done in the patients diagnosed as tuberculous spondylitis on 0.2 T Siemens MRI between June 2011 and December 2014 in a tertiary care hospital in India. Total 529 cases of tubercular spinal lesions were diagnosed. Out of which only 59 patients showed atypical features on MR imaging which resembled neoplastic lesions were included in the study. The diagnosis was confirmed by cytology, histopathology, serology and corroborative findings. Results Lumbo-sacral region involvement (30.5%) is the commonest in our study followed by dorsal and cervical region. Multiple level lesions are seen in 14 cases (23.7%). All the 59 (100%) cases show no involvement of intervetebral disc. Posterior appendage involvement seen in 32 cases (54.2%). Soft tissue component seen in Intraspinal (37.2%) and paraspinal (45.7%) compartments. Cord compression seen in 19 cases (32.2%), out which only 7 cases (11.8%) shows cord oedema. Conclusion On MRI, tubercular spondylitis may have variable pictures on imaging. For any spinal and paraspinal lesions, we should also consider the possibility of tubercular aetiology along with other. Since early diagnosis avoids unnecessary delay in the treatment thereby reducing morbidity and possible complications. PMID:26675162
Lu, Xiaojie; Ji, Li-Juan; Chen, Jin-Lian
Most cancers develop upon the accumulation of genetic alterations that provoke and sustain the transformed phenotype. Several metabolomic approaches now allow for the global assessment of intermediate metabolites, generating profound insights into the metabolic rewiring associated with malignant transformation. The metabolomic profiling of neoplastic lesions growing in mice, irrespective of their origin, can provide invaluable information on the mechanisms underlying oncogenesis, tumor progression, and response to therapy. Moreover, the metabolomic profiling of tumors growing in mice may result in the identification of novel diagnostic or prognostic biomarkers, which is of great clinical significance. Several methods can be applied to the metabolomic profiling of neoplastic lesions in mice, including mass spectrometry-based techniques (e.g., gas chromatography-, capillary electrophoresis-, or liquid chromatography-coupled mass spectrometry) as well as nuclear magnetic resonance. Here, we compare and discuss the advantages and disadvantages of all these techniques to provide a concise and reliable guide for readers interested in this active area of investigation. © 2014 Elsevier Inc. All rights reserved.
Butler, D; Collins, C; Mabruk, M; Barry Walsh, C; Leader, M B; Kay, E W
The fragile histidine triad (FHIT) gene encompasses the common chromosomal fragile site FRA3B. Human papilloma virus (HPV), which is the main aetiological agent in cervical cancers, has been found to be able to integrate its genes into the chromosome 3 fragile site of cultured cells, deleting a piece of DNA which includes the FHIT gene. Eighty-six microdissected archival cervical LLETZ biopsies comprising cases of cervical intraepithelial neoplasia (CIN) 1 (n=27), CIN3 (n=30) and microinvasive carcinoma (n=29) were evaluated for HPV infection and FHIT gene loss of heterozygosity (LOH). FHIT gene LOH was detected by polymerase chain reaction (PCR) using fluorescently labelled intragenic microsatellite markers D3S1300 and D3S4103. PCR products were analysed on a semi-automated DNA sequencer using Fragment Manager(trade mark) software to determine allele loss. The HPV status of the lesions was determined by PCR using generic and type-specific primers in conjunction with restriction endonuclease digestion. The results were analysed using Epi-Info and SPSS-PC statistical analysis software. Haematoxylin and eosin-stained sections from the 86 cases were profiled for six histopathological features, some of which have been previously shown to be associated with microinvasive cancer. FHIT gene LOH was found in 36% of CIN1 cases, 52% of CIN3 cases and 73% of microinvasive cases (p=0.029). HPV 16 DNA was found in 68% of CIN3 cases and 93% of microinvasive cases (p<0.001). The second most prevalent HPV type found was HPV 31, which was present in only four lesions, three of which had FHIT gene LOH. When FHIT gene LOH was evaluated versus HPV 16 and 31 infection using the chi-square test, a statistically significant relationship was found (p=0.014). FHIT gene LOH was found to be independent of the histopathological features evaluated. The finding of a statistically significant relationship between FHIT gene LOH and oncogenic HPV infection suggests a link between the integration
the articulation between C1 and the os odontoideum on flexion imaging. The remainder of his cervical vertebral bodies had normal alignment with no...appears normal. Figure 3. Flexion view of plain cervical spine. This image shows abnormal translation of the articulation between C1 and the C2 os...worldwide. Peer Reviewed Title: Os Odontoideum: Rare Cervical Lesion Journal Issue: Western Journal of Emergency Medicine, 12(4) Author: Robson
Rajamani, Revathishree; Noorunnisa, Naseen; Durairaj, Manimaran
Introduction Thyroperoxidase (TPO) is a protein involved in thyroid hormone synthesis. TPO gene suppression and mutation were involved in thyroid tumours. CK-19 plays important role in the structural integrity of epithelial cells. Reduced TPO expression with increased CK-19 immunoreactivity has been implicated as a marker for differentiating non neoplastic and neoplastic thyroid lesions. Aim To study the histopathological features of thyroid lesions and to evaluate the diagnostic role of thyroperoxidase and CK-19 in non-neoplastic and neoplastic thyroid lesions. Materials and Methods Prospective observational study of 65 thyroid specimens was studied for detailed histopathological examination and Expression of Immunohistochemical Markers Cytokeratin-19 (CK-19) and Thyroperoxidase. Results TPO IHC marker was expressed by non-neoplastic and benign lesions of thyroid but not in malignancy. CK-19 was expressed 100% in papillary carcinoma of thyroid and its variants, focal and weak staining noted in goitre and hyperplastic areas. Conclusion Most of the non-neoplastic and neoplastic lesions were diagnosed based on histopathological features. When the histopathological diagnosis are equivocal, immunohistochemical markers aids in diagnosing malignancy. Diffuse and strong TPO expression indicates non-neoplastic thyroid lesions whereas diffused and strong CK-19 expression indicates thyroid malignancy. PMID:27504290
Shetty, Sumanth M; Shetty, Rashmi G; Mattigatti, Sudha; Managoli, Noopur A; Rairam, Surabhi G; Patil, Ashwini M
Abfraction or Theory of Abfraction is a theory explaining the non-carious cervical lesions (NCCL). It suggests that they are caused by flexural forces, usually from cyclic loading; the enamel, especially at the cementoenamel junction (CEJ), undergoes this pattern of destruction by separating the enamel rods. Clinical aspect importance of these ineart lesions are at most important to be detected for early intervention and treatment modalities as options during the progression of the disease. How to cite this article: Shetty SM, Shetty RG, Mattigatti S, Managoli NA, Rairam SG, Patil AM. No Carious Cervical Lesions: Abfraction. J Int Oral Health 2013; 5(5):142-5. PMID:24324319
Shetty, Sumanth M; Shetty, Rashmi G; Mattigatti, Sudha; Managoli, Noopur A; Rairam, Surabhi G; Patil, Ashwini M
Abfraction or Theory of Abfraction is a theory explaining the non-carious cervical lesions (NCCL). It suggests that they are caused by flexural forces, usually from cyclic loading; the enamel, especially at the cementoenamel junction (CEJ), undergoes this pattern of destruction by separating the enamel rods. Clinical aspect importance of these ineart lesions are at most important to be detected for early intervention and treatment modalities as options during the progression of the disease. How to cite this article: Shetty SM, Shetty RG, Mattigatti S, Managoli NA, Rairam SG, Patil AM. No Carious Cervical Lesions: Abfraction. J Int Oral Health 2013; 5(5):142-5.
Valdivia, Alejandra; Peralta, Raúl; Matute-González, Manuel; García Cebada, Juan Manuel; Casasola, Ivonne; Jiménez-Medrano, Cristina; Aguado-Pérez, Rogelio; Villegas, Vanessa; González-Bonilla, Cesar; Manuel-Apolinar, Leticia; Ibáñez, Miguel; Salcedo, Mauricio
The metalloproteinases (MMP) 11 and 12 have been shown to be expressed in cervical cancer (CC). In order to extend our previous results, these MMPs were evaluated in cervical precursor lesions. One hundred seventeen cervical scrapes: thirty-six normal, thirty-six Low grade squamous lesions (LSIL), thirty-six High grade (HSIL), nine CC; and, also ninety-nine paraffin-embedded cervical lesions: fifteen normal cervices, thirty eight LSIL, sixteen HSIL, and five CC were collected. The samples were analyzed for relative expression by real time RT-PCR or immunohistochemistry assay. We were able to identify a relative increased expression of MMP11 in 75% and 78% from LSIL and HSIL samples, respectively. While MMP12 expression was 64% and 75% in LSIL and HSIL, respectively. Positive samples for MMP11 expression were also positive for MMP12 expression and also increased according to illness progression. In the tissues, MMP11 or MMP12 expression was observed in the cytoplasm of the neoplastic cells, while in the normal epithelium was absent. The reaction was always stronger for MMP12 than MMP11. MMP11 expression was present in 77% and 66% of LSIL and HSIL, while MMP12 expression was 73% and 68%. There was a relationship between MMP11 or MMP12 expression and HPV infection. Our data are showing a relationship between diagnostic of precursor lesions and the MMP11 and 12 expressions, suggesting that their expression could be an early event in the neoplastic lesions of the cervix and could have clinical significance. PMID:22076168
Villanacci, V; Grigolato, P G; Bonardi, M; Gattamelata, M; Moreschetti, R; Ghirardi, M; Di Fabio, F; Nascimbeni, R; Salerni, B
The authors describe the personal experience on colonic lavage cytology in neoplastic or inflammatory diseases. Although the presence of false negative results in the lesions of right colon, the method could be useful in the diagnosis of selected cases.
Jaramillo, E; Watanabe, M; Slezak, P; Rubio, C
Because small flat colorectal neoplastic lesions (i.e., flat adenomas and flat adenocarcinomas) may be as translucent as the surrounding mucosa, they can remain undetected at conventional endoscopy. By combining high-resolution video endoscopy and chromoscopy, we detected 109 colorectal flat neoplastic lesions in 55 of 232 patients studied. Forty-three (78%) of the 55 patients with flat neoplastic lesions were over 60 years of age. No flat neoplastic lesions were seen in patients under 40 years of age. Flat neoplastic lesions were more frequent in men (35%) than in women (15%). Seventy-seven (71%) of the 109 flat neoplastic lesions measured 0.5 cm or less, 23 (21%) between 0.6 and 1.0 cm, and 9 (8%) more than 1.0 cm. Low-grade dysplasia and high-grade dysplasia were found in 94 (86%) and 13 (12%) of the flat neoplastic lesions, respectively. Adenocarcinoma was diagnosed in 3 (3%) flat lesions: 1 (1%) carcinoma originating in a flat adenoma and 2 (2%) adenocarcinomas without recognizable adenomatous elements. No adenocarcinomas were seen in lesions measuring 1.0 cm or less. Fourteen flat neoplastic lesions had a central depression at endoscopy. Flat neoplastic lesions with central depression more frequently showed high-grade dysplasia (43%) than did flat neoplastic lesions without central depression (7%). Central depression in flat neoplastic lesions should be considered a possible endoscopic marker for severe dysplasia. Our results suggest that flat neoplastic lesions occur more frequently than previously reported in Scandinavia. Flat adenomas may play an important role in the histogenesis of colorectal cancer.
van der Sommen, Fons; Zinger, Svitlana; Curvers, Wouter L; Bisschops, Raf; Pech, Oliver; Weusten, Bas L A M; Bergman, Jacques J G H M; de With, Peter H N; Schoon, Erik J
Early neoplasia in Barrett's esophagus is difficult to detect and often overlooked during Barrett's surveillance. An automatic detection system could be beneficial, by assisting endoscopists with detection of early neoplastic lesions. The aim of this study was to assess the feasibility of a computer system to detect early neoplasia in Barrett's esophagus. Based on 100 images from 44 patients with Barrett's esophagus, a computer algorithm, which employed specific texture, color filters, and machine learning, was developed for the detection of early neoplastic lesions in Barrett's esophagus. The evaluation by one endoscopist, who extensively imaged and endoscopically removed all early neoplastic lesions and was not blinded to the histological outcome, was considered the gold standard. For external validation, four international experts in Barrett's neoplasia, who were blinded to the pathology results, reviewed all images. The system identified early neoplastic lesions on a per-image analysis with a sensitivity and specificity of 0.83. At the patient level, the system achieved a sensitivity and specificity of 0.86 and 0.87, respectively. A trade-off between the two performance metrics could be made by varying the percentage of training samples that showed neoplastic tissue. The automated computer algorithm developed in this study was able to identify early neoplastic lesions with reasonable accuracy, suggesting that automated detection of early neoplasia in Barrett's esophagus is feasible. Further research is required to improve the accuracy of the system and prepare it for real-time operation, before it can be applied in clinical practice. © Georg Thieme Verlag KG Stuttgart · New York.
Macovei, Luana-Andreea; Rezuş, Elena
to gather clinical and laboratory data on rheumatoid arthritis patients with cervical spine damage (incidence and prevalence, correlation between duration of disease and the time of lesion onset, to assess signs and symptoms and the role of laboratory investigations). The spine is an axial organ with an important role in support and resistance. It is a pillar with a very complex morphological and functional structure. The vertebral column is crossed by many kinematic chains. The main problem of the cervical spine caused by rheumatoid arthritis is cervical instability which describes all cervical lesions that can lead to neurovascular damage or major disturbance of pain generating statics at movement. The evolving disease shows chronic inflammation of the synovium, which is a self-maintained process and an immunologically induced phenomenon. The chronic inflammation of the synovium forms granulation tissue that invades peripheral joints towards the center and causes ligament cartilage and bone damage. The present paper investigated cervical spine lesions in 107 rheumatoid arthritis patients who were admitted to the 1st Rheumatology Clinic of Iasi Rehabilitation Hospital between January 2013 and December 2014. Our study focused on assessing signs and symptoms seen in spine affected by rheumatic disease. the disease causes destructive lesions due to granulomatous infiltration of rachidian structures and medullary sheaths. These lesions lead to damaged discs and instability that produces subluxations and dislocations. The suboccipital region is most affected; in other regions of the spine, high lesions of C4-C5 prevail, where osteolysis damage of spinal apophyses are found. In atlas and axis joints, rheumatoid arthritis causes the inflammation of bursa, synovium and joint capsule and leads to synovial pannus formation. This causes the destruction of cartilage and subchondral bone. Atlantoaxial dislocation is caused by erosive synovitis of atlanto-epistrophic joint
Cervical cancer (CC) is one of the most malignant tumors and the second or third most common type of cancer in women worldwide. The association between human papillomavirus (HPV) and CC is widely known and accepted (99.7% of cases). At present, the pathogenesis mechanisms of CC are not entirely clear. It has been shown that inactivation of tumor suppressor genes and activation of oncogenes play a significant role in carcinogenesis, caused by the genetic and epigenetic alterations. In the past, it was generally thought that genetic mutation was a key event of tumor pathogenesis, especially somatic mutation of tumor suppressor genes. With deeper understanding of tumors in recent years, increasing evidence has shown that epigenetic silencing of those genes, as a result of aberrant hypermethylation of CpG islands in promoters and histone modification, is essential to carcinogenesis and metastasis. The term epigenetics refers to heritable changes in gene expression caused by regulation mechanisms, other than changes in DNA sequence. Specific epigenetic processes include DNA methylation, chromotin remodeling, histone modification, and microRNA regulations. These alterations, in combination or individually, make it possible to establish the methylation profiles, histone modification maps, and expression profiles characteristic of this pathology, which become useful tools for screening, early detection, or prognostic markers in cervical cancer. This paper reviews recent epigenetics research progress in the CC study, and tries to depict the relationships between CC and DNA methylation, histone modification, as well as microRNA regulations. PMID:22938091
Bedoya, Astrid M; Jaramillo, Roberto; Baena, Armando; Castaño, Jorge; Olaya, Natalia; Zea, Arnold H; Herrero, Rolando; Sanchez, Gloria I
Only a small proportion of women infected with Human Papillomavirus (HPV) develop cervical cancer. Host immune response seems to play a role eliminating the viral infection and preventing progression to cancer. Characterization of tumor infiltrating lymphocytes (TILs) in cervical pre-neoplastic lesions and cervical cancer may be helpful to understand the mechanisms that mediate this protection. The aim of this study was to determine if there are differences in the localization and density (cells/mm(2)) of CD8+ T-cells, CD4+ T-cells and Tregs (CD25 + Foxp3+) in cervical pre-neoplastic lesions and cervical cancer. Immunohistochemical analysis of sections of 96 (26 CIN1, 21 CIN2, 25 CIN3, and 24 SCC) samples revealed that regardless of CIN grades, CD8+ T-cells are more abundant than CD4+, CD25+ and Foxp3+ cells in both the stroma and epithelium. There was a higher density of CD8+ cells in the stroma of cervical cancer compared to CIN3 (OR = 4.20, 95% CI 1.2-15), CIN2 (OR = 7.86, 95% CI 1.7-36.4) and CIN1 (OR = 4.25, 95% CI 1.1-17). Studies evaluating whether these cells are recruited before or after cancer progression will be helpful to understand the role of these cells in the natural history of HPV-induced lesions.
Robson, Kristie A
We report the case of a 22-year-old Marine who presented to the emergency department, after a martial arts exercise, with transient weakness and numbness in all extremities. Computed tomography cervical spine radiographs revealed os odontoideum. Lateral flexion–extension radiographs identified atlanto-axillary instability. This abnormality is rare and can be career ending for military members who do not undergo surgical fusion. PMID:22224150
Cha, Byung Hyo; Hwang, Jin-Hyeok; Lee, Sang Hyub; Kim, Jang Eon; Cho, Jai Young; Kim, Haeryoung; Kim, So Yeon
AIM: To investigate the preoperative factors that can predict neoplastic polypoid lesions of the gallbladder (PLGs) as well as malignant PLGs. METHODS: A retrospective analysis was conducted on the 210 consecutively enrolled patients who underwent cholecystectomy due to a PLG larger than 10 mm, as was determined by preoperative trans-abdominal ultrasonography or endoscopic ultrasonography. We analyzed the medical, laboratory, radiologic data and the pathologic results. RESULTS: In 210 cases, 146 had non-neoplastic polyps (69.5%) and 64 cases were neoplastic polyps (30.5%). An older age (≥ 65 years), the presence of diabetes mellitus (DM) and the size of polyp (≥ 15 mm) were revealed to be independent predictive variables for neoplastic polyps with odd ratios (OR) of 2.27 (P = 0.044), 2.64 (P = 0.021) and 4.94 (P < 0.01), respectively. Among the neoplastic PLGs, an older age (≥ 65 years), the presence of DM and polyp size (≥ 15 mm) were associated with malignancy with ORs of 4.97 (P = 0.005), 6.13 (P = 0.001) and 20.55 (P < 0.001), respectively. CONCLUSION: Among patients with PLGs larger than 10 mm in size, higher risk groups such as elderly patients more than 65 years old, those with DM or a large polyp size (≥ 15 mm) should be managed by cholecystectomy. PMID:21633532
Hassan, Wael Abdo; Udaka, Naoka; Ueda, Akihiko; Ando, Yukio; Ito, Takaaki
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is one of the most common heritable causes of stroke and dementia in adults. The gene involved in the pathogenesis of CADASIL is Notch3; in which mutations affect the number of cysteine residues in its extracellular domain, causing its accumulation in small arteries and arterioles of the affected individuals. Besides the usual neurological and vascular findings that have been well-documented in CADASIL patients, this paper additionally reports multiple neoplastic lesions that were observed in an autopsy case of CADASIL patient; that could be related to Notch3 mutation. The patient was a 62 years old male, presented with a past history of neurological manifestations, including gait disturbance and frequent convulsive attacks. He was diagnosed as CADASIL syndrome with Notch3 Arg133Cys mutation. He eventually developed hemiplegia and died of systemic convulsions. Autopsy examination revealed-besides the vascular and neurological lesions characteristic of CADASIL- multiple neoplastic lesions in the body; carcinoid tumorlet and diffuse idiopathic pulmonary neuro-endocrine cell hyperplasia (DIPNECH) in the lungs, renal cell carcinoma (RCC), prostatic adenocarcinoma (ADC) and adenomatoid tumor of the epididymis. This report describes a spectrum of neoplastic lesions that were found in a case of CADASIL patient that could be related to Notch3 gene mutations.
Szymanska, H; Lechowska-Piskorowska, J; Krysiak, E; Strzalkowska, A; Unrug-Bielawska, K; Grygalewicz, B; Skurzak, H M; Pienkowska-Grela, B; Gajewska, M
The evaluation of spontaneous lesions in classical inbred strains of mice has become increasingly important because genetically engineered mice (GEMs) are created on these backgrounds. Novel inbred strains-genetically diverse from classic strains-are valuable both as a new background for GEM mice and to increase the genetic variation found in laboratory mice. Newly arising spontaneous genetic alterations in commonly used strains may also lead to new and valuable mouse models of disease. This report evaluates gross and histological lesions in relatively new, classic, and rarely explored mouse inbred strains. Pathological lesions of 1273 mice from 12 inbred strains (129S1/SvW, A.CA-H2(f) /W, AKR/W, BALB/cW, BN/aW, C57BL/6 W, C57BL/10 W, C3H/W, C3H (wad) /W, CBA/W, DBA/2 W, and WOM/W) are reported. BN/aW, WOM/W, and C3H (wad) /W are novel inbred strains produced and maintained in the Department of Genetics and Laboratory Animal Breeding at the Center of Oncology, Warsaw, Poland. Both neoplastic and nonneoplastic lesions were examined. The prevalence of lung neoplasms was significantly higher in A.CA-H2(f) /W (33.3%) and BALB/cW (33.8%) mice (P < .01). The prevalence of liver neoplasms was significantly higher in the CBA/W strain (P < .01). Mammary gland neoplasms arose at a greater frequency in C3H/W mice (P < .01). The occurrence of uterine neoplasms was higher in DBA/W and 129S1/SvW mice. AKR/W and WOM/W mice developed T-cell lymphoblastic lymphoma with high frequency (110/121 [90.9%] and 159/175 [90.9%], respectively) before 1 year of age. The occurrence of nonneoplastic lesions in the kidneys of BN/aW mice was increased (P < .01).
Cloward, R B
An opera singer, who "made her living with her diaphragm", developed a post-traumatic unilateral radiculopathy due to cervical disc lesions, C3 to C6. During one year of severe neck and left arm pain she gradually lost the ability to sing difficult operatic passages which brought an end to her music career. Following a three level anterior cervical decompression and fusion, the neck and arm pain was immediately relieved. One week later her voice and singing ability returned to its full strength and power permitting her to resume her activities as a vocalist. The diagnosis of paresis of the left hemi-diaphragm as part of the cervical disc syndrome was implied by postoperative retrospective inference.
Volgareva, Galina; Zavalishina, Larisa; Andreeva, Yulia; Frank, Georgy; Krutikova, Ella; Golovina, Darya; Bliev, Alexander; Spitkovsky, Dimitry; Ermilova, Valeriya; Kisseljov, Fjodor
Background Cervical carcinomas are second most frequent type of women cancer. Success in diagnostics of this disease is due to the use of Pap-test (cytological smear analysis). However Pap-test gives significant portion of both false-positive and false-negative conclusions. Amendments of the diagnostic procedure are desirable. Aetiological role of papillomaviruses in cervical cancer is established while the role of cellular gene alterations in the course of tumor progression is less clear. Several research groups including us have recently named the protein p16INK4a as a possible diagnostic marker of cervical cancer. To evaluate whether the specificity of p16INK4a expression in dysplastic and neoplastic cervical epithelium is sufficient for such application we undertook a broader immunochistochemical registration of this protein with a highly p16INK4a-specific monoclonal antibody. Methods Paraffin-embedded samples of diagnostic biopsies and surgical materials were used. Control group included vaginal smears of healthy women and biopsy samples from patients with cervical ectopia. We examined 197 samples in total. Monoclonal antibody E6H4 (MTM Laboratories, Germany) was used. Results In control samples we did not find any p16INK4a-positive cells. Overexpression of p16INK4a was detected in samples of cervical dysplasia (CINs) and carcinomas. The portion of p16INK4a-positive samples increased in the row: CIN I – CIN II – CIN III – invasive carcinoma. For all stages the samples were found to be heterogeneous with respect to p16INK4a-expression. Every third of CINs III and one invasive squamous cell carcinoma (out of 21 analyzed) were negative. Conclusions Overexpression of the protein p16INK4a is typical for dysplastic and neoplastic epithelium of cervix uteri. However p16INK4a-negative CINs and carcinomas do exist. All stages of CINs and carcinomas analyzed are heterogeneous with respect to p16INK4a expression. So p16INK4a-negativity is not a sufficient reason to
Litonjua, L A; Bush, P J; Andreana, S; Tobias, T S; Cohen, R E
Toothbrush abrasion has been considered to cause cervical lesions. However, some investigators have proposed that occlusal loading factors direct tensile stresses at the cervical area, resulting in wedge-shaped abfraction defects. The purpose of this study is to investigate the role of axial and non-axial load on the development of cervical lesions. Matched paired premolars, extracted for orthodontic purposes, were used in a custom-fabricated toothbrushing apparatus. A periodontal sulcus width of 0b1 mm with 1 mm gingival recession was simulated with denture base resin. In phase 1, eight matched premolar pairs were subjected to 80 h (1b4 million strokes) of brushing and 300 g of toothbrush force. Toothpaste slurry was applied continuously through the toothbrush. One specimen in each pair was subjected to 250 h and 45 kg of continuous axial load, while the other unloaded tooth served as a negative control. In phase 2, 10 matched premolar pairs were subjected to the same conditions; however, the experimental teeth were subjected to 250 h and 45 kg of intermittent non-axial load, directed at a 45 degrees angle to the buccal cusp. Rubber impressions were made of the cervical lesions, then trimmed, weighed, and compared to determine the amount of tooth material lost. When teeth were loaded axially, there was significantly less tooth material loss (P < 0b02); however, when teeth were loaded non-axially, there was no significant difference (P =0b80) when compared with controls. Optical and scanning electron microscopy did not reveal any significant differences in the morphology between pairs. Our data suggest that the application of occlusal load may not necessarily play a significant role in the progression of cervical tooth wear commonly referred to as abfraction.
Szajda, Sławomir Dariusz; Jóźwik, Maciej; Jóźwik, Marcin; Zalewska, Beata; Panek, Grzegorz; Sulkowski, Stanisław; Skrzydlewski, Zdzisław
Cancer procoagulant (CP) is a sulfhydryl proteinase thought to be synthesized mainly by neoplastic cells. Consequently, increased CP activity in blood serum was interpreted as being associated with the presence of a proliferative process in the host's body. To date, CP activity has not been systematically studied in cases of genital carcinoma. The present study is aimed at evaluation of CP activity in women with genital carcinoma. A case-controlled study backed up by histopathological examination. Peripheral blood was sampled preoperatively in a sterile manner from an antecubital vein, from 16 women with cervical carcinoma and 15 women with uterine carcinoma. Blood for the reference group of 12 healthy women was obtained in an identical manner after an overnight fast. The CP activity in serum was determined using the coagulative method according to Gordon and Benson, and was expressed as coagulation time in seconds (s). The CP activity in 10% tissue homogenates (in saline) of genital cancer was determined by the chromogenic method according to Colucci et al. The mean CP activity in serum of women with cervical carcinoma (78.28 +/- 15.25 s) and of women with uterine carcinoma (79.63 +/- 12.02 s) was significantly different (P < 0.0001) from the respective values found in healthy women (281.33 +/- 43.19 s). The CP activity in neoplastic tissue was 28.50 +/- 6.40 nmol pNa/mL for cervical carcinoma, and 28.31 +/- 3.92 nmol pNa/mL for uterine carcinoma, both values being significantly higher (P < 0.0009) than the activity found in the normal tissues. There was no established relationship between neoplastic CP activity and FIGO staging of the disease. This is the first study to demonstrate the concomitant presence of CP activity in serum and neoplastic tissue of women with genital carcinoma. These patients have decreased coagulation time and thus are likely to develop coagulation disturbances in the course of their cancer. There may be a role for CP as a tumor marker of
Ceruti, P; Menicucci, G; Mariani, G D; Pittoni, D; Gassino, G
Non-carious cervical lesions (NCCL) are characterized by a loss of hard dental tissue near the cement-enamel-junction. Commonly, their shape is like a wedge with the apex pointing inwards. Other times, they appear as regular depressions, like a dome or a cup. Their main characteristic is the presence of hard-mineralized tissue. According to the literature, the prevalence of cervical lesions is 85%, while their incidence is about 18% among permanent teeth. NCCL are currently classified as erosion, abrasion, or abfraction. Their etiology seems to be related to different factors: hexogen and endogen acids, mechanical abrasive action, tooth flexion under axial and non-axial loads. Moreover, it seems that a fundamental role is ascribable to tooth bending phenomena due to the strength components parallel or oblique to the occlusal level, which occur during the normal function as well as during parafunctions. The frequent therapeutic failures are probably due to the same factors causing the onset of the original lesion. Several materials have been proposed to restore NCCL: amalgam (abandoned), glass-ionomer cements, compomers, and composite resins. Early failures of these restorations have often been reported in the literature, probably due to the same factors which originally caused the lesions. Further investigations are required to determine more reliable restorative therapies.
Deeba, Farah; Mohammed, Shahed K; Bui, Francis Minhthang; Wahid, Khan A
The detection of non-polypoid superficial neoplastic lesions using current standard of white light endoscopy surveillance and random biopsy is associated with high miss rate. The subtle changes in mucosa caused by the flat and depressed neoplasms often go undetected and do not qualify for further investigation, e.g., biopsy and resection, thus increasing the risk of cancer advancement. This paper presents a screening tool named the saliency-aided visual enhancement (SAVE) method, with an objective of highlighting abnormalities in endoscopic images to detect early lesions. SAVE is a hybrid system combining image enhancement and saliency detection. The method provides both qualitative enhancement and quantitative suspicion index for endoscopic image regions. A study to evaluate the efficacy of SAVE to localize superficial neoplastic lesion was performed. Experimental results for average overlap index >0.7 indicated that SAVE was successful to localize the lesion areas. The area under the receiver-operating characteristic curve obtained for SAVE was 94.91%. A very high sensitivity (100%) was achieved with a moderate specificity (65.45%). Visual inspection showed a comparable performance of SAVE with chromoendoscopy to highlight mucosal irregularities. This paper suggests that SAVE could be a potential screening tool that can substitute the application of burdensome chromoendoscopy technique. SAVE method, as a simple, easy-to-use, highly sensitive, and consistent red flag technology, will be useful for early detection of neoplasm in clinical applications.
Goulart, Viviane P.; dos Santos, Moisés O.; Latrive, Anne; Freitas, Anderson Z.; Correa, Luciana; Zezell, Denise M.
Photodynamic therapy (PDT) has become a promising alternative for treatment of skin lesions such as squamous cell carcinoma. We propose a method to monitor the effects of PDT in a noninvasive way by using the optical attenuation coefficient (OAC) calculated from optical coherence tomography (OCT) images. We conducted a study on mice with chemically induced neoplastic lesions and performed PDT on these lesions using homemade photosensitizers. The response of neoplastic lesions to therapy was monitored using, at the same time, macroscopic clinical visualization, histopathological analysis, OCT imaging, and OCT-based attenuation coefficient measurement. Results with all four modalities demonstrated a positive response to treatment. The attenuation coefficient was found to be 1.4 higher in skin lesions than in healthy tissue and it decreased after therapy. This study shows that the OAC is a potential tool to noninvasively assess the evolution of skin neoplastic lesions with time after treatment.
Pinho, Andreia V.; Mawson, Amanda; Gill, Anthony; Arshi, Mehreen; Warmerdam, Max; Giry-Laterriere, Marc; Eling, Nils; Lie, Triyana; Kuster, Evelyne; Camargo, Simone; Biankin, Andrew V.; Wu, Jianmin; Rooman, Ilse
Metabolic reprogramming is a feature of neoplasia and tumor growth. Sirtuin 1 (SIRT1) is a lysine deacetylase of multiple targets including metabolic regulators such as p53. SIRT1 regulates metaplasia in the pancreas. Nevertheless, it is unclear if SIRT1 affects the development of neoplastic lesions and whether metabolic gene expression is altered. To assess neoplastic lesion development, mice with a pancreas-specific loss of Sirt1 (Pdx1-Cre;Sirt1-lox) were bred into a KrasG12D mutant background (KC) that predisposes to the development of pancreatic intra-epithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC). Similar grade PanIN lesions developed in KC and KC;Sirt1-lox mice but specifically early mucinous PanINs occupied 40% less area in the KC;Sirt1-lox line, attributed to reduced proliferation. This was accompanied by reduced expression of proteins in the glycolysis pathway, such as GLUT1 and GAPDH. The stimulatory effect of SIRT1 on proliferation and glycolysis gene expression was confirmed in a human PDAC cell line. In resected PDAC samples, higher proliferation and expression of glycolysis genes correlated with poor patient survival. SIRT1 expression per se was not prognostic but low expression of Cell Cycle and Apoptosis Regulator 2 (CCAR2), a reported SIRT1 inhibitor, corresponded to poor patient survival. These findings open perspectives for novel targeted therapies in pancreatic cancer. PMID:27494892
Chagas, B S; Gurgel, A P A D; Paiva Júnior, S S L; Lima, R C P; Cordeiro, M N; Moura, R R; Coelho, A V C; Nascimento, K C G; Silva Neto, J C; Crovella, S; Freitas, A C
Human papillomavirus (HPV) infection is considered a risk factor for cervical cancer. Even if the high-risk HPV (HR-HPV) infection is necessary, environmental co-factors and genetic susceptibility also play an important role in cervical cancer development. In this study, a possible association of rs1695 GSTP1 polymorphisms, HR-HPV infection, and oral contraceptive use with cancer lesion development in women was investigated. The study population comprised 441 Brazilian women from the Northeast region including 98 HPV-infected women with high-grade squamous intraepithelial lesions, 77 HPV-infected women with low-grade squamous intraepithelial lesions, and 266 HPV-negative women with no lesion, used as a control. Our data did not show a significant association between the GSTP1 polymorphism A/G (rs1695) and any HPV-related cervical abnormalities. However, considering the use of oral contraceptives, the GSTP1 rs1695 polymorphism was associated with higher susceptibility to the development of cervical lesions in HR-HPV-infected women. Our study suggests a synergic effect of oral contraceptive use, GSTP1 polymorphisms, and HR-HPV infection in the development of cervical lesions. Together, these risk factors may induce neoplastic transformation of the cervical squamous epithelium, setting conditions for secondary genetic events leading to cervical cancer.
Białek, Andrzej; Wiechowska-Kozłowska, Anna; Pertkiewicz, Jan; Karpińska, Katarzyna; Marlicz, Wojciech; Milkiewicz, Piotr; Starzyńska, Teresa
AIM: To investigate the indications, resection rate, and safety of endoscopic submucosal dissection (ESD) for neoplastic lesions in the gastrointestinal tract at a European referral center. METHODS: We carried out a retrospective analysis of the ESD procedures performed in our center for mucosal neoplastic and submucosal lesions of the gastrointestinal tract. The duration of the procedure, en bloc and complete (R0) resection rates, and complication rates were evaluated. Variables were reported as mean ± SD or simple proportions. Univariate analysis and comparisons of procedure times and resection rates were performed using Mann-Whitney U tests, or χ2 tests for dichotomous variables. RESULTS: Between 2007 and 2011, ESD was performed in a total of 103 patients (46.7% male, mean age 64.0 ± 12.7 years). The indications for the procedure were epithelial tumor (n = 54), submucosal tumor (n = 42), or other (n = 7). The total en bloc resection rate was 90.3% (93/103) and R0 resection rate 80.6% (83/103). The median speed of the procedure was 15.0 min/cm2. The complete resection rate was lower for submucosal tumors arising from the muscle layer (68%, 15/22, P < 0.05). Resection speed was quicker for submucosal tumors localized in the submucosal layer than for lesions arising from the muscularis propria layer (8.1 min/cm2 vs 17.9 min/cm2, P < 0.05). The R0 resection rate and speed were better in the last 24 mo (90.1%, 49/54 and 15.3 min/cm2) compared to the first 3 years of treatment (73.5%, 36/49, P < 0.05 and 22.0 min/cm2, P < 0.05). Complications occurred in 14.6% (n = 15) of patients, including perforation in 5.8% (n = 6), pneumoperitoneum in 3.9% (n = 4), delayed bleeding in 1.9% (n = 2), and other in 2.9% (n = 3). Only one patient with delayed perforation required surgical treatment. During the mean follow-up of 26 ± 15.3 mo, among patients with R0 resection, recurrence occurred in one patient (1.2%). CONCLUSION: ESD is an effective and safe method for resection of
Mattarocci, Stefano; Abbruzzese, Claudia; Mileo, Anna M; Carosi, Mariantonia; Pescarmona, Edoardo; Vico, Carmen; Federico, Antonio; Vizza, Enrico; Corrado, Giacomo; Arisi, Ivan; Felsani, Armando; Paggi, Marco G
Cervical carcinoma represents the paradigm of virus-induced cancers, where virtually all cervical cancers come from previous "high-risk" HPV infection. The persistent expression of the HPV viral oncoproteins E6 and E7 is responsible for the reprogramming of fundamental cellular functions in the host cell, thus generating a noticeable, yet only partially explored, imbalance in protein molecular networks and cell signaling pathways. Eighty-eight cellular factors, identified as HPV direct or surrogate targets, were chosen and monitored in a retrospective analysis for their mRNA expression in HPV-induced cervical lesions, from dysplasia to cancer. Real-time quantitative PCR (qPCR) was performed by using formalin-fixed, paraffin embedded archival samples. Gene expression analysis identified 40 genes significantly modulated in LSIL, HSIL, and squamous cervical carcinoma. Interestingly, among these, the expression level of a panel of four genes, TOP2A, CTNNB1, PFKM, and GSN, was able to distinguish between normal tissues and cervical carcinomas. Immunohistochemistry was also done to assess protein expression of two genes among those up-regulated during the transition between dysplasia and carcinoma, namely E2F1 and CDC25A, and their correlation with clinical parameters. Besides the possibility of significantly enhancing the use of some of these factors in diagnostic or prognostic procedures, these data clearly outline specific pathways, and thus key biological processes, altered in cervical dysplasia and carcinoma. Deeper insight on how these molecular mechanisms work may help widen the spectrum of novel innovative approaches to these virus-induced cell pathologies. © 2013 Wiley Periodicals, Inc.
Rimondi, E; Busacca, M; Moio, A; Molinari, M; Nigrisoli, M; Trentani, F; Trentani, P; Tigani, D
To assess the efficacy of percutaneous CT-guided biopsy in the diagnosis and therapeutic planning of neoplastic and flogistic diseases of the pelvis. From July 1990 to December 1999 193 patients (113 males, 80 females: mean age 49, standard deviation 16) were submitted to CT-guided percutaneous biopsy of the pelvic region; 117 biopsies (61%) were performed at iliac, pubic and ischial segments and 76 (39%) at sacral region; 107 patients were admitted to the hospital and 86 were in clinic. Needles were 8 G (4 mm), 10 to 15 cm long. Approach to pelvic lesions was performed according to the specific site. Lesions of the lateral pelvic region have always been approached through the lateral surgical incision according to Enneking. Lesions of the posterior pelvic region have always been approached by the introduction of the needle along the posterior surgical incision according to Enneking. Lesions of the anterior region have always been approached through the anterior surgical incision according to Enneking. From July 1990 to May 1997 pelvic percutaneous biopsies have been carried out with a CT Sytec 3000. From May 1997 to December 1999 the device was replaced by a High Speed CTi. The introduction of spiral CT allowed reduction of performance mean time from 45 minutes (standard deviation 15) to 30 minutes (standard deviation 10). In 154 patients (80%) we observed a neoplastic, inflammatory or not classified degeneration. In 8 patients (4%) the retrieved material ended to be inadequate for a diagnosis. In 31 patients (16%) no disease was revealed at the histological examination. Such patients with negative histological examination have been kept under clinical and radiological control in the following period in order to verify the manifestation or the presence of an alteration previously not observed. On 31-3-2000 none of them had been submitted to a new percutaneous biopsy of the pelvic region. The overall mean accuracy has been 96% considering the negative patients as
Sawaki, M; Enomoto, K; Takahashi, H; Nakajima, Y; Mori, M
The incidence and phenotype of preneoplastic and neoplastic liver lesions appearing in LEC rats after recovery from severe hereditary hepatitis were studied in comparison with the liver lesions appearing in chemical liver carcinogenesis. The livers of 168 rats (90 male, 78 female) were stained for seven histochemical markers at different time periods from the 20th week to the 122nd week of life. Glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and non-specific esterase (ES) were used as negative markers. Gamma-glutamyltransferase (GGT), glutathione S-transferase placental form (GSTP), esterase isozyme L-1 (L1) and alpha-fetoprotein (AFP) were used as positive markers. The study on the incidence of liver lesions in the LEC rats revealed sequential development of liver foci, nodules and hepatocellular carcinomas (HCCs) similar to those seen in chemically induced liver carcinogenesis. These lesions appeared earlier and more frequently in male LEC rats than in female ones, suggesting the importance of hormonal environment in spontaneous HCC development. The histochemical analysis of spontaneous liver lesions in LEC rats showed that GSTP was the most reliable positive marker as previously reported in chemical liver carcinogenesis. There was no essential difference in the expression of the markers in spontaneous and chemically induced liver lesions except for L1, which is considered to be related to xenobiotic metabolism. The results of this study suggest that both spontaneous and chemically induced liver cancer may develop by passing through phenotypically similar preneoplastic processes. In addition, the LEC rat uniquely showed chronic liver damage (hepatocyte death and regeneration) at the promotion stage of carcinogenesis. Such a natural history of HCC development in LEC rats is similar to that of human HCC which is frequently associated with chronic liver damage. Thus, the LEC rat provides a useful model for studying the process and underlying
Nazarian, Rosalynn M; Primiani, Andrea; Doyle, Leona A; Linskey, Katy R; Duncan, Lyn M; Odze, Robert D; Zukerberg, Lawrence R
Diagnosing anal squamous cell carcinoma (SCC), which is often preceded by anal intraepithelial neoplasia (AIN), may be challenging in small biopsies. Cytokeratin 17 (CK17) is a basal/myoepithelial cell keratin induced in activated keratinocytes and associated with disease progression in SCC of the uterine cervix, esophagus, and oral cavity. We investigated the utility of CK17 in diagnosing invasion in anal squamous neoplastic lesions. Immunohistochemical staining for CK17 was evaluated in 11 AINs, 12 invasive SCCs, 8 invasive SCCs with basaloid features (BSCC), and 2 invasive pure basaloid carcinomas. The pattern of staining was scored as surface/central, peripheral/rim, diffuse, or absent. All cases of invasive SCC and BSCC stained positive for CK17. Eleven of 12 (92%) SCCs showed diffuse staining, and 1 of 12 (8%) showed peripheral staining. Six of 8 (75%) BSCCs showed diffuse staining, and 2 of 8 (25%) showed peripheral staining. Both pure basaloid carcinomas were negative for CK17. One of 11 (9%) AINs was diffusely positive for CK17; all other AINs had surface or absent CK17. Of the 6 patients with concurrent AIN and invasive carcinoma, superficial expression of CK17 was present in 1 AIN, whereas all invasive components showed diffuse staining. The sensitivity and specificity of CK17 for identifying invasion in SCC and BSCC was 100% and 91%, respectively. Peripheral or diffuse staining for CK17 is a useful marker of invasion in anal squamous neoplastic lesions. A potential pitfall in the utility of CK17 is that the pure basaloid variant of anal carcinoma is negative for CK17.
Ridola, Lorenzo; Hassan, Cesare; Lorenzetti, Roberto; Boggi, Roberto; Napoli, Massimo; Tomao, Silverio; Zullo, Angelo
Background The association between diverticulosis and colonic neoplastic lesions has been suggested, but data in literature are conflicting. This study aimed to investigate such a relationship in patients participating in a colorectal cancer screening program who underwent high-quality colonoscopy. Methods Data from consecutive individuals 50–75 years of age with a positive faecal immunological test were considered. Diverticulosis was categorised as present or absent. The prevalence of neoplastic lesions (adenoma, advanced adenoma, and cancer) between individuals with and those without diverticula was compared. A multivariate analysis was performed. Results Overall, data from 970 consecutive individuals were evaluated, and diverticulosis was detected in 354 (36.5%) cases. At least one adenoma was detected in 490 (50.5%) people, at least one advanced adenoma in 264 (27.2%), multiple adenoma in 71 (7.3%), whilst a cancer was diagnosed in 48 (4.9%) cases. At univariate analysis, the adenoma detection rate in patients with diverticula was significantly higher than in controls (55.9% vs 47.4%; p = 0.011). At multivariate analysis, presence of diverticulosis was an independent risk factor for both adenoma detection rate (OR = 1.58; 95% CI = 1.14–2.18; p = 0.006) and advanced adenoma (OR = 1.57; 95% CI = 1.10–2.24; p = 0.013), but not for colorectal cancer. Conclusions In a colorectal screening setting, the adenoma detection rate was significantly higher in individuals with diverticulosis than in controls. PMID:28405332
Pope, Jenny P; Steeil, James; Ramsay, Edward C; Reel, Danielle; Newman, Shelley J
Based on microscopic and immunohistochemical characterization, we documented spontaneous proliferative and neoplastic lesions in the thyroid and parathyroid glands of nondomestic felids. Ten animals (4 leopards, 3 tigers, and 3 cougars), all with a previous diagnosis of thyroid neoplasia were identified from the University of Tennessee College of Veterinary Medicine database. The mean age of affected animals was 15.9 y. Twelve neoplasms were identified; 2 animals had 2 concurrent neoplasms. After immunohistochemical characterization using a panel of chromogranin A, thyroglobulin, and calcitonin, 7 of the former thyroid neoplasms were diagnosed as thyroid adenomas, 1 was diagnosed as a thyroid carcinoma, and 4 were diagnosed as parathyroid adenomas. No thyroid medullary neoplasms (C-cell tumors) were diagnosed in the current study. Most of the diagnosed neoplasms were benign (11 of 12), and metastasis was not documented in the single carcinoma. Only 2 animals were suspected to have functional neoplasms (1 thyroid adenoma and 1 parathyroid adenoma), based on associated tissue lesions or serum biochemistry. Other documented lesions in the thyroid and parathyroid glands included thyroid nodular hyperplasia ( n = 7), parathyroid hyperplasia associated with chronic renal disease ( n = 2), a thyroid abscess, and a branchial cyst. Parathyroid adenomas were more commonly diagnosed than expected in comparison with domestic cats. We demonstrated that an immunohistochemistry panel for thyroglobulin, calcitonin, and chromogranin A can be used to differentiate neoplasms of thyroid from parathyroid origin in nondomestic felids.
de Sá, V.K.; Rocha, T.P.; Moreira, AL.; Soares, F.A.; Takagaki, T.; Carvalho, L.; Nicholson, A.G.; Capelozzi, V.L.
We collected a series of 136 lung/bronchial and 56 matched lung parenchyma tissue samples from patients who underwent lung/bronchial biopsies and presented invasive carcinoma after lung surgery. The lung/bronchial samples included basal cell hyperplasia, squamous metaplasia, moderate dysplasia, adenomatous hyperplasia, severe dysplasia, squamous cell carcinoma and adenocarcinoma. Matched lung parenchyma tissue samples included 25 squamous cell carcinomas and 31 adenocarcinomas. Immunohistochemistry was performed to analyze for the distribution of hyaluronidase (Hyal)-1 and −3, and hyaluronan synthases (HAS)-1, −2, and −3. Hyal-1 showed significantly higher expression in basal cell hyperplasia than in moderate dysplasia (P=0.01), atypical adenomatous hyperplasia (P=0.0001), or severe dysplasia (P=0.03). Lower expression of Hyal-3 was found in atypical adenomatous hyperplasia than in basal cell hyperplasia (P=0.01) or moderate dysplasia (P=0.02). HAS-2 was significantly higher in severe dysplasia (P=0.002) and in squamous metaplasia (P=0.04) compared with basal cell hyperplasia. HAS-3 was significantly expressed in basal cell hyperplasia compared with atypical adenomatous hyperplasia (P=0.05) and severe dysplasia (P=0.02). Lower expression of HAS-3 was found in severe dysplasia compared with squamous metaplasia (P=0.01) and moderate dysplasia (P=0.01). Epithelial Hyal-1 and −3 and HAS-1, −2, and −3 expressions were significantly higher in pre-neoplastic lesions than in neoplastic lesions. Comparative Cox multivariate analysis controlled by N stage and histologic tumor type showed that patients with high HAS-3 expression in pre-neoplastic cells obtained by lung/bronchial biopsy presented a significantly higher risk of death (HR=1.19; P=0.04). We concluded that localization of Hyal and HAS in lung/bronchial pre-neoplastic and neoplastic lesions was inversely related to malignancy, which implied that visualizing these factors could be a useful diagnostic
Martin, B; Verdebout, J-M; Mascaux, C; Paesmans, M; Rouas, G; Verhest, A; Ninane, V; Sculier, J-P
p53 alteration has been reported to be an early event in bronchial carcinogenesis. Our study purpose was to determine the rate of p53 expression in the various preneoplastic and early neoplastic bronchial lesions obtained by biopsy during fluorescence bronchoscopy and to analyse its association with patients characteristics. Various stages of preneoplastic lesions as well as radio-occult lung cancer were studied in biopsies obtained by fluorescence bronchoscopy. We assessed the expression of p53 by immunohistochemistry using monoclonal antibody clone DO7. The p53 expression was considered as positive if > or = 1% of cells were positive and the level of positivity was expressed in percentage of positive cells. Fourteen patients were included in each category of preneoplastic lesions. At the threshold of 1% of positive cells p53 expression was observed in 28.5% of the patients with a histologically normal epithelium. This number of positive patients increased with the severity of preneoplastic lesions and reached 100% in the mild dysplasia. The mean rates of p53 positive cells for normal epithelium, hyperplasia, metaplasia, mild and severe dysplasia, carcinoma in situ and invasive radio-occult carcinoma were respectively 0.9, 3.4, 9.1, 20.5, 50.2, 34.7 and 42.5%. There was no statistically significant correlation between p53 expression and patient characteristics such as sex, age, smoking habits and indication for fluorescence bronchoscopy. The alteration of p53 expression in patients with high risk of lung cancer was an early event: this abnormality increased with the severity of the lesions, without significant correlation with patient characteristics.
Veitz-Keenan, Analia; Barna, Julie Ann; Strober, Brad; Matthews, Abigail G.; Collie, Damon; Vena, Donald; Curro, Frederick A.; Thompson, Van P.
Background The Practitioners Engaged in Applied Research and Learning (PEARL) Network conducted a three-armed randomized clinical study to determine the comparative effectiveness of three treatments for hypersensitive noncarious cervical lesions (NCCLs): use of a potassium nitrate dentifrice for treatment of hypersensitivity, placement of a resin-based composite restoration and placement of a sealant. Methods Seventeen trained practitioner-investigators (P-Is) in the PEARL Network enrolled participants (N = 304) with hypersensitive posterior NCCLs who met enrollment criteria. Participants were assigned to treatments randomly. Evaluations were conducted at baseline and at one, three and six months thereafter. Primary outcomes were the reduction or elimination of hypersensitivity as measured clinically and by means of patient-reported outcomes. Results Lesion depth and pretreatment sensitivity (mean, 5.3 on a 0- to 10-point scale) were balanced across treatments, as was sleep bruxism (present in 42.2 percent of participants). The six-month participant recall rate was 99 percent. Treatments significantly reduced mean sensitivity (P < .01), with the sealant and restoration groups displaying a significantly higher reduction (P < .01) than did the dentifrice group. The dentifrice group’s mean (standard deviation) sensitivity at six months was 2.1 (2.1); those of the sealant and restoration groups were 1.0 (1.6) and 0.8 (1.4), respectively. Patient-reported sensitivity (to cold being most pronounced) paralleled clinical measurements at each evaluation. Conclusions Sealing and restoration treatments were effective overall in reducing NCCL hypersensitivity. The potassium nitrate dentifrice reduced sensitivity with increasing effectiveness through six months but not to the degree offered by the other treatments. Practical Implications Sealant or restoration placement is an effective method of immediately reducing NCCL sensitivity. Although a potassium nitrate dentifrice
Martinez, Emmanuelle; Crenon, Isabelle; Silvy, Françoise; Del Grande, Jean; Mougel, Alice; Barea, Dolores; Fina, Frederic; Bernard, Jean-Paul; Ouaissi, Mehdi; Lombardo, Dominique; Mas, Eric
Pancreatic adenocarcinoma (PDAC) is a dismal disease. The lack of specific symptoms still leads to a delay in diagnosis followed by death within months for most patients. Exon 11 of the bile salt-dependent lipase (BSDL) gene encoding variable number of tandem repeated (VNTR) sequences has been involved in pancreatic pathologies. We hypothesized that BSDL VNTR sequences may be mutated in PDAC. The amplification of BSDL VNTR from RNA extracted from pancreatic SOJ-6 cells allowed us to identify a BSDL amplicon in which a cytosine residue is inserted in a VNTR sequence. This insertion gives rise to a premature stop codon, resulting in a truncated protein and to a modification of the C-terminal amino-acid sequence; that is PRAAHG instead of PAVIRF. We produced antibodies directed against these sequences and examined pancreatic tissues from patients with PDAC and PanIN. Albeit all tissues were positive to anti-PAVIRF antibodies, 72.2% of patient tissues gave positive reaction with anti-PRAAHG antibodies, particularly in dysplastic areas of the tumor. Neoplastic cells with ductal differentiation were not reactive to anti-PRAAHG antibodies. Some 70% of PanIN tissues were also reactive to anti-PRAAHG antibodies, suggesting that the C insertion occurs early during pancreatic carcinogenesis. Data suggest that anti-PRAAHG antibodies were uniquely reactive with a short isoform of BSDL specifically expressed in pre-neoplastic lesions of the pancreas. The detection of truncated BSDL reactive to antibodies against the PRAAHG C-terminal sequence in pancreatic juice or in pancreatic biopsies may be a new tool in the early diagnosis of PDAC. PMID:27602750
Malhotra, Saurabh; Kazlouskaya, Viktoryia; Andres, Christian; Gui, Jiang; Elston, Dirk
Background Distinguishing cellular abnormalities in reactive and malignant lesions is challenging. We compared the incidence and severity of cytological abnormalities in malignant/premalignant and benign epidermal lesions. Methods One hundred fifty-two biopsies representing 69 malignant/premalignant squamous lesions and 83 benign conditions were studied. Cytological features, including nuclear hyperchromasia, nuclear overlap (crowding), irregular nuclei, high nuclear/cytoplasmic (N/C) ratio, conspicuous nucleoli, delicate inconspicuous nucleoli, clumped chromatin, pleomorphic parakeratosis, normal and abnormal mitotic figures and necrotic keratinocytes, were evaluated and graded. Statistical analysis was performed. Results Irregular nuclei, increased N/C ratio, conspicuous single prominent nucleoli, nuclear overlap (crowding), pleomorphic parakeratosis, nuclear hyperchromasia, necrotic keratinocytes, normal and abnormal mitotic figures and coarse chromatin were seen more frequently in malignant neoplasms (p < 0.05). Abnormal mitotic figures, although uncommon (20.3%), were only noted in the malignant/premalignant group. Certain cytological features were common among both malignant and benign lesions, suggesting that they are of little value. Conclusion In the setting of an atypical cutaneous squamous proliferation, nuclear irregularity, increased N/C ratio, conspicuous nucleoli, crowding and hyperchromasia are the most useful indicators of malignancy. In contrast, mitotic figures, necrotic cells and coarse chromatin are less useful. The presence of abnormal mitotic figures is very helpful when present; however, their overall rarity limits their utility. PMID:23398548
Kingsbury, Jeffrey S.; Margarone, Joseph E., III; Satchidanand, S.; Liebow, Charles
Surgical incision may have promotional effects on neoplastic lesions, possibly through release of tissue growth factors (e.g., EGF, FGF(beta) , IGF, TGF(alpha) ). The CO2 laser may precipitate altered release of these factors. To test this, .5 cm laser, and scalpel incisions were made into fields treated by application of .5% DMBA in acetone, 3 times a week for 6 weeks (group 1) and 12 weeks (group 2). DMBA is a complete carcinogen (initiator and promoter). At 6 weeks, chemically, but not histologically, definable premalignant lesions are seen. Treatment for 12 weeks causes histologic neoplasia which can be graded with T-N-M classification. For both groups, the surgical sites were examined clinically and histologically 4 weeks post-op in a blind fashion. Standard criteria were utilized for defining neoplasia. For group 1, 3 out of 6 laser treated animals developed large exophytic squamous cell carcinomas, but no lesions developed in 12 contralateral, 3 control and 3 scalpel treated pouches. For group 2, 12 of 16 laser treated animals developed tumor with mean grade of 1.75 and mean size of 7.4 mm, 5 of 6 scalpel treated animals developed tumor with mean grade of 1.83 and mean size of 3.6 mm and 3 of 6 control animals developed tumor with mean grade of 1.00 and mean size of 1.5 mm. By the Student 't' test on the binomial distribution lasers cause significant promotion (p < .01). These results suggest that laser surgery may have earlier and more profound promotional effects than scalpel on initiated cells relative to tumor size in the vicinity of the wound site by increased release of growth factors.
Background Atypical adenomatous hyperplasia (AAH) and squamous cell dysplasia (SCD) are associated with the development of malignant lesions in the lung. Accurate diagnosis of AAH and SCD could facilitate earlier clinical intervention and provide useful information for assessing lung cancer risk in human populations. Detection of AAH and SCD has been achieved by imaging and bronchoscopy clinically, but sensitivity and specificity remain less than satisfactory. We utilized the ability of the immune system to identify lesion specific proteins for detection of AAH and SCD. Methods AAH and SCD tissue was surgically removed from six patients of Chinese descent (3 AAH and 3 SCD) with corresponding serum samples. Total RNA was extracted from the tissues and a cDNA library was generated and incorporated into a T7 bacteriophage vector. Following enrichment to remove "normal" reactive phages, a total of 200 AAH related and 200 SCD related phage clones were chosen for statistical classifier development and incorporation into a microarray. Microarray slides were tested with an independent double-blinded population consisting of 100 AAH subjects, 100 SCD subjects and 200 healthy control subjects. Results Sensitivity of 82% and specificity of 70% were achieved in the detection of AAH using a combination of 9 autoantibody biomarkers. Likewise, 86% sensitivity and 78% specificity were achieved in the detection of SCD using a combination of 13 SCD-associated markers. Sequencing analysis identified that most of these 22 autoantibody biomarkers had known malignant associations. Conclusions Both diagnostic values showed promising sensitivity and specificity in detection of pre-neoplastic lung lesions. Hence, this technology could be a useful non-invasive tool to assess lung cancer risk in human populations. PMID:24708840
Gupta, J.; Pilotti, S.; Rilke, F.; Shah, K.
The authors examined paraffin sections from 85 genital tract tissues from 49 cases for the presence of human papillomavirus (HPV) Types 6/11, 16, and 18 by stringent in situ hybridization using 35S-labeled viral DNA probes, and for viral capsid antigen by the immunoperoxidase test. The cases, selected mostly on the basis of vulvar pathology, were distributed as follows: early neoplasia (Group I, 6 cases); early neoplasia with viral cytopathic effect (CE) (Group II, 24 cases); and papillomavirus infection (PVI) (Group III, 19 cases). Available tissues from all affected sites were examined when the disease was multicentric. One or more viral DNAs were identified in 58% of 77 tissues from Groups II and III and in 2 of 8 tissues from Group I. HPV-6/11, HPV-16 and HPV-18 DNAs were detected, respectively, in 25, 24, and 2 tissues; 3 tissues were infected simultaneously with either two or three viruses. Viral DNA was identified at more than one site in 14 of 30 DNA-positive patients; in 10 of these, a single type was detected at all sites in the same patient. The viral DNA was localized mostly in areas showing viral cytopathology. The presence of HPV-16 correlated with neoplasia. HPV-16 DNA was identified in the 2 virus-positive tissues showing neoplasia, in 17 of 20 (85%) of the DNA-positive tissues showing neoplasia with CE, and in 5 of 25 (20%) of the DNA-positive tissues showing PVI. Conversely, HPV-6/11 was found in 25% of the DNA-positive tissues showing neoplasia with CE and in 80% of the cases of PVI. An HPV genome was identified in neoplastic cells in 14 instances; in all but 1 case, the genome was HPV-16. The association of HPV-16 with neoplasia was seen for both vulvar and cervical lesions. Viral antigen was detected in 83% of lesions associated with HPV 6/11 and in 62% of lesions associated with HPV-16. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:3034064
Uhrenholt, Lars; Grunnet-Nilsson, Niels; Hartvigsen, Jan
A systematic critical literature review. To determine whether occult pathoanatomical lesions in the cervical spine of road traffic fatalities exist and if they can be identified using optimal autopsy techniques. Previous investigations have examined pathoanatomical conditions of the cervical spine of road traffic fatalities. However, different methods of investigation have been used, and results of studies are conflicting. Hence, potential pathoanatomical conditions in fatalities and survivors remain a controversial issue. Articles were retrieved searching the MEDLINE, Mantis, and Cochrane libraries. Studies examining the cervical spine of road traffic fatalities at autopsy were included and evaluated according to a set of quality criteria. For in-depth review, only studies using surface cryoplaning microtomy autopsy technique and a control group were included. Twenty-seven articles of which three fulfilled the quality criteria were reviewed. In these studies, subtle pathoanatomical lesions were found in the cervical intervertebral discs, cartilaginous endplates, and the articular surfaces and capsules of the zygapophysial joints. The lesions were found exclusively in the traumatized patients and in none of the patients in the control group. Occult pathoanatomical lesions in the cervical intervertebral disc and zygapophysial joints after fatal road traffic trauma may exist. Present imaging methods, especially conventional radiography, do not visualize these subtle lesions; hence, underreporting of pathoanatomical lesions during standard autopsy is probably common. These findings may have clinical relevance in the management of road traffic trauma survivors with potentially similar pathoanatomy.
Anidjar, Maurice; Cussenot, Oliver; Avrillier, Sigrid; Ettori, Dominique; Teillac, Pierre; Le Duc, Alain
We have designed a program using laser induced autofluorescence spectroscopy as a possible way to characterize urothelial tumors of the bladder. The autofluorescence spectra were compared between normal, suspicious and tumor areas of human bladder. Three different pulsed laser wavelengths were used for excitation: 308 nm (excimer), 337 nm (nitrogen) and 480 nm (dye laser). Excitation light was delivered by a specially devised multifiber catheter introduced through the working channel of a regular cystoscope under saline irrigation. The fluorescence light was focused into an optical multichannel analyzer detection system. The data was evaluated in 25 patients immediately before resection of a bladder tumor. Spectroscopic results were compared with histopathology. Upon 337 nm and 480 nm excitations, the overall intensity of the fluorescence spectra from bladder tumors was clearly reduced in comparison with normal urothelium, regardless of the stage and the grade of the tumor. upon 308 nm excitation, the shape of tumor fluorescence spectra, including carcinoma in situ, differed drastically from that of normal tissue. In this case, no absolute intensity measurements are needed and clear diagnosis can be achieved from fluorescence intensity ratio (360/440 nm). This spectroscopic study could be particularly useful for the design of a simplified autofluorescence imaging device for real-time routine detection of occult urothelial neoplastic lesions.
Carlus, Marine; Elies, Laëtitia; Fouque, Marie-Claude; Maliver, Pierre; Schorsch, Frédéric
Incidences of neoplastic lesions were evaluated in untreated Hannover Wistar Rats RjHan: WI (470 males and 470 females) used as control animals in eight carcinogenicity studies. All these studies were performed in a similar environment either for the in vivo and the postmortem evaluation. The major neoplastic lesions were found in the endocrine, integumentary and reproductive systems. Pituitary adenoma was the most frequent neoplasm and occurred in 33.9% of the males and 54.6% of the female rats. The other most frequent tumors in males were thyroid C-cell adenoma (8.6%), pancreatic islet cell adenoma (8.1%), subcutaneous fibrosarcoma (6.6%), subcutaneous fibroma (4.7%), benign pheochromocytoma (3.4%), and cutaneous keratoacanthoma (3.4%). In females, the other highest incidences were mammary fibroadenoma (29%), uterine endometrial stromal polyp (18.1%), mammary adenocarcinoma (14.2%), mammary fibroadenoma with atypia (13.7%), thyroid C-cell adenoma (7.5%), benign thymoma (3.7%), and subcutaneous fibrosarcoma (3.6%). All these data were compared to previously published historical control data. This retrospective analysis was undergone in order to illustrate the result of a stable organization which guarantees a robust historical data base for neoplastic and non neoplastic findings.
Loomba, Kapil; Bains, Rhythm; Bains, Vivek Kumar; Loomba, Anju
Noncarious cervical lesions often present with overlapping symptoms and have a multifactorial etiology. The dimensions of the lesion axially (depth) and occlusogingivally (width), along with the orientation of the walls of the lesion to each other (angle), are the 3 factors that can be quantified to classify the lesion and assess its progress over time. This article analyzes these factors and proposes a simple classification system based upon the clinical appearance of the lesion in order to derive simple, therapeutic, treatment-based classifications.
Ma, Li; Cong, Xiao; Shi, Mai; Wang, Xiu-Hong; Liu, Hai-Yan; Bian, Mei-Lu
The aims of the present study were to investigate the distribution of human papillomavirus (HPV) genotypes in cervical lesions, and the association between different HPV genotypes and cervical lesions. Between January 2013 and June 2014, the HPV type determinations of nucleic acid by use of fluorescence polymerase chain reaction (PCR) method of 15,192 outpatients in China-Japan Friendship Hospital were performed and the infection status was analyzed. The results showed that: i) 2,366 Cases were HPV positive and 12,826 cases were HPV negative, the overall infection rate was 15.57% (2,366/15,192), in which a single genotype of HPV infection rate was 11.63% (1,767/15,192), and multiple genotypes of HPV infection rate was 3.94% (599/15,192); ii) HPV16, HPV52 and HPV58 infections were the most common HPV genotypes, the infection rates were 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively; and iii) According to the gold standard of histopathological analysis via hematoxylin-eosin staining, HPV16, HPV52 and HPV58 accounted for 58.80% (154/267) of all CIN2 or above squamous epithelial lesions. Furthermore, three cases with pathological changes of the cervical severe glandular epithelium were all HPV18 infection. The difference was statistically significant (χ2=60.74, P<0.001). Single HPV subtype infection was primarily associated with HPV16, HPV52 and HPV58. In conclusion, HPV type detection had a may be important in screening of cervical lesions as a difference in pathogenic ability was noted among different HPV genotypes. As cervical cancer is an infectious disease, HPV testing may help detect more precancerous lesions, thus reducing the morbidity and mortality of cervical cancer. HPV16, HPV52 and HPV58 were associated with severe cervical squamous epithelial lesions; HPV18 was associated with cervical severe glandular cell pathological changes, although it was not the most common HPV genotype in China. When positive, a clinical cervical
Tasaki, Masako; Umemura, Takashi; Kijima, Aki; Inoue, Tomoki; Okamura, Toshiya; Kuroiwa, Yuichi; Ishii, Yuji; Nishikawa, Akiyoshi
It was recently shown that 1-year chronic exposure of rats to tocotrienol (TT) induced highly proliferative liver lesions, nodular hepatocellular hyperplasia (NHH), and independently increased the number of glutathione S-transferase placental form (GST-P)-positive hepatocytes. Focusing attention on the pathological intrinsic property of NHH, a 104-week carcinogenicity study was performed in male and female Wistar Hannover rats given TT at concentrations of 0, 0.4 or 2% in the diet. The high-dose level was adjusted to 1% in both sexes from week 51 because the survival rate of the high-dose males dropped to 42% by week 50. At necropsy, multiple cyst-like nodules were observed, as in the chronic study, but were further enlarged in size, which consequently formed a protuberant surface with a partly pedunculated shape in the liver at the high dose in both sexes. Unlike the chronic study, NHH was not always accompanied by spongiosis, and instead angiectasis was prominent in some nodules. However, several findings in the affected hepatocytes such as minimal atypia, no GST-P immunoreactivity and heterogeneous proliferation, implied that NHH did not harbor neoplastic characteristics from increased exposure despite sustained high cell proliferation. On the other hand, in the high-dose females, the incidence of hepatocellular adenomas was significantly higher than in the control. There was no TT treatment-related tumor induction in any other organs besides the liver. Thus, the overall data clearly suggested that NHH is successively enlarged by further long-term exposure to TT, but does not become neoplastic. In contrast, TT induces low levels of hepatocellular adenomas in female rats.
Velázquez-Márquez, Noé; Santos-López, Gerardo; Jiménez-Aranda, Lucio; Reyes-Leyva, Julio; Vallejo-Ruiz, Verónica
Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumour progression and metastases. Altered expression of glycosidic antigens has been reported in cervical cancer. In cervix premalignant lesions, an increased expression of sialic acid has been reported. In the present study we determined the expression profiles of the glycosidic antigens Tn, sialyl Tn (sTn), Lewis a (Lea), sialyl Lewis a (sLea), Lewis x (Lex) and sialyl Lewis x (sLex) in cervical scrapes with cytological diagnoses of normal, low-grade squamous intraepithelial lesions (LGSIL) and highgrade squamous intraepithelial lesions (HGSIL). Cervical scrapings were collected to detect tumour antigens expressions by flow cytometry using monoclonal antibodies. Cytometry analysis of Tn, sTn, Lea and Lex did not reveal differences at the expression level among groups. The number of positive cells to sLea antigen increased in the HGSIL group with respect to the normal group (p=0.0495). The number of positive cells to sLex antigen in the samples increased with respect to the grade of squamous intraepithelial lesion (SIL) (p less than 0.001, Mann-Whitney U test). The intensity of expression of this antigen increased in the HGSIL samples with respect to normal samples (p less than 0.0068). sLex antigen could be a candidate to be used as biomarker for the early diagnosis of cervical cancer.
Setien, Victor; Armstrong, Steven R; Vargas, Marcos A
One of the authors has used this technique successfully for the past three years in various clinical situations that involve both difficult access anterior and posterior teeth. This is a tooth-structure conserving clinical procedure that can provide a simplified approach for restoring otherwise difficult clinical lesions.
Petruzzi, Massimo; Lucchese, Alberta; Nardi, Gianna Maria; Lauritano, Dorina; Favia, Gianfranco; Serpico, Rosario; Grassi, Felice Roberto
The objective was to compare toluidine blue (TB) and autofluorescence (AF) for the detection of oral dysplasia and squamous cell carcinoma (OSCC) in clinically suspicious lesions according to conventional examination. Fifty-six clinically suspicious lesions were subjected to AF and TB examination. Data were compared using two different scenarios: in the first, mild dysplasia was considered as positive, while in the second, it was considered as negative. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), accuracy, and concordance were calculated. AF sensitivity and specificity were 70.0 and 57.7%, respectively, while TB showed a sensitivity of 80% and a specificity of 61.5%. The sensitivity increased in the second scenario in both AF (76.5%) and TB (88.2%). The specificity decreased in AF and TB, showing the same value (51.3%). PPV was higher in TB than in AF (70.6 versus 65.6%) and similarly for NPV (72.7 versus 62.5%). In the second scenario, TB PPV was 44.1% and NPV was 90.9% AF PPV was 40.6% and NPV was 83.3%. TB showed greater accuracy than AF in the first scenario (62.5 versus 58.9%). AF and TB are both sensitive but not specific in OSCC and dysplasia diagnosis.
Pitris, Constantinos; Goodman, Annekathryn; Boppart, Stephen A.; Drexler, Wolfgang; Jesser, Christine; Stamper, Debra L.; Brezinski, Mark E.; Fujimoto, James G.
A technology capable of imaging tissue, at or near the cellular level, could lead to the detection of neoplasias at earlier stages than currently possible. This could significantly improve patient outcomes, since once cancer becomes metastatic, cure is difficult. Optical coherence tomography (OCT), a recently developed imaging technology, has ben shown to achieve resolution in the cellular and subcellular range, and it could improve the diagnostic range of clinical imaging procedures. To assess the clinical applicability of OCT, neoplastic specimens from the urinary, gastrointestinal and female reproductive tract were imaged. Sharp differentiation of structures included the mucosa/submucosal/muscularis boundaries, epithelium, glands, supportive tissue, and intramural cysts. The ability of optical coherence tomography to image tissue microstructure at or near the cellular level make it a potentially powerful technology for minimally invasive assessment of tissue microstructure. The resolution of optical coherence tomography, which is greater than any current clinical imaging modality, make it particularly attractive for the assessment of early neoplastic changes.
Panjković, Milana; Ivković-Kapicl, Tatjana
Cervical cancer is the second most common gynecological malignancy in the world. Human papilloma virus (HPV) infection is the leading ethiologic agent in the development of premalignant and malignant cervical diseases. HPV is a member of the Papovaviridae family and until now over 100 types have been recognized There are two types of viral infection: latent and productive. Virus induced oncogenesis is the result of interaction between virus oncoproteins E6 and E7 and tumor supresor host genes p53 and Rb. Many cofactors such as immunosuppression, early sexual relationship, multiple sexual partners, other sexualy transsmited infections and smoking are contributing factors of the precancerous and invasive cervical lesions. According to the oncogenic potential HPV are divided into three groups: low, intermediate and high oncogenic risk viruses. Molecular technics which are used for the virus detection are: In situ hibridisation, Hyybrid capture test and polymerasa chain reaction. Human papilloma virus testing has an important role in the follow up and treatment of women with "atypical squamous cells of unknown significant" changes in cervical smears and low-grade squamous intraepithelial lesions, changes in punch biopsy.
Carlo, Bonfanti; Piccinelli, Giorgio; Faus-Matoses, Vicente; Cerutti, Antonio
Background Non carious cervical lesions associated to muscle hyperfunctions are increasing. Microhybrid resin composites are used to restore cervical abfractions. The purpose of this study was to investigate if resin composites modify tooth plaque, inducing an increment of cariogenic microflora and evaluate their effect, in vivo and in vitro, against S. mutans. Material and Methods Eight abfractions were restored with two microhybrid resin composites (Venus, Heraeus-Kulzer® and Esthet-X, Dentsply®), after gnatological therapy, in three patients with muscle hyperfunctions. For each abfraction three samples of plaque were taken from the cervical perimeter: before the restoration, one week and three months after restoration. The samples were evaluated both by traditional microbiological methods and by Polymerase Chain Reaction (PCR). In vitro, disk-shaped specimens of the two composites were prepared to estimate the effects against pre-cultured S. mutans, after incubation at 37°C for 24h and assessed by a turbidimetric technique. Results In vivo no differences were found in plaque growth, for all samples, before and after restoration with both composites; in vitro, instead, a significant reduction of S. mutans growth was found between specimens of two composites (Mann-Whitney U-test p>0,06). Conclusions In this study a relevant consideration was elicited: composite materials, in vivo, do not modify plaque composition of non carious cervical lesions to a potential cariogenic plaque. Key words:Abfraction, restoration, S. mutans, composite, class V. PMID:28149461
Ciocîrlan, M; Lupu, A; Ciora, C; Fanică, Dana; Ispas, Maria; Preda, Carmen; Mănuc, M; Diculescu, M
Neoplastic lesions of the gastrointestinal tract have a large prevalence worldwide and in Romania. Their therapy is tailored to their TNM stage, which can be estimated using non invasive or minimally invasive imaging studies. Precursor lesions and superficial carcinomas are amenable to endoscopic therapy, providing that their endoscopic and/or endoscopic ultrasound aspect suggest a maximal extension to the submucosal layer. Polypectomy, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are ablative techniques used for their curative intent treatment. Large superficial carcinomas are to be removed by ESD as "en bloc" resection is essential to post procedure histological appraisal of the curative oncology nature of their resection. ESD complications rates and duration are nowadays reduced with the aid of "water-jet" technology, by combining submucosal fluid jet injection and electro-resection in a single knife.
Heikkilä, Annukka; Fermér, Christian; Hagström, Jaana; Louhimo, Johanna; Mäenpää, Hanna; Siironen, Päivi; Heiskanen, Ilkka; Nilsson, Olle; Arola, Johanna; Haglund, Caj
Follicular thyroid lesions are the bane of cytopathology. Differentiation between adenoma and carcinoma is impossible, and often these neoplasms are indistinguishable even from uninodular goitre. In other cancers as well, a theory of stem cells as the origin of cancer has been discussed in thyroid carcinogenesis. We aimed to examine a novel stem cell associated marker identified by monoclonal antibody HESC5:3 in follicular lesions in an attempt to find a marker for differential diagnosis in thyroid cytopathology. HESC5:3 was raised against and is specific for undifferentiated human embryonic stem cells. The epitope of this novel antibody is to be defined. Immunohistochemical expression of HESC5:3 was examined in clinical material comprised of follicular neoplasms (83 adenomas, 43 carcinomas) and non-neoplastic lesions (41 goitrous, 22 hyperplastic, 23 normal tissue specimens). Staining differed significantly between neoplastic and non-neoplastic lesions. Nuclear staining was increased in non-neoplastic cells, whereas in neoplastic cells expression was mainly cytoplasmic. There was no difference between benign and malignant lesions, suggesting a role in early tumourigenesis. In conclusion, the HESC5:3 epitope may be of benefit as a neoplasia marker in distinguishing between uninodular goitre and neoplasia. Characterization of the epitope would increase the interest in this promising new stem cell associated marker.
Hobbie, K R; DeAngelo, A B; George, M H; Law, J M
Small fish models have been used for decades in carcinogenicity testing. Demonstration of common morphological changes associated with specific mechanisms is a clear avenue by which data can be compared across divergent phyletic levels. Dimethylnitrosamine, used in rats to model human alcoholic cirrhosis and hepatic neoplasia, is also a potent hepatotoxin and carcinogen in fish. We recently reported some striking differences in the mutagenicity of DMN in lambda cII transgenic medaka fish vs. Big Blue(®) rats, but the pre-neoplastic and neoplastic commonalities between the two models are largely unknown. Here, we focus on these commonalities, with special emphasis on the TGF-β pathway and its corresponding role in DMN-induced hepatic neoplasia. Similar to mammals, hepatocellular necrosis, regeneration, and dysplasia; hepatic stellate cell and "spindle cell" proliferation; hepatocellular and biliary carcinomas; and TGF-β1 expression by dysplastic hepatocytes all occurred in DMN-exposed medaka. Positive TGF-β1 staining increased with increasing DMN exposure in bile preductular epithelial cells, intermediate cells, immature hepatocytes and fewer mature hepatocytes. Muscle specific actin identified hepatic stellate cells in DMN-exposed fish. Additional mechanistic comparisons between animal models at different phyletic levels will continue to facilitate the interspecies extrapolations that are so critical to toxicological risk assessments.
Berman-Booty, Lisa D; Thomas-Ahner, Jennifer M; Bolon, Brad; Oglesbee, Michael J; Clinton, Steven K; Kulp, Samuel K; Chen, Ching-Shih; La Perle, Krista M D
Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of preneoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubuloacinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here, we describe the histologic and immunohistochemical features of 2 novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice and in male TRAMP mice without histologically apparent prostate tumors. In this article, we also calculate the incidences of the urethral carcinomas and renal tubuloacinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice.
Background Abnormal expression of Rho-GTPases has been reported in several human cancers. However, the expression of these proteins in cervical cancer has been poorly investigated. In this study we analyzed the expression of the GTPases Rac1, RhoA, Cdc42, and the Rho-GEFs, Tiam1 and beta-Pix, in cervical pre-malignant lesions and cervical cancer cell lines. Methods Protein expression was analyzed by immunochemistry on 102 cervical paraffin-embedded biopsies: 20 without Squamous Intraepithelial Lesions (SIL), 51 Low- grade SIL, and 31 High-grade SIL; and in cervical cancer cell lines C33A and SiHa, and non-tumorigenic HaCat cells. Nuclear localization of Rac1 in HaCat, C33A and SiHa cells was assessed by cellular fractionation and Western blotting, in the presence or not of a chemical Rac1 inhibitor (NSC23766). Results Immunoreacivity for Rac1, RhoA, Tiam1 and beta-Pix was stronger in L-SIL and H-SIL, compared to samples without SIL, and it was significantly associated with the histological diagnosis. Nuclear expression of Rac1 was observed in 52.9% L-SIL and 48.4% H-SIL, but not in samples without SIL. Rac1 was found in the nucleus of C33A and SiHa cells but not in HaCat cells. Chemical inhibition of Rac1 resulted in reduced cell proliferation in HaCat, C33A and SiHa cells. Conclusion Rac1 is expressed in the nucleus of epithelial cells in SILs and cervical cancer cell lines, and chemical inhibition of Rac1 reduces cellular proliferation. Further studies are needed to better understand the role of Rho-GTPases in cervical cancer progression. PMID:22443139
Zhang, Qingwei; Xie, Wenyan; Wang, Feng; Li, Rong Hong; Cui, Lina; Wang, Huifen; Fu, Xiuhong; Song, Jiayu
BACKGROUND This cross-sectional study aimed to investigate the prevalence of cervical lesions and evaluate risk factors for cervical intraepithelial neoplasia (CIN) among women taking part in cervical cancer screening in rural areas of Henan province, China. MATERIAL AND METHODS Cervical cancer screening using the ThinPrep cytologic test (TCT) and gynecologic exam was conducted on 1315 women age 20-68 years in rural areas of Henan province, China. Colposcopy and biopsies were carried out for histopathologic diagnosis when indicated. Univariate and multivariate logistic regressions were performed to evaluate risk factors associated with cervical lesions. RESULTS Among 1315 women screened, CIN prevalence detected by histopathology was 1.22% (0.38% of CIN 1, 0.76% of CIN 2, and 0.08% of CIN 3). Cervical cancer prevalence was 2.66%. Multivariate analysis confirmed risk factors for cervical lesions included older age (the 21-40 age group vs. the 41-66 age group, OR=0.13, 95% CI: 0.03~0.57), postmenopause (OR=0.11, 95% CI: 0.03~0.45), cervical inflammation (OR=0.06, 95% CI: 0.01~0.31), and smoking (OR=6.78, 95% CI: 1.20~38.23). CONCLUSIONS Older age (41-66 years), presence of HPV infection, postmenopause, cervical inflammation, and smoking are strong risk factors for cervical lesions among women in rural areas of Henan province, China. Particular efforts should be made to provide cervical cancer screening for these women.
Background Human Papillomavirus (HPV) high-risk (HR) types are the causal factor for cervical cancer and premalignant dysplasia. Data on frequency of HPV types provide a basis to design and evaluate HPV prevention programs. Taking into account the heterogeneity of HPV types across and within populations this study aims to access the HPV frequency in Brazilian women. Results We identified 24 different types of HPV, including a Betapapillomavirus and a likely new type, previously reported, from 132 women positive for the virus analysed by Hybrid Capture II assay. These women were infected by a single or multiple HPV types and 142 HPV strains were identified. HR types were found in 75% of women and HPV types 16, 18, 45, 58, and 66 had the highest frequency. Significant differences in frequency of HR HPV types were found for presence of cervical lesions, and for different HPV species and women age. Conclusions Compared with previous studies in Brazil, our data indicated differences in frequency and HPV type diversity, a significant association of other HR-types but HPV16 and 18 and cervical lesions, and a trend for distinct distribution of HPV types by age. PMID:21208414
Vazmitel, Marina; Pavlovsky, Michal; Kacerovska, Denisa; Michal, Michal; Kazakov, Dmitry V
Anogenital mammary-like glands (AMLG) may give rise to various pathologic lesions identical to those known in mammary pathology. Pseudoangiomatous stromal hyperplasia (PASH), a relatively frequent hormonal change associated with different benign and malignant processes in the breast, was only once mentioned in the literature concerning the pathology of AMLG. We present here a new case of PASH in a lesion of AMLG. The present case of PASH is remarkable because of its occurrence within a complex lesion evidencing the changes identical to or reminiscent of blunt duct adenosis, fibroadenoma and hidradenoma papilliferum. 2009 John Wiley & Sons A/S.
Andrews, C W; Jessup, J M; Goldman, H; Hayes, D F; Kufe, D W; O'Hara, C J; Steele, G D
The expression of DF3 was assessed by a monoclonal antibody in normal, inflammatory, and neoplastic conditions in the large bowel. Using immunohistochemistry, expression was examined in formalin-fixed paraffin-embedded biopsy and resection samples of 19 normal colonic mucosal specimens, 49 inflammatory lesions, 34 adenomas, and 38 primary colonic adenocarcinomas. In addition, Western blots of normal colonic mucosa and adenocarcinoma were examined. DF3 expression was detected in 84% of the adenocarcinomas with coarse membrane staining, intense positivity of luminal secretions, and focal cytoplasmic and intracytoplasmic vacuole staining. Nine of 32 areas of transitional mucosa revealed reactivity along apical membranes in crypt cells. Five adenomas containing carcinoma revealed DF3 positivity in the malignant areas only, whereas the remaining 29 were negative. Staining was membrane, luminal, and intracytoplasmic. Two examples of active ulcerative colitis revealed focal reactivity along the apical membrane of crypt cells. No other areas of staining were noted, including 12 cases containing dysplasia. Four of 10 other inflammatory lesions also revealed similar membrane reactivity in crypt cells. Normal colonic mucosa was nonreactive. Examples of normal colonic mucosa were negative for DF3 by Western blot analysis, whereas two carcinoma samples that reacted immunohistochemically were positive. DF3 is not detectable in normal colonic tissues. It is expressed focally and predominantly along the apical membrane of crypt cells in some inflammatory lesions and in the transitional mucosa of primary adenocarcinomas. Most adenocarcinomas of the colon and adenomas with foci of invasive carcinoma demonstrate reactivity in the cytoplasm and luminal secretions.
Burrai, Giovanni Pietro; Tanca, Alessandro; Cubeddu, Tiziana; Abbondio, Marcello; Polinas, Marta; Addis, Maria Filippa; Antuofermo, Elisabetta
Canine mammary tumors represent the most common neoplasm in female dogs, and the discovery of cancer biomarkers and their translation to clinical relevant assays is a key requirement in the war on cancer. Since the description of the 'Warburg effect', the reprogramming of metabolic pathways is considered a hallmark of pathological changes in cancer cells. In this study, we investigate the expression of two cancer-related metabolic enzymes, transketolase (TKT) and transketolase-like 1 (TKTL1), involved in the pentose phosphate pathway (PPP), an alternative metabolic pathway for glucose breakdown that could promote cancer by providing the precursors and energy required for rapidly growing cells. TKT and TKTL1 protein expression was investigated by immunohistochemistry in canine normal (N = 6) and hyperplastic glands (N = 3), as well as in benign (N = 11) and malignant mammary tumors (N = 17). TKT expression was higher in hyperplastic lesions and in both benign and malignant tumors compared to the normal mammary gland, while TKTL1 levels were remarkably higher in hyperplastic lesions, simple adenomas and simple carcinomas than in the normal mammary glands (P < 0.05). This study reveals that the expression of a key PPP enzyme varies along the evolution of canine mammary neoplastic lesions, and supports a role of metabolic changes in the development of canine mammary tumors.
Pereira, Celestino Esteves; Lynch, Jose Carlos
Background: The occurrence of a brain tumor or intracranial vascular lesion during pregnancy is a rare event, but when it happens, it jeopardizes the lives of both the mother and infant. It also creates challenges of a neurosurgical, obstetric, and ethical nature. A multidisciplinary approach should be used for their care. Methods: Between 1986 and 2015, 12 pregnant women diagnosed with brain tumors and 17 women with intracranial vascular lesion underwent treatment at the Neurosurgery Department of the Servidores do Estado Hospital and Rede D’Or/São Luis. The Neurosurgery Department teamed up with Obstetrics Anesthesiology Departments in establishing the procedures. The patients’ records, surgical descriptions, imaging studies, and histopathological material were reviewed. Results: Among 12 patients presenting with brain tumors, there were neither operative mortality nor fetal deaths. Among the vascular lesions, aneurysm rupture was responsible for bleeding in 6 instances. Arteriovenous malformation was diagnosed in 7 patients. In this subgroup, the maternal and fetal mortality rates were 11.7% and 23.7%, respectively. Conclusions: We can assert that the association between a brain tumor and vascular lesions with pregnancy is a very unusual event, which jeopardizes both the lives of the mother and infant. It remains incompletely characterized due to the rare nature of these potentially devastating events. Knowing the exact mechanism responsible for the interaction of pregnancy and with these lesions will improve the treatment of these patients. PMID:28303207
Freeman, Hugh J; Webber, Douglas L; Meneghetti, Adam T
A 65-year-old man with a history of previously resected colonic adenomas had an apparent cecal lesion detected during colonoscopy. The polyp proved to be a tubulovillous adenoma with high-grade dysplasia involving most of the body of the appendix along with the base of the cecum. The appendiceal mucosa is biologically similar to the colonic mucosa, yet remains relatively 'hidden' in screening and surveillance studies, which suggests important implications for evolving detection strategies in the follow-up of patients with a previous colon polyp or cancer resections. Although endoscopic removal of the appendix has been reported, treatment of these localized appendiceal lesions requires a wide surgical excision.
Herrington, C S
The terminology of non-invasive epithelial abnormalities associated with an elevated risk of having or developing invasive cervical carcinoma (pre-invasive lesions) has been modified frequently over time as understanding of the underlying biology, and approaches to disease management, have changed. The arguments are now converging on the conclusion that the most appropriate terminology for cervical squamous intraepithelial abnormalities should be two-tier rather than three-tier. Given the findings of the Lower Anogenital Squamous Terminology (LAST) project in the USA, which have recently been endorsed by the World Health Organisation classification of tumours of female reproductive organs, the recommended terms are low-grade and high-grade squamous intraepithelial lesion (SIL), with the option of including the relevant cervical intraepithelial neoplasia (CIN) grade in parentheses. Although, at first sight, this appears to represent only a small change, there is a fundamental conceptual difference between the systems. The CIN system requires, first, the identification of a CIN lesion and, second, the determination of its grade on a continuum, with subsequent division into three grades. The SIL system is based on the existence of two different forms of human papillomavirus (HPV) infection, with productive infection leading to low-grade SIL and transforming infection leading to high-grade SIL.
Li, J; Wang, Y Y; Nan, X; Tian, X F; Yan, T; Wang, P; Yin, Y; Liu, Y; Yuan, R; Wang, G Q; Fu, Y L
This study aimed to investigate human papilloma virus (HPV) genotypes among women with cervical lesions in Shaanxi Province, China, to obtain information regarding cervical lesion prevention and treatment. The study included 4508 HPV-positive subjects; cervical swab specimens were collected and tested for HPV infection status and HPV genotypes using polymerase chain reaction and reverse dot-blot hybridization. Women positive for HPV with cervical lesions, including chronic cervicitis, cervical intraepithelial neoplasia, and cervical squamous cell carcinoma (SCC), were examined; HPV-positive women with no cervical lesions were controls. Data were pooled and weighted estimates have been presented. For women with no cervical lesions and positive for one HPV genotype, HPV 52, 16, 58, 81, 33, and 56 were the most common; for multiple-HPV genotype infection, HPV 16, 52, 6, 18, 58, and 66 were the most common. Collectively, HPV 16, 58, 52, 18, 33, and 81 were the most common in women with cervical lesions. HPV 16 comprised 26.71% of single-genotype and 15.64% of multiple-genotype infections. The proportion of HPV-16-positive cases was 29.15%, which was the highest among all HPV genotypes (P < 0.01). Single-HPV genotype infection was the most common in cervical HPV infection (77.48%); infection with two HPV genotypes comprised 72.22% of multiple-genotype infections. The proportion of single-low-risk HPV genotype infections decreased with increase in cervical lesion severity; there were no single- or multiple-low-risk genotype HPV infections in cervical SCC patients. The proportion of multiple-genotype HPV infections with at least one high-risk genotype increased with cervical lesion severity.
Freeman, Hugh J; Webber, Douglas L; Meneghetti, Adam T
A 65-year-old man with a history of previously resected colonic adenomas had an apparent cecal lesion detected during colonoscopy. The polyp proved to be a tubulovillous adenoma with high-grade dysplasia involving most of the body of the appendix along with the base of the cecum. The appendiceal mucosa is biologically similar to the colonic mucosa, yet remains relatively ‘hidden’ in screening and surveillance studies, which suggests important implications for evolving detection strategies in the follow-up of patients with a previous colon polyp or cancer resections. Although endoscopic removal of the appendix has been reported, treatment of these localized appendiceal lesions requires a wide surgical excision. PMID:19440570
Eighteen years of experience with cervical screening in the Center for Social Gynecology in Marseilles has demonstrated the existence of a group at high risk of cervical dysplasia. Its characteristics are early initiation of sexual activity, sexually transmitted disease, sexual promiscuity, and an unfavorable socioeconomic environment. Precancerous lesions are sometimes observed before the age of 18. Pap tests are done during preabortion consultations at the Center except in very young patients, those who are too emotionally distressed, and those with inflammations from vaginitis. The test may be done before the abortion because in the first trimester the cells do not yet show changes that would interfere with interpretation of the Pap smear. Bleeding after the abortion interferes with reading the slide. Results of 405 Pap tests conducted during a reference period from August 1992 to July 1993 among women seeking abortions at the Center for Social Gynecology were compared to those of 1601 women undergoing gynecological examinations at two other centers. Among patients at the Center for Social Gynecology and the other two centers respectively, 3.5% and 1.4% were diagnosed with condylomas, 1.5% and 1.2% with dysplasia, and 1.25% and 0.5% with condylomas and dysplasia. During the reference period, only 20% of women were screened. The number of lesions detected suggests that a higher proportion of women should be screened in this population of women often lacking regular medical care.
Yin, Aijun; Zhang, Qing; Kong, Xiangnan; Jia, Lin; Yang, Ziyan; Meng, Lihua; Li, Li; Wang, Xiao; Qiao, Yunbo; Lu, Nan; Yang, Qifeng; Shen, Keng; Kong, Beihua
DNA methylation is clinically relevant to important tumorigenic mechanisms. This study evaluated the methylation status of candidate genes in cervical neoplasia and determined their diagnostic performance in clinical practice. Cervical cancer and normal cervix tissue was used to select the top 5 discriminating loci among 27 loci in 4 genes (CCNA1, CADM1, DAPK1, JAM3), and one locus of JAM3 (region M4) was identified and confirmed with 267 and 224 cervical scrapings from 2 independent colposcopy referral studies. For patients with atypical squamous cells of unknown significance and those with low-grade squamous intraepithelial lesion, with JAM3-M4 compared to a triage marker of hrHPV testing, the specificity for cervical intraepithelial neoplasia 3 CIN3 and cancer cases (CIN3+) / no neoplasia and CIN1 (CIN1−) was significantly increased, from 21.88 to 81.82 and 15.38 to 85.18, respectively. The corresponding positive predictive value (PPV) was increased from 26.47 to 57.14 and 18.52 to 63.64, respectively. For hrHPV-positive patients, compared to a triage marker of cytology testing, JAM3-M4 showed increased specificity and PPV, from 30.67 to 87.65 and 38.82 to 82.14, respectively. We assessed whether JAM3-M4 could distinguish productive from transforming CIN2; the coincidence rate of JAM3-M4 and P16 was as high as 60.5%. PMID:26517242
Zhang, Lei; Bi, Qingqing; Deng, Hua; Xu, Jing; Chen, Juan; Zhang, Meilian; Mu, Xiaofeng
Cervical cancer and its precursor, high-grade cervical intraepithelial neoplasia (CIN2/3), are associated with persistent high-risk human papillomavirus (HPV) infection. HPV genotype prevalence varies with severity of cervical lesions, patient age and geographical location. The aim of this study was to investigate HPV genotypes prevalence and attribution according to the severity of cervical lesions among Chinese women. A 4-year surveillance study was performed. A total of 1664 female patients were included and their cervical histological diagnosis consisted of cervical intraepithelial neoplasia grade 1 (CIN1, 376 cases), grade 2 (CIN2, 408 cases), grade 3 (CIN3, 336 cases) and invasive cervical cancers (ICC, 544 cases). HPV genotypes prevalence and attribution to cervical lesions were calculated and analyzed. The 95% confidence interval (CI) for proportion was also calculated. HPV positivity rates increased directly with cervical lesions severity (72.4% for CIN1, 81.4% for CIN2, 88.1% for CIN3 and 90.4% for ICC). Infections with multiple HPV types were inversely related to cervical lesions severity. HPV16, 52, 31, 33 and 58 were the most prevalent genotypes in ICC. 49.1% of squamous cell carcinoma, 65.1% of adenocarcinoma and 12.0-43.3% of cervical intraepithelial neoplasia could be attributed to vaccine-covered high-risk genotypes (HPV16/18). Inclusion of HPV52 and HPV31 in future vaccines would provide the highest marginal benefit in protection for individuals residing in this region. These findings provide information about HPV genotypes in this region which may be important to target with future vaccination and screening programs.
Knapp, Piotr A.
A CO2 laser device was used for treating cervical lesions in 1574 patients. Of the total, 163 were diagnosed as CIN. Patients were selected for the study as a result of mass screening during the period from 1988 to 1992 of Bialystok Province, Poland. Treatment of cervical lesions with laser proved to be effective. In the author's opinion it is an essential step in preventing cervical malignancy.
Guinot, Anna; Lehmann, Holger; Wild, Peter J; Frew, Ian J
The von Hippel-Lindau (VHL) tumour suppressor gene is bi-allelically inactivated in the majority of cases of clear cell renal cell carcinoma (ccRCC); however, Vhl knockout mouse models do not recapitulate human ccRCC, implying that additional mutations are required for tumour formation. Mutational inactivation of VHL sensitises renal epithelial cells to lose the primary cilium in response to other mutations or extracellular stimuli. Loss of cilia is believed to represent a second hit in VHL mutant cells that causes the development of cystic lesions that, in some cases, can progress to ccRCC. Supporting this idea, genetic ablation of the primary cilium by deletion of the kinesin family member 3A (Kif3a) gene cooperates with loss of Vhl to accelerate cyst formation in mouse kidneys. Additionally, aged Vhl/Trp53 double-mutant mice develop renal cysts and tumours at a relatively low incidence, suggesting that there is a genetic cooperation between VHL and TP53 mutation in the development of ccRCC. Here we generated renal epithelium-specific Kif3a/Trp53 and Vhl/Kif3a/Trp53 mutant mice to investigate whether primary cilium deletion would accelerate the development of cystic precursor lesions or cause their progression to ccRCC. Longitudinal microcomputed tomography (μCT) imaging and histopathological analyses revealed an increased rate of cyst formation, increased proportion of cysts with proliferating cells, higher frequency of atypical cysts as well as the development of neoplasms in Vhl/Kif3a/Trp53 mutant kidneys compared to Kif3a/Trp53 or Vhl/Kif3a mutant kidneys. These findings demonstrate that primary cilium loss, in addition to Vhl and Trp53 losses, promotes the transition towards malignancy and provide further evidence that the primary cilium functions as a tumour suppressor organelle in the kidney. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Ward, J M; Bernal, E; Buratto, B; Goodman, D G; Strandberg, J D; Schueler, R
Tetrachlorvinphos was fed at 8,000 or 16,000 ppm in diets to male and female (C57BL/6N X C3H/HeN)F1 mice for 80 weeks. Surviving mice were killed at 92 weeks, and all mice were completely necropsied. A high incidence of unusual nonneoplastic hepatic lesions in treated mice was present and characterized by pericellular fibrosis, hepatocyte nuclear pleomorphism, and intrasinusoidal foci of macrophages with intracytoplasmic crystalline structures. From 84 to 94% of the treated male mice and from 21 to 23% of the treated females had hepatocellular neoplasms. Only 17% of the control males and 7% of the control females had liver tumors. The induced tumors were frequently multiple in the liver, whereas the tumors in the controls were usually singular. The morphology of 241 liver tumors in 110 treated mice was different from that of tumors in controls. Liver tumors in control mice were generally composed of small basophillic hepatocytes. In treated mice, tumors were hepatocellular carcinomas composed of solid sheets of large basophilic or eosinophilic hepatocytes. Foci of prominent trabecular formation were seen in 51 tumors. Fifteen tumors were composed of small basophilic hepatocytes with oval cells interposed among them. Foci of capillary formation were noted in 3 of these tumors. In addition, 7 more typical hemangiosarcomas forming sinusoids and with thrombosis were observed.
Murta, Eddie Fernando Candido; de Souza, Flávio Henrique Caetano; de Souza, Maria Azniv Hazarabedian; Adad, Sheila Jorge
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.
Morosetti, Giulia; Criscuolo, Anna Angela; Santi, Flavia; Perno, Carlo Federico; Piccione, Emilio; Ciotti, Marco
Ellagic acid is a phenolic compound naturally present in nuts and berries. Several studies have demonstrated that this bioactive compound has antioxidant, chemopreventive and antiviral activity. Annona muricata is a type of fruit tree with a long history of traditional use. A number of properties have been attributed to different parts of the plant, including anticancer and antioxidant activities. In the current study, a complex based on ellagic acid, Annona Muricata and antioxidant factors (an ellagic acid complex) was administered to a group of human papilloma virus (HPV) infected women with and without cervical lesions, for 12 months. Its effect on HPV clearance and cervical cytological outcomes was assessed and a group of women with the same clinical features who did not receive the ellagic acid complex served as a control. A positive correlation was observed between intake of ellagic acid complex and negative Pap test following 6 and 12 months of treatment (χ(2) test: 0.041 and 0.014, respectively). Women treated with the ellagic acid complex were less likely to be diagnosed with an abnormal Pap smear at 6 months [Odds ratio (OR): 0.39; 95% confidence interval (CI) 0.14-1.06] and 12 months (OR: 0.35; 95% CI 0.13-0.89), compared with the control group. After adjusting for confounding factors including age and smoking habit, this association remained significant. No effect was observed on HPV clearance or viral integration. The data from the current study suggest a protective effect of the ellagic acid complex on cervical cells, possibly through apoptosis, cell cycle arrest and repair mechanisms.
Morosetti, Giulia; Criscuolo, Anna Angela; Santi, Flavia; Perno, Carlo Federico; Piccione, Emilio; Ciotti, Marco
Ellagic acid is a phenolic compound naturally present in nuts and berries. Several studies have demonstrated that this bioactive compound has antioxidant, chemopreventive and antiviral activity. Annona muricata is a type of fruit tree with a long history of traditional use. A number of properties have been attributed to different parts of the plant, including anticancer and antioxidant activities. In the current study, a complex based on ellagic acid, Annona Muricata and antioxidant factors (an ellagic acid complex) was administered to a group of human papilloma virus (HPV) infected women with and without cervical lesions, for 12 months. Its effect on HPV clearance and cervical cytological outcomes was assessed and a group of women with the same clinical features who did not receive the ellagic acid complex served as a control. A positive correlation was observed between intake of ellagic acid complex and negative Pap test following 6 and 12 months of treatment (χ2 test: 0.041 and 0.014, respectively). Women treated with the ellagic acid complex were less likely to be diagnosed with an abnormal Pap smear at 6 months [Odds ratio (OR): 0.39; 95% confidence interval (CI) 0.14–1.06] and 12 months (OR: 0.35; 95% CI 0.13–0.89), compared with the control group. After adjusting for confounding factors including age and smoking habit, this association remained significant. No effect was observed on HPV clearance or viral integration. The data from the current study suggest a protective effect of the ellagic acid complex on cervical cells, possibly through apoptosis, cell cycle arrest and repair mechanisms. PMID:28454338
Rollins, Andrew M.; Westphal, Volker; Das, Ananya; Pfau, Patrick; Chak, Amitabh; Wong, Richard C. K.; Sivak, Michael J., Jr.; Izatt, Joseph A.
Optical coherence tomography (OCT) is a novel biomedical imaging technique that uses low-coherence optical interferometry to obtain micron-scale resolution cross- sectional images of tissue microstructure noninvasively. OCT fills a valuable niche in imaging of tissue structure, providing subsurface imaging with high spatial resolution (on the order of 10 micrometers) and penetration depths of 1 - 2 mm with no contact or matching medium needed between the probe and the tissue. An OCT system for gastrointestinal (GI) endoscopy has been developed using a small-diameter rotary-scanning probe compatible with standard GI endoscopes and capable of imaging in real-time. To date more than 100 volunteers have been imaged during routine upper and lower endoscopic procedures. Results of imaging in normal organs have demonstrated visualization of morphological layers (epithelium, lamina propria, muscularis mucosa, submucosa, muscularis propria) and microscopic structures (glands, villi, crypts, vessels) in all endoscopically accessible GI organs. It has been observed in more than 30 patients that the EOCT appearance of Barrett's mucosa is clearly differentiable from normal gastric or esophageal mucosa. Furthermore, the EOCT appearance of dysplasia and neoplastic lesions, including adenocarcenoma in Barrett's and villous tumor in colon have been observed and are under investigation. Preliminary data indicate the potential of EOCT for routine clinical diagnostics in GI tissues, including early cancer detection and staging and detection of tumor margins.
Munday, John S; French, Adrienne F
Oral squamous cell carcinomas (OSCCs) are common feline cancers. Why OSCCs are so common in cats is unknown; however, 25% of human OSCCs are caused by papillomaviruses (PVs). Two feline oral PVs (FcaPV-1 and 4) are recognized. As PVs are highly host and location specific, if PVs do cause feline OSCCs, FcaPV-1 and 4 are the most likely etiological agents. PCR primers specific for FcaPV-1 amplified DNA from 1 of 36 feline OSCCs and 1 of 16 inflammatory oral lesions. No DNA was amplified by primers specific for FcaPV-4. PV DNA was not amplified from any additional sample using consensus primers. No PV cytopathology was visible in the OSCC that contained FcaPV-1 DNA, but viral cytopathology was present in a focus of epithelial hyperplasia in the non-neoplastic sample. This study does not support a PV etiology of feline OSCCs, but shows that FcaPV-1 can asymptomatically infect the mouth of cats. Copyright © 2015 Elsevier Ltd. All rights reserved.
Jakupović, Selma; Anić, Ivica; Ajanović, Muhamed; Korać, Samra; Konjhodžić, Alma; Džanković, Aida; Vuković, Amra
Objective: The present study aims to investigate the influence of presence and shape of cervical lesions on biomechanical behavior of mandibular first premolar, subjected to two types of occlusal loading using three-dimensional (3D) finite element method (FEM). Materials and Methods: 3D models of the mandibular premolar are created from a micro computed tomography X-ray image: model of sound mandibular premolar, model with the wedge-shaped cervical lesion (V lesion), and model with saucer-shaped cervical lesion (U lesion). By FEM, straining of the tooth tissues under functional and nonfunctional occlusal loading of 200 (N) is analyzed. For the analysis, the following software was used: CTAn program 1.10 and ANSYS Workbench (version 14.0). The results are presented in von Mises stress. Results: Values of calculated stress in all tooth structures are higher under nonfunctional occlusal loading, while the functional loading is resulted in homogeneous stress distribution. Nonfunctional load in the cervical area of sound tooth model as well as in the sub-superficial layer of the enamel resulted with a significant stress (over 50 [MPa]). The highest stress concentration on models with lesions is noticed on the apex of the V-shaped lesion, while stress in saucer U lesion is significantly lower and distributed over wider area. Conclusion: The type of the occlusal teeth loading has the biggest influence on cervical stress intensity. Geometric shape of the existing lesion is very important in the distribution of internal stress. Compared to the U-shaped lesions, V-shaped lesions show significantly higher stress concentrations under load. Exposure to stress would lead to its progression. PMID:27403064
Li, Guiming; Rivas, Paul; Bedolla, Roble; Thapa, Dinesh; Reddick, Robert L; Ghosh, Rita; Kumar, Addanki P
SIRT1 (mammalian ortholog of the yeast silent information regulator 2) is a NAD-dependent histone deacetylase belonging to the multigene family of sirtuins. Anecdotal and epidemiologic observations provide evidence for beneficial effects of the calorie restriction mimetic resveratrol (RES), a SIRT1 activator in preventing cardiovascular diseases and cancer. Although SIRT1 possesses both tumorigenic and antitumorigenic potential, the molecular mechanisms underlying SIRT1-mediated tumor progression or inhibition are poorly understood. In this study, we investigated the role of SIRT1 in multiple human prostate cancer cell lines and prostate-specific PTEN knockout mouse model using resveratrol. Androgen-independent prostate cancer cell lines (C42B, PC3, and DU145) express higher levels of SIRT1 than androgen-responsive (LNCaP) and nontumorigenic prostate cells (RWPE-1). Resveratrol enhanced this expression without any significant effect on SIRT1 enzymatic activity. Inhibition of SIRT1 expression using shRNA enhanced cell proliferation and inhibited autophagy by repressing phosphorylation of S6K and 4E-BP1. These biologic correlates were reversed in the presence of resveratrol. Analysis of prostates from dietary intervention with resveratrol showed a significant reduction in prostate weight and reduction in the incidence of high-grade prostatic intraepithelial neoplastic (HGPIN) lesions by approximately 54% with no significant change in body weight. Consistent with the in vitro findings, resveratrol intervention in the PTEN knockout mouse model was associated with reduction in the prostatic levels of mTOR complex 1 (mTORC1) activity and increased expression of SIRT1. These data suggest that SIRT1/S6K-mediated inhibition of autophagy drives prostate tumorigenesis. Therefore, modulation of SIRT1/S6K signaling represents an effective strategy for prostate cancer prevention. ©2012 AACR.
Konstantinova, Anastasia M; Kacerovska, Denisa; Michal, Michal; Kazakov, Dmitry V
Anogenital mammary-like glands (AGMLG) are nowadays considered a normal component of the anogenital area. Lesions affecting AGMLG are similar to those seen in breast. We present a case of a complex neoplastic lesion of the AGMLG with mixed features of fibroadenoma and hidradenoma papilliferum combined with pseudoangiomatous stromal hyperplasia. Multinucleated cells were detected in the pseudoangiomatous stromal hyperplasia areas as seen in some patients with neurofibromatosis type 1. The neoplasm is similar to rare mammary composite neoplasms that feature simultaneously patterns of a fibroepithelial neoplasms and intraductal papilloma.
Rodrigues, L C; Speck, N M de Gois; Focchi, G R de Azevedo; Schimidt, M A; Marques, R M; Ribalta, J C Lascasas
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.
Altavilla, Giuseppe; Trabanelli, Cecilia; Merlin, Michela; Caputo, Antonella; Lanfredi, Massimo; Barbanti-Brodano, Giuseppe; Corallini, Alfredo
To study the role in AIDS pathogenesis of the human immunodeficiency virus type 1 (HIV-1) Tat protein, a transactivator of viral and cellular genes, we generated transgenic mice with a recombinant DNA containing BK virus (BKV) early region and the HIV-1 tat gene, directed by its own promoter-enhancer. DNA hybridization revealed that the transgene is stably maintained in all organs of transgenic mice as a tandem insertion in a number of copies ranging from 5 to 20 per cell. In addition, tat and BKV RNA were expressed in all tissues. Transgenic mice developed three types of lesions: 1) tumors, 2) hyperplastic and dysplastic lesions, and 3) non-neoplastic lesions. Tumors of different histotypes, such as lymphomas, adenocarcinomas of skin glands, leiomyosarcomas, skin squamous cell carcinomas, hepatomas, hepatocarcinomas, and cavernous liver hemangiomas, developed in 29% of transgenic animals. The majority of tumors were malignant, invasive, and producing metastases. Conversely, tumors of only two histotypes (lymphomas and adenocarcinomas of skin glands) appeared in control mice. Hyperplastic and dysplastic lesions were more frequent in transgenic than in control mice and involved the skin or its adnexes, the liver and the rectum, indicating multiple targets for the activity of the transgene. Pyelonephritis, frequently complicated with hydronephrosis, inflammatory eye lesions, and amyloid depositions represented the most frequent non-neoplastic lesions detected in transgenic mice. Many of the pathological findings observed in this animal model are comparable to similar lesions appearing in AIDS patients, suggesting a relevant role for Tat in the pathogenesis of such lesions during the course of AIDS. PMID:10233861
Sadaf, Durre; Ahmad, Zubair
To assess the association of occlusal forces and brushing with non-carious cervical lesions (NCCL). It was a Cross-sectional study. The study was conducted in Dental clinics, Department of Surgery, The Aga Khan University Hospital Karachi. The study duration was from 1(st) January 2009 to 28(th) Feb 2009. Ninety patients visiting dental clinic were examined clinically. Presence of Non- carious cervical lesions, broken restorations, fractured cusps, presence of occlusal facets, brushing habits, Para functional habits were assessed. All the relevant information and clinical examination were collected on a structured Performa and was analyzed using SPSS version 14.0. . Chi square χ(2) test was applied to assess association among different categorical variables. Twenty three (26%) females and 67 (74%) males were included in the study. Thirty five of them (38.9%) were found to have Non-carious cervical lesions. Presence of NCCL has no association with gender (P value 0.458). A significant association was found between NCCL and teeth sensitivity (P value 0.002).The association between use of hard tooth brush and Non-carious cervical lesions was found significant (P value <0.001). However the association among Non-carious cervical lesions and fractured cups, broken restoration, teeth grinding, jaw clenching, pan chalia chewing and frequency of teeth brushing were insignificant. Hard tooth brushing and teeth sensitivity have significant association with Non-carious cervical lesions. The role of occlusal wear in the formation of NCCL is not significant.
Xiao, Meizhu; Xu, Qiuxiang; Li, Hongyan; Gao, Huiqiao; Bie, Yachun; Zhang, Zhenyu
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
Santos, Sara; Bastos, Estela; Baptista, Cláudia S.; Sá, Daniela; Caloustian, Christophe; Guedes-Pinto, Henrique; Gärtner, Fátima; Gut, Ivo G.; Chaves, Raquel
The human ERBB2 proto-oncogene is widely considered a key gene involved in human breast cancer onset and progression. Among spontaneous tumors, mammary tumors are the most frequent cause of cancer death in cats and second most frequent in humans. In fact, naturally occurring tumors in domestic animals, more particularly cat mammary tumors, have been proposed as a good model for human breast cancer, but critical genetic and molecular information is still scarce. The aims of this study include the analysis of the cat ERBB2 gene partial sequences (between exon 17 and 20) in order to characterize a normal and a mammary lesion heterogeneous populations. Cat genomic DNA was extracted from normal frozen samples (n = 16) and from frozen and formalin-fixed paraffin-embedded mammary lesion samples (n = 41). We amplified and sequenced two cat ERBB2 DNA fragments comprising exons 17 to 20. It was possible to identify five sequence variants and six haplotypes in the total population. Two sequence variants and two haplotypes show to be specific for cat mammary tumor samples. Bioinformatics analysis predicts that four of the sequence variants can produce alternative transcripts or activate cryptic splicing sites. Also, a possible association was identified between clinicopathological traits and the variant haplotypes. As far as we know, this is the first attempt to examine ERBB2 genetic variations in cat mammary genome and its possible association with the onset and progression of cat mammary tumors. The demonstration of a possible association between primary tumor size (one of the two most important prognostic factors) and the number of masses with the cat ERBB2 variant haplotypes reveal the importance of the analysis of this gene in veterinary medicine. PMID:22489125
Santos, Sara; Bastos, Estela; Baptista, Cláudia S; Sá, Daniela; Caloustian, Christophe; Guedes-Pinto, Henrique; Gärtner, Fátima; Gut, Ivo G; Chaves, Raquel
The human ERBB2 proto-oncogene is widely considered a key gene involved in human breast cancer onset and progression. Among spontaneous tumors, mammary tumors are the most frequent cause of cancer death in cats and second most frequent in humans. In fact, naturally occurring tumors in domestic animals, more particularly cat mammary tumors, have been proposed as a good model for human breast cancer, but critical genetic and molecular information is still scarce. The aims of this study include the analysis of the cat ERBB2 gene partial sequences (between exon 17 and 20) in order to characterize a normal and a mammary lesion heterogeneous populations. Cat genomic DNA was extracted from normal frozen samples (n = 16) and from frozen and formalin-fixed paraffin-embedded mammary lesion samples (n = 41). We amplified and sequenced two cat ERBB2 DNA fragments comprising exons 17 to 20. It was possible to identify five sequence variants and six haplotypes in the total population. Two sequence variants and two haplotypes show to be specific for cat mammary tumor samples. Bioinformatics analysis predicts that four of the sequence variants can produce alternative transcripts or activate cryptic splicing sites. Also, a possible association was identified between clinicopathological traits and the variant haplotypes. As far as we know, this is the first attempt to examine ERBB2 genetic variations in cat mammary genome and its possible association with the onset and progression of cat mammary tumors. The demonstration of a possible association between primary tumor size (one of the two most important prognostic factors) and the number of masses with the cat ERBB2 variant haplotypes reveal the importance of the analysis of this gene in veterinary medicine.
Botezatu, Anca; Socolov, Demetra; Iancu, Iulia V; Huica, Irina; Plesa, Adriana; Ungureanu, Carmen; Anton, Gabriela
The aim of this study was to investigate the role of methylenetetrahydrofolate reductase (MTHFR) polymorphisms and MTHFR methylation pattern in cervical lesions development among women from Romania, a country with high prevalence of human papillomavirus (HPV) cervical infections. To achieve this goal, blood samples and cervical cytology specimens (n = 77)/tumour tissue specimens (n = 23) were investigated. As control, blood and negative cytological smears (n = 50) were used. A statistically significant association was found between T allele of C677T polymorphism and cervical lesions, heterozygote women presenting a threefold increased risk (normal/cervical lesions and tumours: wild homozygote 34/41 (0.68/0.41), heterozygote 14/51 (0.28/0.51), mutant homozygote 2/8 (0.04/0.08); OR = 3.081, P = 0.0035). Using χ square test for the control group, the HPV-negative and HPV-positive patients with cervix lesions, a significant correlation between viral infection and T allele of C677T polymorphism (P = 0.0287) was found. The MTHFR promoter was methylated in all HGSIL and tumour samples, significant differences being noted between HPV-positive samples, control group and cases of cervical dysplastic lesions without HPV DNA (P < 0. 0001) and between samples from patients with high-risk (hr)HPV versus low-risk (lr)HPV (P = 0.0026). No correlations between polymorphisms and methylation were observed. In Romania, individuals carrying T allele are susceptible for cervical lesions. MTHFR promoter methylation is associated with cervical severity lesions and with hrHPV. PMID:23444906
Botezatu, Anca; Socolov, Demetra; Iancu, Iulia V; Huica, Irina; Plesa, Adriana; Ungureanu, Carmen; Anton, Gabriela
The aim of this study was to investigate the role of methylenetetrahydrofolate reductase (MTHFR) polymorphisms and MTHFR methylation pattern in cervical lesions development among women from Romania, a country with high prevalence of human papillomavirus (HPV) cervical infections. To achieve this goal, blood samples and cervical cytology specimens (n = 77)/tumour tissue specimens (n = 23) were investigated. As control, blood and negative cytological smears (n = 50) were used. A statistically significant association was found between T allele of C677T polymorphism and cervical lesions, heterozygote women presenting a threefold increased risk (normal/cervical lesions and tumours: wild homozygote 34/41 (0.68/0.41), heterozygote 14/51 (0.28/0.51), mutant homozygote 2/8 (0.04/0.08); OR = 3.081, P = 0.0035). Using χ square test for the control group, the HPV-negative and HPV-positive patients with cervix lesions, a significant correlation between viral infection and T allele of C677T polymorphism (P = 0.0287) was found. The MTHFR promoter was methylated in all HGSIL and tumour samples, significant differences being noted between HPV-positive samples, control group and cases of cervical dysplastic lesions without HPV DNA (P < 0. 0001) and between samples from patients with high-risk (hr)HPV versus low-risk (lr)HPV (P = 0.0026). No correlations between polymorphisms and methylation were observed. In Romania, individuals carrying T allele are susceptible for cervical lesions. MTHFR promoter methylation is associated with cervical severity lesions and with hrHPV. © 2013 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Francisconi, Luciana Fávaro; Scaffa, Polliana Mendes Candia; de Barros, Vivian Rosa dos Santos Paes; Coutinho, Margareth; Francisconi, Paulo Afonso Silveira
Glass ionomer based materials are clinically popular in several areas of restorative dentistry, but restoration of cervical lesions has proven particularly successful. Various etiologies, conformations, locations and structural characteristics make non-carious cervical lesions more challenging to adhesive restorative procedures and marginal seal in the long run. Due to their characteristics, glass ionomer cements (GICs) have precise indication for these cases. Moreover, the use of a GIC base underneath composite resin, the so-called "sandwich" or mixed technique, allows associating the good characteristics of composite resins and GICs, and has been considered quite useful in the restoration of non-carious cervical defects. The aim of this paper is to critically review the literature and discuss peculiar features of GICs regarding their role in the restoration of non-carious cervical lesions. PMID:19936509
Background Infection with human papillomavirus (HPV) is associated with uterine cervical intraepithelial neoplasia (CIN) and invasive cancers (ICC). Approximately 80% of ICC cases are diagnosed in under-developed countries. Vaccine development relies on knowledge of HPV genotypes characteristic of LSIL, HSIL and cancer; however, these genotypes remain poorly characterized in many African countries. To contribute to the characterization of HPV genotypes in Northeastern Tanzania, we recruited 215 women from the Reproductive Health Clinic at Kilimanjaro Christian Medical Centre. Cervical scrapes and biopsies were obtained for cytology and HPV DNA detection. Results 79 out of 215 (36.7%) enrolled participants tested positive for HPV DNA, with a large proportion being multiple infections (74%). The prevalence of HPV infection increased with lesion grade (14% in controls, 67% in CIN1 cases and 88% in CIN2-3). Among ICC cases, 89% had detectable HPV. Overall, 31 HPV genotypes were detected; the three most common HPV genotypes among ICC were HPV16, 35 and 45. In addition to these genotypes, co-infection with HPV18, 31, 33, 52, 58, 68 and 82 was found in 91% of ICC. Among women with CIN2-3, HPV53, 58 and 84/83 were the most common. HPV35, 45, 53/58/59 were the most common among CIN1 cases. Conclusions In women with no evidence of cytological abnormalities, the most prevalent genotypes were HPV58 with HPV16, 35, 52, 66 and 73 occurring equally. Although numerical constraints limit inference, findings that 91% of ICC harbor only a small number of HPV genotypes suggests that prevention efforts including vaccine development or adjuvant screening should focus on these genotypes. PMID:22081870
Silva, Daliana Caldas; Gonçalves, Ana Katherine; Cobucci, Ricardo Ney; Mendonça, Roberta Cecília; Lima, Paulo Henrique; Cavalcanti, Geraldo
This study evaluated the immunohistochemical (IHC) expression of p16, p53 and Ki-67 in precancerous lesions and in cervical cancer (CC). Identification and review of publications assessing IHC expression in cervical intraepithelial neoplasia (CIN) and CC until February 15, 2017. Systematic review of studies in women with and without cervical lesions in order to evaluate whether there is overexpression of these biomarkers. A total of 28 publications met the criteria which included 6005 patients. The analysis showed that there is higher IHC expression of these biomarkers associated with the more severe lesions. Nineteen out of 22 evaluated studies have shown that there is a higher p16 expression in more severe lesions (CC), while in p53 expression only 4 out of the 9 studies showed a higher expression among more severe cases. Regarding the Ki-67 expression, it was observed that 9 out of 14 studies showed higher expression in more severe lesions. A complete absence of or just minimal IHC expression was observed in the normal cervical epithelium, whilst a significant increase in the expression of these biomarkers was detected according to the severity of lesions. Results suggest that these biomarkers can be considered useful tools for discriminating between the stages of the progressive cervical disease. Copyright © 2017. Published by Elsevier GmbH.
Rakheja, Rajan; Chandarana, Hersh; DeMello, Linda; Jackson, Kimberly; Geppert, Christian; Faul, David; Glielmi, Christopher; Friedman, Kent P
The purpose of this study was to assess the correlation between standardized uptake value (SUV) and apparent diffusion coefficient (ADC) of neoplastic lesions in the use of a simultaneous PET/MRI hybrid system. Twenty-four patients with known primary malignancies underwent FDG PET/CT. They then underwent whole-body PET/MRI. Diffusion-weighted imaging was performed with free breathing and a single-shot spin-echo echo-planar imaging sequence with b values of 0, 350, and 750 s/mm(2). Regions of interest were manually drawn along the contours of neoplastic lesions larger than 1 cm, which were clearly identified on PET and diffusion-weighted images. Maximum SUV (SUVmax) on PET/MRI and PET/CT images, mean SUV (SUVmean), minimum ADC (ADCmin), and mean ADC (ADCmean) were recorded on PET/MR images for each FDG-avid neoplastic soft-tissue lesion with a maximum of three lesions per patient. Pearson correlation coefficient was used to asses the following relations: SUVmax versus ADCmin on PET/MR and PET/CT images, SUVmean versus ADCmean, and ratio of SUVmax to mean liver SUV (SUV ratio) versus ADCmin. A subanalysis of patients with progressive disease versus partial treatment response was performed with the ratio of SUVmax to ADCmin for the most metabolically active lesion. Sixty-nine neoplastic lesions (52 nonosseous lesions, 17 bone metastatic lesions) were evaluated. The mean SUVmax from PET/MRI was 7.0 ± 6.0; SUVmean, 5.6 ± 4.6; mean ADCmin, 1.10 ± 0.58; and mean ADCmean, 1.48 ± 0.72. A significant inverse Pearson correlation coefficient was found between PET/MRI SUVmax and ADCmin (r = -0.21, p = 0.04), between SUVmean and ADCmean (r = -0.18, p = 0.07), and between SUV ratio and ADCmin (r = -0.27, p = 0.01). A similar inverse Pearson correlation coefficient was found between the PET/CT SUVmax and ADCmin. Twenty of 24 patients had previously undergone PET/CT; five patients had a partial treatment response, and six had progressive disease according to Response Evaluation
Ritter, André V; Grippo, John O; Coleman, Thomas A; Morgan, Michèle E
The purpose of this study was to report the prevalence of carious and non-carious cervical lesions in the teeth of five archaeological populations. A secondary purpose was to report the association between age, gender, diet, tooth wear, carious cervical lesions, and non-carious cervical lesions. One hundred and four archaeological specimens from subjects originating from five distinct geographical areas were examined to detect the presence of carious cervical lesions, non-carious cervical lesions, and tooth wear. Data were tabulated and statistics used to describe prevalence and non-causal associations. Carious cervical lesions were prevalent in all populations except among Labradoreans, while non-carious cervical lesions were found predominantly in Mexicans. The authors found no association between non-carious cervical lesions and age, gender, and diet in any of the populations. Tooth wear was noted in all populations, but the highest rates of severe wear were noted among the Labradoreans and New Mexicans. Age was associated with tooth wear in all populations except Ohioans. There was no association between tooth wear and non-carious cervical lesions. The prevalence of carious cervical lesions among the five archaeological populations studied ranged from 0 to 65%. Non-carious cervical lesions were not prevalent among these populations, being found predominantly in Mexicans (26%). CLINICAL SIGNIFICANCE Historically, carious and non-carious cervical lesions can be found in individuals with no access to modern oral hygiene tools. The findings of this study are not conclusive, however, as the associations described are not causal. (J Esthet Restor Dent 21:324-335, 2009).
Wang, Wenpeng; An, Jusheng; Song, Yan; Wang, Minjie; Huang, Manni; Wu, Lingying
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
Lu, Rong; Xiao, Ying; Liu, Minhui; Shi, Dazun
This study aimed to evaluate the clinical value of ultrasound elastography in the differential diagnosis of benign and malignant cervical lesions and to compare the accuracy of the elasticity score and strain ratio in differentiating cervical lesions. B-mode sonography and ultrasound elastography were performed on 84 cervical lesions (40 benign and 44 malignant) in 84 patients. All of the images were obtained transvaginally. The elasticity score was determined by a 5-point scoring method. Calculation of the strain ratio was based on a comparison of the average strain measured in the lesion with the adjacent tissue of the same depth, size, and shape. The findings were compared with histopathologic results. With the use of receiver operating characteristic curves, the diagnostic value of the elasticity score and strain ratio methods was determined. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the elasticity score in the differential diagnosis of cervical lesions were 81.8%, 85.0%, 83.3%, 85.7%, and 81.0%, respectively, whereas those of the strain ratio were 90.9%, 90.0%, 90.5%, 90.9%, and 90.0%. A strain ratio cutoff value of 4.525 was used as a standard to distinguish benign from malignant lesions. The strain ratio values of malignant lesions were much higher than those of benign lesions (range, 4.85-8.91 versus 0.62-4.50). The differences were statistically significant (P < .01). Ultrasound elastography is a promising technique that is easy and rapid to perform and can help identify cervical lesions that are likely to be malignant. It is obvious that the strain ratio yielded better results than the elasticity score. Both methods are semiquantitative, but quantification of the strain ratio is finer than that of the elasticity score.
Porzionato, Andrea; Macchi, Veronica; Aprile, Anna; De Caro, Raffaele
Cervical soft tissue lesions have rarely been described in the shaken baby syndrome; they include ruptures of intervertebral discs and haemorrhages in the ligamenta flava, and in the interspinal and sternocleidomastoid muscles. We present here the autopsy case of a 30-month old girl who suffered an assault with multiple injury mechanisms, i.e., beating, sexual abuse and shaking trauma. External examination of the neck did not reveal bruises or excoriations, but cervical dissection showed haemorrhagic infiltration of the clavicular head of the sternocleidomastoid muscle, carotid region, posterior musculature of the pharynx and oesophagus, and retro-pharyngeal/oesophageal spaces. These findings were ascribed to the repeated violent movements of shaking trauma. The case presented confirms the occurrence of cervical soft tissue lesions in the shaken baby syndrome and reports injuries which have not previously been described. In suspected cases of shaken baby syndrome, particular attention must be paid to the examination of cervical soft tissue structures.
Meta-analysis of type-specific human papillomavirus prevalence in Iranian women with normal cytology, precancerous cervical lesions and invasive cervical cancer: Implications for screening and vaccination.
Jalilvand, Somayeh; Shoja, Zabihollah; Nourijelyani, Keramat; Tohidi, Hamid Reza; Hamkar, Rasool
To predict the impact of current vaccines on cervical cancer and for the improvement of screening programs, regional data on distribution of human papillomavirus (HPV) types in women with or without cervical cancer is crucial. The present meta-analysis intend to comprehensively evaluate the HPV burden in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology, as these data will help decision making in regards with screening programs and HPV vaccination in Iran. To determine the HPV prevalence and type distribution in Iranian women with or without cervical cancer, 20 published studies were included in this meta-analysis. In total, 713, 124, 104, 60, and 2577 women invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal were reviewed, respectively. Overall HPV prevalence in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology were 77.4%, 71.8%, 65.3%, 61.7%, and 8.4%, respectively. The six most common types were HPV 16, 18, 6/11, 31, and 33; among them HPV 16 was the most frequent type in all five different groups. According to this study, it was estimated that HPV vaccines could have a great impact on prevention of cervical cancer in Iran. In conclusion, this meta-analysis highlights the necessity of introducing vaccination program in Iran.
Sequetto, Priscila L; Oliveira, Tânia T; Maldonado, Izabel R S C; Augusto, Luís Eugênio F; Mello, Vanessa J; Pizziolo, Virginia R; Almeida, Márcia R; Silva, Marcelo E; Novaes, Rômulo D
The aim of this study was to investigate the effect of Naringin on pre-neoplastic colorectal lesions induced by chemical carcinogen in rats. Female Wistar rats weighing 130.8±27.1 g received weekly one subcutaneous injection of 1,2-dimethylhydrazine (DMH, 20 mg/kg) for 10 weeks. The animals were divided into 5 groups with 6 animals in each group. Group 1: 0.9% saline; Group 2: DMH+0.9% saline; Group 3: DMH+Naringin (10 mg/kg); Group 4: DMH+Naringin (100 mg/kg); Group 5: DMH+Naringin (200 mg/kg). G2 and G3 showed a significant increase in ACF number, AgNOR/nucleus and mitosis compared to G1. G4 and G5 presented a significant reduction in these parameters compared to G2. The number of cells producing acidic and neutral mucins, red blood cells and the level of antioxidant minerals, such as copper, magnesium, selenium and zinc, were significantly reduced in G2 and G3, but similar in G4 and G5 compared to G1. Naringin, especially at 200 mg/kg, was effective in reducing the number of pre-neoplastic lesions in rats exposed to DMH. Some of these effects may be due to reduction in cellular proliferation and tissue levels of iron together with the recovery of antioxidant mineral levels induced by this flavonoid.
Ducancelle, A; Legrand, M C; Pivert, A; Veillon, P; Le Guillou-Guillemette, H; De Brux, M A; Beby-Defaux, A; Agius, G; Hantz, S; Alain, S; Catala, L; Descamps, P; Postec, E; Caly, H; Charles-Pétillon, F; Labrousse, F; Lunel, F; Payan, C
Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HR-HPV). Conventional human papillomavirus (HPV) testing requires cervical sampling. However, vaginal and urine self-sampling methods are more acceptable for patients and result in increased participation when they are available in screening programs. In this context, we have developed a non-invasive screening method via the detection of HPV DNA in urine samples. To compare HPV viral loads and genotypes in paired cervical and urine samples, and to assess correlation between virological and cytological results in women seeking gynecological consultation. Paired urine and cervical specimens were collected and analyzed from 230 of 245 women participating in the previously described prospective PapU study. HPV DNA detection and quantification were performed using a real-time PCR method with short fragment PCR primers. Genotyping was carried out using the INNO-LiPA HPV genotyping assay. The prevalence of HPV in the 230 paired urine and cervical smear samples was 42 and 49 %, respectively. Overall agreement for HPV positivity and negativity between the paired samples was 90 % (κ = 0.80). High HPV viral load in both cervical and urine samples was associated with cytological abnormalities. HPV-positive women were mostly infected with HR-HPV types. The agreement between high- and low-risk HPV (LR-HPV) detection in both samples was 97 % (κ = 0.95 for HR-HPV and κ = 0.97 for LR-HPV). High concordance rates for HPV-DNA quantification and high/low-risk HPV genotyping in paired urine/cervical samples suggest that urinary HPV DNA testing could be useful for cervical lesion screening.
Niccolai, Linda M; Julian, Pamela J; Meek, James I; McBride, Vanessa; Hadler, James L; Sosa, Lynn E
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.
Sadaf, Durre; Ahmad, Zubair
Objective: To assess the association of occlusal forces and brushing with non-carious cervical lesions (NCCL). Methodology: It was a Cross-sectional study. The study was conducted in Dental clinics, Department of Surgery, The Aga Khan University Hospital Karachi. The study duration was from 1st January 2009 to 28th Feb 2009. Ninety patients visiting dental clinic were examined clinically. Presence of Non- carious cervical lesions, broken restorations, fractured cusps, presence of occlusal facets, brushing habits, Para functional habits were assessed. All the relevant information and clinical examination were collected on a structured Performa and was analyzed using SPSS version 14.0. . Chi square χ2 test was applied to assess association among different categorical variables. Result: Twenty three (26%) females and 67 (74%) males were included in the study. Thirty five of them (38.9%) were found to have Non-carious cervical lesions. Presence of NCCL has no association with gender (P value 0.458). A significant association was found between NCCL and teeth sensitivity (P value 0.002).The association between use of hard tooth brush and Non-carious cervical lesions was found significant (P value <0.001). However the association among Non-carious cervical lesions and fractured cups, broken restoration, teeth grinding, jaw clenching, pan chalia chewing and frequency of teeth brushing were insignificant. Conclusion: Hard tooth brushing and teeth sensitivity have significant association with Non-carious cervical lesions. The role of occlusal wear in the formation of NCCL is not significant. PMID:25598758
Pereira, Analice Giovani; Teixeira, Daniela Navarro Ribeiro; Soares, Michelle Pereira Costa Mundim; Gonzaga, Ramon Corrêa de Queiroz; Fernandes-Neto, Alfredo Júlio; Soares, Paulo Vinícius
The association between the presence of gingival recession and non-carious cervical lesions is a common finding in dentistry. These diseases have multifactorial etiology and the treatment should be multidisciplinary. Although traditionally the majority of professionals treat non-carious cervical lesions only with conventional restorative procedures, in most cases a combination of periodontal and restorative treatments provides the best functional and esthetic results. Thus, the objective of this case report was to present a new option for treatment, which consists of a subepithelial connective tissue graft associated with a coronally advanced flap placed on dentin and non-carious cervical lesions restored with lithium disilicate partial veneers. A patient complaining about the esthetic aspects of her teeth and cervical dentin hypersensitivity was submitted to occlusal adjustments and daily diet analysis in order to manage etiologic factors. Experienced operators then performed restorative and surgical treatments. Periodontal clinical attachment level (probing depth + gingival margin), bleeding on probing, plaque index, and the integrity of the restorations were observed. During the monitoring period, the treatment was effective, with good functional and esthetic results. The hypersensitivity disappeared, and neither inflammatory characteristics in gingival tissue nor failures in restorations were noted. It might be concluded that treatment with a combination of techniques can be effective and predictable for patients with gingival recession and non-carious cervical lesions that may or may not require restorative procedures under controlled conditions. Copyright© by the International Academy of Periodontology.
Sheikhzadeh, Fahime; Ward, Rabab K.; Carraro, Anita; Chen, Zhaoyang; van Niekerk, Dirk; MacAulay, Calum; Follen, Michele; Lane, Pierre; Guillaud, Martial
We examined and established the potential of ex-vivo confocal fluorescence microscopy for differentiating between normal cervical tissue, low grade Cervical Intraepithelial Neoplasia (CIN1), and high grade CIN (CIN2 and CIN3). Our objectives were to i) use Quantitative Tissue Phenotype (QTP) analysis to quantify nuclear and cellular morphology and tissue architecture in confocal microscopic images of fresh cervical biopsies and ii) determine the accuracy of high grade CIN detection via confocal microscopy. Cervical biopsy specimens of colposcopically normal and abnormal tissues obtained from 15 patients were evaluated by confocal fluorescence microscopy. Confocal images were analyzed and about 200 morphological and architectural features were calculated at the nuclear, cellular, and tissue level. For the purpose of this study, we used four features to delineate disease grade including nuclear size, cell density, estimated nuclear-cytoplasmic (ENC) ratio, and the average of three nearest Delaunay neighbors distance (3NDND). Our preliminary results showed ENC ratio and 3NDND correlated well with histopathological diagnosis. The Spearman correlation coefficient between each of these two features and the histopathological diagnosis was higher than the correlation coefficient between colposcopic appearance and histopathological diagnosis. Sensitivity and specificity of ENC ratio for detecting high grade CIN were both equal to 100%. QTP analysis of fluorescence confocal images shows the potential to discriminate high grade CIN from low grade CIN and normal tissues. This approach could be used to help clinicians identify HGSILs in clinical settings.
Liang, Ming-Tai; Chen, Clayton Chi-Chang; Wang, Ching-Ping; Wang, Chen-Chi; Lin, Whe-Dar; Liu, Shih-An
The aim of this study was to determine if volume of cervical lymph node measured via computed tomography (CT) could differentiate metastatic from benign lesions in head and neck cancer patients. We conducted a retrospective review of chart and images in a tertiary referring center in Taiwan. Patients with head and neck cancers underwent radical, modified radical or functional neck dissection were enrolled. The CT images before operation were reassessed by a radiologist and were compared with the results of pathological examination. A total of 102 patients were included for final analyses. Most patients were male (n = 96, 94%) and average age was 50.1 years. Although the average nodal volume in patients with cervical metastases was higher than those of patients without cervical metastases, it was not an independent factor associated with cervical metastasis after controlling for other variables; however, central nodal necrosis on enhanced CT image [odds ratio (OR) 18.95, P = 0.008) and minimal axial diameter >7.5 mm (OR 6.868, P = 0.001) were independent factors correlated with cervical metastasis. Therefore, the volume of cervical lymph node measured from CT images cannot predict cervical metastases in head and neck cancer patients. Measurement of minimal axial diameter of the largest lymph node is a simple and more accurate way to predict cervical metastasis instead.
Carestiato, Fernanda Nahoum; Afonso, Larissa Alves; Moysés, Natalia; Almeida, Gutemberg Leão; Velarde, Luis Guillermo Coca; Cavalcanti, Silvia Maria Baeta
SUMMARY High-risk human papillomavirus (hr-HPV) infection is necessary but not sufficient for cervical cancer development. Recently, P16INK4A gene silencing through hypermethylation has been proposed as an important cofactor in cervical carcinogenesis due to its tumor suppressor function. We aimed to investigate P16INK4A methylation status in normal and neoplastic epithelia and evaluate an association with HPV infection and genotype. This cross-sectional study was performed with 141 cervical samples from patients attending Hospital Moncorvo Filho, Rio de Janeiro. HPV detection and genotyping were performed through PCR and P16INK4A methylation by nested-methylation specific PCR (MSP). HPV frequency was 62.4% (88/141). The most common HPV were HPV16 (37%), HPV18 (16.3%) and HPV33/45(15.2%). An upward trend was observed concerning P16INK4A methylation and lesion degree: normal epithelia (10.7%), low grade lesions (22.9%), high grade (57.1%) and carcinoma (93.1%) (p < 0.0001). A multivariate analysis was performed to evaluate an association between methylation, age, tobacco exposure, HPV infection and genotyping. A correlation was found concerning methylation with HPV infection (p < 0.0001), hr-HPV (p = 0.01), HSIL (p < 0.0007) and malignant lesions (p < 0.0001). Since viral infection and epigenetic alterations are related to cervical carcinoma, we suggest that P16INK4A methylation profile maybe thoroughly investigated as a biomarker to identify patients at risk of cancer. PMID:24037287
Makuza, Jean Damascène; Nsanzimana, Sabin; Muhimpundu, Marie Aimee; Pace, Lydia Eleanor; Ntaganira, Joseph; Riedel, David James
Cervical cancer prevalence in Rwanda has not been well-described. Visual inspection with acetic acid or Lugol solution has been shown to be effective for cervical cancer screening in low resource settings. The aim of the study is to understand the prevalence and risk factors for cervical cancer and pre- cancerous lesions among Rwandan women between 30 and 50 old undergoing screening. This cross-sectional analytical study was done in 3 districts of Rwanda from October 2010 to June 2013. Women aged 30 to 50 years screened for cervical cancer by trained doctors, nurses and midwives. Prevalence of pre-cancerous and cancerous cervical lesions was determined. Bivariate and multivariate logistic regressions were used to assess risk factors associated with cervical cancer. The prevalence of pre-cancer and invasive cervical cancer was 5.9% (95% CI 4.5, 7.5) and 1.7% (95% CI 0.9, 2.5), respectively. Risk factors associated with cervical cancer in multivariate analysis included initiation of sexual activity at less than 20 years (OR=1.75; 95% CI=(1.01, 3.03); being unmarried (single, divorced and widowed) (OR=3.29; 95% CI=( 1.26, 8.60)); Older age of participants (OR= 0.52; 95% CI= (0.28, 0.97)), older age at the first pregnancy (OR=2.10; 95% CI=(1.20, 3.67) and higher number of children born (OR=0.42; 95%CI =(0.23, 0.76)) were protective. Cervical cancer continues to be a public health problem in Rwanda, but screening using VIA is practical and feasible even in rural settings.
Makuza, Jean Damascène; Nsanzimana, Sabin; Muhimpundu, Marie Aimee; Pace, Lydia Eleanor; Ntaganira, Joseph; Riedel, David James
Introduction Cervical cancer prevalence in Rwanda has not been well-described. Visual inspection with acetic acid or Lugol solution has been shown to be effective for cervical cancer screening in low resource settings. The aim of the study is to understand the prevalence and risk factors for cervical cancer and pre- cancerous lesions among Rwandan women between 30 and 50 old undergoing screening. Methods This cross-sectional analytical study was done in 3 districts of Rwanda from October 2010 to June 2013. Women aged 30 to 50 years screened for cervical cancer by trained doctors, nurses and midwives. Prevalence of pre-cancerous and cancerous cervical lesions was determined. Bivariate and multivariate logistic regressions were used to assess risk factors associated with cervical cancer. Results The prevalence of pre-cancer and invasive cervical cancer was 5.9% (95% CI 4.5, 7.5) and 1.7% (95% CI 0.9, 2.5), respectively. Risk factors associated with cervical cancer in multivariate analysis included initiation of sexual activity at less than 20 years (OR=1.75; 95% CI=(1.01, 3.03); being unmarried (single, divorced and widowed) (OR=3.29; 95% CI=( 1.26, 8.60)); Older age of participants (OR= 0.52; 95% CI= (0.28, 0.97)), older age at the first pregnancy (OR=2.10; 95% CI=(1.20, 3.67) and higher number of children born (OR=0.42; 95%CI =(0.23, 0.76)) were protective. Conclusion Cervical cancer continues to be a public health problem in Rwanda, but screening using VIA is practical and feasible even in rural settings. PMID:26664527
Kaito, Takashi; Hosono, Noboru; Ohshima, Shirou; Ohwaki, Hajime; Takenaka, Shota; Fujiwara, Hiroyasu; Makino, Takahiro; Yonenobu, Kazuo
A retrospective cohort analysis. To determine the effect of biological agents (BAs) on the development and progression of cervical spine lesions and identify predictors of lesion progression. The introduction of BAs has facilitated advances in the treatment of rheumatoid arthritis (RA). BAs reduce disease activity and limit structural joint damage. However, the effect of BAs on cervical spine lesions remains unclear. Thirty-eight subjects who received more than 2 years of continuous BA treatment were enrolled. The mean x-ray interval was 4.4 years. RA activity was evaluated by disease activity score (DAS)-C reactive protein (CRP) and matrix metalloproteinase (MMP)-3. Radiographical definitions of cervical lesions were atlanto-dental interval (ADI) more than 3 mm for atlanto-axial subluxation (AAS), Ranawat value less than 13 mm for vertical subluxation (VS), and anterior or posterior listhesis more than 2 mm for subaxial subluxation (SS). Definitions of radiographical progression were an increase of ADI more than 2 mm for AAS, a decrease of both Ranawat and Redlund-Johnell values more than 2 mm for VS, and an increase of listhesis more than 2 mm for SS. RA activity responded dramatically to BA therapy (DAS-CRP from 4.3 to 2.3, P < 0.01; MMP-3 from 207.9 ng/mL to 105.6 ng/mL, P < 0.01). Baseline radiographical evaluation showed no pre-existing cervical spine lesions in 12 cases, AAS in 15 cases, and VS in 11 cases. Radiological progression was found in 1 (8%) patient in the no lesion group, 12 patients (80%) in the AAS group, and 9 patients (80%) in the VS group. The incidence of progression was significantly lower in the no lesion group compared with the other groups. Multivariate regression analysis showed that the presence of pre-existing cervical lesions was the single greatest predictor of progression. BAs prevented the development of de novo cervical spine lesions in patients with RA, but failed to inhibit progression of pre-existing RA lesions.
Schneider, A; Wagner, K; Rakozy, C; Stolte, C; Bothur-Schäfer, P; Welcker, T; Choly, N; Roesgen, A; Rothe, H; Böhmer, G
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).
Mohan, Vasavi; Ponnala, Shivani; Reddy, Hemakumar M; Sistla, Radha; Jesudasan, Rachel A; Ahuja, Yog Raj; Hasan, Qurratulain
AIM: To detect aneusomic changes with respect to chromosome 11 copy number in esophageal precancers and cancers wherein the generation of cancer-specific phenotypes is believed to be associated with specific chromosomal aneuploidies. METHODS: We performed fluorescence in situ hybridization (FISH) on esophageal tissue paraffin sections to analyze changes in chromosome 11 copy number using apotome-generated images by optical sectioning microscopy. Sections were prepared from esophageal tumor tissue, tissues showing preneoplastic changes and histologically normal tissues (control) obtained from patients referred to the clinic for endoscopic evaluation. RESULTS: Our results demonstrated that aneusomy was seen in all the cancers and preneoplastic tissues, while none of the controls showed aneusomic cells. There was no increase in aneusomy from precancers to cancers. CONCLUSION: Our results suggest that evaluation of chromosome 11 aneusomy in esophageal tissue using FISH with an appropriate signal capture-analysis system, can be used as an ancillary molecular marker predictive of early neoplastic changes. Future studies can be directed towards the genes on chromosome 11, which may play a role in the neoplastic transformation of esophageal precancerous lesions to cancers. PMID:17278214
Pereira, Fabrícia Araújo; Zeola, Livia Fávaro; de Almeida Milito, Giovana; Reis, Bruno Rodrigues; Pereira, Rodrigo Dantas; Soares, Paulo Vinícius
To evaluate the influence of restorative materials used on the rehabilitation of MOD cavities and loading type, on biomechanical behavior of wedge-shaped (WS) lesions in endodontically treated maxillary premolars. The investigation was conducted by 3D finite element analysis (FEA) and strain gauge test. Six models were generated, with MOD cavities and endodontic treatment: A (MOD amalgam restoration), R (MOD composite restoration), AL (A + cervical lesion (L)), RL, ALR (A + cervical lesion restored with composite (LR)), and RLR. Each model underwent two compressive loading (100N): axial and oblique-45° angle to the long axis on the buccal cusp. The models were analyzed by von Mises criteria. For strain gauge test, 14 standardized maxillary premolars were treated according to the groups described for FEA. Two strain gauges were bonded on each sample submitted to compressive loading in a mechanical testing machine. A presented higher stress concentration and strain values than R. Oblique loading promoted highest stress concentration and strain rates for all groups. ALR and RLR presented similar stress-strain distribution pattern when compared to A and R. The interaction between MOD cavity restored with amalgam and oblique loading propitiated the highest stress concentration and strain values on cervical region and WS lesion. The MOD cavity restored with composite resin is a better option than amalgam to improve the biomechanical behavior of wedge-shaped lesion, avoiding dental failure. In addition, the occlusal interferences must be removed, allowing homogeneous contact distribution and preventing WS lesion progression.
Nahvijou, Azin; Sari, Ali Akbari; Zendehdel, Kazem; Marnani, Ahmad Barati
Cervical cancer is a common, preventable and manageable disease in women worldwide. This study was conducted to determine the cost of follow-up for suspicious precancerous cervical lesions within a screening program using Pap smear or HPV DNA test through the decision tree. Patient follow-up processes were determined using standard guidelines and consultation with specialists to design a decision tree model. Costs of treatment in both public and private sectors were identified according to the national tariffs in 2010 and determined based on decision tree and provided services (visits to specialists, colposcopy, and conization) with two modalities: Pap smear and HPV DNA test. The number of patients and the mean cost of treatment in each sector were calculated. The prevalence of lesions and HPV were obtained from literature to estimate the cost of treatment for each woman in the population. Follow-up costs were determined using seven processes for Pap smear and 11 processes for HPV DNA test. The total cost of using Pap smear and HPV DNA process for each woman in the population was 36.1$ and 174 $ respectively. The follow-up process for patients with suspicious cervical lesions needs to be included in the existing screening program. HPV DNA test is currently more expensive than Pap smear, it is suggested that we manage precancerous cervical lesions with this latter test.
Precursor lesions of invasive cancer of uterine cervix begin at the squamocolumnar junction. On this zone in permanent transformation, human papillomavirus (HPV) gives condylomatous lesions, pure or associated with neoplasic transformation of the epithelium. For 50 years, various histological classifications have been proposed. First, four groups have been designed: light, moderate, severe dysplasia and in situ carcinoma. Secondly, Richart proposed the cervix intraepithelial neoplasia classification (CIN) with three grades (1 to 3) according to their severity. Progression from CIN 1 to CIN 3 and invasive carcinoma is admitted and is consistent with the concept of lesional continuum. However, because of the elevated rate of spontaneous regression of CIN 1, it is probably a lesion of very low potential aggressivity and its role as a precursor is uncertain. Now two groups of different evolutivity are currently considered: low grade and high grade lesions. The last one's, at the opposite of the first, are monoclonal, have major epithelial abnormalities with sometimes abnormal mitoses and are frequently aneuploid. Aggressivity depends on the persistence of HR HPV more than on progressive morphologic transformation. By integrating in-host genoma, it induces modifications on cellular cycle proteins. Revelation by immunohistochemistry brings help to diagnosis of high grade lesions when traditional morphology is ambiguous.
Tramm, Trine; Kim, Jee-Yeon; Tavassoli, Fattaneh A
The presence of myoepithelial (ME) cells is considered an important feature in the vast majority of benign breast lesions. Recently, a case showing the absence of myoepithelium in a mammary duct with apocrine metaplasia was reported. To investigate the status of ME cells associated with apocrine metaplasia, the distribution of ME cells in 59 metaplastic and intraductal proliferative apocrine lesions was evaluated using immunohistochemical expression of p63 and Calponin. p63 showed a diminished number of ME cells and increased intermyoepithelial nuclear distance in ducts with all variants of apocrine metaplasia and proliferation compared with normal glands. In the majority of cases, Calponin showed a continuous ME layer. In 6 cases, including an apocrine papilloma, there were definitive ME gaps confirmed by both markers, in the absence of atypia and with preservation of the basement membrane. In all cases, there was frequent heterogeneity in the distribution of ME cells in ducts harboring apocrine cells and even in various papillae within papillary lesions. In summary, benign and noninvasive apocrine lesions can show reduction and occasional complete loss of ME cells. This observation is particularly important when evaluating apocrine papillary proliferations, in which the absence of ME cells may lead to overdiagnosis of atypia and/or malignancy. The observation suggests that at least 2 ME markers should be used when evaluating apocrine lesions, and that a malignant diagnosis should be based on features of the proliferating cells until more data become available on the significance, if any, of the absence of ME cells in apocrine lesions.
Jaiswal, Aruna S; Panda, Harekrushna; Pampo, Christine A; Siemann, Dietmar W; Gairola, C Gary; Hromas, Robert; Narayan, Satya
Adenomatous polyposis coli (APC) is a multifunctional protein having diverse cellular functions including cell migration, cell-cell adhesion, cell cycle control, chromosomal segregation, and apoptosis. Recently, we found a new role of APC in base excision repair (BER) and showed that it interacts with DNA polymerase β and 5′-flap endonuclease 1 and interferes in BER. Previously, we have also reported that cigarette smoke condensate (CSC) increases expression of APC and enhances the growth of normal human breast epithelial (MCF10A) cells in vitro. In the present study, using APC overexpression and knockdown systems, we have examined the molecular mechanisms by which CSC and its major component, Benzo[α]pyrene, enhances APC-mediated accumulation of abasic DNA lesions, which is cytotoxic and mutagenic in nature, leading to enhanced neoplastic transformation of MCF10A cells in an orthotopic xenograft model. PMID:23555190
Calil, L N; Edelweiss, M I A; Meurer, L; Igansi, C N; Bozzetti, M C
Cellular cycle proteins like the p16(INK4a) and the Ki67 proliferation nuclear antigen have been used as oncogenicity cellular markers. The E6 and E7 oncoproteins interact with tumor suppressor genes p53 and pRb, culminating with the p16(INK4a) overexpression. The objective of this study was to evaluate the presence of HPV-DNA in 174 cervical biopsies and correlate the different histological grades with the p16(INK4a) and Ki67 immunohistochemical expression (IHC). A cross-sectional study that enrolled a total of 174 women who underwent uterine cervical biopsies between February 2003 and December 2006, in southern Brazil, was performed. Cervical smear samples were analyzed for the presence of HPV-DNA through polymerase chain reaction (PCR), and biopsy samples were examined for p16(INK4A) and Ki67 expression through IHC techniques. The presence of HPV-DNA was observed in 89% of the tested patients, among which 52% were positive for high-risk (HR) viral types [16, 18 and 31]. Regarding p16(INK4a), an expression of 69% was observed, being expressed in 100% of the high-grade squamous lesions (HSIL) and HR-HPV-DNA positives. Ki67 expression was associated with the lesion grade, being more expressive in the most severe lesions (p<0.001). p16(INK4A) and Ki67 markers coexpression was present in 86% of the samples (p<0.001), being 100% among those positive to HR-HPV-DNA with HSIL (p<0.001). The results suggest an association between the presence of HR-HPV infection and the p16(INK4a) and Ki67 expression and which is even stronger among women with HSIL. Copyright © 2014 Elsevier GmbH. All rights reserved.
Kierkegaard, O; Byralsen, C; Hansen, K C; Frandsen, K H; Frydenberg, M
The relation between eight specific colposcopic diagnostic findings and the histologic grade of a cervical lesion in 896 women was evaluated. The size of the transformation zone (TZ), the size of the lesion, the intensity of the color tone, distinct margins, the pathology of the vessels, and the presence of micropapillae as single findings were highly statistically correlated to the histologic grade (P < 0.0001). By logistic regression analysis the risk for a higher histologic grade when assessed by colposcopy was greatest in women with variation of the acetowhite color (odds ratio (OR) = 16.0; 95% CI, 10.0-26.0) followed by coarse vessels (OR = 10.0; CI, 3.2-34.0). Lesion-size larger than 50% of the visible cervix had an OR of 3.6 (CI, 2.1-6.3). Extention beyond TZ had an OR of 0.4 (CI, 0.2-0.4) and larger TZ had an OR of 0.5 (CI, 0.3-0.9). In conclusion we found that the size of the cervical lesion had some independent predictive value and should be considered in future trials.
Basturk, Olca; Hong, Seung-Mo; Wood, Laura D.; Adsay, N. Volkan; Albores-Saavedra, Jorge; Biankin, Andrew V.; Brosens, Lodewijk A.A.; Fukushima, Noriyoshi; Goggins, Michael; Hruban, Ralph H.; Kato, Yo; Klimstra, David S.; Klöppel, Günter; Krasinskas, Alyssa; Longnecker, Daniel S.; Matthaei, Hanno; Offerhaus, G. Johan A.; Shimizu, Michio; Takaori, Kyoichi; Terris, Benoit; Yachida, Shinichi; Esposito, Irene; Furukawa, Toru
International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following: 1) To improve concordance and to align with practical consequences, a two-tiered system (low vs. high-grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low-grade. Thus, “high-grade dysplasia” is to be reserved for only the uppermost end of the spectrum (“carcinoma in situ” type lesions). 2) Current data indicate that PanIN of any grade at a margin of a resected pancreas with invasive carcinoma does not have prognostic implications; the clinical significance of dysplasia at a margin in a resected pancreas with IPMN lacking invasive carcinoma remains to be determined. 3) Intraductal lesions 0.5–1 cm can be either large PanINs or small IPMNs. The term “incipient IPMN” should be reserved for lesions in this size with intestinal- or oncocytic-papillae or GNAS mutations. 4) Measurement of the distance between an IPMN and invasive carcinoma and sampling of intervening tissue are recommended to assess concomitant versus associated status. Conceptually, concomitant invasive carcinoma (in contrast with the “associated” group) ought to be genetically distinct from an IPMN elsewhere in the gland. 5) “Intraductal spread of invasive carcinoma” (aka, “colonization”) is recommended to describe lesions of invasive carcinoma invading back into and extending along the duct system, which may morphologically mimic high-grade PanIN or even IPMN. 6) “Simple mucinous cyst” is recommended to describe cysts > 1 cm having gastric-type flat mucinous lining at most minimal atypia without
Sequetto, Priscila L; Oliveira, Tânia T; Soares, Italo A C; Maldonado, Izabel R S C; Mello, Vanessa J; Pizziolo, Virginia R; Almeida, Márcia R; Novaes, Rômulo D
Phenolic compounds are naturally occurring, bioactive substances with marked antioxidant and anti-inflammatory potential. The flavonoid chrysin, found in high levels in honey bee propolis, inhibits the activity of enzymes involved in carcinogenesis. We have investigated the effect of chrysin on pre-neoplastic colorectal lesions (ACF, aberrant crypt foci) in a rat model of chemical carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Female Wistar rats weighing 137.2 ± 24.3 g received weekly one subcutaneous injection of DMH (20 mg/kg) for 10 weeks. The animals were divided into five groups each with seven animals: Group 1, 0.9% saline; Group 2, DMH+0.9% saline; Group 3, DMH+chrysin (10 mg/kg); Group 4, DMH+chrysin (100 mg/kg); Group 5, DMH+chrysin (200 mg/kg). Groups 2 and 3 showed a significant increase in ACF number, nucleolus organizer regions per enterocyte nucleus and nitrite/nitrate serum levels compared with Group 1. Groups 4 and 5 presented a significant reduction in all these parameters compared with Group 2. The levels of antioxidant minerals (copper, magnesium, selenium, zinc) and the number of enteroendocrine and mucin-producing cells were significantly reduced in Groups 2 and 3 but were similar in Groups 4 and 5 compared with Group 1. Chrysin, at 100 mg/kg and 200 mg/kg, was effective in attenuating pathological colorectal remodeling, reducing the number of pre-neoplastic lesions in rats exposed to DMH. Some of these effects might be attributable to the recovery of antioxidant mineral levels, a reduction in systemic nitrosative stress and an inhibition of the cellular proliferation induced by this flavonoid.
Lee, HyeJin; Jin, Sung-Ho
Non-carious cervical lesions (NCCLs) with gingival recession require specific consideration on both aspects of hard and soft tissue lesion. In the restorative aspect, careful finishing and polishing of the restorations prior to mucogingival surgery is the critical factor contributing to success. Regarding surgery, assessment of the configuration of the lesion and the choice of surgical technique are important factors. The precise diagnosis and the choice of the proper treatment procedure should be made on the basis of both restorative and surgical considerations to ensure the successful treatment of NCCLs. PMID:27508164
Molteni, Gabriele; Greco, Marco Giuseppe; Presutti, Livio
The Da Vinci robotic surgical system is increasingly being used by head and neck surgeons in transoral approaches for head and neck cancer. Our experience using the Da Vinci system for transoral robotic-assisted surgery (TORS) is presented. The feasibility of TORS for lesions involving the anterior portion of C1-C2 and the cranio-cervical junction has been evaluated from an anatomical viewpoint in a cadaveric laboratory. Two patients treated using the Da Vinci system to reach C1-C2 benign lesions are presented. The anatomical cadaveric study showed that this approach is safe and feasible. The first two cases which we describe confirmed the advantages of the Da Vinci system in the anterior approach to the cervical spine and allowed the limitations of this procedure to be assessed. TORS may be useful to reach anterior lesions of the cervical spine localized at the level of C1 and C2: first, for removal of small benign and well-delineated lesions; and second, for diagnostic purposes with biopsy of large lesions. Further studies and new instruments are needed to confirm the safety and results of this approach in terms of morbidity.
Differentiating between endocervical glandular neoplasia and high grade squamous intraepithelial lesions in endocervical crypts: cytological features in ThinPrep and SurePath cervical cytology samples.
Thiryayi, Sakinah A; Marshall, Janet; Rana, Durgesh N
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.
Faye, B; Sarr, M; Kane, A W; Toure, B; Leye, F; Gaye, F; Dieng, M B
The non carious cervical lesion (NCCL) is a loss of tooth tissue at the neck of affected teeth that is unrelated to tooth decay. They are commonly encountered in clinical practice and present in a variety of forms. The purpose of this paper is to determine the prevalence of the NCCL in a Senegalese population. From 655 patients, 112 with cervical lesions were identified i.e. a global prevalence of 17.10%. The prevalence rate for abrasion was reported to be 77.70%, 12.50% for abfraction and 9.80% for erosion. Etiological factors were studied for abrasion and erosion. 54% of the patients with abrasion used their toothbrush horizontally. For erosion, only external factors were identified: consumption of acidic drinks (9 patients) or alcohol (1 patient) and professional environment (1 patient). Dentists should consider these lesions in their daily practice.
Zhang, Ling; Du, Hui; Zhang, Wei; Yang, Bin; Wang, Chun; Belinson, Jerome L; Wu, Ruifang
To investigate the value of multiply biopsies and endocervical curettage (ECC) on diagnosing cervical lesions. For the detection of cervical lesions, Shenzhen cervical cancer screening trial II (SHENCCAST II) program combined methods of HPV screening with liquid-based cytology (LBC), any positive indicators was then performed multiply biopsies and ECC under colopscopy. A total of 2,558 clear colposcopic images and pathological diagnoses were reviewed. To analyse the pathological results and primary screening results of the negative colopscopic images for discussing the value of multiply biopsies and ECC. Overall 2,558 women's colposcopic images and sampling results were completed and validated. 69.98% (1,790/2,558) women had normal colposcopy appearances. Among them, 2.23% (40/1,790) were diagnosed as cervical intraepithelial neoplasia II or worse (CIN II+). The odds ratio of high-grade squamous intraepithelial lesion (HSIL) was 28.37 (P=0.000) and atypical squamous cell cannot exclude HSIL (ASC-H) was 15.07 (P=0.001). HPV types 16, 52, 58, 31, 33 and 18 were related to high-grade cervical lesion with the odds ratio of 3.11 (P=0.017). Hybrid capture II (HC-II) DNA test results shown that women with HPV positive were 3.58 times more risky than those of HPV negative, which was related to high-grade cervical lesion (P=0.025). Among the 2,558 women, CIN II+ detective rate from ECC were 40.7% (44/108) in older group (≥40 years) were higher than that of 19.2% (24/125) in younger group (<40 years; χ2=13.01, P=0.000). CIN II+ detective rate from multiply biopsies were 90.7% (98/108) in older group (≥40 years) were higher than that of 88.8% (111/125) in younger group (<40 years; χ2=0.24, P>0.05). The highest risky items of detecting CIN II+ were as follows: (1) HSIL or ASC-H; (2) HPV types 16, 18, 52 and 58 positive (either one); (3) HC-II HPV positive, at least 2 of the 3 items were included among 32 cases of the 40 CIN II+ with normal colposcopy appearances. The
Long, Shuyu; Yang, Xingliang; Liu, Xiaojiao; Yang, Pei
The association between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and the susceptibility to cervical lesions was unclear. This study was designed to investigate their precise association using a large-scale meta-analysis. The previous 16 studies were identified by searching PubMed, Embase and CBM databases. The crude odds ratios and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the MTHFR C677T/A1298C polymorphisms and the susceptibility to the cervical lesions. The subgroup analyses were made on the following: pathological history, geographic region, ethnicity, source of controls and source of DNA for genotyping. Neither of the polymorphisms had a significant association with the susceptibility to the cervical lesions in all genetic models. Similar results were found in the subgroup analyses. No association was found between the MTHFR C677T polymorphism and the cervical lesions in the Asia or the America populations though a significant inverse association was found in the Europe population (additive model: P = 0.006, OR = 0.83, 95% CI = 0.72-0.95; CT vs. CC: P = 0.05, OR = 0.83, 95% CI = 0.69-1.00; TT vs. CC: P = 0.05, OR = 0.73, 95% CI = 0.53-1.00). Interestingly, women with the MTHFR A1298C polymorphisms had a marginally increased susceptibility to invasive cancer (ICC) when compared with no carriers but no statistically significant difference in the dominant model (P = 0.06, OR = 1.21, 95% CI = 0.99-1.49) and AC vs. AA (P = 0.09, OR = 1.21, 95% CI = 0.97-1.51). The MTHFR C677T and A1298C polymorphisms may not increase the susceptibility to cervical lesions. However, the meta-analysis reveals a negative association between the MTHFR C677T polymorphisms and the cervical lesions, especially in the European populations. The marginal association between the MTHFR A1298C polymorphisms and the susceptibility to cervical cancer requires a further study.
Liu, Xiaojiao; Yang, Pei
Background The association between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and the susceptibility to cervical lesions was unclear. This study was designed to investigate their precise association using a large-scale meta-analysis. Methods The previous 16 studies were identified by searching PubMed, Embase and CBM databases. The crude odds ratios and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the MTHFR C677T/A1298C polymorphisms and the susceptibility to the cervical lesions. The subgroup analyses were made on the following: pathological history, geographic region, ethnicity, source of controls and source of DNA for genotyping. Results Neither of the polymorphisms had a significant association with the susceptibility to the cervical lesions in all genetic models. Similar results were found in the subgroup analyses. No association was found between the MTHFR C677T polymorphism and the cervical lesions in the Asia or the America populations though a significant inverse association was found in the Europe population (additive model: P = 0.006, OR = 0.83, 95% CI = 0.72–0.95; CT vs. CC: P = 0.05, OR = 0.83, 95% CI = 0.69–1.00; TT vs. CC: P = 0.05, OR = 0.73, 95% CI = 0.53–1.00). Interestingly, women with the MTHFR A1298C polymorphisms had a marginally increased susceptibility to invasive cancer (ICC) when compared with no carriers but no statistically significant difference in the dominant model (P = 0.06, OR = 1.21, 95% CI = 0.99–1.49) and AC vs. AA (P = 0.09, OR = 1.21, 95% CI = 0.97–1.51). Conclusions The MTHFR C677T and A1298C polymorphisms may not increase the susceptibility to cervical lesions. However, the meta-analysis reveals a negative association between the MTHFR C677T polymorphisms and the cervical lesions, especially in the European populations. The marginal association between the MTHFR A1298C
Janardhan, Kyathanahalli S; Rebolloso, Yvette; Hurlburt, Geoffrey; Olson, David; Lyght, Otis; Clayton, Natasha P; Gruebbel, Margarita; Picut, Catherine; Shackelford, Cynthia; Herbert, Ronald A
Methyl eugenol induces neuroendocrine (NE) cell hyperplasia and tumors in F344/N rat stomach. Detailed histopathological and immunohistochemical (IHC) characterization of these tumors has not been previously reported. The objective of this study was to fill that data gap. Archived slides and paraffin blocks were retrieved from the National Toxicology Program Archives. NE hyperplasias and tumors were stained with chromogranin A, synaptophysin, amylase, gastrin, H(+)/K(+) adenosine triphosphatase (ATPase), pepsinogen, somatostatin, and cytokeratin 18 (CK18) antibodies. Many of the rats had gastric mucosal atrophy, due to loss of chief and parietal cells. The hyperplasias and tumors were confined to fundic stomach, and females were more affected than the males. Hyperplasia of NE cells was not observed in the pyloric region. Approximately one-third of the females with malignant NE tumors had areas of pancreatic acinar differentiation. The rate of metastasis was 21%, with liver being the most common site of metastasis. Immunohistochemically, the hyperplasias and tumors stained consistently with chromogranin A and synaptophysin. Neoplastic cells were also positive for amylase and CK18 and negative for gastrin, somatostatin, H(+)/K(+) ATPase, and pepsinogen. Metastatic neoplasms histologically similar to the primary neoplasm stained positively for chromogranin A and synaptophysin. Based on the histopathological and IHC features, the neoplasms appear to arise from enterochromaffin-like cells.
Albarran-Somoza, Benibelks; Franco-Topete, Ramon; Delgado-Rizo, Vidal; Cerda-Camacho, Felipe; Acosta-Jimenez, Lourdes; Lopez-Botet, Miguel; Daneri-Navarro, Adrian
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is an adhesion molecule expressed in a wide variety of tissues including epithelial cells, leukocytes, and tumors that may establish both homotypic and heterotypic interactions. The aim of this work was to study the protein expression pattern of CEACAM1 in cervical cancer and precursor lesions in the context of human papillomavirus (HPV) infection. We used immunohistochemistry to analyze CEACAM1 expression in formalin-fixed, paraffin-embedded cervical tissues from 15 healthy women, 15 patients with low-grade squamous intraepithelial lesions (SIL), 15 patients with high-grade SIL, and 15 patients with squamous carcinomas. HPV types were identified by PCR. CEACAM1 was either undetectable (13/15) or low (2/15) in normal cervical tissues. By contrast, CEACAM1 expression was increased in high-grade SIL (10 samples staining intermediate/high and 4 samples staining low) as compared with low-grade SIL with undetectable (n=3) or low (n= 12) expression. CEACAM1 expression was undetectable or low in cervical carcinoma. Our results suggest that CEACAM1 may be an interesting progression marker in SIL and cervical cancer, in particular due to reported immunoregulatory properties. PMID:16924126
Baussano, Iacopo; Ronco, Guglielmo; Segnan, Nereo; French, Katherine; Vineis, Paolo; Garnett, Geoff P
The patterns of transmission, clearance, and progression of HPV infection and the related precancerous lesions are key to accurately model cervical cancer epidemiology and prevention. We have developed an age-structured dynamic model of the transmission of HPV-16 infection. This mathematical model accounts, for the first time, for the effect of infection and precancerous lesions duration on the natural history of HPV-16 infection and precancerous lesions. The model's output has been fitted to contemporaneous sets of data from Turin, Italy, to estimate parameters that have had been indirectly tested by comparing them with other estimates reported in the literature. The average probability of HPV-16 infection transmission per sexual partnership was about 40%. The HPV-16 clearance and progression rates decreased as the length of time with infection increased, clearance ranging between 1.6 per woman-year (in the first 6 months of infection) and 0.036 (after more than 6 years of infection), and progression between 0.072 and 0.018 per woman-year. The rate of clearance of precancerous lesions (CIN2+) was inversely dependent on age, while the progression of CIN2+ toward invasive cervical cancer increased as the precancerous lesions persisted. The present study also suggests that an exclusive role of women's age in shaping the rate of progression to cancer is unlikely. These results should inform future analyses. Including more accurately the role of the duration of infection and precancerous lesions as determinants of the cervical cancer occurrence in models of cervical cancer control may influence predictors of the effectiveness of intervention strategies.
Kanthiya, Kanjana; Khunnarong, Jakkapan; Tangjitgamol, Siriwan; Puripat, Napaporn; Tanvanich, Sujitra
To evaluate the expression of p16 and Ki67 in cervical intraepithelial neoplasia (CIN) and cancer. We performed a immunohistochemical study of p16 and Ki67 in 243 cervical tissues 53 nondysplastic lesions, 106 CIN1, 61 CIN2/3 and 23 squamous cell carcinomas. The expression of p16 and Ki67 was interpreted independently by 2 researchers and the sensitivity and specificity to detect clinically significant lesions (≥ CIN2) were determined. The overall agreement results of positive or negative immunostaining of intrainter observer variability were 0.659 for p16 and 0.808 for Ki67. p16 expression was demonstrated in 91.3% of invasive carcinomas, 78.7% of CIN2/3, 10.4% of CIN1 and 9.4% of nondysplasic lesions. The corresponding Ki67 expression was: 100% of all invasive carcinomas, 75.4% of CIN2/3, 22.6% of CIN1, and 11.3% with nondysplasia. The expression was significantly different between CIN2/3 vs CIN1 for both p16 and Ki67 (pvalues <0.001 both), and cancer vs CIN2/3 for Ki67 (pvalue 0.008). The differences were not significant between CIN1 vs nondysplasia (pvalues 1.000 for p16 and 0.130 of Ki67), and cancer vs CIN2/3 for p16 (p value 0.219). The sensitivity and specificity to detect > CIN2 were 84.5% and 90.5% by p16 and 82.1% and 88.6% by Ki67. The rates for 16 and Ki67 expression were directly associated with the severity of cervical lesions. Significant differences in these markers expression may be useful in cases with equivocal histologic features among cervical intraepithelial lesions, but not between CIN1 and nondysplastic lesions. The two markers had high sensitivity and specificity in determining >CIN2.
Iljazović, Ermina; Ljuca, Dzenita; Sahimpasić, Ademir; Avdić, Silvija
Cervical dysplasia, a premalignant lesion that can progress to cervical cancer, is caused primarily by a sexually transmitted infection with an oncogenic strain of the human papillomavirus (HPV). The HPV infections are treated through destroying the clinical lesions: laser, cryotherapy, podophyllin... The hope is that by causing local tissue inflammation that the body will be stimulated to mount an antibody response and thereby prevent recurrence. In contrast to other prevention approaches, vaccines can reduce susceptibility in uninfected partners by stimulating the immune system. Aloe vera has also been reported to retard tumour growth and stimulate the immune response to viruses. A list of possible actions of propolis includes: antibacterial, antifungal, antiviral, antioxidant, anticarcinogenic, antithrombotic and immunomodulatory. Research on the possible role of some B vitamins in preventing cancer began in the last few decades, but however this complex have an influence on immune status. The aim of our study is to try to treat the HPV infection as confirmed cause of neoplastic transformation with some herbal therapy and interferon and to try define the guidelines in the management of the HPV positive patients. Goal of this paper is to search for evidence of efficacy of any treatment for HPV infection of the cervix mostly in woman with no concomitant CIN. Fifty five woman affected by HPV genital infection were enrolled in the study from September 2005 to April 2006. Patients were classified according to the results of the HPV testing prior and after the therapy. Patients were randomized into two groups: the first group was HPV positive woman treated with other than recommended therapy (n=20), (control group); the second group was pharmacologically treated with intravaginal administration of an interferon and aloe vera-propolis in recommended scheme (n=35) with treatment of the possible fungal or bacterial genital infection prior to the specific therapy. The
Padberg, B. C.; Schröder, S.; Jochum, W.; Kastendieck, H.; Roth, J.; Heitz, P. U.; Komminoth, P.
We investigated the possible role of RET proto-oncogene mutations in the development of sporadic hyperplastic, benign, and malignant parathyroid lesions. DNA extracted from paraffin-embedded specimens of forty parathyroid lesions was screened for RET proto-oncogene point mutations in exons 10, 11, and 16 by nonisotopic polymerase chain reaction-based single-strand conformation polymorphism and heteroduplex gel electrophoresis. The nucleotide sequence of samples with aberrant band patterns was identified by nonisotopic direct sequencing of polymerase chain reaction-amplified DNA. Parathyroids of seven patients with multiple endocrine neoplasia type 2A (MEN 2A) and MEN 2B served as positive controls. None of the eight hyperplastic lesions, three cases of parathyromatosis, ten parathyroid adenomas, eleven carcinomas or one normal parathyroid gland contained mutations in each of the three RET exons tested. Six MEN-2A-associated hyperplastic glands exhibited identical band shifts in the polymerase chain reaction single-strand conformation polymorphism analysis of exon 11, which corresponded to a Cys 634-->Arg substitution in the nucleotide sequence analysis (TGC-->CGC), whereas in the MEN 2B parathyroid specimen a point mutation was found at codon 918 of exon 16 (ATG-->ACG), causing a Met 918-->Thr substitution. Our data indicate that RET mutations of the MEN 2 loci in exons 10, 11, and 16 are not involved in the development of sporadically occurring benign or malignant parathyroid lesions. Furthermore, our results are in accordance with the observation that MEN 2A patients with Cys 634-->Arg (germline) mutations have a higher risk of developing parathyroid disease than those with other mutations at codon 634. Images Figure 1 Figure 2 PMID:7495285
Jolly, Pauline E; Mthethwa-Hleta, Simangele; Padilla, Luz A; Pettis, Jessica; Winston, ShaCoria; Akinyemiju, Tomi F; Turner, Hannah J; Ejiawoko, Amarachi; Brooks, Raina; Preko, Lena; Preko, Peter O
Cervical Cancer (CC) is the number one cancer among women in sub-Saharan Africa. Although CC is preventable, most women in developing countries do not have access to screening. This cross-sectional study was conducted to determine the prevalence and risk factors for cervical lesions using visual inspection with acetic acid (VIA) among 112 HIV positive and 161 negative women aged 18-69 years. The presence of cervical lesions was greater among HIV positive (22.9%) than HIV negative women (5.7%; p < 0.0001). In logistic models, the risk of cervical lesions among HIV positive women was 5.24 times higher when adjusted by age (OR 5.24, CI 2.31-11.88), and 4.06 times higher in a full model (OR 4.06, CI 1.61-10.25), than among HIV negative women. In the age-adjusted model women who had ≥2 lifetime sexual partners were 3 times more likely (OR 3.00, CI 1.02-8.85) to have cervical lesions compared to women with one lifetime partner and the odds of cervical lesions among women with a history of STIs were 2.16 greater (OR 2.16, CI 1.04-4.50) than among women with no previous STI. In the fully adjusted model women who had a previous cervical exam were 2.5 times more likely (OR 2.53, CI 1.06-6.05) to have cervical lesions than women who had not. The high prevalence of HIV infection and the strong association between HIV and cervical lesions highlight the need for substantial scale-up of cervical screening to decrease the rate of CC in Swaziland.
Kobaek-Larsen, Morten; El-Houri, Rime B; Christensen, Lars P; Al-Najami, Issam; Fretté, Xavier; Baatrup, Gunnar
Falcarinol (FaOH) and falcarindiol (FaDOH) are found in many food plants of the Apiaceae family. Carrots are a major dietary source of these polyacetylenes. Feeding azoxymethane (AOM)-induced rats with carrots and purified FaOH have previously been shown to inhibit neoplastic transformations in the colon. FaOH and FaDOH have also shown to have a synergistic effect in vitro, resulting in a significant increased cytotoxic activity. Based on these findings the antineoplastic effect of FaOH and FaDOH (purity > 99%) was investigated in the AOM-induced rat model. Twenty rats received rat diet containing 7 μg FaOH per g feed and 7 μg FaDOH per g feed and 20 rats were controls receiving only rat diet. Then carcinogenesis was induced in all 40 rats with the carcinogen AOM. All animals received the designated diet for 2 weeks before AOM induction and continued on the designated diet throughout the experiment. Rats were euthanized 18 weeks after the first AOM injection and macroscopic polyp/cancers were measured, harvested and stained for histology. The difference in sizes of aberrant crypt foci (ACF) were analysed in a Wilcoxon rank sum test, in which the median number of small ACF was 218 in controls and 145 in polyacetylene treated rats (P < 0.001). Fifteen control rats and 8 treated rats had macroscopic tumors (P = 0.027). The number of tumors larger than 3 mm were 6 and 1 in control and treated rats, respectively (P = 0.032). In conclusion dietary supplements with FaOH and FaDOH reduced the number of neoplastic lesions as well as the growth rate of the polyps suggesting a preventive effect of FaOH and FaDOH on the development of colorectal cancer.
Srivastava, Shikha; Shahi, U P; Dibya, Arti; Gupta, Sadhana; Roy, Jagat K
Human papilloma virus (HPV) is considered as the main sexually transmitted etiological agent for the cause and progression of preneoplastic cervical lesions to cervical cancer. This study is discussing the prevalence of HPV and its genotypes in cervical lesions and invasive cervical cancer tissues and their association with various risk factors in women from Varanasi and its adjoining areas in India. A total of 122 cervical biopsy samples were collected from SS Hospital and Indian Railways Cancer Institute and Research Centre, Varanasi and were screened for HPV infection by PCR using primers from L1 consensus region of the viral genome. HPV positive samples were genotyped by type-specific PCR and sequencing. The association of different risk factors with HPV infection in various grades of cervical lesion was evaluated by chi-square test. A total of 10 different HPV genotypes were observed in women with cervicitis, CIN, invasive squamous cell cervical carcinoma and adenocarcinoma. Increased frequency of HPV infection with increasing lesion grade (p=0.002) was observed. HPV16 being the predominant type was found significantly associated with severity of the disease (p=0.03). Various socio- demographic factors other than HPV including high parity (p<0.0001), rural residential area (p<0.0001), elder age (p<0.0001), low socio-economic status (p<0.0001) and women in postmenopausal group (p<0.0001) were also observed to be associated with cervical cancer.These findings show HPV as a direct cause of cervical cancer suggesting urgent need of screening programs and HPV vaccination in women with low socio-economic status and those residing in rural areas. PMID:25035855
Kishen, A.; Tan, K. B. C.; Asundi, A.
This study aims to examine the biomechanical factor underlying the origin of Non-Carious-Cervical-Lesions by examining the strain distribution in the enamel and dentine. A digital moire interferometry was utilized for this purpose. It is observed from this study that the enamel displayed marked strains in the lateral direction, while the dentine experienced marked strains in the axial and lateral directions during compression. The strains in the enamel and the dentine displayed both normal and shear components. The shear strain in the lateral direction within the enamel and the normal and shear strains in the axial and lateral directions within the coronal dentine concentrated at the cervical region. These experiments highlights that the biting loads will contribute to the loss of hard tissue in the cervical region.
Pista, Angela; de Oliveira, Carlos Freire; Lopes, Carlos; Cunha, Maria J
To estimate the potential impact of the nonavalent HPV vaccine for high-grade cervical lesions and invasive cervical cancer (ICC) in Portugal. The present secondary analysis used data collected in the CLEOPATRE II study on the prevalence of HPV 6/11/16/18/31/33/45/52/58 among female patients aged 20-88 years. The prevalence of HPV types in patients with cervical intraepithelial neoplasia (CIN) grades 2/3 and ICC was examined. Data were included from 582 patients. There were 177, 341, and 64 patients with CIN2, CIN3, and ICC, respectively, and 169 (95.5%), 339 (99.4%), and 62 (96.9) of them had HPV infections. Of patients with HPV infections, HPV 16, 18, 31, 33, 45, 52, and 58 infections were identified in 150 (88.8%), 329 (97.1%), and 60 (96.8%) patients with CIN2, CIN3, and ICC, respectively. HPV genotypes 6, 11, 16, 18, 31, 33, 45, 52, and 58 were identified in 540 (94.7%) of the patients with HPV infections. The addition of the five HPV genotypes included in the nonavalent HPV vaccine (HPV 31/33/45/52/58) could result in the new HPV vaccine preventing 94.7% of CIN2/3 and ICC occurrences. © 2017 International Federation of Gynecology and Obstetrics.
Park, Jeong Su; Shin, Sue; Kim, Eui-Chong; Kim, Ji Eun; Kim, Yong Beom; Oh, Sohee; Roh, Eun Youn; Yoon, Jong Hyun
Persistent human papillomavirus type 16 (HPV16) is the major risk factor for cervical cancer. HPV16 intratypic variants differ in their geographical distribution and oncogenic potential. This study aimed to analyze the distribution of HPV16 variants and their association with cervical lesion histopathology in Korean women. In total, 133 HPV16-positive cervical samples from women admitted to Seoul National University Boramae Hospital were analyzed by sequencing E6, E7, and L1 genes and the long control region (LCR), and the variant distribution according to cervical lesion grade was determined. Isolates were grouped into a phylogenetic lineage, and A1-3, A4, C, and D sublineages were detected in 54.1, 37.8, 0.7, and 7.4% of samples, respectively. The most commonly observed LCR variations were 7521G>A (91.5%), 7730A>C (59.6%), and 7842G>A (59.6%). Furthermore, A4 or D sublineage-positive women had a higher risk for cervical cancer than women who were positive for A1-3. Among HPV phylogenetic clusters, A1-3 was the predominant sublineage, and within A1-3, the 350G polymorphism was highly frequent. These results differed from those of previous studies in Korea and other Asian countries. The findings suggest that cervical neoplasia incidence in HPV16-infected patients could be affected by the distribution of HPV16 variants in the population. © 2016 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Medical Microbiology and Pathology.
Spiryda, Lisa Beth; Whitaker, Kara M.; Messersmith, Amy; Banister, Carolyn E.; Creek, Kim E.; Pirisi-Creek, Lucia A.
Objective Although human papillomavirus (HPV) infection is necessary for cervical squamous intraepithelial lesion (SIL/CIN) and cancer to develop, exposure to HPV is not predictive of which women will develop cervical squamous intraepithelial lesion and cancer. This study examines mRNA expression of several potential biomarkers in exfoliated cervical cells collected from college age women. Methods Freshman female students were recruited into the Carolina Women’s Care Study (CWCS) which was designed to prospectively evaluate factors that contribute to persistent HPV infections. One component of this study was to extract mRNA from exfoliated cervical cells. In this study, mRNA expression of FZD, GDF15, IL1β and N-cadherin was assessed through real-time PCR. Statistical analysis was performed with a Student’s t-test; all results were standardized with GAPDH. Results Fifty samples were selected that reflected the demographics of the CWCS participants. IL1β mRNA expression was 9.4-fold higher in cervical cells from women with abnormal Pap tests (p=0.0018); LSIL had 12.7-fold higher expression than negatives (p=0.0011). FZD mRNA expression was 5.7-fold higher in CIN2 as compared to CIN1 (p=0.0041) and 8.5-fold higher compared to cytology/pathology-negative (p=0.0014). Other differences in mRNA expression showed trends but not reaching statistical significance for each condition. Conclusions It appears that several biomarkers involved in the cytokine/inflammatory pathway (IL1 β), cell adhesion pathway (N-cadherin), growth factors (GDF-15), WNT signaling pathway (FZD) may be potential biomarkers in conjunction with the Pap test and HPV that help predict which women are at highest risk for developing CIN3 and cervical cancer. PMID:26579841
Cui, Changxu; Takamatsu, Reika; Doguchi, Hiroshi; Matsuzaki, Akiko; Saio, Masanao; Yoshimi, Naoki
Aberrant crypt foci (ACF) and mucin-depleted foci (MDF) have recently been recognized as pre-neoplastic lesions in the colon of carcinogen-treated rodents. In the present study, we analyzed the sequential development of ACF and MDF histopathologically in the colon of rats from 5 to 40 weeks after DMH treatment. The numbers of ACF per colon increased over time during the experiment, and were much higher than the number in tumors, while the number of MDF per colon remained unchanged from the early stage (the 5th week after carcinogen exposure), and approximate to those in tumors. The incidence of ACF, which was much higher than that of tumors, also increased gradually in a time-dependent manner. The incidence of MDF, however, was similar to that of tumors and did not change significantly during the whole experiment. No lesion as dysplasia with high-grade (DHG) or adenocarcinoma (AC) were found in any large ACF from the 5th to 40th week histopathologically, whereas all of the large MDF showed DHG or AC features. Even at 5 weeks, MDF showed features of DHG. We classified these into two forms of MDF: flat and protruded MDF. At 40 weeks, the number of flat MDF per colon decreased significantly compared with that at 20 weeks (p<0.05), however, the number of protruded MDF per colon increased (p<0.01), and the percentage of DHG in a protruded MDF lesion decreased but that of AC increased remarkably. In conclusion, MDF may develop into cancer through the so-called 'de novo cancer' pathway.
McDorman, Kevin S; Hooth, Michelle J; Starr, Thomas B; Wolf, Douglas C
Disinfection of surface water for human consumption results in the generation of a complex mixture of chemicals in potable water. Cancer risk assessment methodology assumes additivity of carcinogenic effects in the regulation of mixtures. A rodent model of hereditary renal cancer was used to investigate the carcinogenic response to a mixture of drinking water disinfection by-products (DBPs). Rats carrying a mutation in the Tsc2 tumor suppressor gene (Eker rats) readily develop renal preneoplastic and neoplastic lesions, and are highly susceptible to the effects of renal carcinogens. Male and female Eker rats were exposed via drinking water to individual or a mixture of DBPs for 4 or 10 months. Potassium bromate, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), chloroform, and bromodichloromethane were administered at low concentrations of 0.02, 0.005, 0.4 and 0.07 g/l, respectively, and high concentrations of 0.4, 0.07, 1.8 and 0.7 g/l, respectively. Low and high dose mixture solutions were comprised of all four chemicals at either low concentrations or high concentrations, respectively, Following necropsy, each kidney was examined microscopically for preneoplastic lesions (atypical tubules and hyperplasias) and tumors. While some of the mixture responses observed in male rats did fall within the range expected for an additive response, especially at the high dose, predominantly antagonistic effects on renal lesions were observed in response to the low dose mixture in male rats and the high dose mixture in female rats. These data suggest that current default risk assessments assuming additivity may overstate the cancer risk associated with exposure to mixtures of DBPs at low concentrations. Copyright 2003 Elsevier Science Ireland Ltd.
López-Morales, Dolores; Reyes-Leyva, Julio; Santos-López, Gerardo; Zenteno, Edgar; Vallejo-Ruiz, Verónica
Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue. Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied Maackia amurensis lectin, which interacts with α2,3-linked sialic acid and Sambucus nigra lectin specific for α2,6-linked sialic acid. The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL). These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases. These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation.
Background Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue. Methods Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied Maackia amurensis lectin, which interacts with α2,3-linked sialic acid and Sambucus nigra lectin specific for α2,6-linked sialic acid. Results The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL). These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases. Conclusions These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation. PMID:21092209
Queiroz, Conceição; Silva, Tânia Correia; Alves, Venâncio A F; Villa, Luisa L; Costa, Maria Cecília; Travassos, Ana Gabriela; Filho, José Bouzas Araújo; Studart, Eduardo; Cheto, Tatiana; de Freitas, Luiz Antonio R
Interaction of human papilloma virus oncoproteins E6 and E7 with cell cycle proteins leads to disturbances of the cell cycle mechanism and subsequent alteration in the expression of some proteins, such as p16INK4a, cyclin D1, p53 and KI67. In this study, we compared alterations in the expression of these proteins during several stages of intraepithelial cervical carcinogenesis. Accordingly, an immunohistochemical study was performed on 50 cervical biopsies, including negative cases and intraepithelial neoplasias. The expression patterns of these markers were correlated with the histopathological diagnosis and infection with HPV. The p16INK4a, followed by Ki67, showed better correlation with cancer progression than p53 and cyclin D1, which recommends their use in the evaluation of cervical carcinogenesis. These monoclonal antibodies can be applied to cervical biopsy specimens to identify lesions transformed by oncogenic HPV, separating CIN 1 (p16INK4a positive) and identifying high-grade lesions by an increase in the cellular proliferation index (Ki67). In this way, we propose immunomarkers that can be applied in clinical practice to separate patients who need a conservative therapeutic approach from those who require a more aggressive treatment.
Development of HPV-associated cancers not only depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage, but also relies on immune evasion that enable the virus to go undetected for long periods of time. In this way, HPV-related tumors usually present MHC class I down-regulation, impaired antigen-processing ability, avoidance of T-cell mediated killing, increased immunosuppression due to Treg infiltration and secrete immunosuppressive cytokines. Thus, these are the main obstacles that immunotherapy has to face in the treatment of HPV-related pathologies where a number of different strategies have been developed to overcome them including new adjuvants. Although antigen-specific immunotherapy induced by therapeutic HPV vaccines was proved extremely efficacious in pre-clinical models, its progression through clinical trials suffered poor responses in the initial trials. Later attempts seem to have been more promising, particularly against the well-defined precursors of cervical, anal or vulvar cancer, where the local immunosuppressive milieu is less active. This review focuses on the advances made in these fields, highlighting several new technologies (such as mRNA vaccine, plant-derived vaccine). The most promising immunotherapies used in clinical trials are also summarized, along with integrated strategies, particularly promising in controlling tumor metastasis and in eliminating cancer cells altogether. After the early promising clinical results, the development of therapeutic HPV vaccines need to be implemented and applied to the users in order to eradicate HPV-associated malignancies, eradicating existing perception (after the effectiveness of commercial preventive vaccines) that we have already solved the problem. PMID:24667138
Shen, Guohua; Ma, Huan; Liu, Bin; Ren, Pengwei; Kuang, Anren
Diffusion-weighted imaging and fluorine-18-fluorodeoxyglucose PET are increasingly being recognized as feasible oncological techniques. The apparent diffusion coefficient (ADC) measured by diffusion-weighted imaging and the standardized uptake value (SUV) from fluorine-18-fluorodeoxyglucose PET have similar clinical applications. The aim of this study was to assess the correlation between these two parameters in various cancers. Several major databases were searched for eligible studies. The correlation coefficient (ρ) values were pooled in a random-effects model. Begg's test was used to analyze the existence of publication bias and the sources of heterogeneity were explored in subgroup analyses on the basis of study design, diagnostic method, scanning modality, and tumor type. Thirty-five articles were accepted. The pooled ρ value of all of the accepted studies was -0.30 (95% confidence interval: -0.33 to -0.27), and notable heterogeneity was present (I=69.4%, P<0.001), which indicated a relatively weak negative correlation. The pooled ρ values were -0.26, -0.33, -0.32, and -0.33 for the SUVmax/ADCmean, SUVmax/ADCmin, SUVmean/ADCmean, and SUVmean/ADCmin relationships, respectively. The study design and diagnostic method were potential sources of heterogeneity. Lung cancer showed a stronger correlation (ρ=-0.42) than head and neck cancer (ρ=-0.27), cervical cancer (ρ=-0.21), and breast cancer (ρ=-0.23). A Begg's test indicated no significant publication bias among the accepted studies (P>0.05). The two functional parameters of ADC and SUV showed a very weak inverse correlation, which may contribute toward a sophisticated characterization of tumor biology. However, the findings require further validation with trials with large samples and different tumor types.
Stojanac, I L; Premovic, M T; Ramic, B D; Drobac, M R; Stojsin, I M; Petrovic, L M
The aim of this two-year prospective clinical study was to evaluate and compare the clinical performance of three different adhesive esthetic materials in noncarious cervical lesions. A total of 90 restorations (30 per material) were placed in 30 patients who ranged in age between 18 and 50 years and of both genders, by a single operator with no previous preparation. The restoration of noncarious cervical lesions was done with either a microfilled composite (Esthet.X/Dentsply/De Trey, Konstanz, Germany, and Prime&Bond NT/Dentsply/De Trey), a nanohybrid composite (TetricEvoCeram/Vivadent, Schaan, Liechtenstein, and AdheSE/Vivadent), or a compomer (Dyract eXtra/Dentsply/De Trey and Xeno III Dentsply/De Trey). All restorations were evaluated by independent examiners using a modified US Public Health Service criteria at baseline and after 12 and 24 months for six clinical categories. Data were analyzed statistically by Pearson's chi-square or the Fisher's exact test at 5% significance level (p<0.05). Results showed that most of the restorations were clinically satisfactory after 12 and 24 months, with no statistically significant differences among the three groups for all evaluated criteria. Treatment of noncarious cervical lesions using composite and compomer materials, combined with the appropriate adhesive systems and properly implemented restorative procedures, gives satisfactory results after a two-year evaluation period.
García-Espinosa, Benjamín; Nieto-Bona, Ma Paz; Rueda, Sonsoles; Silva-Sánchez, Luís Fernando; Piernas-Morales, Ma Concepción; Carro-Campos, Patricia; Cortés-Lambea, Luís; Moro-Rodríguez, Ernesto
Background The HVP vaccine is a useful tool for preventing cervical cancer. The purpose of this study is to determine the most frequent HPV genotypes in Equatorial Guinea in order to develop future vaccination strategies to apply in this country. Methods A campaign against cervical cancer was carried out in the area on a total of 1,680 women. 26 of the women, following cytological screening, were treated surgically with a loop electrosurgical excision procedure (LEEP). Cases were studied histologically and were genotyped from paraffin blocks by applying a commercial kit that recognized 35 HPV types. Results Cytological diagnoses included 17 HSIL, 1 LSIL, 5 ASC-H and 3 AGUS. Histological diagnosis resulted in 3 cases of microinvasive squamous cell carcinoma stage IA of FIGO, 9 CIN-3, 8 CIN-2, 2 CIN-1, 3 flat condylomas and mild dysplasia of the endocervical epithelium. Fifteen of twenty-five cases genotyped were positive for HPV (60%). HPV 16 and 33 were identified in four cases each, HPV 58 in two other cases, and HPV 18, 31, 52, and 82 in one case, with one HPV 16 and 58 coinfection. Conclusion The frequency of HPV types in the African area varies in comparison to other regions, particularly in Europe and USA. Vaccination against the five most common HPV types (16, 33, 58, 18, and 31) should be considered in the geographic region of West Africa and specifically in Equatorial Guinea. PMID:19740435
Bernichtein, Sophie; Pigat, Natascha; Capiod, Thierry; Boutillon, Florence; Verkarre, Virginie; Camparo, Philippe; Viltard, Mélanie; Méjean, Arnaud; Oudard, Stéphane; Souberbielle, Jean-Claude; Friedlander, Gérard; Goffin, Vincent
Epidemiological studies that have investigated whether dairy (mainly milk) diets are associated with prostate cancer risk have led to controversial conclusions. In addition, no existing study clearly evaluated the effects of dairy/milk diets on prostate tumor progression, which is clinically highly relevant in view of the millions of men presenting with prostate pathologies worldwide, including benign prostate hyperplasia (BPH) or high-grade prostatic intraepithelial neoplasia (HGPIN). We report here a unique interventional animal study to address this issue. We used two mouse models of fully penetrant genetically-induced prostate tumorigenesis that were investigated at the stages of benign hyperplasia (probasin-Prl mice, Pb-Prl) or pre-cancerous PIN lesions (KIMAP mice). Mice were fed high milk diets (skim or whole) for 15 to 27 weeks of time depending on the kinetics of prostate tumor development in each model. Prostate tumor progression was assessed by tissue histopathology examination, epithelial proliferation, stromal inflammation and fibrosis, tumor invasiveness potency and expression of various tumor markers relevant for each model (c-Fes, Gprc6a, activated Stat5 and p63). Our results show that high milk consumption (either skim or whole) did not promote progression of existing prostate tumors when assessed at early stages of tumorigenesis (hyperplasia and neoplasia). For some parameters, and depending on milk type, milk regimen could even exhibit slight protective effects towards prostate tumor progression by decreasing the expression of tumor-related markers like Ki-67 and Gprc6a. In conclusion, our study suggests that regular milk consumption should not be considered detrimental for patients presenting with early-stage prostate tumors.
Boutillon, Florence; Verkarre, Virginie; Camparo, Philippe; Viltard, Mélanie; Méjean, Arnaud; Oudard, Stéphane; Souberbielle, Jean-Claude; Friedlander, Gérard; Goffin, Vincent
Epidemiological studies that have investigated whether dairy (mainly milk) diets are associated with prostate cancer risk have led to controversial conclusions. In addition, no existing study clearly evaluated the effects of dairy/milk diets on prostate tumor progression, which is clinically highly relevant in view of the millions of men presenting with prostate pathologies worldwide, including benign prostate hyperplasia (BPH) or high-grade prostatic intraepithelial neoplasia (HGPIN). We report here a unique interventional animal study to address this issue. We used two mouse models of fully penetrant genetically-induced prostate tumorigenesis that were investigated at the stages of benign hyperplasia (probasin-Prl mice, Pb-Prl) or pre-cancerous PIN lesions (KIMAP mice). Mice were fed high milk diets (skim or whole) for 15 to 27 weeks of time depending on the kinetics of prostate tumor development in each model. Prostate tumor progression was assessed by tissue histopathology examination, epithelial proliferation, stromal inflammation and fibrosis, tumor invasiveness potency and expression of various tumor markers relevant for each model (c-Fes, Gprc6a, activated Stat5 and p63). Our results show that high milk consumption (either skim or whole) did not promote progression of existing prostate tumors when assessed at early stages of tumorigenesis (hyperplasia and neoplasia). For some parameters, and depending on milk type, milk regimen could even exhibit slight protective effects towards prostate tumor progression by decreasing the expression of tumor-related markers like Ki-67 and Gprc6a. In conclusion, our study suggests that regular milk consumption should not be considered detrimental for patients presenting with early-stage prostate tumors. PMID:25938513
DA Cruz Paula, Arnaud; Marques, Oriana; Sampaio, Rita; Rosa, Ana; Garcia, José; Rêma, Alexandra; DE Fátima Faria, Maria; Silva, Paula; Vizcaíno, Ramón; Lopes, Carlos
Cancer stem cells are tumor cells that present self-renewal, clonal tumor initiation capacity and clonal long-term repopulation potential. We have previously demonstrated that the co-expression of the breast cancer stem cell (BCSC) markers hyaluronan receptor (CD44) and aldehyde dehydrogenase-1 (ALDH1) in ductal carcinomas in situ could be determinant for disease progression. Combining these established BCSC markers with Ki-67 to evaluate quiescence we sought to identify, evaluate the distribution and estimate the mean percentages of CD44(+)ALDH1(+)Ki-67(-) breast cells. Triple-immunohistochemistry for CD44, ALDH1 and Ki-67 was applied in a series of 16 normal, 54 non-malignant and 155 malignant breast tissues. Clinical relevance was inferred by associations with markers of breast cancer behavior, progression and survival. The mean percentages of cells with this phenotype increased significantly from non-malignant lesions to high-grade ductal carcinomas in situ, decreasing in invasive ductal carcinomas, as also evidenced by an inverse correlation with histological grade and tumor size. The mean percentage of CD44(+)ALDH1(+)Ki-67(-) cells was also significantly higher in women who developed distant metastasis and died due to breast cancer, and a significant association with human epidermal growth factor type 2 (HER2) negativity was observed. Our novel findings indicate that CD44(+)ALDH1(+)Ki-67(-) tumor cells may favor distant metastasis and can predict overall survival in patients with ductal carcinomas of the breast. More importantly, quiescence may have a crucial role for tumor progression, treatment resistance and metastatic ability of BCSCs. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
Kennedy, Ann R.; Davis, James G.; Carlton, William; Ware, Jeffrey H.
Malignancy is considered to be a particular risk associated with exposure to the types of ionizing radiation encountered during extended space flight. In the present study, two dietary preparations were evaluated for their ability to prevent carcinogenesis in CBA mice exposed to different forms of space radiation: protons and highly energetic heavy particles (HZE particles). One preparation contained a mixture of antioxidant agents. The other contained the soybean-derived Bowman-Birk protease inhibitor (BBI), used in the form of BBI Concentrate (BBIC). The major finding was that there was a reduced risk of developing malignant lymphoma in animals exposed to space radiation and maintained on diets containing the antioxidant formulation or BBIC compared to the irradiated animals maintained on the control diet. In addition, the two different dietary countermeasures also reduced the yields of a variety of different rare tumor types observed in the animals exposed to space radiation. These results suggest that dietary supplements could be useful in the prevention of malignancies and other neoplastic lesions developing from exposure to space radiation. PMID:18494549
Spiryda, Lisa Beth; Whitaker, Kara M; Messersmith, Amy; Banister, Carolyn E; Creek, Kim E; Pirisi-Creek, Lucia A
Although human papillomavirus (HPV) infection is necessary for cervical squamous intraepithelial lesion (SIL/CIN) and cancer to develop, exposure to HPV is not predictive of which women will develop SIL/CIN and cancer. This study examines mRNA expression of several potential biomarkers in exfoliated cervical cells collected from college-aged women. Freshman female students were recruited into the Carolina Women's Care Study, which was designed to prospectively evaluate factors that contribute to persistent HPV infections. One component of this study was to extract mRNA from exfoliated cervical cells. In this study, mRNA expression of Frizzled (FZD), growth differentiating factor 15, interleukin 1 beta (IL1β), and N-cadherin was assessed through real-time polymerase chain reaction. Statistical analysis was performed with a Student t test; all results were standardized with glyceraldehyde 3-phosphate dehydrogenase. Fifty samples were selected that reflected the demographics of the Carolina Women's Care Study participants. IL1β mRNA expression was 9.4-fold higher in cervical cells from women with abnormal Pap tests (p = .0018); low-grade squamous intraepithelial lesion had 12.7-fold higher expression than negatives (p = .0011). The FZD mRNA expression was 5.7-fold higher in CIN 2 as compared with CIN 1 (p = .0041) and 8.5-fold higher compared with cytology/pathology negative (p = .0014). Other differences in mRNA expression showed trends but not reaching statistical significance for each condition. It seems that several biomarkers involved in the cytokine/inflammatory pathway (IL1β), cell adhesion pathway (N-cadherin), growth factor (growth differentiating factor 15), and Wingless (WNT) signaling pathway (FZD) may be potential biomarkers in conjunction with the Pap test and HPV that help predict which women are at highest risk for developing CIN 3 and cervical cancer.
Gow, Alex M; Kelleher, Martin G
There are many reported cases of cervical abrasion/erosion cavities in the literature with various theories offered in support of their pathogenesis. The vast majority of these cases involve the labial cervical regions of the affected teeth. This case report describes an unusual dental presentation of severe lingual cervical and interproximal lesions predominantly affecting the upper and lower anterior and premolar teeth. The differential diagnosis is presented, along with the likely cause of the lesions: in this case, a bizarre oral hygiene technique. The proposed treatment plan is outlined and the problems associated with restoring such cavities are highlighted.
Bornman, M S; Barnhoorn, I E J; de Jager, C; Veeramachaneni, D N R
The purpose of the study was to compare wildlife in the proximity and away from the sources of known industrial pollution. Macroscopic, focal, gritty areas that appeared white were observed in the testes of all 24 South African eland (Tragelaphus oryx) culled in the Rietvlei Nature Reserve (RNR; n=17) between 2001 and 2003 and Suikerbosrand Nature Reserve (SNR; n=7) in 2004. Histopathological evaluation of testes showed multiple intratubular dystrophic calcifications, focal areas of sperm stasis and interstitial chronic cell infiltrates with fibrosis. Spermatogenesis was generally impaired; a few atypical germ cells were also encountered. Sertoli cell vacuolization and sloughing of the seminiferous epithelium were evident. Adenomatous changes of the rete testis, reflective of possible chronic estrogenic exposure, were found. In testes collected from three reference eland in 2007 from the Molopo Nature Reserve (MNR) in the Kalahari/Kgalagadi Desert, except for one focal area of sperm stasis and another with microcalcification, the seminiferous epithelium as well as collecting/rete tubules were normal. Analyses of fat tissue for environmental pollutants showed that 11 out of 17 RNR eland contained a detectable estrogenic chemical p-nonylphenol (mean+/-SD: 184.8+/-24.6 microg/kg fat); no organochlorine chemicals or polychlorinated biphenyls were detected. Of the 7 SNR eland, 5 had detectable octylphenol residues (50.2+/-30.9 microg/kg fat), 3 had detectable p-nonylphenol (137.8+/-77.9 microg/kg fat), 3 had o-p'-DDT (114.9+/-31.1 microg/kg fat), 3 had p-p'-DDT (127.3+/-49.9 microg/kg(79.5+/-30.4 microg/kg fat) and 5 contained o-p'-DDE (27.7+/-9.9 microg/kg fat). One eland from the MNR contained one 70.6 microg o-p'-DDT/kg fat and another p-p'-DDE 61.3 microg/kg fat. Therefore, in eland with testicular abnormalities, significant amounts of various estrogenic chemicals were bioaccumulated in fat samples. It therefore seems likely that the lesions found in RNR and SNR
Soares, P V; Santos-Filho, P C F; Soares, C J; Faria, V L G; Naves, M F; Michael, J A; Kaidonis, J A; Ranjitkar, S; Townsend, G C
The aim of this study was to measure the effect of simulating two different loads on maxillary incisors displaying eight morphological types of non-carious cervical lesions, unrestored and restored with an adhesive restoration, by quantifying the stress distributions generated using finite element analysis. Virtual models of maxillary incisors were generated using the CAD software (RhinoCeros). After composing virtual dental and supporting structures with and without non-carious cervical lesions, each model was meshed using a control mesh device (ANSYS Finite Element Analysis Software). All of the virtual models were subjected to two load types, oblique load and vertical load, to simulate occlusal forces of 100 N each. Comparisons were made between simulated teeth with non-carious cervical lesions, with and without composite resin restorations, and a simulated sound tooth. Data summarizing the stress distributions were obtained in MPa using von Mises criteria. Oblique loading on simulated non-carious cervical lesions resulted in greater stress concentration compared with vertical loading, and non-carious cervical lesions with acute angles displayed higher stress concentrations at the depth of the lesion. Restoring the lesions with an adhesive restoration, such as composite resin, appeared to overcome this stress concentration. Restoring NCCLs with adhesive restorative materials, such as a nanohybrid composite resin, appears to recover the biomechanical behaviour similar to sound teeth. © 2013 Australian Dental Association.
Lee, Chien-Hung; Yang, Sheau-Fang; Peng, Chiung-Yu; Li, Ruei-Nian; Chen, Yu-Chieh; Chan, Te-Fu; Tsai, Eing-Mei; Kuo, Fu-Chen; Huang, Joh-Jong; Tsai, Hsiu-Ting; Hung, Yu-Hsiu; Huang, Hsiao-Ling; Tsai, Sharon; Wu, Ming-Tsang
Although cooking emission from high-temperature frying has been deemed a Group 2A carcinogen by the International Agency for Research on Cancer, little is known about its impact on cervical tumorigenesis. To investigate the precancerous consequence of cooking oil fumes on cervical intraepithelial neoplasm (CIN), a community-based case-control study, which takes all known risk factors into consideration, was conducted in Taiwan. From 2003 to 2008, in a Pap smear screening and biopsy examination network, 206 pathology-verified women with inflammations/atypical squamous cells of undetermined significance or CIN grade-1 (CIN1) and 73 with CIN2-3 (defined as low-grade squamous intraepithelial lesions (LGSIL) and high-grade squamous intraepithelial lesions (HGSIL), respectively); and 1,200 area-and-age-matched controls with negative cytology were recruited. Multinomial logistic regression was applied in the multivariate analysis to determine the likelihood of contracting LGSIL or HGSIL. The risks of the two lesions increased with the increase of carcinogenic high-risk human papillomavirus DNA load, with a clear dose-response relationship. Chefs were observed to experience a 7.9-fold elevated HGSIL risk. Kitchens with poor fume ventilation during the main cooking life-stage correlated to a 3.7-fold risk of HGSIL, but not for LGSIL. More than 1 hr of daily cooking in kitchens with poor fume conditions appeared to confer an 8.4-fold HGSIL risk, with an 8.3-fold heterogeneously higher odds ratio than that (aOR = 1.0) for LGSIL. Similar risk pattern has been reproduced among never-smoking women. Our findings demonstrate the association between indoor exposure to cooking fumes from heated oil and the late development of cervical precancerous lesions. This final conclusion needs to be verified by future research.
Milutin Gašperov, Nina; Sabol, Ivan; Planinić, Pavao; Grubišić, Goran; Fistonić, Ivan; Ćorušić, Ante; Grce, Magdalena
Change in the host and/or human papillomavirus (HPV) DNA methylation profile is probably one of the main factors responsible for the malignant progression of cervical lesions to cancer. To investigate those changes we studied 173 cervical samples with different grades of cervical lesion, from normal to cervical cancer. The methylation status of nine cellular gene promoters, CCNA1, CDH1, C13ORF18, DAPK1, HIC1, RARβ2, hTERT1, hTERT2 and TWIST1, was investigated by Methylation Specific Polymerase Chain Reaction (MSP). The methylation of HPV18 L1-gene was also investigated by MSP, while the methylated cytosines within four regions, L1, 5’LCR, enhancer, and promoter of the HPV16 genome covering 19 CpG sites were evaluated by bisulfite sequencing. Statistically significant methylation biomarkers distinguishing between cervical precursor lesions from normal cervix were primarily C13ORF18 and secondly CCNA1, and those distinguishing cervical cancer from normal or cervical precursor lesions were CCNA1, C13ORF18, hTERT1, hTERT2 and TWIST1. In addition, the methylation analysis of individual CpG sites of the HPV16 genome in different sample groups, notably the 7455 and 7694 sites, proved to be more important than the overall methylation frequency. The majority of HPV18 positive samples contained both methylated and unmethylated L1 gene, and samples with L1-gene methylated forms alone had better prognosis when correlated with the host cell gene promoters’ methylation profiles. In conclusion, both cellular and viral methylation biomarkers should be used for monitoring cervical lesion progression to prevent invasive cervical cancer. PMID:26057381
Ichim, I P; Schmidlin, P R; Li, Q; Kieser, J A; Swain, M V
It is still largely unknown as to what material parameter requirements would be most suitable to minimise the fracture and maximising the retention rate of the restoration of cervical non-carious lesions (NCCL). The present paper, as a first of its kind, proposes a radical approach to address the problems of material improvement, namely: numerical-based, fracture and damage mechanics materials optimisation engineering. It investigates the influence of the elastic modulus (E) on the failure of cervical restorative materials and aims to identify an E value that will minimise mechanical failure under clinically realistic loading conditions. The present work relies on the principle that a more flexible restorative material would partially buffer the local stress concentration. We employ a "most favourable" parametric analysis of the restorative's elastic modulus using a fracture mechanics model embedded into finite element method. The advanced numerical modelling adopts a Rankine and rotating crack material fracture model coupled to a non-linear analysis in an explicit finite element framework. The present study shows that the restorative materials currently used in non-carious cervical lesions are largely unsuitable in terms of resistance to fracture of the restoration and we suggest that the elastic modulus of such a material should be in the range of 1GPa. We anticipate that the presented methodology would provide more informative guidelines for the development of dental restorative materials, which could be tailored to specific clinical applications cognisant of the underlying mechanical environment.
Pitta, Denise Rocha; Campos, Elisabete Aparecida; Sarian, Luis Otávio; Rovella, Marcello Silveira; Derchain, Sophie Françoise Mauricette
To determine the prevalence of HPV 16, 18, 31 and 45 in cervical screening samples of women with cellular changes and/or colposcopy suggestive of persistent high grade or low grade lesion who were submitted to conization. A total of 120 women were included in the study. Histological analysis of the cervical cones revealed 7 cases of cervicitis, 22 of CIN1, 31 of CIN2, 54 of CIN3, and 6 invasive carcinomas. The cervical screening samples were analyzed before conization for the presence of HPV-DNA by PCR using the consensus primers PGMY09/11. HPV-DNA-positive samples were tested for the presence of HPV16, 18, 31 and 45 using type-specific primers for these HPV. HPV-DNA was detected in 67.5% of the studied women. HPV 16 (40%) was the most prevalent type in most ilesions, followed by HPV 31 (13.3%), 45 (13.3%), and 18 (4.1%). Multiple infections occurred in 15% of the cases and infections with other HPV types were detected in 14% of the sample. HPV 16 and 18 infections do not always occur as a single infection, and may be associated with other HPV types on different occasions.
von der Meden Alarcón, J W; Ruiz Moreno, J A; García León, J F; Kably Ambe, A
Cervico-uterine cancer is the most frequent gynecological neoplasia in Mexico and cervico-vaginal cytology is the most practical and dependable resource in lesions detection. During the last years precursory lesions detection (NIC and HPV infection) has increased. So, every patient presenting with an abnormal cytology should be included in an evaluation program, that includes a colposcopic study with biopsy of suspicious lesions, in order to know cellular abnormality degree, as these studies combination increases diagnosis certainty. Ninety three patients were evaluated by colposcopy, as the Papanicolaou showed abnormality ICN type in any degree or HPV infection data, during the first three years of the Unidad de Colposcopia de la Beneficiencia del Hospital ABC. In 49 patients histopathological study, was done. A correlation of all studies was carried out. There was a correlation cytology-histopathology of 59.18%; and colposcopy-histopathology of 89.79%. It was concluded that evaluation by cytology is insufficient to establish a final diagnosis and treatment, and that colposcopic study is fundamental in the evaluation of the patient with abnormal exfoliative cytology.
Hur, B; Kim, H-C; Park, J-K; Versluis, A
The aetiology of non-carious cervical lesions (NCCLs) is not well understood and still controversial. The aim of this ex-vivo study was to examine the morphological characteristics of NCCLs for clinical evidence of enamel loss above the cemento-enamel junction (CEJ) as suggested by the abfraction theory. Fifty extracted human teeth with various types of NCCLs were collected and scanned by micro computed tomography. The reconstructed three-dimensional models were evaluated from multiple aspects, including longitudinal cross-section series. The location of internal line angle and proximal exits of the lesions were evaluated in relation to the level of CEJ. The coronal margins of the lesions were inspected for evidence of enamel loss above the CEJ using the bucco-lingual longitudinal sectional images. Coronal margins of the lesions were located along and/or under the CEJ for all of the 50 samples. In most of the lesions, regardless of lesion type, the proximal exits and internal line angles were located below the CEJ. This study did not detect clinical evidence of enamel loss above the occlusal margin of NCCLs as would have been expected according to the general abfraction mechanism.
Sugita, Iori; Nakashima, Syozi; Ikeda, Asaomi; Burrow, Michael F; Nikaido, Toru; Kubo, Shisei; Tagami, Junji; Sumi, Yasunori
This longitudinal pilot study aimed to morphologically and quantitatively investigate the progress of non-carious cervical lesions (NCCLs) by using swept-source optical coherence tomography (SS-OCT). The samples examined comprised sets of NCCL epoxy resin replicas obtained from 10 lesions in 6 patients who attended annual dental visits over 4 or 5 years. SS-OCT images of the replicas were analyzed in terms of the maximum depth (Dmax) and corresponding vertical width (VW) - using an image analyzer to estimate progression of the NCCLs over time. It was found that differences between wedge- and saucer-shaped lesions were morphologically distinguished well by the OCT images. There were significant differences in dimensions among Dmax, VW and horizontal width (HW). HW was the largest and Dmax was the smallest. Although no significant differences in absolute values of annual progression rates were found among Dmax, VW and HW, the percentage increase in Dmax was significantly greater compared to VW and HW. The ratios of Dmax to corresponding VW ranged from 0.49 to 1.01 for the wedge-shaped lesions and from 0.13 to 0.44 for saucer-shaped lesions, respectively. The dimensional analysis demonstrated notable progression with large variations. The wedge-shaped lesions appeared to show greater Dmax values compared to the saucer-shaped lesions. With respect to the depth, the wedge-shaped lesions may progress at a greater rate compared to the saucer-shaped lesions. Copyright © 2016 Elsevier Ltd. All rights reserved.
Soares, P V; Machado, A C; Zeola, L F; Souza, P G; Galvão, A M; Montes, T C; Pereira, A G; Reis, B R; Coleman, T A; Grippo, J O
The present study analysed the effects of different occlusal loading on premolars displaying various non-carious cervical lesions morphologies, restored (or not) with composites, by 3D finite element analysis. A three-dimensional digital model of a maxillary premolar was generated using CAD software. Three non-carious cervical lesions morphological types were simulated: wedged-shaped, saucer and mixed. All virtual models underwent three loading types (100 N): vertical, buccal and palatal loading. The simulated non-carious cervical lesions morphologies were analysed with and without restorations to consider specific regions, such as the occlusal and gingival walls as well as the depth of the lesions. Data summarizing the stress distribution were obtained in MPa using Maximum Principal Stress. Palatal loads were responsible for providing the highest values of accumulated tensile stress on the buccal wall; 27.66 MPa and 25.76 MPa for mixed and wedged-shaped morphologies, respectively. The highest tensile values found on non-carious cervical lesions morphologies restored with composite resin were 5.9 MPa in the mixed morphology, similar to those found on sound models despite their morphologies and occlusal loading. The various non-carious cervical lesions morphologies had little effect on stress distribution patterns, whereas the loading type and presence of composite restorations influenced the biomechanical behaviour of the maxillary premolars. © 2015 Australian Dental Association.
Fernandes, JV; Carvalho, MGF; de Fernandes, TAAM; Araújo, JMG; Azevedo, PRM; Azevedo, JCV; Meissner, RV
Background: Human papillomavirus (HPV) has been recognized as a necessary, but not sufficient, cause of cervical cancer. Aim: In this study, we investigated the prevalence of HPV and the genotype distribution in women from Natal, North-East Brazil, with normal cytology and with cervical lesions of different degrees. Subjects and Methods: Included in this study were 110 women with a normal cytology and 315 with a previous history of cervical cytological abnormalities. The patients were enrolled between January 2005 and December 2008. The cytopathological analyzes were performed by the Pap smear exam, and the pre-malignant and maligant lesions were confirmed based on the histopathological analysis. The presence of HPV was detected by polymerase chain reaction with genotyping by dot blot hybridization. All the data were included in a database, using the software SPSS, Version 10.0 (Chicago Il, USA). Results: Overall HPV prevalence was 65.2% (277/425), with 85.9% (238/277) single and 14.1% (39/277) multiple infection. The most prevalent HPV types were HPVs 16, 58, 18, 31, and 45. HPV 16 was the most prevalent genotype, independently of the health status of patients. HPV 58 was the second most prevalent type in women with normal cytology and in those who had mild or moderate dysplasia. HPV 58 presented equal prevalence to HPV 18 in patients with severe dysplasia. However, it was less prevalent than HPV 18 in women with cervical cancer. Conclusions: The results show a high prevalence of HPV 58, especially in women with mild and moderate dysplasia, revealing the high-frequency circulation of this genotype of HPV in the local population. This finding suggests the need to include this genotype in future HPV vaccines targeting women in this region. PMID:24379999
Mejía, Lorena; Muñoz, Diana; Trueba, Gabriel; Tinoco, Leopoldo; Zapata, Sonia
Human Papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it is responsible for most cases of uterine cancer. In Ecuador there is limited information about HPV types (and variants) in cancerous lesions; however, identifying the type-specific HPV prevalence in cervical lesions of women living in Ecuador is important to better predict the impact of HPV prophylactic vaccination in this country. We studied the prevalence of HPV types in cervical cancerous or precancerous lesions from 164 Ecuadorian women and found that 86.0% were HPV positive. The most common types were HPV16 (41.8%) and HPV58 (30.5%). Interestingly, HPV18 was detected only in 2.8% of the HPV-positive samples. Fifteen DNA sequences (genes E6 and L1) from 16 samples positive for HPV16 belonged to the European lineage, considered one of the least carcinogenic lineages, and 1 (6.25%) to the Asian-American lineage. Similar analysis in 12 HPV58 positive samples showed that 10 (83.3%) sequences grouped in sublineage A2, which belongs to the oldest HPV58 lineage, 1 belonged to A3 and 1 to lineage C. This study suggests that the currently used HPV vaccines (bivalent and tetravalent) may have lower effectiveness in Ecuador than in other geographic locations where HPV18 is more prevalent.
Wilder, Aldridge D; Swift, Edward J; Heymann, Harald O; Ritter, André V; Sturdevant, John R; Bayne, Stephen C
The authors conducted a study to evaluate the clinical performance of a dual-cured, three-step dentin adhesive (OptiBond Dual Cure, Kerr, a subsidiary of Sybron Dental Specialties, Orange, Calif.; no longer on the market) at 12 years. The authors restored 100 noncarious cervical lesions without use of macromechanical retention or enamel bevels. In one-half of the lesions (group A), the authors etched only the enamel; in the other half (group B), they etched both enamel and dentin. After etching, they applied a light-cured primer and dual-cured adhesive to enamel and dentin in both groups. They restored the preparations with a resin-based composite. They performed direct evaluations by using modified U.S. Public Health Service criteria at insertion (baseline) and at one year and 12 years after insertion. The 12-year retention rates were 93 percent in group A and 84 percent in group B, for an overall retention rate of 89 percent. Except for marginal discoloration in both groups and retention in group B, the restorations in both groups had Alfa ratings of 88 percent or greater in all of the direct clinical evaluation categories. The 12-year clinical performance, including retention rate, of a dual-cured dental adhesive was excellent and was not affected by dentin acid-etching. This clinical study provides additional evidence for the long-term durability of a three-step etch-and-rinse adhesive in non-carious cervical lesions.
Damião, Paciência de Almeida; Oliveira-Silva, Michelle; Moreira, Miguel Ângelo; Poliakova, Natalia; de Lima, Maria Emilia RT; Chiovo, José; Nicol, Alcina Frederica
Introduction Cervical cancer is the leading cause of cancer deaths among females in Angola and human papillomavirus (HPV) is the main risk factor for the development of pre-cancerous squamous intraepithelial lesions. The diversity and frequency of HPV types in Angola has yet to be reported. Aim To determine the frequency of HPV among women with squamous intraepithelial lesions from women in Luanda, Angola. Methods Study participants included women diagnosed with cytological abnormalities that voluntarily provided Pap smears (n = 64). Genomic DNA was extracted from the samples for use as templates in the PCR amplification of HPV sequences. PCR products were sequenced to determine HPV type. Results HPV DNA was detected in 71.9% (46/64) in the samples. A higher diversity of HPV types was found in the cytological lesions, such as ASCUS and LSIL (HPV16, 6, 18, 31, 58, 66, 70 and 82, in order of frequency) than that detected for HSIL and SSC (HPV16, 18, 6 and 33). The most prevalent HPV type were: HPV16, HPV6 and HPV18. Conclusion This is the first report on HPV type diversity and frequency in woman of Angola. The results suggest that large-scale studies across Africa would improve our understanding of interrelationship between HPV infections and cervical cancer. More directly, the identification of the HPV types most prevalent suggests that women in Angola would benefit from currently available HPV vaccines. PMID:28154623
Schaffer, Paula A; Wobeser, Bruce; Martin, Laura E R; Dennis, Michelle M; Duncan, Colleen G
To identify epidemiological trends in cutaneous neoplasms affecting equids in central North America and compare them with previously reported trends. Retrospective case series. 3,351 cutaneous biopsy specimens from 3,272 equids with a neoplastic diagnosis. Diagnostic reports from 2 diagnostic laboratories (Colorado State University and Prairie Diagnostic Services Inc) were reviewed for frequency of specific lesions and epidemiological trends. Variables included in analyses (if known) were age, sex, breed, geographic location, date of diagnosis, location of neoplasm on the body, and presence or absence of ulceration. Sarcoid, squamous cell carcinoma (SCC), and melanoma were the 3 most common tumors diagnosed. Tumors associated with UV radiation (SCC, SCC in situ, hemangioma, hemangiosarcoma) were 2.3 (95% confidence interval [CI], 1.8 to 3.0) times as common in biopsy specimens received by Colorado State University than in specimens received by Prairie Diagnostic Services Inc. Appaloosa horses and American Paint horses, respectively, were 7.2 (95% CI, 5.6 to 9.2) and 4.4 (95% CI, 3.6 to 5.4) times as likely as other breeds to have tumors associated with UV radiation. Thoroughbreds were predisposed to cutaneous lymphoma, whereas Arabians were more likely to have melanomas. Draft and pony breeds were 3.1 (95% CI, 1.9 to 5.1) times as likely as other breeds to have benign soft tissue tumors. Morgans and pony breeds more commonly had basal cell tumors. Tumors in the perianal region were significantly more likely to be SCC or melanoma while tumors on the limbs were more likely to be giant cell tumor of soft parts. Signalment, anatomic location of the mass, and geographic location of the horse can be used to help equine practitioners formulate differential diagnoses for cutaneous masses. Further research is necessary to identify the biological basis for the development of many equine cutaneous neoplasms.
de Oliveira, Pollyanna Francielli; de Andrade, Kelly Jacqueline Barbosa; Paula, Marcela Cristina Ferreira; Oliveira Acésio, Nathália; da Silva Moraes, Thais; Borges, Priscilla Scalon Freitas; Barcelos, Gustavo Rafael Mazzaron; Tavares, Denise Crispim
Bixin is a carotenoid found in the seeds of Bixa orellana L., a plant native to tropical America that is used in the food industry. The aim of this study was to investigate the effect of bixin on DNA damage and pre-neoplastic lesions induced by 1,2-dimethylhydrazine (DMH) in the liver and colon of Wistar rats. The animals received bixin at daily doses of 0.1, 1.0 and 10mg/kg body weight (bw) by gavage. For the assessment of DNA damage in hepatocytes and colon cells with the comet assay, the administration of bixin was for 7 days. The animals received a single subcutaneous injection of 25mg/kg bw of DMH, and were euthanized 4h later. For the evaluation of the frequency of aberrant crypt foci (ACF), the animals were treated with the different doses of bixin for 4 weeks. Four doses of 40mg/kg bw DMH, two doses in the first week and two doses in the second week, were administered and euthanasia occurred at 4 weeks after the beginning of treatment. Bixin reduced the frequency of DNA damage in hepatocytes at the highest two doses tested (1.0 and 10mg/kg bw). On the other hand, no differences in the frequency of DNA damage in colon cells were observed between animals treated with bixin plus DMH and those treated with DMH alone. In addition, the frequency of ACF did not differ significantly between the group treated with bixin plus DMH and the DMH group. The results suggest that bixin does not suppress the formation of ACF, indicating the absence of a protective effect against colon carcinogenesis.
Silva, Maicon F; Sivieri, Kátia; Rossi, Elizeu A
Purpose In this study the influence of moderate or intense physical exercise, alone or in combination with the consumption of a soya product fermented with Enterococcus faecium, on the development of colon cancer induced chemically in rats with 1,2-dimethylhydrazine (DMH), was investigated. Methods Eighty male Wistar SPF rats were randomly allocated to 8 groups (n = 10). One week after the start of the program of product ingestion and/or physical activity, all animals except the controls (group I) were injected subcutaneously with 50 mg/kg b.w. of 1,2-dimethylhydrazine (DMH). This procedure was repeated at the end of the second week. At the end of the 6-week experiment, all the animals were euthanized; the colons were removed and numbers of ACF was estimated. Results Twenty-four days after the induction of pre-neoplastic lesions, it was evident that the formation of ACF was not significantly reduced by the ingestion of the fermented product, by intense or moderate physical activity or by a combination of these factors, in comparison with the positive control group of rats (p < 0.05). On the other hand, the performance of intense exercise, on its own, increased the number of ACF. Conclusion The results reported in this article show that consumption of the fermented soy product described here and the practice of physical exercise (intense or moderate) were incapable, separately or combined, of inhibiting the formation of ACF in DMH-induced rats. The intense physical exercise led to an increased number of foci in the colons of these rats and, probably, to greater susceptibility to colorectal cancer. PMID:19660118
Dávila-Sánchez, Andrés; Montenegro, Andrés Fernando; Alfonso, Arana-Gordillo; Farago, Paulo Vitor; Loguercio, Alessandro D; Reis, Alessandra
To evaluate the occlusive potential of four toothpastes by atomic force microscopy (AFM) before and after bleaching and quantify the hydrogen peroxide (HP) diffusion into the pulp chamber after application of desensitizing toothpastes in teeth with cervical lesions. In 52 human extracted premolars, 2-mm deep artificial cervical lesions (ACL) were prepared and rinsed with EDTA for 10 seconds. Then teeth were adapted in a brushing machine and brushed with one of the following toothpastes [Regular toothpaste with no occlusive compounds Colgate Cavity Protection (CP), Oral-B Pro Health (OB), Colgate ProRelief (PR) and Sensodyne Rapid Relief (RR)] under constant loading (250 g; 4.5 cycles/seconds; 3 minutes). In 13 teeth (control group), no artificial cervical lesion was prepared. After that, the teeth were bleached with 35% HP with three 15-minute applications. The HP diffusion was measured spectrophotometrically as a stable red product based on HP reaction with 4-aminoanthipyrine and phenol in presence of peroxidase, at a wavelength of 510 nm and the dentin surfaces of ACL were evaluated before and after bleaching by AFM. Data was statistically analyzed by one-way ANOVA and Tukey's test (alpha = 0.05). In the AFM images, some modifications of the dentin surface were observed after application of OB and RR. However, only for RR the formation of a surface deposit was produced, which occluded the majority of the dentin tubules. Also, only for RR, this deposit was not modified/removed by bleaching. Despite this, all groups with ACL showed higher HP penetration than sound teeth, regardless of the toothpaste used (P < 0.001).
Owens, Barry M
This article describes an expedited, atraumatic technique of restoring cervical abrasion-erosion, abfraction or carious lesions using an alternative placement sequence of the dental rubber dam for adequate field isolation. As shown by this technique, the rubber dam retainer is modified and positioned on the tooth with subsequent placement of the dental dam material over theretainer and tooth. This technique saves time and provides good retraction of the gingival tissue and isolation of the cavity preparation from contamination (saliva, hemorrhage) that can potentially cause post-operative symptoms and possible restoration replacement.
Grippo, John O; Simring, Marvin; Coleman, Thomas A
Hitherto, noncarious cervical lesions (NCCLs) of teeth have been generally ascribed to either toothbrush-dentifrice abrasion or acid "erosion." The last two decades have provided a plethora of new studies concerning such lesions. The most significant studies are reviewed and integrated into a practical approach to the understanding and designation of these lesions. A paradigm shift is suggested regarding use of the term "biocorrosion" to supplant "erosion" as it continues to be misused in the United States and many other countries of the world. Biocorrosion embraces the chemical, biochemical, and electrochemical degradation of tooth substance caused by endogenous and exogenous acids, proteolytic agents, as well as the piezoelectric effects only on dentin. Abfraction, representing the microstructural loss of tooth substance in areas of stress concentration, should not be used to designate all NCCLs because these lesions are commonly multifactorial in origin. Appropriate designation of a particular NCCL depends upon the interplay of the specific combination of three major mechanisms: stress, friction, and biocorrosion, unique to that individual case. Modifying factors, such as saliva, tongue action, and tooth form, composition, microstructure, mobility, and positional prominence are elucidated. By performing a comprehensive medical and dental history, using precise terms and concepts, and utilizing the Revised Schema of Pathodynamic Mechanisms, the dentist may successfully identify and treat the etiology of root surface lesions. Preventive measures may be instituted if the causative factors are detected and their modifying factors are considered. © 2011 Wiley Periodicals, Inc.
Saturnino, Ana Conceição Ribeiro Dantas; Diniz, Veruska Cassandra; Sisenando, Herbert Ary Arzabe Anteza Costa Nóbrega; de Souza, Eroisa Maria Conceição Oliveira; de Paiva, Magnus Sérgio Martins; de Brito, Maria Helena Marques Fonseca; Ramos, Eleni Souto Nóbrega
The aim of the present study was confront the results of the cytological examination with hybrid capture II in the diagnosis of induced cervical intraepithelial lesion-HPV, correlating the cytological findings with biomoleculares. The research was carried through in a group of 160 sexually active women who had espontaneamente looked its gynecologists for consultation of routine, having been submitted to the collection of cervicovaginal material for cytology and for examination of hybrid capture II in the Centro de Patologia Clínica and the Hospital e Maternidade Promater, in the city of the Natal-RN. The results had shown to relatively high numbers of positive cases for HPV using hybrid capture II (41.87%) and the cytology (23.75%). The agreement between the two studied methods relatively was raised (59.38%). It was evident also that the viruses with high oncogênico potential had presented found in the compatible cytology with Lesion of low risk (11.88%), followed of Lesion of high risk (NIC II and III); already the viruses with low oncogênico potential were more associates the Lesion of low risk (6.25%), followed of Lesion of high risk. The cytology, exactly with its limitations, is an important method in the detention of attributable patologias to the HPV, emphasizing that the molecular method comes to complement it and to consolidate the cytological findings.
Miyata, Hajime; Hori, Tomokatsu; Vinters, Harry V.
Among epilepsy-associated non-neoplastic lesions, mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and malformation of cortical development (MCD) including focal cortical dysplasia (FCD), are the two most frequent causes of drug-resistant focal epilepsies constituting about 50% of all surgical pathology of epilepsy. Several distinct histological patterns have been historically recognized in both HS and FCD, and several studies have tried to perform clinicopathological correlation; results, however, have been controversial, particularly in terms of postsurgical seizure outcome. Recently, the International League Against Epilepsy constituted a Task Forces of Neuropathology and FCD within the Commission on Diagnostic Methods, to establish an international consensus of histological classification of HS and FCD, respectively, based on agreement with the recognition of the importance of defining a histopathological classification system that reliably has some clinicopathological correlation. Such consensus classifications are likely to facilitate future clinicopathological study. Meanwhile, we reviewed neuropathology of 41 surgical cases of mTLE, and confirmed three type/patterns of HS along with no HS, based on the qualitative evaluation of the distribution and severity of neuronal loss and gliosis within hippocampal formation; i.e., HS type 1 (61%) equivalent to ‘classical’ Ammon’s horn sclerosis, HS type 2 (2%) representing CA1 sclerosis, HS type 3 (17%) equivalent to end folium sclerosis, and no HS (19%). Furthermore we performed a neuropathological comparative study on mTLE-HS and dementia associated HS (d-HS) in elderly, and confirmed that neuropathological features differ between mTLE-HS and d-HS in the distribution of hippocampal neuronal loss and gliosis, morphology of reactive astrocytes and their protein expression, and presence of concomitant neurodegenerative changes particularly Alzheimer type and TDP-43 pathologies. These
Guerini-Rocco, Elena; Piscuoglio, Salvatore; Ng, Charlotte K Y; Geyer, Felipe C; De Filippo, Maria R; Eberle, Carey A; Akram, Muzaffar; Fusco, Nicola; Ichihara, Shu; Sakr, Rita A; Yatabe, Yasushi; Vincent-Salomon, Anne; Rakha, Emad A; Ellis, Ian O; Wen, Y Hannah; Weigelt, Britta; Schnitt, Stuart J; Reis-Filho, Jorge S
Microglandular adenosis (MGA) is a rare proliferative lesion of the breast composed of small glands lacking myoepithelial cells and lined by S100-positive, oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative epithelial cells. There is evidence to suggest that MGA may constitute a non-obligate precursor of triple-negative breast cancer (TNBC). We sought to define the genomic landscape of pure MGA and of MGA, atypical MGA (AMGA) and associated TNBCs, and to determine whether synchronous MGA, AMGA, and TNBCs would be clonally related. Two pure MGAs and eight cases of MGA and/or AMGA associated with in situ or invasive TNBC were collected, microdissected, and subjected to massively parallel sequencing targeting all coding regions of 236 genes recurrently mutated in breast cancer or related to DNA repair. Pure MGAs lacked clonal non-synonymous somatic mutations and displayed limited copy number alterations (CNAs); conversely, all MGAs (n = 7) and AMGAs (n = 3) associated with TNBC harboured at least one somatic non-synonymous mutation (range 3-14 and 1-10, respectively). In all cases where TNBCs were analyzed, identical TP53 mutations and similar patterns of gene CNAs were found in the MGA and/or AMGA and in the associated TNBC. In the MGA/AMGA associated with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified. At diagnosis, MGAs associated with TNBC were found to display subclonal populations, and clonal shifts in the progression from MGA to AMGA and/or to TNBC were observed. Our results demonstrate the heterogeneity of MGAs, and that MGAs associated with TNBC, but not necessarily pure MGAs, are genetically advanced, clonal, and neoplastic lesions harbouring recurrent mutations in TP53 and/or other cancer genes, supporting the notion that a subset of MGAs and AMGAs may constitute
Okawa, Shinpei; Sei, Kiguna; Hirasawa, Takeshi; Irisawa, Kaku; Hirota, Kazuhiro; Wada, Takatsugu; Kushibiki, Toshihiro; Furuya, Kenichi; Ishihara, Miya
For diagnosis of cervical cancer, screening by colposcope and successive biopsy are usually carried out. Colposcope, which is a mesoscope, is used to examine surface of the cervix and to find precancerous lesion grossly. However, the accuracy of colposcopy depends on the skills of the examiner and is inconsistent as a result. Additionally, colposcope lacks depth information. It is known that microvessel density and blood flow in cervical lesion increases associated with angiogenesis. Therefore, photoacoustic imaging (PAI) to detect angiogenesis in cervical lesion has been studied. PAI can diagnose cervical lesion sensitively and provide depth information. The authors have been investigating the efficacy of PAI in the diagnoses of the cervical lesion and cancer by use of the PAI and ultrasonography system with transvaginal probe developed by Fujifilm Corporation. For quantitative diagnosis by use of PAI, it is required to take the light propagation in biological medium into account. The image reconstruction of the absorption coefficient from the PA image of cervix by use of the simulation of light propagation based on finite element method has been tried in this study. Numerical simulation, phantom experiment and in vivo imaging were carried out.
Ortega-Cervantes, Laura; Aguilar-Lemarroy, Adriana; Rojas-García, Aurora Elizabeth; Barrón-Vivanco, Briscia Socorro; Vallejo-Ruiz, Verónica; León, David Cantú-De; Hernández, Yael Yvette Bernal; Jáuregui-Martínez, Armando; Medina-Díaz, Irma Martha
In Mexico cervical cancer (CC) is the most common cause of death from neoplasia in women. Study aimed to analyze the current distribution of Human papillomavirus (HPV) types in women from Nayarit, Mexico, with Squamous intraepithelial lesions (SIL) and Cervical cancer (CC). Between January 2011 and July 2013, cervical samples were collected from female residents of the Mexican state of Nayarit and were analyzed by means of a LINEAR ARRAY® HPV genotyping test. Data analyses were performed using Stata ver. 8.0 statistical software. Of the samples analyzed, 91.2%, HPV DNA was detected. Of these positive samples, 82% were High-risk (HR) viral types. The most prevalent HPV genotypes identified were 16, 58, 31, 18, and 70. Forty two percent of participants had a single infection, while 23 and 26% of participants were infected with two or more HPV genotypes, respectively. HPV 16 was the most prevalent genotype identified and was frequently present as a co-infection with HPV types 18, 51, 52, 59, 66, or 70. Women <20 years of age were most often infected with HPV, and the HPV Quadrivalent vaccine (types 16, 18, 6, and 11), currently available in Mexico, no confers protection against a subset of the HPV genotypes identified in the present study (58, 31, 70, and 35). Thus, it is important evaluate the geographical distribution of specific HPV genotypes in all health of center across Mexico in order to implement a successful vaccination program and to diagnose CC in its early stages.
Ngonzi, Joseph; Bajunirwe, Francis; Wistrand, Charlotte; Mayanja, Ronald; Altman, Daniel; Thorsell, Malin; Wikström Shemer, Elisabeth Andrea
This study aimed to determine if criterion standard colposcopy could be provided by a pocket-sized battery-driven colposcope, the Gynocular. The study was a randomized, crossover, pilot clinical trial for evaluating agreement of diagnosis of cervical lesions by colposcopy using a standard colposcope and a pocket-sized battery-driven colposcope, the Gynocular, in 69 women positive for visual inspection with acetic acid. Swede scores were used at the time of colposcopy and compared with the final histological diagnosis after directed cervical biopsy. To test the level of agreement between the colposcopy and Gynocular, we calculated the percentage agreement and the κ statistic. We calculated the detection rates of cervical lesions of the Gynocular and a standard colposcope using biopsy results as criterion standards. All included patients also underwent a Pap smear. The level of agreement of Swede score between the Gynocular and colposcope was 70.1% and the κ statistic was 0.65 (p < .001). Biopsy identified 4 women (6.7%) with cervical intraepithelial neoplasia 1 (CIN 1) and 1 woman (1.7%) with CIN 2; 2 women (3.4%) had CIN 3, and 2 women had invasive cervical cancer (CIN 3+). Pap smear detected 2 women (3.1%) with CIN 1 but did not identify any high-grade cervical lesion. Cervicitis was present in 17 (27.4%) of the Pap smears and in 34 (57.6%) of the biopsies. The study shows that in visual inspection with acetic acid-positive women, a battery-driven, pocket-sized colposcope has a significant level of agreement with stationary colposcopy in assessing cervical lesions.
Waxman, Alan G; Chelmow, David; Darragh, Teresa M; Lawson, Herschel; Moscicki, Anna-Barbara
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.
Waxman, Alan G.; Chelmow, David; Darragh, Teresa M.; Lawson, Herschel; Moscicki, Anna-Barbara
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
Iljazović, Ermina; Mustadenagić-Mujanović, Jasminka; Karasalihović, Zinaida; Cickusić, E; Avdić, S
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.
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
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.
de Carvalho, Luana Dutra; Gondo, Renata; Lopes, Guilherme Carpena
To evaluate the one-year clinical performance of composite restorations in noncarious cervical lesions placed in smoking and non-smokers using a multimode adhesive system with two adhesive strategies. Among the selected cervical lesions, four experimental groups were formed based on the patients' smoking habit and bonding strategies with a multimode adhesive system (n = 38): G1: etchand- rinse in non-smokers; G2: selective enamel etching in non-smokers; G3: etch-and-rinse in smokers; G4: selective enamel etching in smokers. The restorations were paired, ie, each patient received at least two restorations. A nanofilled resin composite was applied and light cured incrementally in all groups by one operator. Two calibrated examiners evaluated the restorations at baseline, 6 and 12 months after placement. The modified USPHS criteria were used for evaluation. Data were analyzed using the chi-square (for associations between groups) and McNemar tests. No statistically significant difference was found between groups for the criteria of retention, marginal discoloration, color match, marginal integrity, or sensitivity after 6 and 12 months. The assessments over time showed a statistically significant difference only for marginal discoloration at 12 months for groups 1, 3, and 4 when compared to baseline (p = 0.031). There were no statistical differences for any criteria evaluated among smokers and non-smokers, except for color match, where a difference was found after the baseline evaluation. Regarding the adhesive strategy, etch-and-rinse resulted in a clinical performance similar to that of selective enamel etching over 12 months. Neither cigarette smoking habit nor adhesive strategy influenced the clinical performance of resin composite cervical restorations over the first year.
Gedefaw, Abel; Astatkie, Ayalew; Tessema, Gizachew Assefa
The magnitude of precancerous cervical cancer lesions as well as invasive cervical cancer is higher in HIV-infected women than non HIV-infected women. Thus, screening targeting HIV-infected women is being undertaken in developing countries, including Ethiopia. However, data on the prevalence and determinants of precancerous cervical cancer lesion among HIV-infected women in southern Ethiopia is lacking. Thus, this study aimed to assess the prevalence of and factors associated with precancerous cervical cancer lesion among HIV- infected women in southern Ethiopia. A hospital-based cross-sectional study was conducted from October 2012 to February 2013 among HIV-infected women in Southern Ethiopia. Four hundred forty eight HIV-infected women who had been screened and treated for precancerous cervical cancer lesion were included in the study. Data were collected by using structured and pretested questionnaire. Visual inspection with acetic acid was applied for screening and treatment. SPSS version 16.0 was used for data entry and analysis. Logistic regression analysis was fitted and odds ratios with 95% Confidence intervals and p-values were computed to identify factors associated with precancerous cervical cancer lesion. Out of 448 study participants, 99 (22.1%) were found to be positive for precancerous cervical cancer. Being currently on highly active antiretroviral treatment (AOR=0.52, 95%CI: 0.35, 0.92), history of sexually transmitted disease (AOR=2.30, 95%CI: 1.23, 4.29) and having only one lifetime sexual partner (AOR=0.33, 95%CI: 0.20, 0.56) were factors associated with precancerous cervical cancer lesion. The prevalence of precancerous cervical cancer lesion among HIV-infected women in southern Ethiopia was found to be high. Intervention to access all HIV-infected women like scaling up the limited services and awareness creation should be undertaken. Measures aimed at preventing the acquisition and transmission of sexually transmitted diseases and reducing
Depuydt, Christophe; Benoy, Ina; Bogers, Johannes; Antoine, Jerome; Arbyn, Marc; Pawlita, Michael
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
Prabitha, Vasumathi Gopala; Suchetha, Sambasivan; Jayanthi, Jayaraj Lalitha; Baiju, Kamalasanan Vijayakumary; Rema, Prabhakaran; Anuraj, Koyippurath; Mathews, Anita; Sebastian, Paul; Subhash, Narayanan
Diffuse reflectance (DR) spectroscopy is a non-invasive, real-time, and cost-effective tool for early detection of malignant changes in squamous epithelial tissues. The present study aims to evaluate the diagnostic power of diffuse reflectance spectroscopy for non-invasive discrimination of cervical lesions in vivo. A clinical trial was carried out on 48 sites in 34 patients by recording DR spectra using a point-monitoring device with white light illumination. The acquired data were analyzed and classified using multivariate statistical analysis based on principal component analysis (PCA) and linear discriminant analysis (LDA). Diagnostic accuracies were validated using random number generators. The receiver operating characteristic (ROC) curves were plotted for evaluating the discriminating power of the proposed statistical technique. An algorithm was developed and used to classify non-diseased (normal) from diseased sites (abnormal) with a sensitivity of 72 % and specificity of 87 %. While low-grade squamous intraepithelial lesion (LSIL) could be discriminated from normal with a sensitivity of 56 % and specificity of 80 %, and high-grade squamous intraepithelial lesion (HSIL) from normal with a sensitivity of 89 % and specificity of 97 %, LSIL could be discriminated from HSIL with 100 % sensitivity and specificity. The areas under the ROC curves were 0.993 (95 % confidence interval (CI) 0.0 to 1) and 1 (95 % CI 1) for the discrimination of HSIL from normal and HSIL from LSIL, respectively. The results of the study show that DR spectroscopy could be used along with multivariate analytical techniques as a non-invasive technique to monitor cervical disease status in real time.
Delivery of granulocyte-macrophage colony-stimulating factor in bioadhesive hydrogel stimulates migration of dendritic cells in models of human papillomavirus-associated (pre)neoplastic epithelial lesions.
Hubert, Pascale; Evrard, Brigitte; Maillard, Catherine; Franzen-Detrooz, Elizabeth; Delattre, Luc; Foidart, Jean-Michel; Noël, Agnes; Boniver, Jacques; Delvenne, Philippe
Because of the central role of dendritic cells and/or Langerhans cells(DC/LC) in the induction of cellular immune responses, pharmacological agents that modulate the recruitment of these cells might have a clinical interest. The present study was designed to evaluate the capacity of several pharmaceutical formulations to topically deliver granulocyte-macrophage colony-stimulating factor (GM-CSF) on human papillomavirus (HPV)-associated genital (pre)neoplastic lesions. The formulations were evaluated for their bioactivity and for their potential to recruit DC in organotypic cultures of HPV-transformed keratinocytes. We found that a bioadhesive polycarbophil gel (Noveon) at pH 5.5 is able to maintain the bioactivity of GM-CSF at 4 or 37 degrees C for at least 7 days, whereas a decreased activity of GM-CSF was observed when the molecule is included in other polymer gels. GM-CSF incorporated in the polycarbophil gel was also a potent factor in enhancing the colonization of DC into organotypic cultures of HPV-transformed keratinocytes since the infiltration of DC in the in vitro-formed (pre)neoplastic epithelium was very low under basal conditions and dramatically increased in the presence of GM-CSF gel. We next demonstrated that GM-CSF incorporated in polycarbophil gel induces the recruitment of human DC in a human (pre)neoplastic epithelium grafted into NOD/SCID mice. The efficacy of GM-CSF in this formulation was equivalent to that observed with liquid GM-CSF. These results suggest that GM-CSF incorporated in polycarbophil gel could play an important role in the recruitment of DC/LC in mucosal surfaces and be useful as a new immunotherapeutic approach for genital HPV-associated (pre)neoplastic lesions.
Ezechi, Oliver Chukwujekwu; Pettersson, Karen Odberg; Okolo, Clement Abu; Ujah, Innocent Achaya O.; Ostergren, Per Olof
Introduction Findings from studies that evaluated the effect of antiretroviral drug use on the development of cervical squamous intraepithelial lesion differed in their conclusions. This study investigated the association between HIV infection, antiretroviral drug use and cervical squamous intraepithelial lesion in a high HIV and cervical cancer burden setting- Nigeria. Methods A cross sectional study among 1140 women of known HIV status enrolled in a randomised study to determine the test characteristics of visual inspection in detecting cytology diagnosed squamous intraepithelial lesion. Multivariate analysis was used to determine the association between HIV infection, antiretroviral drug use and the twin outcome variables of cervical squamous intraepithelial lesion (SIL) and High grade squamous intraepithelial lesion (HSIL) while controlling for confounders. Results Prevalence of cervical squamous intraepithelial lesion was 8.5%, with a higher prevalence of 14.3% in HIV positive compared to 3.3% in HIV negative women (aOR: 5.4; 95% CI: 2.9–8.8). Not using antiretroviral drugs was found to be associated with an increased risk of SIL (aOR: 2.1; 95% CI: 1.4–3.5) and HSIL (aOR: 2.6; 95% CI: 1.1–6.4). Participants who had a CD4 cell count <200 cells/mm3, were also found to be at increased risk for SIL (aOR: 1.9; 95% CI: 1.1–5.9) and HSIL (aOR: 5.7; 95% CI: 1.1–7.2). Conclusion HIV infection and severe immunosuppression were found to be associated with increased risk of cervical squamous intraepithelial lesion but not viral load. For the first time, in the West African sub-region with specific HIV type and strains, we established the protective effect of antiretroviral drug use against the development of SIL. Integration of cervical cancer screening programme into HIV services and early initiation of antiretroviral drug in HIV positive women especially those with severe immune-suppression could therefore prove to be useful in preventing and controlling
Zouheir, Yassine; Fechtali, Taoufiq; Elgnaoui, Nadia
Cervical cancer is a major public health problem in Morocco. The cervical cancer has a long precancerous period that provides an opportunity for the screening and treatment. Improving screening tests is a priority goal for the early diagnosis of cervical cancer. This study was conducted to evaluate the combination of p16(INK4a) protein expression, human papillomavirus (HPV) typing, and histopathology for the identification of cervical lesions with high risk to progress to cervical cancer among Moroccan women. A total of 96 cervical biopsies were included in this study. Signal amplification in situ hybridization with biotinylated probes was used to detect HPV. Immunohistochemistry was used to evaluate the expression of p16(INK4a) protein. HPV DNA was detected in 74.0% of the biopsies (71/96). Of the seventy-one positive HPV cases, we detected 67.6% (48/71) of high risk (HR)-HPV (HPV 16 and 18), 24% of low risk-HPV (HPV 6 and 11), 1.4% intermediate risk-HPV (HPV 31, 33, and 35), and 7% coinfections (HPV 6/11 and 16/18). Overexpression of p16(INK4a) protein was observed in 72.9% (70/96) of the biopsies. In addition, p16(INK4a) protein detection was closely correlated with recovery of HR HPV. Our result showed that p16(INK4a) expression level is correlated with HR-HPV status.
Bratt, A M; Cassel, J C; Neufang, B; Greene, P L; Jackisch, R; Hertting, G; Will, B E
This longitudinal study, extending over 12 months, assessed the behavioural and biochemical effects of hippocampal sympathetic ingrowth (HSI) into the partially denervated hippocampus. Male Long-Evans rats received fimbria-fornix lesions (FIFO) or sham operations at 90 days of age. At the same time half of the rats from each group sustained bilateral ablation of the superior cervical ganglia (SCGX). A battery of behavioural tests, measuring spontaneous alternation, activity in the open field and home cage, and radial-maze performance, were employed, starting after one very short (16 days) and one extended (216 days) post-operative delay. Neurochemical analyses measuring choline acetyltransferase (ChAT) activity, high-affinity choline (HACU) and noradrenaline uptake by hippocampal synaptosomes (HANU), hippocampal noradrenaline ([NA]), serotonin ([5-HT]) and 5-hydroxyindoleacetic acid ([5-HIAA]) concentrations were carried out in a dorsal, a "middle" and a ventral region of the hippocampus. Lesion of the FIFO induced a significant and enduring deficit in radial-maze performance, in addition to a persistent locomotor hyperactivity. ChAT and HACU were significantly depleted in all three regions of the hippocampus at 12 months, and these deficits were negatively correlated with maze performance. SCGX in the presence of the FIFO lesion significantly reduced [NA] in the middle region of the hippocampus, as compared to SCGX rats, and contributed to a restoration of lesion-induced depletions in [5-HT] and [5-HIAA] in the middle and ventral hippocampal regions, whilst failing to elicit any behavioural changes at either time point. It is concluded that if lesion-induced HSI indeed occurred, as is suggested by neurochemical evidence, it had no effect upon the observed behavioural deficits elicited by transection of the FIFO in the rat.
Aarabi, Bizhan; Simard, J Marc; Kufera, Joseph A; Alexander, Melvin; Zacherl, Katie M; Mirvis, Stuart E; Shanmuganathan, Kathirkamanthan; Schwartzbauer, Gary; Maulucci, Christopher M; Slavin, Justin; Ali, Khawar; Massetti, Jennifer; Eisenberg, Howard M
The authors performed a study to determine if lesion expansion occurs in humans during the early hours after spinal cord injury (SCI), as has been established in rodent models of SCI, and to identify factors that might predict lesion expansion. The authors studied 42 patients with acute cervical SCI and admission American Spinal Injury Association Impairment Scale Grades A (35 patients) and B (7 patients) in whom 2 consecutive MRI scans were obtained 3-134 hours after trauma. They recorded demographic data, clinical information, Injury Severity Score (ISS), admission MRI-documented spinal canal and cord characteristics, and management strategies. The characteristics of the cohort were as follows: male/female ratio 37:5; mean age, 34.6 years; and cause of injury, motor vehicle collision, falls, and sport injuries in 40 of 42 cases. The first MRI study was performed 6.8 ±2.7 hours (mean ± SD) after injury, and the second was performed 54.5 ± 32.3 hours after injury. The rostrocaudal intramedullary length of the lesion on the first MRI scan was 59.2 ± 16.1 mm, whereas its length on the second was 88.5 ± 31.9 mm. The principal factors associated with lesion length on the first MRI study were the time between injury and imaging (p = 0.05) and the time to decompression (p = 0.03). The lesion's rate of rostrocaudal intramedullary expansion in the interval between the first and second MRI was 0.9 ± 0.8 mm/hour. The principal factors associated with the rate of expansion were the maximum spinal cord compression (p = 0.03) and the mechanism of injury (p = 0.05). Spinal cord injury in humans is characterized by lesion expansion during the hours following trauma. Lesion expansion has a positive relationship with spinal cord compression and may be mitigated by early surgical decompression. Lesion expansion may be a novel surrogate measure by which to assess therapeutic effects in surgical or drug trials.
Distéfano, A L; Picconi, M A; Alonio, L V; Dalbert, D; Mural, J; Bartt, O; Bazán, G; Cervantes, G; Lizano, M; Carrancá, A G; Teyssié, A
OBJECTIVE: The aim of this study was to identify human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) lesions and to evaluate the persistence of viral DNA after diathermic large loop excision (DLLE) treatment. STUDY DESIGN: Biopsies from 36 patients with low- and high-grade CIN lesions were studied before and after DLLE treatment looking for HPV sequences. DNA was extracted to perform a radioactive polymerase chain reaction (PCR) using GP 5,6 generic primers. PCR products were analyzed by the single-stranded conformational polymorphism (SSCP) which is a simultaneous detection and typing method. Dot-blot hybridization with generic and type-specific biotinylated oligonucleotide probes was applied in some cases. RESULTS: HPV DNA was found in all pretreatment samples, and the viral type was identified in 80% of them, HPV 16 being the most prevalent. The viral type coincided with that detected in the first biopsy in all except one case. Seventy five percent of the patients (27 cases) were negative for CIN at follow up, but 50% of them remained HPV DNA positive. CONCLUSION: DLLE treatment was effective in removing the CIN lesion but not the HPV. This fact points out the need to asses the presence of HPV in DNA during the follow-up, since viral persistence has been considered a high risk factor for recurrence and/or malignant transformation. PMID:9894176
Karan, Kunal; Yao, Xiaomei; Xu, Changqi; Wang, Yong
Objective The molecular structural nature of the dentin substrate in non-carious cervical lesions (NCCLs) is poorly understood. This investigation characterized the chemical structure including inhomogeneities, composition, mineral crystallinity, collagen organization of normal dentin and affected dentin substrates within NCCLs using Raman micro-spectroscopic mapping/imaging. Materials and Methods Three extracted human pre-molars affected with NCCLs were selected and cavities matching the natural lesion with respect to size and location were prepared on the lingual/palatal surface of each tooth to serve as controls. The specimens were sectioned to expose the gingival and occlusal margins of the NCCLs and the control cavities. Micro-Raman spectra and imaging acquired at 1.5 micrometer spatial resolution at positions perpendicular to the lesion surfaces. Results The Raman spectra and imaging comparisons showed the distinct compositional and structural alterations in mineral and matrix components of NCCL affected dentin. A heterogeneous hyper-mineralized layer, with characteristic features such as high phosphate/low carbonate content, high degree of crystallinity and partially denatured collagen were revealed in affected dentin substrate of NCCLs. Significance Generating Raman images based on different strategies from the same data set provides a powerful means to study the structural alterations within heterogeneous dental tissues. Direct overlay of the images indicated that the changes in chemical structure and composition are synchronized. Further studies are required to understand the role that these alterations play in response to acid etching and bonding to these clinically-relevant substrates. PMID:19464050
Stoica, Eniko T.; Marcauteanu, Corina; Bradu, Adrian; Sinescu, Cosmin; Topala, Florin Ionel; Negrutiu, Meda Lavinia; Duma, Virgil Florin; Podoleanu, Adrian Gh.
Non-carious cervical lesions (NCCL) are defined as the loss of tooth substance at the cemento-enamel junction and are caused by abrasion, erosion and/or occlusal overload. In this paper we proved that our fast swept source OCT system is a valuable tool to track the evolution of NCCL lesions in time. On several extracted bicuspids, four levels of NCCL were artificially created. After every level of induced lesion, OCT scanning was performed. B scans were acquired and 3D reconstructions were generated. The swept source OCT instrument used in this study has a central wavelength of 1050 nm, a sweeping range of 106 nm (measured at 10 dB), an average output power of 16 mW and a sweeping rate of 100 kHz. A depth resolution determined by the swept source of 12 μm in air was experimentally obtained. NCCL were measured on the B-scans as 2D images and 3D reconstructions (volumes). For quantitative evaluations of volumes, the Image J software was used. By calculating the areas of the amount of lost tissue corresponding to each difference of Bscans, the final volumes of NCCL were obtained. This swept source OCT method allows the dynamic diagnosis of NCCL in time.
Ortega-Cervantes, Laura; Aguilar-Lemarroy, Adriana; Rojas-García, Aurora Elizabeth; Barrón-Vivanco, Briscia Socorro; Vallejo-Ruiz, Verónica; León, David Cantú-De; Hernández, Yael Yvette Bernal; Jáuregui-Martínez, Armando; Medina-Díaz, Irma Martha
Objective In Mexico cervical cancer (CC) is the most common cause of death from neoplasia in women. Study aimed to analyze the current distribution of Human papillomavirus (HPV) types in women from Nayarit, Mexico, with Squamous intraepithelial lesions (SIL) and Cervical cancer (CC). Methodology Between January 2011 and July 2013, cervical samples were collected from female residents of the Mexican state of Nayarit and were analyzed by means of a LINEAR ARRAY® HPV genotyping test. Data analyses were performed using Stata ver. 8.0 statistical software. Results Of the samples analyzed, 91.2%, HPV DNA was detected. Of these positive samples, 82% were High-risk (HR) viral types. The most prevalent HPV genotypes identified were 16, 58, 31, 18, and 70. Forty two percent of participants had a single infection, while 23 and 26% of participants were infected with two or more HPV genotypes, respectively. HPV 16 was the most prevalent genotype identified and was frequently present as a co-infection with HPV types 18, 51, 52, 59, 66, or 70. Conclusion Women <20 years of age were most often infected with HPV, and the HPV Quadrivalent vaccine (types 16, 18, 6, and 11), currently available in Mexico, no confers protection against a subset of the HPV genotypes identified in the present study (58, 31, 70, and 35). Thus, it is important evaluate the geographical distribution of specific HPV genotypes in all health of center across Mexico in order to implement a successful vaccination program and to diagnose CC in its early stages. PMID:27610056
Park, Soyeong; Park, Jung Wook; Pitot, Henry C; Lambert, Paul F
Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of Bi-L E7 transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative. IMPORTANCE : Fanconi anemia (FA) patients are at high risk for developing squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) frequently cause cancer. Yet these SCCs are often HPV negative. FA patients have a genetic defect in their capacity to repair damaged DNA. HPV oncogenes cause an accumulation of DNA
Park, Soyeong; Park, Jung Wook; Pitot, Henry C.
ABSTRACT Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of Bi-L E7 transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative. Importance Fanconi anemia (FA) patients are at high risk for developing squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) frequently cause cancer. Yet these SCCs are often HPV negative. FA patients have a genetic defect in their capacity to repair damaged DNA. HPV oncogenes cause an
Bartlett, D W; Shah, P
The terms 'abfraction' and 'abrasion' describe the cause of lesions found along the cervical margins of teeth. Erosion, abrasion, and attrition have all been associated with their formation. Early research suggested that the cause of the V-shaped lesion was excessive horizontal toothbrushing. Abfraction is another possible etiology and involves occlusal stress, producing cervical cracks that predispose the surface to erosion and abrasion. This article critically reviews the literature on abrasion, erosion, and abrasion, and abfraction. The references were obtained by a MEDLINE search in March, 2005, and from this, hand searches were undertaken. From the literature, there is little evidence, apart from laboratory studies, to indicate that abfraction exists other than as a hypothetical component of cervical wear.
Liebenberg, W H
While it is arguable that the operative procedures depicted in this article could have been done equally well with alternative forms of isolation, it is indisputable that rubber dam provides for the most thorough 'isolation' in the comprehensive sense of the term. It allows for the finite control over peripheral variables such as access and controlled gingival retraction. This in turn permits meticulous execution of restorative procedures within the luxury of 'true four-handed dentistry'. Most operative procedures are done within the limitations of single handed dentistry as the other 'three hands' are involved with retraction, fluid evacuation and access control. The rubber dam is indeed indispensable and with the increased awareness of infection control it is conceivable that rubber dam isolation will continue to be associated with quality patient care. Part 2 of this article will detail the application of the 'Modified Gingival Retractor' in the isolation of cervical lesions.
Gutiérrez-Fragoso, K.; Acosta-Mesa, H. G.; Cruz-Ramírez, N.; Hernández-Jiménez, R.
Cervical cancer has remained, until now, as a serious public health problem in developing countries. The most common method of screening is the Pap test or cytology. When abnormalities are reported in the result, the patient is referred to a dysplasia clinic for colposcopy. During this test, a solution of acetic acid is applied, which produces a color change in the tissue and is known as acetowhitening phenomenon. This reaction aims to obtaining a sample of tissue and its histological analysis let to establish a final diagnosis. During the colposcopy test, digital images can be acquired to analyze the behavior of the acetowhitening reaction from a temporal approach. In this way, we try to identify precursor lesions of cervical cancer through a process of automatic classification of acetowhite temporal patterns. In this paper, we present the performance analysis of three classification methods: kNN, Naïve Bayes and C4.5. The results showed that there is similarity between some acetowhite temporal patterns of normal and abnormal tissues. Therefore we conclude that it is not sufficient to only consider the temporal dynamic of the acetowhitening reaction to establish a diagnosis by an automatic method. Information from cytologic, colposcopic and histopathologic disciplines should be integrated as well.
Velez-Perez, Anneliese; Wang, Xiaohong I; Li, Min; Zhang, Songlin
Invasive squamous cell carcinoma (SCC) of the cervix involves the progression of premalignant cervical intraepithelial neoplasia (CIN) and is associated with persistent human papillomavirus infection. Most CINs will regress, and the challenge is to identify the lesions likely to progress to invasive cancer. We evaluated Sirtuin 1 (SIRT1) expression in nonneoplastic cervix, CINs, and SCCs as a potential biomarker to predict disease progression. A total of 101 cases were selected including 29 CIN 1s, 32 CIN 2s, 16 CIN 3s, 2 microinvasive SCCs, and 22 invasive SCCs. Cervical nonneoplastic squamous epithelium showed weak positivity of SIRT1 in the basal layer. SIRT1 cytoplasmic overexpression was found in 13.8% of CIN 1s (4/29), 40.6% of CIN 2s (13/32), and 50% of CIN 3s (8/16), and it was statistically significant between CIN 1 and CIN 2/3 lesions (P=.01). All 24 cases of invasive and microinvasive SCC showed SIRT1 overexpression, with 25% (6/24) showing cytoplasmic staining only, 4.2% (1/24) showing nuclear staining only, and 70.8% (17/24) showing both nuclear and cytoplasmic staining. From CIN 1 to SCC, SIRT1 expression showed steady and statistically significant increase (CIN 1 versus CIN 2-3, P=.01; CIN 2-3 versus SCC, P=.0001). Thus, SIRT1 may serve as a potential biomarker for predicting the progression of CIN to invasive SCC. Copyright © 2016 Elsevier Inc. All rights reserved.
ELİGUZELOGLU DALKILİC, Evrim; OMURLU, Huma
Objectives Adhesive systems are continuously being introduced to Dentistry, unfortunately often without sufficient clinical validation. The aim of this study was to evaluate the clinical performance of cervical restorations done with three different adhesive systems. Material and methods 158 non-carious cervical lesions of 23 patients were restored with a nanofilled composite resin (Filtek Supreme, 3M/ESPE) combined with Single Bond (3M/ESPE, group SI), Clearfil SE (Kuraray Medical Inc., group CL) and Xeno III (De Trey Dentsply, group XE). In groups SI-B, CL-B and XE-B, the outer surface of the sclerotic dentin was removed by roughening with a diamond bur before application of the respective adhesive systems. In groups CL-BP and XE-BP, after removal of the outer surface of the sclerotic dentin with the bur, the remaining dentin was etched with 37% phosphoric acid and the self-etch adhesive systems Clearfil SE and Xeno III were applied, respectively. Lesions were evaluated at baseline, and restorations after 3 months, 1 year and 2 years using modified USPHS criteria. Results After 2 years, no significant difference was found between the retention rates of the groups (p >0.05). Although groups CL and SI showed significantly better marginal adaptation than group XE (p<0.05) at 2 years, no significant difference was found between the marginal adaptation of the groups SI-B, CL-B and XE-B (p>0.05). After 2 years no significant difference was observed among the marginal staining results of all groups (p>0.05). Conclusion Although all adhesive systems showed similar retention rates, Clearfil SE and Single Bond showed better marginal adaptation than Xeno III after 2 years of follow-up. PMID:22666836
Sağlam, Arzu; Usubütün, Alp; Dolgun, Anıl; Mutter, George L; Salman, M Coşkun; Kurtulan, Olcay; Akyol, Aytekin; Özkan, Eylem Akar; Baykara, Sema; Bülbül, Dilek; Calay, Zerrin; Eren, Funda; Gümürdülü, Derya; Haberal, Nihan; Ilvan, Şennur; Karaveli, Şeyda; Koyuncuoğlu, Meral; Müezzinoğlu, Bahar; Müftüoğlu, Kamil Hakan; Özen, Özlem; Özdemir, Necmettin; Peştereli, Elif; Ulukuş, Çağnur; Zekioğlu, Osman
Inter-observer differences in the diagnosis of HPV related cervical lesions are problematic and response of gynecologists to these diagnostic entities is non-standardized. This study evaluated the diagnostic reproducibility of "cervical intraepithelial neoplasia" (CIN) and "squamous intraepithelial lesion" (SIL) diagnoses. 19 pathologists evaluated 66 cases once using H&E slides and once with immunohistochemical studies (p16, Ki-67 and Pro-ExC). Management response to diagnoses was evaluated amongst 12 gynecologists. Pathologists and gynecologists were also given a questionnaire about how additional information like smear results and age modify diagnosis and management. We show moderate interobserver diagnostic reproducibility amongst pathologists. The overall kappa value was 0.50 and 0.59 using the CIN and SIL classifications respectively. Impact of immunohistochemical evaluation on interpretation of cases differed and there was lack of statistically significant improvement of interobserver diagnostic reproducibility with the addition of immunohistochemistry. We saw that choice of treatment methods amongst gynecologists varied and overall concordance was only fair to moderate. The CIN2 diagnostic category was seen to have the lowest percentage agreement amongst both pathologists and gynecologists. We showed that pathologists had diagnostic "styles" and gynecologists had management "styles". In summary each pathologist had different diagnostic tendencies which were affected not only by histopathology and marker studies, but also by the patient management tendencies of the gynecologist that the pathologist worked with. The two-tiered modified Bethesda system improved diagnostic agreement. We concluded that immunohistochemistry should be used only to resolve problems in select cases and not for every case.
Alvarez Fernández, J; Bustos López, H H; Villanueva Díaz, C; Zambrana Castañeda, M C; Coria Soto, I; Aranda Flores, C
Human papilloma virus (HPV) infections frequently cause cervical lesions of different morphologies. We have previously reported a 53.5% pregnancy rate after treatment in a group of women with infertility associated to HPV infection of the cervix uteri. In that paper it was stated that a controlled study should be conducted in order to confirm this finding. Present work was aimed to find if there is any correlation between HPV infections of the cervix uteri and infertility in a retrospective design using an historical cohort of patients studied between 1991 and 1996 in our clinic. A total of 61 women attending the Infertility Clinic at the Instituto Nacional de Perinatología were included into two group. Group 1 (n = 45) included women with HPV lesions of the cervix and group II (n = 16) was formed by women with other type of cervical lesions who had no evidence of HPV infections on colposcopy. Cervico-vaginal citology, colposcopyc study and biopsy specimens were evaluated in all this medical records and the patients status (pregnant-not pregnant) at one year after treatment was registered. The mean duration time of infertility was 4.86 in group I and 3.5 in group II. Pregnancy rate was 16/45 (35.55%) in group I and 6/16 (37.5%) in group II. Seventy five percent of patients in group I and 66% in group II achieved a spontaneous pregnancy after specific treatment of cervical lesions whereas 25% and 33.3% required only ovarian stimulation with clomiphene or hMG. Pregnancies occurred approximately at 9 months after treatment in group I and at 7 months in group II. An association of cervical lesions and a tuboperitoneal factor (excluding endometriosis) was found on 53.57% of women in group I and on 46.66% of women in group II. Cervico-vaginal cytology was suspicious of HPV infection in less than 25% of cases. Present study emphasizes the need for a colposcopic study for the diagnosis of HPV infection in infertile women with cervical lesions even in cases with a negative
de Souza, André Mattos Brito; Colares, Regina Claudia Ramos; Mendonça, Juliano Satori; Rodrigues, Lidiany Karla Azevedo; Santiago, Sérgio Lima
Context: Non-carious cervical lesions are usually associated with dentin hypersensitivity. The use of oxalic acid in restorations of these lesions could be beneficial in relieving pain. Aims: To evaluate the use of oxalic acid in restorations of non-carious cervical lesions. Settings and Design: A randomized clinical trial. Subjects and Methods: One operator placed 90 restorations in 20 volunteers of both sexes, with at least two lesions to be restored with the techniques: Control — Restoration with total-etch technique and Experimental — Restoration with pretreatment with oxalic acid followed by application of adhesive system. The restorative adhesive system used was XP Bond/Durafill. The restorations were directly assessed by two independent examiners using a modified United States Public Health Service (USPHS) method at baseline, 6 and 12 months, taking into account the following criteria: Retention (R), marginal integrity (MI), marginal discoloration (MD), postoperative sensitivity (S), caries (C), and anatomic form (AF). Statistical analysis used: The data were statistically analyzed using the Fisher exact and McNemar tests. The level of significance was set at 5%. Results: After 1 year, the results of restorations clinically satisfactory obtained for the control and experimental group respectively were: R (97% / 89%), MI (100% / 100%), MD (100% / 100%), S (100% / 100%), C (100% / 100%), and AF (100% / 100%). Conclusions: The use of oxalic acid as an agent of dentin pretreatment did not influence the clinical performance of restorations in non-carious cervical lesions after 1 year. PMID:25298641
Cavatorta, Ana Laura; Di Gregorio, Alejandra; Bugnon Valdano, Marina; Marziali, Federico; Cabral, Mariela; Bottai, Hebe; Cittadini, Jorge; Nocito, Ana Lia; Gardiol, Daniela
Human Discs large tumour suppressor (DLG1) participates in regulating cell polarity and proliferation, suggesting an important connection between epithelial organization and cellular growth control. However, it was demonstrated that DLG1 could acquire oncogenic attributes in some specific contexts. In this work, we evaluated the expression of DLG1 and its contribution to the progress of cervical lesions in order to investigate a potential role of this polarity protein in human oncogenic processes. We analyzed cervical biopsies from women with low-grade squamous intraepithelial lesion (LSIL) diagnosis (n=30), for DLG1 expression by immunohistochemistry. These results were correlated with the clinical monitoring of the patients during a 24-month follow-up period. Our data indicate that while all LSIL patients with a DLG1 staining pattern similar to normal tissues are significantly more likely to regress (n=23, Pattern I), all LSIL biopsy specimens showing a diffuse and intense DLG1 staining likely progress to high-grade lesions (n=4, Pattern II). Finally, all persistent LSIL analyzed showed an undetermined DLG1 staining, with a diffuse distribution without a strong intensity (n=3, Pattern III). We found a significant association between the expression pattern of DLG1 and the evolution of the lesion (p<0.00001). This work contributes to the knowledge of DLG1 biological functions, suggesting that its expression may have an important role in the progression of early dysplastic cervical lesions, giving prognostic information. Copyright © 2016 Elsevier Inc. All rights reserved.
de Souza, André Mattos Brito; Colares, Regina Claudia Ramos; Mendonça, Juliano Satori; Rodrigues, Lidiany Karla Azevedo; Santiago, Sérgio Lima
Non-carious cervical lesions are usually associated with dentin hypersensitivity. The use of oxalic acid in restorations of these lesions could be beneficial in relieving pain. To evaluate the use of oxalic acid in restorations of non-carious cervical lesions. A randomized clinical trial. One operator placed 90 restorations in 20 volunteers of both sexes, with at least two lesions to be restored with the techniques: Control - Restoration with total-etch technique and Experimental - Restoration with pretreatment with oxalic acid followed by application of adhesive system. The restorative adhesive system used was XP Bond/Durafill. The restorations were directly assessed by two independent examiners using a modified United States Public Health Service (USPHS) method at baseline, 6 and 12 months, taking into account the following criteria: Retention (R), marginal integrity (MI), marginal discoloration (MD), postoperative sensitivity (S), caries (C), and anatomic form (AF). The data were statistically analyzed using the Fisher exact and McNemar tests. The level of significance was set at 5%. After 1 year, the results of restorations clinically satisfactory obtained for the control and experimental group respectively were: R (97% / 89%), MI (100% / 100%), MD (100% / 100%), S (100% / 100%), C (100% / 100%), and AF (100% / 100%). The use of oxalic acid as an agent of dentin pretreatment did not influence the clinical performance of restorations in non-carious cervical lesions after 1 year.
The growing awareness of the need for emergency centers specializing in the care of trauma patients, together with advances in diagnostic imaging technology, have led to the occasional indiscriminate use of diagnostic methods to the detriment of ordering diagnostic tests based on the risk of fracture and of the clinical examination itself. In many institutions, this practice is carried out without appropriate controls and without analyzing the risks and benefits of a particular clinical conduct. This is particularly true in cases of multiple trauma with suspected traumatic lesions of the cervical spine. For many years, radiological examination was based on plain-film radiography, with CT playing a complementary role. Over the last decade, since the introduction of helical CT, and more recently multidetector CT scanners, the diagnostic approach has undergone rapid, significant changes. This article summarizes the experience based on publications centered on establishing the diagnostic effectiveness of CT in comparison to plain-film radiography and the importance of recognizing risk factors when determining the diagnostic strategy. On the other hand, the importance of avoiding unnecessary tests and excessive radiation in providing appropriate and efficient medical care is stressed. In general, the evidence indicates that CT should be the first-line approach in high-risk patients and plain-film radiography should be reserved for the initial evaluation of patients with a low risk of traumatic lesions.
Blunck, Uwe; Knitter, Katharina; Jahn, Klaus-Roland
To evaluate the 6-month clinical performance of the etch-and-rinse one-bottle adhesive system XP BOND, used in combination with the composite resin Ceram X duo for the restoration of Class V noncarious cervical lesions (NCCL). XP BOND was tested in a total of 40 patients who received two Class V Ceram X duo restorations, Adper Scotchbond 1 XT was used as a control. After cleaning the teeth, the surface of the NCCL was treated using a carbide bur in dentin and a 40-microm diamond bur in enamel with no retentive preparations. The lesions were filled with two increments of Ceram X duo after the application of the respective adhesive by a single operator according to manufacturer's instructions. After 6 months, the retention and the marginal integrity were evaluated. Thirty-eight of 40 patients were evaluated after 6 months by two clinicians according to modified USPHS criteria, and all restorations using XP BOND were still in place. In the control group (using Adper Scotchbond 1XT), one restoration was lost. The statistical evaluation (chi2 test) showed no significant differences in any of the criteria. No difference of marginal integrity was found between the two adhesive systems. XP BOND meets the ADA success criteria after 6 months.
Goel, A; Gandhi, G; Batra, S; Bhambhani, S; Zutshi, V; Sachdeva, P
Evaluation of visual inspection of the cervix with acetic acid (VIA) for screening cervical intraepithelial neoplasia. In this prospective study, 400 women were screened using the Papanicolaou (PAP) smear, VIA and colposcopy. Those who had positive results with any of the screening methods underwent large loop excision of the transformation zone (LLETZ). The sensitivity and specificity of each of the screening methods was analyzed. The sensitivity of VIA (96.7%) was much higher than that of the Pap smear (50%), and almost as high as that of colposcopy (100%). The specificity of VIA (36.4%) was lower than that of the Pap smear (97%) and colposcopy (96.9%), resulting in high false-positive rates for VIA. Two cases of endocervical lesions were missed with VIA. Visual inspection of the cervix with acetic acid is very sensitive for ectocervical lesions. The advantages of the VIA method are its low cost and ease of use (it can be used by paramedical workers), its high sensitivity and its immediate results (it is possible to "see and treat" at the first visit). Its main limitation is a high rate of false-positive results, which may lead to overtreatment if a "see and treat" policy is applied.
Aromseree, Sirinart; Chaiwongkot, Arkom; Ekalaksananan, Tipaya; Kongyingyoes, Bunkerd; Patarapadungkit, Natcha; Pientong, Chamsai
To understand the potential role in cervical cancer development of the three most common high-risk human papillomavirus (HR-HPVs) in Thai women, HPV genotypes and viral genome statuses in different cervical lesions were investigated. Cervical tissues consisting of no cervical intraepithelial neoplasia (84 cases), grade I cervical intraepithelial neoplasia (176 cases), grade II-III cervical intraepithelial neoplasia (91 cases), and squamous cell carcinoma (66 cases) were subjected for HPV genotyping by polymerase chain reaction (PCR) and reverse line blot hybridization assay and for HPV genome status determination by amplification of papillomavirus oncogene transcripts (APOT) assay. HPV prevalence was 28.6% in no cervical intraepithelial neoplasia, 40.3% in grade I cervical intraepithelial neoplasia, 70.3% in grade II-III cervical intraepithelial neoplasia and 86.4% in squamous cell carcinoma cases. The three most common HR-HPV types were HPV 16, 58, and 18 which were distributed in all cervical lesions. HPV physical statuses could be investigated in 4 no cervical intraepithelial neoplasias, 2 grade I cervical intraepithelial neoplasias, 28 grade II-III cervical intraepithelial neoplasias and 31 squamous cell carcinomas. The integrated-derived transcripts were found 3.6% in grade II-III cervical intraepithelial neoplasia and 48.4% in squamous cell carcinoma, whereas no viral genome integration was found in the group of no cervical intraepithelial neoplasia or grade I cervical intraepithelial neoplasia samples. The frequencies of HR-HPV integration in squamous cell carcinoma were found 40%, 100%, 20% of HPV 16, 18, and 58. This study indicates the oncogenic potential ability of the three most common HR-HPVs associated with cervical cancer progression. © 2014 Wiley Periodicals, Inc.
Torg, J S; Ramsey-Emrhein, J A
Conditions involving the cervical spine in the athlete requiring management decisions are numerous. The purpose of this paper is to present appropriate guidelines for return to collision activities in those with congenital, developmental, or post-injury lesions. Collision activities include boxing, football, ice hockey, lacrosse, rugby and wrestling. Information compiled from over 1200 cervical spine lesions documented by the National Football Head and Neck Injury Registry, an extensive literature review, as well as an understanding of injury mechanisms have resulted in reasonable management guidelines. Each of the congenital, developmental and post-traumatic conditions presented are identified as either no contraindication, relative contraindication, or an absolute contraindication on the basis of a variety of parameters. Conditions involved in the discussion include: odontoid anomalies, spina bifida occulta, atlanto-occipital fusion, K1ippel-Feil syndrome, cervical canal stenosis, spear tackler's spine; and traumatic conditions of the upper, middle and lower cervical spine including ligamentous injuries and fractures, intervertebral disc injuries and post-cervical spine fusion. It should be emphasized that the proposed guidelines should be used in the decision making process and in conjunction with other such factors as age, experience, ability of the individual, level of participation, position played, as well as the attitude and desires of the athlete and his parents, where applicable following an informed discussion of the problem with particular regard to potential risk.
Ganesan, Sornam; Subbiah, Vasantha N.; Michael, Jothi Clara J.
Objective: To identify the associated factors of cervical pre-malignant lesions among the married fisher women residing in the coastal areas of Sadras, Tamil Nadu. Methods: The study was conducted in five fishermen communities under Sadras, a coastal area in Tamil Nadu, India. Two hundred and fifty married fisher women residing in the area. Quantitative descriptive approach with a cross-sectional study design was used. Data were collected using a structured interview schedule for identifying the associated factors and Pap smear test was performed for identifying the pre-malignant cervical lesions among the married fisher women. Data were analyzed using descriptive and inferential statistics. Results: Among 250 women, about six (2.4%) of them presented with pre-cancerous lesions such as atypical squamous cell of undifferentiated significance (ASCUS) — five (2%) and mild dysplasia one (0.4%). Majority of the women, about 178 (71.2%) women, had abnormal cervical findings. Statistical analysis showed a significant association of risk factors such as advanced age, lack of education, low socioeconomic status, using tobacco, multiparity, premarital sex, extramarital relationship, using cloth as sanitary napkin, etc. Conclusion: The study findings clearly show the increased vulnerable state of the fisher women for acquiring cervical cancer as they had many risk factors contributing to the same. PMID:27981091
Le Donne, Maria; Giuffrè, Giuseppe; Caruso, Carmela; Nicotina, Piero Antonio; Alibrandi, Angela; Scalisi, Rosalba; Simone, Angela; Chiofalo, Benito; Triolo, Onofrio
To determine human papillomavirus (HPV) types distribution in cervical lesions in a Southern Italian female population in Messina and their relationship between HPV type and grade of colposcopic and histopathological abnormality, a total of 253 women aged 17-68 years, with previous cytological abnormalities, were included in this study. HPV-DNA testing, colposcopy and biopsy were performed. For each sample, cervical cells were collected by centrifugation and DNA was extracted, followed by a PCR-based HPV-DNA assay and reverse dot blot genotyping. HPV-16 was found the most common type (46.6 %) followed by HPV-31 (26.9 %), -6 (18.6 %), -58 (8.8 %), -18 (6.7 %), -66 (5.7 %), -52 and -53 (4.7 %). Out of 62 women with abnormal transformation zone (ATZ) area compatible with squamous intraepithelial lesion (SIL) or cervical cancer (CC), 64.5 % was found high risk (HR) HPV-positive. Moreover the severity of the colposcopic diagnosis was positively correlated with the higher HPV oncogenicity risk (HPV-16 P = 0.023; and HPV-53 P = 0.047). The HPV-16 was found the most prevalent type within each histological category: 66.7 %, 31.2 %, 44 % and 37.2 % of CC, high grade (H)SIL, low grade (L)SIL and chronic cervicitis respectively; followed by HPV-31 present in 25 %, 8 %, and 13.3 % of HSIL, LSIL and chronic cervicitis respectively. A higher HPV incidence than the rest of Italy was found, in agreement with that detected by other authors for the South of the country. These data provide further information about the types prevalence in women with cervical lesions living in Eastern Sicily, suggesting the introduction of new targeted vaccines against a wider spectrum of HPV.
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
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.
Rodrigues-Coutlée, Catherine; Archambault, Jacques; Money, Deborah; Ramanakumar, Agnihotram V; Raboud, Janet; Hankins, Catherine; Koushik, Anita; Richardson, Harriet; Brassard, Paul; Franco, Eduardo L; Coutlée, Francois
The genomic diversity of high-risk human papillomaviruses (HPV) has been associated with viral persistence and HPV-induced lesions. Studies on HPV56 persistence are still pending. To assess the association between HPV56 polymorphism and HPV56 persistence and presence of high-grade cervical intraepithelial neoplasia (CIN2,3) or cancer. HPV56-positive cervical specimens from 204 women selected from a total of 4669 participants recruited in 5 epidemiological studies (parent studies) were further analyzed by PCR-sequencing of the long control region (LCR). Of the 81 women followed prospectively in cohort studies who could be classified, 34 had persistent and 47 had transient HPV56 infections. Variant HPV56-LCR-MTL-21 was detected more frequently in persistent infections (52.9%, 95% CI: 36.7-68.6%) than in transient infections (25.5%, 95% CI: 15.1-39.4). Considering only women recruited in a cohort of women infected or at high risk for HIV infection, infection with variant HPV56-LCR-MTL-21 (OR=4.4, 95% CI: 1.3-14.5) was significantly associated with HPV56 persistence controlling in multivariate analysis for high risk HPV detection and HIV infection. A variation at nucleotide 7800 in HPV56-LCR-MTL-21 resulted in the loss of a binding site for Elf-1 embedded in one of the E2 binding sites, a potential activator or repressor of expression of the HPV genome. HPV56 polymorphism was not associated with CIN2,3 or cancer in women enrolled in cross-sectional and case-control studies. Polymorphism in HPV56 may influence the risk that infections with this type will persist. Copyright © 2013 Elsevier B.V. All rights reserved.
Costa, Carlota; Espinet, Blanca; Molina, Miguel A; Salgado, Rocio; Salido, Marta; Baró, Teresa; Fusté, Pere; Mancebo, Gemma; Carreras, Ramón; Solé, Francesc; Serrano, Sergi; Alameda, Francesc
Cervical displasia are classified as CIN-I, CIN-II and CIN-III. It has been observed that in at least 60% of CIN-I and CIN-II, the pathology disappears spontaneously, while around 30% persist at 24 months, 10% progress to CIN-III and 1% develops as a SCC. The factors involved in the evolution of the pathology are not defined, although infection of HPV is a necessary condition, but not the only one. For this reason, the identification of genetic changes is an essential element for understanding the carcinogenic process. It can also serve as a helpful tool for identifying patients who may be susceptible to its evolution and treatment, from patients whose lesions could regress spontaneous and for whom periodic follow-ups would be enough. Fifty three cervical biopsies from patients with dysplasia and ISCC were included in the study. These biopsies were set into nine macroarrays. Eight genes and five proteins were examined in each samples (hTERT, PIK3CA, hTERC, MYC, CCND1, BCL2, ZNF217 and p16) by fluorescence in situ hybridization (FISH) and/or immunohistochemistry (IHC). The results reflected that the genetic alterations of PIK3CA, ZNF217 and CCND1 were associated with the evolution of normal tissue to CIN I, those of hTERC and ERBB with the evolution of LSIL to HSIL, those of hTERT and MYC with the evolution of CIN-II/CIN-III to ISCC, and those of BCL-2 with the inception of ISCC. With regards to proteins, the expression of MYC and CCND1 in the initial stages of the illness would help in the acquisition of the altered cellular phenotype.
Leal, Noélia M S; Silva, Juscelino L; Benigno, Maria Ivone M; Bemerguy, Eliane A; Meira, Josete B C; Ballester, Rafael Y
To introduce an experimental non-carious cervical lesion (NCCL) model for studying the influence of presence and type of stress (tension or compression) on acid effects involved in NCCL formation on the enamel near the cement-enamel junction (CEJ). 108 bovine incisors were cut into 18 × 3×3 mm(3) beams, with a notch in the cervical region to generate a standardized area of stress concentration. Half of the specimens were immersed in distilled water and the other half in acetic acid solution (pH 4.5) for 72h. Each group was divided into three subgroups. Two subgroups underwent 800gf static loading, with the specimen positioned in a bending jig with the buccocervical region under either tension or compression. The load was applied simultaneously to immersion (in water or in acid). The third subgroup was not subjected to loading. Transversal and longitudinal 0.05 mm plates of the specimens were analyzed under a light microscope (40, 100 and 200×) to measure the enamel demineralization depth and to assess the presence of cracks, fractures and gaps at the enamel-dentin junction. The demineralization depth data were submitted to ANOVA and Tukey's test at a 5% significance level. Enamel demineralization depth (μm) was higher under tension (158±19 in transversal sections and 229±32 in longitudinal sections) than under compression (transversal: 129±16 and longitudinal: 167±10) or unstressed condition (transversal: 138±21 and longitudinal: 187±21). Specimens immersed in acid and subjected to tensile stress presented enamel micro fractures and wider gaps in the dentin-enamel junction. Enamel demineralization was significantly higher in the presence of tensile stress, due to wider gaps between dentin and enamel, stress corrosion cracking and increased enamel permeability to acid. Copyright © 2016 Elsevier Ltd. All rights reserved.
Kietpeerakool, Chumnan; Kleebkaow, Pilaiwan; Srisomboon, Jatupol
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.
Grippo, John O; Chaiyabutr, Yada; Kois, John C
Although there is a high prevalence of noncarious cervical lesions (NCCLs), the etiology of these lesions remains contentious. To evaluate the combined effects of cyclic fatigue stress and biocorrosion activity on NCCLs. Extracted premolar teeth were allocated into four groups (N = 10). Two groups were cyclically fatigue loaded (100 N; 72 cycles per minute; 9,200 cycles) and placed in either hydrochloric acid gel (pH = 0.1) or orange juice (pH = 4). The other two groups were stored in identical chemical solutions without fatigue load. The buccal-lingual width of each tooth was measured before and after testing. The depth of biocorrosion, normalized by the percentage change in buccolingual width, normalized by time (hour) was calculated. The data were analyzed using a two-way analysis of variance and Tukey's HSD multiple comparison test (α = 0.05). Mean (SD) of the depth of biocorrosion values were as follows: teeth receiving fatigue loading with hydrochloric acid gel exposure (1.003%/hour [0.063]) revealed a significantly higher depth of biocorrosion than the fatigue-loaded group with orange juice exposure (0.511%/hour [0.281]) (p < 0.01). For the groups without fatigue loading, those with hydrochloric acid gel (0.022%/hour [0.006]) had a significantly higher depth of biocorrosion than the group with orange juice (0.009%/hour [0.004]) (p < 0.01). The cyclically fatigue-loaded teeth with hydrochloric acid gel had a significantly greater depth of biocorrosion than either group without fatigue loading (p < 0.001). Cyclic fatigue stress-acidic biocorrosion had a significant effect on the depth of the NCCLs. In order to manage the destructive NCCLs lesions properly, it is essential to understand the etiology of these lesions. The present study indicated that the combined mechanisms of cyclic fatigue stress and biocorrosion could contribute to the formation of NCCLs. © 2013 Wiley Periodicals, Inc.
Martins, Toni Ricardo; Mendes de Oliveira, Cristina; Rosa, Luciana Reis; de Campos Centrone, Cristiane; Rodrigues, Célia Luiza Regina; Villa, Luisa Lina; Levi, José Eduardo
Human Papillomavirus (HPV) genotype distribution varies according to the method of assessment and population groups. This study analyzed type-specific HPV infections among women ranging from 14-95 years old, displaying normal and abnormal cytology, from São Paulo and Barretos cities, Brazil. Women found positive for High Risk-HPVs DNA by either the Hybrid Capture 2 (HC2) or Cobas HPV Test (n = 431) plus a random sample of 223 negative by both assays and 11 samples with indeterminate results, totalizing 665 samples, were submitted to HPV detection by the PapilloCheck test. Cytological distribution included 499 women with a cytological result of Negative for Intraepithelial Lesion or Malignancy and 166 with some abnormality as follows: 54 Atypical Squamous Cells of Undetermined Significance; 66 Low-Grade Squamous Intraepithelial Lesion; 43 High-Grade Squamous Intraepithelial Lesion and 3 (0.5 %) Invasive Cervical Cancer. From the 323 samples (48.6 %) that had detectable HPV-DNA by the PapilloCheck assay, 31 were HPV negative by the cobas HPV and HC2 assays. Out of these 31 samples, 14 were associated with HR-HPVs types while the remaining 17 harbored exclusively low-risk HPVs. In contrast, 49 samples positive by cobas HPV and HC 2 methods tested negative by the PapilloCheck assay (19.8 %). Overall, the most frequent HR-HPV type was HPV 16 (23.2 %), followed by 56 (21.0 %), 52 (8.7 %) and 31 (7.7 %) and the most frequent LR-HPV type was HPV 42 (12.1 %) followed by 6 (6.2 %). Among the HR-HPV types, HPV 56 and 16 were the most frequent types in NILM, found in 19.1 and 17.7 % of the patients respectively while in HSIL and ICC cases, HPV 16 was the predominant type, detected in 37.2 and 66.7 % of these samples. In the population studied, HPV 16 and 56 were the most frequently detected HR-HPV types. HPV 56 was found mainly in LSIL and NILM suggesting a low oncogenic potential. HPV 16 continues to be the most prevalent type in high-grade lesions whereas HPV
Migdalska-Sęk, Monika; Karowicz-Bilińska, Agata; Pastuszak-Lewandoska, Dorota; Czarnecka, Karolina H; Nawrot, Ewa; Domańska-Senderowska, Daria; Kiszałkiewicz, Justyna; Brzeziańska-Lasota, Ewa
In the present study, we analyzed (1) the type of HPV infection and (2) the frequency of loss of heterozygosity and microsatellite imbalance (LOH/MSI) in normal cytology and cervical intraepithelial neoplasia (CIN1-3). The cytological material included: low-grade squamous intraepithelial lesions (CIN1, n = 11), high-grade lesions (CIN2 and CIN3, n = 13), and cytologically normal cells from non-neoplastic cervical samples (n = 8). HPV genotyping was done using RealLine HPV 16/18 kit. We used 20 microsatellite markers from: 1p31.2, 3p14.3, 3p21.3, 3p22.2, 3p24.2, 3p25.3, 7q32.2, 9p21.3, 11p15.5, 12q23.2, and 16q22.1. LOH/MSI was correlated with clinicopathological parameters. The presence of HPV DNA was revealed in 78.13 % samples, including normal cytology. LOH/MSI was the most frequent for: 3p25.3 (39 %), 3p22.2 (20.83 %), 3p24.2 (20 %), and 3p14.3 (16.67 %). It was demonstrated that D3S1234 (FHIT; 3p14.3), D3S1611 (MLH1; 3p22.2), D3S1583 (RARB; 3p24.2), D3S1317 and D3S3611 (VHL; 3p25.3) could differentiate patients with CIN2/CIN3 versus CIN1, showing significantly higher frequency in CIN2/CIN3. LOH/MSI frequency for other than 3p markers was lower, 10-22.2 %. The simultaneous occurrence of LOH/MSI for several markers (OFAL) was higher in CIN2/CIN3. Significant differences in OFAL were found between samples with versus without HPV infection. In HPV-positive patients, significant differences in OFAL were found between normal cytology, CIN1 and CIN2/CIN3. HPV infection influences the increase in LOH/MSI frequency, especially in tumor suppressor gene loci. Several studied microsatellite markers seem to be useful for CIN grading. Hopefully, the obtained results, if confirmed on larger patient cohort, would allow creating a panel of markers supporting clinical diagnosis in patients with HPV infection.
Toro de Méndez, Morelva; Ferrández Izquierdo, Antonio; Llombart-Bosch, Antonio
We aimed to explore the expression pattern of p16(INK4alpha)/Ki-67 immunocytochemical dual-staining and to establish the potential clinical utility for early detection of cervical lesions. Liquid-based cytologies of cervical specimens of cervical cancer screening were processed for p16(INK4alpha)/Ki-67 immunocytochemical dual-staining using the CINtec Plus Kit. HPV testing was performed with the INNO-LiPA HPV genotyping Extra Reverse Hybridization Line Probe Assay kit. One hundred and fifteen cervical cytologies were analyzed with the following results: 11(9.6%) were negative for intraepithelial lesions or malignancy (NILM); 32 (27.8%) presented atypical squamous cells of undetermined significance (ASC-US); 62 (53.9%) exhibited low grade squamous intraepithelial lesions (LSIL) and 10 (8.7%) showed high grade squamous intraepithelial lesions (HSIL). No cases of cervical cancer were detected. The overall prevalence of DNA HPV detection was 81.7% (94/115). The following specific HPV genotypes were identified in 42 (45.0%) cases: HPV16 (26.2%), HPV51 (21.4%), HPV52 (14.3%) and HPV66 (7.1%). Viral sequences of an unknown single HPV were detected in 23.8% of the cases. A total of 42/115 (36.5%) were p16(IVK4alpha)/Ki-67 dual-staining-positive, being more frequent in HSIL (70.0%), decreasing in LSIL (44.0%), detected in a minority of ASC-US (25.0%) and negative in NILM cases (p < 0.001). 40/115 cases (34.8%) were positive for both oncogenic HPV and p16(INK4alpha)/Ki-67 dual-staining, including 6/32 (18.8%) ASC-US, 26/62 (42.0%) LSIL and 8/10 (80.0%) HSIL, which represent a strong association between positivity for HPV, p16(INK4alpha)/Ki-67 staining and severe cytological abnormalities (p < 0.001). This methodology could be used to detect unnoticed cervical lesions.
Yoshizaki, K T; Francisconi-Dos-Rios, L F; Sobral, M A P; Aranha, A C C; Mendes, F M; Scaramucci, T
Determining the factors associated with NCCLs and DH in populations could guide the implementation of specific preventive measures. This study evaluated the clinical features and factors associated with non-carious cervical lesions (NCCLs) and dentin hypersensitivity (DH) in a Brazilian population. The participants were 118 patients at the Dentistry Clinic of our dental school. They completed an interview to obtain personal information and determine the possible factors associated with NCCLs and DH. Clinical examination was undertaken to record the NCCLs, shape of the lesion and certain occlusal factors. DH was diagnosed by air and probe tests. Data were analysed with the multilevel Poisson regression and prevalence ratios, and the respective 95% confidence intervals were calculated. The prevalence of NCCLs and DH among patients was 67·8% and 51·7%, respectively. Of a total number of 2902 teeth examined, 9·65% had NCCLs and 5·82% were sensitive to air. The most affected teeth for both conditions were the premolars. Most of the NCCLs were wedge-shaped and located in the maxilla. The factors associated with NCCLs and DH were age and presence of premature occlusal contacts. NCCLs were also significantly associated with consumption of wine and alcoholic beverages, and DH with consumption of acidic fruits and juices. NCCLs were a common finding, with higher frequency in more advanced age groups, the maxilla and premolars. A significant association occurred between NCCLs, premature contacts and consumption of wine and alcoholic beverages. DH was associated with NCCLs, premature contacts and with the consumption of acidic fruits and juices. © 2016 John Wiley & Sons Ltd.
Martínez-Pérez, R; Paredes, I; Cepeda, S; Ramos, A; Castaño-León, A M; García-Fuentes, C; Lobato, R D; Gómez, P A; Lagares, A
In patients with spinal cord injury after blunt trauma, several studies have observed a correlation between neurologic impairment and radiologic findings. Few studies have been performed to correlate spinal cord injury with ligamentous injury. The purpose of this study was to retrospectively evaluate whether ligamentous injury or disk disruption after spinal cord injury correlates with lesion length. We retrospectively reviewed 108 patients diagnosed with traumatic spinal cord injury after cervical trauma between 1990-2011. Plain films, CT, and MR imaging were performed on patients and then reviewed for this study. MR imaging was performed within 96 hours after cervical trauma for all patients. Data regarding ligamentous injury, disk injury, and the extent of the spinal cord injury were collected from an adequate number of MR images. We evaluated anterior longitudinal ligaments, posterior longitudinal ligaments, and the ligamentum flavum. Length of lesion, disk disruption, and ligamentous injury association, as well as the extent of the spinal cord injury were statistically assessed by means of univariate analysis, with the use of nonparametric tests and multivariate analysis along with linear regression. There were significant differences in lesion length on T2-weighted images for anterior longitudinal ligaments, posterior longitudinal ligaments, and ligamentum flavum in the univariate analysis; however, when this was adjusted by age, level of injury, sex, and disruption of the soft tissue evaluated (disk, anterior longitudinal ligaments, posterior longitudinal ligaments, and ligamentum flavum) in a multivariable analysis, only ligamentum flavum showed a statistically significant association with lesion length. Furthermore, the number of ligaments affected had a positive correlation with the extension of the lesion. In cervical spine trauma, a specific pattern of ligamentous injury correlates with the length of the spinal cord lesion in MR imaging studies
Jenkins, Marjorie; Chiriva-Internati, Maurizio; Mirandola, Leonardo; Tonroy, Catherine; Tedjarati, Sean S.; Davis, Nicole; D’Cunha, Nicholas; Tijani, Lukman; Hardwick, Fred; Nguyen, Diane; Kast, W. Martin; Cobos, Everardo
As the second most common cause of cancer-related death in women, human papilloma virus (HPV) vaccines have been a major step in decreasing the morbidity and mortality associated with cervical cancer. An estimated 490,000 women are diagnosed with cervical cancer each year. Increasing knowledge of the HPV role in the etiology of cervical cancer has led to the development and introduction of HPV-based vaccines for active immunotherapy of cervical cancer. Immunotherapies directed at preventing HPV-persistent infections. These vaccines are already accessible for prophylaxis and in the near future, they will be available for the treatment of preexisting HPV-related neoplastic lesions. PMID:22251005
Trahmono; Lusiana, N.; Indarti, J.
The aim of this study was to compare the performance of multimodal hyperspectral spectroscopy (MHS), which combines fluorescence and reflectance spectroscopy, with that of conventional laboratory-based screening tests, such as the Papanicolaou (Pap) smear test and human papilloma virus (HPV) DNA test, for detecting precancerous lesions of the cervix. The study utilized a cross-sectional design, and the kappa test was used in the analytical assessment. MHS scans were obtained from a sample of 70 consecutive patients, followed by sample collection for Pap and HPV DNA analysis and colposcopy referral, if indicated. Of the 70 patients evaluated, the results of cervical spectroscopy were normal in 38 (54.3%) patients, and they were abnormal in 32 (45.7%) patients. Based on the cytology results, 45 (64.3%) samples were normal, and 25 (35.7%) samples were abnormal. According to the results of the HPV DNA test, 47 (67.14%) samples were normal, and 17 (24.28%) samples were abnormal. Based on the results of the kappa test, the agreement between MHS and cytology was 0.793 (p < 0.001). The agreement between MHS and the HPV DNA test was 0.195 (p = 0.086), and the agreement between MHS and colposcopy was 0.479 (p < 0.001).
Belfort-Mattos, Patrícia Napoli; Focchi, Gustavo Rubino de Azevedo; Ribalta, Julisa Chamorro Lascasas; Megale De Lima, Tatiana; Nogueira Carvalho, Carmen Regina; Kesselring Tso, Fernanda; De Góis Speck, Neila Maria
VEGF and podoplanin (PDPN) have been identified as angiogenesis and/or lymphangiogenesis regulators and might be essential to restrict tumor growth, progression, and metastasis. In the present study, we evaluate the association between the expression of these markers and CIN grade. Immunohistochemistry was performed in 234 uterine cervical samples using conventional histologic sections or TMA with the monoclonal antibodies to VEGF (C-1 clone) and podoplanin (D2-40 clone). Positive-staining rates of VEGF in 191 CIN specimens were significantly associated with histological grade (P < 0.001). Negative and/or focal immunostaining for PDPN were more frequent in CIN 3 (P = 0.016). We found that patients with CIN 3 more frequently had strong and more diffuse staining for VEGF and diminished staining for PDPN (P = 0.018). Strong and more diffuse VEGF immunoexpressions in CIN 2 and CIN 3 were detected when compared to CIN 1. Negative and/or focal PDPN immunoexpression appear to be more frequent in CIN 3. Moderate to strong VEGF expression may be a tendency among patients with high-grade lesions and diminished PDPN expression. PMID:27313335
Adeleke; Oginni, Ao
The clinical performance of various tooth-coloured materials used to restore Non-Carious Cervical Lesions (NCCLs) has been evaluated. However, most of these evaluations were in western societies where soft diets requiring little mastication were common. The present study sets out to evaluate resin composite and RMGIC in the restoration of NCCLs among a Nigerian subpopulation group with fibrous diet requiring more rigorous mastication. The study included all adult patients that presented at the Dental Hospital, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria with non-carious cervical lesions over a period of six months. The teeth with non-carious cervical lesions in each patient were allocated into treatment with either resin composite or resin-modified glass ionomer cement by simple random sampling using ballots. The depth of the NCCLs was measured using a graduated flat ash periodontal probe. All the treatment was done by the first author according to the manufacturer's instructions. Patients were recalled and evaluated at 48- hours, 3- months, 6- months and 12- months using the USPHS criteria. Data analysis was done using SPSS version 15. The level of significance was put at 0.05. At the end of 12 months, 143 resin composite and 144 RMGIC restorations were evaluated, out of which 37 resin composite and 13 RMGIC restorations were dislodged, giving a retention rate of 74.1% and 91.0% respectively. The difference was statistically significant (p<0.05). For marginal discolouration, marginal adaptation, abrasion wear resistance, post operative sensitivity, and secondary caries, there were no statistically significant differences in the performance of resin composite and RMGIC. There was more retention failure of both resin composite and RMGIC restorations in NCCLs in mandibular teeth than in maxillary teeth. The differences were statistically significant (p<0.05). RMGIC demonstrated a higher retention rate in the restoration of non
de Oliveira, Gisele R; Vieira, Valdimara C; Ávila, Emiliana C; Finger-Jardim, Fabiana; Caldeira, Thaís DM; Gatti, Fabiane AA; Gonçalves, Carla V; Oliveira, Sandro G; da Hora, Vanusa P; Soares, Marcelo A; de Martinez, Ana MB
BACKGROUND Increasing evidence suggests that human papillomavirus (HPV) intratype variants (specific lineages and sublineages) are associated with pathogenesis and progression from HPV infection to persistence and the development of cervical cancer. OBJECTIVES This study aimed to verify the prevalence of HPV infection and distribution of HPV types and HPV16 variants in southern Brazil in women with normal cytology or intraepithelial lesions. METHODS HPV typing was determined by L1 gene sequencing. To identify HPV16 variants, the LCR and E6 regions were sequenced, and characteristic single nucleotide variants were identified. FINDINGS A total of 445 samples were studied, with 355 from cervical scrapes and 90 from cervical biopsies. HPV was detected in 24% and 91% of these samples, respectively. The most prevalent HPV types observed were 16 (cervical, 24%; biopsies, 57%) and 58 (cervical, 12%; biopsies, 12%). Seventy-five percent of the HPV16-positive samples were classified into lineages, with 88% defined as lineage A, 10% as lineage D, and 2% as lineage B. MAIN CONCLUSIONS This study identified a high frequency of European and North American HPV16 lineages, consistent with the genetic background of the human population in southern Brazil. PMID:28591310
Hildesheim, Allan; Gonzalez, Paula; Kreimer, Aimee R; Wacholder, Sholom; Schussler, John; Rodriguez, Ana C; Porras, Carolina; Schiffman, Mark; Sidawy, Mary; Schiller, John T; Lowy, Douglas R; Herrero, Rolando
Human papillomavirus vaccines prevent human papillomavirus infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an human papillomavirus-associated lesion is not fully understood. To determine whether human papillomavirus-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions. We included 1711 women (18-25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted human papillomavirus-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2 or greater. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated. Median follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human
Liu, Enju; McCree, Renicha; Mtisi, Expeditho; Fawzi, Wafaie W; Aris, Eric; Lema, Irene A; Hertzmark, Ellen; Chalamilla, Guerino; Li, Nan; Vermund, Sten H; Spiegelman, Donna
To determine the prevalence and predictors of cervical squamous intraepithelial lesions (SIL) among HIV-infected women in Tanzania, a cross-sectional study was conducted among HIV-infected women at HIV care and treatment clinics. A Papanicolaou (Pap) smear was used as a screening tool for detection of cervical SIL. From December 2006 to August 2009, 1365 HIV-infected women received cervical screening. The median age was 35 (interquartile range [IQR]: 30-42) years, and the median CD4 + cell count was 164 (IQR: 80-257) cells/mm(3). The prevalence of cervical SIL was 8.7% (119/1365). In multivariate analysis, older age (≥50 versus 30-<40 years: prevalence ratio [PR], 2.36; 95% confidence interval [CI], 1.45-3.84, p for trend = 0.001), lower CD4 + cell counts (<100 versus ≥200 cells/mm(3): PR, 1.55; 95% CI, 1.01-2.36, p for trend = 0.03) and cervical inflammation (PR, 1.73; 95% CI, 1.16-2.60, p = 0.008) were associated with an increased risk of cervical SIL. Women with advanced WHO HIV disease stage (IV versus I/II: PR, 3.45; 95% CI, 1.35-8.85, p for trend = 0.01) had an increased risk for high-grade SIL. In resource-limited settings where it is not feasible to provide cervical cancer prevention services to all HIV-infected women, greater efforts should focus on scaling-up services among those who are older than 50 years, with lower CD4 cell counts and advanced HIV disease stage. © The Author(s) 2015.
dos Santos, Erinaldo Ubirajara Damasceno; de Lima, Géssica Dayane Cordeiro; Oliveira, Micheline de Lucena; Heráclio, Sandra de Andrade; da Silva, Hildson Dornelas Angelo; Crovella, Sergio; Maia, Maria de Mascena Diniz; de Souza/, Paulo Roberto Eleutério
Polymorphisms in chemokine receptors play an important role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Our study examined the association of CCR2-64I (rs1799864) andCCR5-Δ32 (rs333) polymorphisms with susceptibility to develop cervical lesion (CIN and CC) in a Brazilian population. The genotyping of 139 women with cervical lesions and 151 women without cervical lesions for the CCR2-64I and CCR5-Δ32 polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism. The individuals carrying heterozygous or homozygous genotypes (GA+AA) for CCR2-64I polymorphisms seem to be at lower risk for cervical lesion [odds ratio (OR) = 0.37, p = 0.0008)]. The same was observed for the A allele (OR = 0.39, p = 0.0002), while no association was detected (p > 0.05) with CCR5-Δ32 polymorphism. Regarding the human papillomavirus (HPV) type, patients carrying the CCR2-64Ipolymorphism were protected against infection by HPV type 16 (OR = 0.35, p = 0.0184). In summary, our study showed a protective effect ofCCR2-64I rs1799864 polymorphism against the development of cervical lesions (CIN and CC) and in the susceptibility of HPV 16 infection. PMID:26982176
Waalkes, M P; Anver, M R; Diwan, B A
Based on the occurrence of pulmonary cancers in exposed populations, cadmium is classified as a human carcinogen. More controversial target sites for cadmium in humans include the prostate and kidney, where some studies have shown a link between cadmium and cancer. In Wistar rats cadmium induces tumors in the ventral prostate. The relevance of such lesions to humans is debated since the rat ventral lobe, unlike the dorsolateral lobe, has no embryological homolog in the human prostate. Cadmium has not been linked with renal tumors in rodents but is a potent nephrotoxin. In this work we studied the effects of oral cadmium in the Noble (NBL/Cr) rat with particular attention to proliferative lesions of the prostate and kidneys. Cadmium (as CdCl2) was given ad libitum throughout the study in the drinking water at doses of 0, 25, 50, 100, and 200 ppm Cd to groups (initial n = 30) of male rats, which were observed for up to 102 wk. At the lower doses of cadmium (< or =50 ppm) a clear dose-related increase in total proliferative lesions of the prostate (ventral and dorsolateral lesions combined) occurred (0 ppm = 21% incidence, 25 ppm = 46%, 50 ppm = 50%; trend p < .03). These lesions were described as intraepithelial hyperplasia with occasional areas of atypical epithelial cells without stromal invasion. The lesions occurred primarily in the dorsolateral prostate with cadmium exposure and most frequently showed three or more foci within each specimen. At higher doses, prostatic proliferative lesions declined to control levels. The loss of prostatic response at the higher doses was likely due to diminished testicular function secondary to cadmium treatment. This was reflected in lesions indicative of testicular hypofunction at the highest cadmium dose, namely, interstitial cell hyperplasia, and a strong correlation between cadmium dose and total proliferative lesions of the testes (hyperplasias and tumors combined). Renal tumors (mainly mesenchymal and pelvic transitional
New Dimensional Staging of Bisphosphonate-Related Osteonecrosis of the Jaw Allowing a Guided Surgical Treatment Protocol: Long-Term Follow-Up of 266 Lesions in Neoplastic and Osteoporotic Patients from the University of Bari
Franco, Simonetta; Miccoli, Simona; Limongelli, Luisa; Tempesta, Angela; Favia, Giorgio; Maiorano, Eugenio; Favia, Gianfranco
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the most serious side effect in patients receiving bisphosphonates (BPs) for neoplastic disease and osteoporosis. The aim of this study is to propose a new dimensional stage classification, guiding the surgical treatment of BRONJ patients, and to evaluate the success rate of this new management. From 2004 to 2013, 203 neoplastic and osteoporotic patients with 266 BRONJ lesions were referred to the Odontostomatology Unit of the University of Bari. All patients underwent surgery after suspension of BPs therapy and antibiotic treatment. The surgical procedure was complemented by piezosurgery and followed by the application of hyaluronate and amino acids. The new dimensional staging suggests the choice of the surgical approach, and allows the prediction of postoperative complications and soft and hard tissues healing time, guiding the surgical treatment protocol. This protocol could be a successful management strategy for BRONJ, considering the low recurrences rate and the good stabilisation of the surgical sites observed after a long-term follow-up. PMID:24995017
Hariri, Susan; Steinau, Martin; Rinas, Allen; Gargano, Julia W.; Ludema, Christina; Unger, Elizabeth R.; Carter, Alicia L.; Grant, Kathy L.; Bamberg, Melanie; McDermott, James E.; Markowitz, Lauri E.; Brewer, Noel T.; Smith, Jennifer S.
Background HPV typing using formalin fixed paraffin embedded (FFPE) cervical tissue is used to evaluate HPV vaccine impact, but DNA yield and quality in FFPE specimens can negatively affect test results. This study aimed to evaluate 2 commercial assays for HPV detection and typing using FFPE cervical specimens. Methods Four large North Carolina pathology laboratories provided FFPE specimens from 299 women ages18 and older diagnosed with cervical disease from 2001 to 2006. For each woman, one diagnostic block was selected and unstained serial sections were prepared for DNA typing. Extracts from samples with residual lesion were used to detect and type HPV using parallel and serial testing algorithms with the Linear Array and LiPA HPV genotyping assays. Findings LA and LiPA concordance was 0.61 for detecting any high-risk (HR) and 0.20 for detecting any low-risk (LR) types, with significant differences in marginal proportions for HPV16, 51, 52, and any HR types. Discordant results were most often LiPA-positive, LA-negative. The parallel algorithm yielded the highest prevalence of any HPV type (95.7%). HR type prevalence was similar using parallel (93.1%) and serial (92.1%) approaches. HPV16, 33, and 52 prevalence was slightly lower using the serial algorithm, but the median number of HR types per woman (1) did not differ by algorithm. Using the serial algorithm, HPV DNA was detected in >85% of invasive and >95% of pre-invasive lesions. The most common type was HPV16, followed by 52, 18, 31, 33, and 35; HPV16/18 was detected in 56.5% of specimens. Multiple HPV types were more common in lower grade lesions. Conclusions We developed an efficient algorithm for testing and reporting results of two commercial assays for HPV detection and typing in FFPE specimens, and describe HPV type distribution in pre-invasive and invasive cervical lesions in a state-based sample prior to HPV vaccine introduction. PMID:22479516
Sari Aslani, Fatemeh; Safaei, Akbar; Pourjabali, Masoumeh; Momtahan, Mozhdeh
Background: Cervical intraepithelial neoplasia (CIN) is a premalignant lesion capable of progressing to cervical cancer. Despite the existing well-defined criteria, the histomorphologic diagnosis is subject to high rates of discordance among pathologists. The aim of this study was to evaluate Ki-67 (MIB-1), CK17 and p16 INK4a (p16) markers by immunohistochemical methods in differentiating CIN from benign cervical lesions. Methods: The present study reviewed and re-classified 77 cervical biopsies, originally diagnosed as 31 non-CIN, and 46 CIN, as 54 non-CIN, and 23 CIN based on at least two similar diagnoses. Immunostaining by Ki67, p16 and CK17 markers was performed on all cases and the results were compared with pervious and consensus diagnosis. Results: The overall agreement between pervious and consensus diagnosis was 67.5% (Kappa=0.39, P<0.001). The sensitivity and specificity of Ki67 immunostaining were 95.6% and 85.1% respectively, while for p16 the corresponding values were 91.3% and 98.1%. The overall agreement, for both p16 and Ki67, with consensus diagnosis were significant (P<0.001). The sensitivity and specificity of CK17 negative staining in CIN detection were 39.1% and 40.7% respectively. Conclusion: Ki67 and p16 markers are recommended as complementary tests for differentiating between dysplastic and non-dysplastic lesions. CK17 does not discriminate between immature metaplasia with and without dysplasia. PMID:23645953
Grozdanov, Petar; Hadjidekova, Savina; Dimova, Ivanka; Nikolova, Ivanka; Toncheva, Draga; Ganchev, Gancho; Zlatkov, Victor; Galabov, Angel S
Cervical carcinoma is the second most common malignancy among women in both incidence and mortality. Although much is known about the etiology and treatment of cervical cancer, the role of genetic alterations in the multistep pathway of cervical tumorigenesis is largely unknown. The aim of this study was to characterize the genomic changes in the cervical pre-cancerous lesions and tumors, induced by different types of human papillomaviruses. In this research was used the BlueGnome CytoChip oligo 2 × 105 K microarray for whole-genome oligo-array CGH. Microarray CGH analysis of 40 specimens was carried out-12 specimens from patients with early-stage squamous cell carcinomas; 19 specimens from patients with mild to moderate dysplasia and 9 with severe dysplasia. First we performed microarray CGH analysis of five DNA pools which contained the DNA from homogeneous groups of patients. The results revealed presence of micro chromosomal aberrations in chromosome region 14q11.2. According to the genome database these aberrations represent polymorphisms. Microarray analysis of DNA from 9 separate carcinoma lesions revealed a total of 26 aberrations in 14 chromosomes of nine patients. Our results showed the advantages of high-resolution chips in the clinical diagnosis of patients with cancerous and precancerous lesions caused by viral infection with HPV, but also highlight the need for extensive population studies revealing the molecular nature and clinical significance of different CNVs and the creation of detailed maps of variations in the Bulgarian population. This would facilitate extremely precise interpretation of specific genomic imbalances in the clinical aspect.
Zeola, L F; Pereira, F A; Machado, A C; Reis, B R; Kaidonis, J; Xie, Z; Townsend, G C; Ranjitkar, S; Soares, P V
Information on fracture biomechanics has implications in materials research and clinical practice. The aim of this study was to analyse the influence of non-carious cervical lesion (NCCL) size, restorative status and direction of occlusal loading on the biomechanical behaviour of mandibular premolars, using finite element analysis (FEA), strain gauge tests and fracture resistance tests. Ten buccal cusps were loaded on the outer and inner slopes to calculate the strain generated cervically. Data were collected for healthy teeth at baseline and progressively at three lesion depths (0.5 mm, 1.0 mm and 1.5 mm), followed by restoration with resin composite. The magnitude and distribution of von Mises stress and maximum principal stress were simulated at all stages using FEA, and fracture strength was also determined (n = 7 per group). There were significant effects of the lesion size and loading directions on stress, strain and fracture resistance (p < 0.05). Fracture resistance values decreased with increase in lesion size, but returned to baseline with restorations. Combined assessment of computer-based and experimental techniques provide an holistic approach to characterize the biomechanical behaviour of teeth with both unrestored and restored NCCLs. © 2016 Australian Dental Association.
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.
Zafar, Nadeem; Balazs, Louisa; Benstein, Barbara D
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.
Xiao, Di; Huang, Weihuang; Ou, Meiling; Guo, Congcong; Ye, Xingguang; Liu, Yang; Wang, Man; Zhang, Baohuan; Zhang, Na; Huang, Shiqi; Zang, Jiankun; Zhou, Zixing; Wen, Zihao; Zeng, Chengli; Wu, Chenfei; Huang, Chuican; Wei, Xiangcai; Yang, Guang; Jing, Chunxia
Human papillomavirus (HPV) infection is a definite risk factor for cervical cancer. Nevertheless, only some infected individuals actually develop cervical cancer. The cGAS-STING pathway in innate immunity plays an important role in protecting against HPV infection. Chen et al. described that the rs2516448 SNP in the MHC locus may affect susceptibility to cervical cancer, a finding that we attempted to replicate in a Chinese population. To investigate the effects of cGAS, STING and MHC polymorphisms on susceptibility to cervical precancerous lesions, 9 SNPs were analyzed in 164 cervical precancerous lesion cases and 428 controls. Gene-gene and gene-environment interactions were also evaluated. We found a significantly decreased risk of cervical precancerous lesions for the GG genotype of rs311678 in the cGAS gene (ORadjusted = 0.40, 95% CI: 0.16-0.98). Moreover, MDR analysis identified a significant three-locus interaction model, involving HPV infection, age at menarche and rs311678 in cGAS. Additionally, a significant antagonistic interaction between HPV infection and rs311678 was found on an additive scale. In conclusion, our results indicate that the rs311678 polymorphism in the cGAS gene confers genetic susceptibility to cervical precancerous lesions. Moreover, the three-way gene-environment interactions further demonstrate that the rs311678 polymorphism in cGAS can significantly decrease the risk of HPV infection and the elder at menarche.
Alshenawy, Hanan AlSaeid
Cervical dysplasia, a potentially precancerous lesion, has increased in young women. Detection of cervical dysplasia is important for reducing morbidity and mortality in cervical cancer. This study analyzes the immunohistochemical expression of p16, HPV L1 capsid protein and Ki-67 in cervical intraepithelial lesions, and correlates them with lesion grade to develop a set of markers for diagnosis and detect the prognosis of cervical cancer precursors. Seventy-five specimens were analyzed, including 15 cases of CIN 1, 28 cases of CIN 2, 20 cases of CIN 3, and 12 cervical squamous carcinomas, besides 10 normal cervical tissues. They were stained for p16, HPV L1 and Ki-67. Sensitivity, specificity, predictive values and accuracy were evaluated for each marker. p16 expression increased during progression from CIN 1 to carcinoma. HPV L1 positivity was detected in CIN 2 and decreased gradually as the CIN grade increased but disappeared in carcinoma. Strong Ki-67 expression was observed in high grades CIN and carcinoma. p16, HPV L1 and Ki-67 were sensitive but with variable specificity in detecting CIN lesions. p16, HPV L1 and Ki-67 are useful markers in establishing the risk of high-grade CIN. They complete each other to reach an accurate diagnosis and to detect the prognosis. Copyright © 2014 Elsevier GmbH. All rights reserved.
Cerebral neoplastic enhancing lesions: multicenter, randomized, crossover intraindividual comparison between gadobutrol (1.0M) and gadoterate meglumine (0.5M) at 0.1 mmol Gd/kg body weight in a clinical setting.
Anzalone, Nicoletta; Scarabino, Tommaso; Venturi, Carlo; Cristaudo, Concetto; Tartaro, Armando; Scotti, Giuseppe; Zimatore, Domenico; Floris, Roberto; Carriero, Alessandro; Longo, Marcello; Cirillo, Mario; Cova, Maria Assunta; Gatti, Simona; Voth, Matthias; Colosimo, Cesare
Two macrocyclic extracellular contrast agents, one-molar neutral gadobutrol and ionic gadoterate meglumine, were compared to determine the overall preference for one or the other in a clinical setting. Multicenter, randomized, single-blind, intra-individually controlled, comparison study with a corresponding blinded read. Efficacy analysis was based on 136 patients who underwent identical MRI examinations: group A first received 1.0M gadobutrol followed by 0.5M gadoterate meglumine 48 h to 7 days later; group B had a reversed administration order. Three independent blinded readers assessed off-site their overall diagnostic preference (primary efficacy parameter) based on a matched pairs approach. Superiority of gadobutrol over gadoterate meglumine was demonstrated for the qualitative assessment of overall preference across all readers by a statistically significant difference between both contrast agents for this primary endpoint. Preferences in lesion enhancement (secondary endpoint) were also found significantly in favor of gadobutrol. For preference in lesion delineation from surrounding tissue/edema and for internal structure only a trend towards a higher proportion for gadobutrol was found (except for internal structure reported by one reader, which showed a result of statistical significance). Lesion contrast and relative lesion enhancement (quantitative parameters) were statistically significantly higher for gadobutrol compared to gadoterate meglumine. Contrast-enhanced MRI of neoplastic brain lesions at a dose of 0.1 mmol Gd/kg body weight, assessed in a standardized off-site blinded reading, results in a significantly higher qualitative and quantitative preference for gadobutrol compared to gadoterate meglumine. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
May, Sabine; Cieplik, Fabian; Hiller, Karl-Anton; Buchalla, Wolfgang; Federlin, Marianne; Schmalz, Gottfried
To evaluate the clinical performance of two flowable composites for restoring Class-V non-carious cervical lesions (NCCLs), one with novel (ND; N'Durance(®) Dimer Flow, Septodont) and one with modified conventional matrix composition (FS; Filtek™ Supreme XTE Flow, 3M-ESPE). The null hypothesis was that both flowable composites perform equally regarding clinical quality and survival. 50 patients received one ND and one FS restoration of NCCLs in premolars using Clearfil Protect Bond (Kuraray) as an adhesive. Restorations were evaluated by two examiners at baseline (BL), 18 and 36 months employing FDI criteria. Non-parametric statistical analyses and χ(2) tests were applied (α=0.05). 48 patients with both restorations under risk participated in the 36-mo recall. One patient terminated participation after the 18-mo recall. One ND restoration failed at the 18-mo recall (fracture). One FS restoration failed during clinical examination at the 36-mo recall (debonding). 95.8% of restorations each were rated clinically acceptable at 36-mo. No significant differences for all selected FDI criteria were recorded between ND and FS at each examination time point except for the criteria surface staining at 36-mo and marginal staining at 18-mo and 36-mo, where FS showed significantly better results. For each material, no significant differences over time were detected, except for loss of surface lustre for FS (BL to 18 months). Within the limitations of the study, the null hypothesis that materials perform equally could not be rejected. Both flowable composites performed equally regarding survival and similarly regarding clinical performance. Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.
Mamaladze, M; Khutsishvili, L; Zarkua, E
The current study aims at differentiating carious and/or non-carious diseases developed in Class 5 region and detecting the distribution rate at the age aspects. The study was conducted at the Dental Clinicand Educational-Research Center "Unident" LTD and Dental Clinic "Dens". 256 patients were involved in the study. All patients underwent a routine dental examination, while rentgenovisiography and CT were performed in case of need. For gathering the detailed medical history and integrated study of Class 5 defects, a special questionnaire/survey, providing detailed information on each patient, was developed. The conducted study revealed the following: The patients were divided into 3 age groups: 16-30 of ages (77 patients, I study group), 30-50 of ages (97 patients, II study group) and 50-70 of ages (82, III study group), respectively. In total 5802 teeth were examined. The subject of our interest was identification of intact and damaged teeth (affected with caries and non-carious diseases) in the above-mentioned contingent. It was found that carious disease of cervical zone of tooth (Class 5) most often was revealed in 30-50 age group (202 cases), which is 1.8-fold higher than the same index in the I study group (144) and 1.4-fold higher in the III study group (183), respectively; The highest rate of non-carious lesions (erosion, abrasion, abfraction) of dental neck was recorded in examined 50-70 age group (294 cases), which was 4.6 -fold higher than in the I study group (64) and 2.1 -fold higher in II study group (140), respectively; The lowest incidence of gingival recession was in the I study group (65 cases), which is 6.3 -fold lower than in the II study group (412) and 7.5-fold lower than - the III group (493).
Santos, Maria Jacinta Moraes Coelho; Ari, Nilgun; Steele, Shawn; Costella, John; Banting, David
The aim of this review was to assess the effect of different adhesive systems and tooth preparation on the retention of tooth-colored restorative materials placed in non-carious cervical lesions (NCCLs). Randomized clinical trials with a minimum of 3 years of follow-up that evaluated the effectiveness of tooth-colored materials, adhesive systems, and preparation techniques for the restoration of NCCLs were selected. The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE (OVID), the Latin American and Caribbean Health Sciences Literature database (LILACS), and Medline (OVID) electronic databases were searched from 1990 to 2013. Twenty-seven randomized clinical trials were included and reviewed. Meta-analysis was used to determine the relative risk of loss of tooth-colored NCCL restorations between different categories of adhesive systems. The effect of tooth preparation could not be similarly analyzed. The current best evidence indicates that a glass ionomer cement has a significantly lower risk of loss of a NCCL restoration compared to either a three-step etch-and-rinse or a two-step etch-and-rinse adhesive system; a three-step etch-and-rinse adhesive system has a significantly lower risk of loss of a NCCL restoration compared to a two-step etch-and-rinse adhesive system. No significant difference could be observed in the risk of loss of a tooth-colored NCCL restoration between a three-step etch-and-rinse adhesive system and either a two-step self-etch or a one-step self-etch adhesive system.
Tsuda, H; Ozaki, K; Uwagawa, S; Yamaguchi, S; Hakoi, K; Aoki, T; Kato, T; Sato, K; Ito, N
Development of preneoplastic lesions in the rat liver under the influence of various modifiers was investigated with particular attention to changes in simultaneous expression of altered enzyme phenotype within the lesions (conformity) and proliferation potential. Degree of conformity of marker enzymes such as glutathione S-transferase placental form (GST-P), glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase, adenosine triphosphatase and gamma-glutamyltranspeptidase was compared with levels of 5-bromo-2-deoxyuridine labeling. After initiation with diethylnitrosamine, rats were administered the hepatopromoter sodium phenobarbital (PB, 0.05%), the antioxidant ethoxyquin (EQ, 0.5%), or a peroxisome proliferator, clofibrate (CF, 1.0%) or di(2-ethylhexyl)-phthalate (0.3%) and killed at week 16 or 32. The PB promoting regimen was clearly associated with increase in the numbers of high conformity class lesions simultaneously expressing three to five enzymes, and elevated proliferation potential. The inhibitor, EQ, in contrast, brought about a time-dependent decrease in conformity so that only 1 or 2 alterations were most commonly observed at week 32. Lesion populations in the peroxisome proliferator- and especially CF-treated cases were characterized by obvious dissociation between degree of conformity and proliferative status. Such treatment-dependent differences were not always correlated with the size of the lesion. The results thus suggested that the conformity and proliferation potential of preneoplastic lesions are dependent on modification treatment. Overall, GST-P was found to be the most reliable marker, although G6PD was less influenced in the peroxisome proliferator cases.
Folwaczny, M; Loher, C; Mehl, A; Kunzelmann, K H; Hinkel, R
The recently developed resin-modified glass ionomer cements and the polyacid-modified composites are promising alternatives to conventional materials for restoring cervical defects. This clinical study evaluated the clinical condition of cervical fillings 24 months following placement. The study subjects were 197 cervical restorations placed on incisors, canines and premolars in 37 patients for restoration of erosion/non-carious lesions (69 cases), primary carious lesions (57 cases) and the replacement of deficient restorations (71 cases). The teeth were randomly divided into four groups for restoration with either Tetric (composite, Group A: n = 36), Dyract (compomer, Group B: n = 79), Fuji II LC (resin-modified glass ionomer cement, Group C: n = 51) or Photac-Fil (resin-modified glass ionomer cement, Group D: n = 31). The evaluation was done single-blind at baseline, 8 and 24 months after the placement of the fillings, according to a modified USPHS rating scale. The assessment criteria were color stability, anatomical form, surface texture, marginal integrity, marginal discoloration and loss of filling. Statistical analysis was completed using Pearson chi-square and Fisher's exact test at a significance level of 5% (p < 0.05). After the 24-month period, the composite restorations showed superior results. The compomer fillings demonstrated conditions that were only slightly worse. A substantial number of the resin-modified glass-ionomer fillings were evaluated with bravo or even charlie scores in respect to at least one of the criteria assessed.
Blanco-Luquin, Idoia; Guarch, Rosa; Ojer, Amaya; Pérez-Janices, Noemí; Martín-Sánchez, Esperanza; Maria-Ruiz, Sergio; Monreal-Santesteban, Iñaki; Blanco-Fernandez, Laura; Pernaut-Leza, Eduardo; Escors, David; Guerrero-Setas, David
Cervical cancer is the third most common cancer in women worldwide. The hypermethylation of P16, TSLC-1 and TSP-1 genes was analyzed in squamous cell carcinomas (SCC), cervical intraepithelial lesions (CIN) and adenocarcinomas (ADC) of the uterine cervix (total 181 lesions). Additionally human papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 hypermethylation were tested in ADC and the results were compared with those obtained previously by our group in SCC. P16, TSLC-1 and TSP-1 hypermethylation was more frequent in SCCs than in CINs. These percentages and the corresponding ones for EPB41L3, RASSF1 and RASSF2 genes were also higher in SCCs than in ADCs, except for P16. The presence of HPV in ADCs was lower than reported previously in SCC and CIN. Patients with RASSF1A hypermethylation showed significantly longer disease-free survival (P = 0.015) and overall survival periods (P = 0.009) in ADC patients. To our knowledge, this is the first description of the EPB41L3 and RASSF2 hypermethylation in ADCs. These results suggest that the involvement of DNA hypermethylation in cervical cancer varies depending on the histological type, which might contribute to explaining the different prognosis of patients with these types of tumors.
Comparative study of HPV16 integration in cervical lesions between ethnicities with high and low rates of infection with high-risk HPV and the correlation between integration rate and cervical neoplasia.
Han, Lili; Maimaitiming, Tuerxunayi; Husaiyin, Sulaiya; Wang, Lin; Wusainahong, Kunduozi; Ma, Chunhua; Niyazi, Mayinuer
The etiology of a high incidence of cervical cancer in populations with a low human papillomavirus (HPV) infection rate is unclear. The current study aimed to investigate the role of HPV16 DNA integration in cervical lesions in women of Han and Uygur ethnicity and to explore the association between viral integration and a high cervical cancer morbidity with a low HPV infection rate. DNA was extracted from the biopsy specimens of cervical lesions of 379 patients of Uygur ethnicity and 464 patients of Han ethnicity, and multiple quantitative polymerase chain reaction (qPCR) assays were performed to determine the copy numbers of the HPV16 E2 and E6 genes. The copy number of the HPV16 DNA was evaluated according to the E2/E6 ratio. Among these cases, 122 Uygur and 121 Han specimens were found to be HPV16 positive. In the two populations, the percentage of cases with HPV16 integration (the sum of integrated-type infection only or a mixture of free-and integrated-type infection) increased with the grade of the cervical lesions (P<0.001). Within groups with the same cervical lesion grade, no significant differences in HPV16 integration were found between women of Uygur and Han ethnicity (rank sum test, P>0.05). No significant differences in the distribution of the HPV16 integration rate according to lesion grade were found in either population (P>0.05). When the two subpopulations were considered as one sample population, the integration rate significantly increased with lesion grade (P=0.02). These results indicate that the integration rate of HPV16 E2 may serve as a molecular biological marker for the development of cervical lesions.
Bowra, G T; Duffield, D P; Osborn, A J; Purchase, I F H
ABSTRACT Skin lesions have been identified in 20 workers manufacturing 4,4'-bipyridyl. The lesions were on the face, neck, and backs of the hands and arms. Larger localised lesions were removed surgically and examined histopathologically, but other lesions have been treated topically with fluorouracil cream. Histological diagnosis showed a progression from keratosis to Bowen's disease and, in six cases, to squamous cell carcinoma. Over 550 individuals associated with 4,4'-bipyridyl processes between 1961 and 1980 have been examined or questioned. All 20 patients identified worked in now obsolete production plants; 15 of whom were found among the 147 shift process operators. The time taken for the lesions to appear from first working on a 4,4'-bipyridyl plant was 6-19 years (average 12 years). Starting in the early 1960s three processes have been successively used to convert pyridine into 4,4'-bipyridyl. These differ in the reaction conditions used and in the efficiency of the conversion. In the two earlier plants a substantial quantity of pyridine was converted into polypyridyls and “tarry” byproducts, which caused operating difficulties and increased the risk of worker exposure. The exposure and occupational histories of the cases, including the fact that two had worked only on the obsolete production plants, indicates that the causative agent was present in these earlier processes. In-vitro tests for potential carcinogenicity on materials from the present plant and from an earlier process gave positive tests on the tarry byproducts from the earlier process, suggesting that they were the cause of the lesions. Tar impurity production on the present plant is minimal, and worker exposure to chemicals is low. No similar skin lesions have been seen in those who have worked only on the present plant. This observation supports the view that the causative agent was present only on the earlier plants but is not conclusive because of the shorter time that has elapsed
Jyothi, Kn; Annapurna, S; Kumar, Anil S; Venugopal, P; Jayashankara, Cm
To evaluate and compare the clinical performance of Giomer (Beautifil II) and RMGIC (Fuji II LC) in noncarious cervical lesions. Thirty-two subjects with one or two pairs of noncarious cervical lesions were included in the study. Each pair of lesion was restored with either giomer or RMGIC assigned randomly. Clinical evaluation of restorations was done using USPHS criteria. Data was formulated in a predesigned format and subjected to statistical analysis using the chi square test. Statistically significant difference was found between RMGIC and Giomer with respect to surface roughness with P value <0.001. Giomer showed superior surface finish compared to RMGIC. Both Giomer and RMGIC showed equal retention ability.
... growth of normal bacteria in the vagina (bacterial vaginosis) can also cause cervicitis. ... a microscope (may show candidiasis , trichomoniasis , or bacterial vaginosis) Pap test Tests for gonorrhea or chlamydia Rarely, ...
Gruia, Alexandra; Gazinska, Patrycja; Herman, Diana; Ordodi, Valentin; Tatu, Calin
Aristolochic acid (AA) has, in the last decade, become widely promoted as the cause of the Balkan endemic nephropathy and associated renal or urothelial tumours, although without substantial focal evidence of the quantitative dietary exposure via bread in specific households in hyperendemic villages. Occasional ethnobotanical use of Aristolochia clematitis might be a source of AA, and Pliocene lignite contamination of well-water is also a putative health risk factor. The aim of this study was two-fold: to verify if extracts of A. clematitis and Pliocene, or AA by itself, could induce the development of renal or urothelial tumours, and to test the utility of the ribosomal protein p-S6 to identify preneoplastic transformation. Rats were given extracts of A. clematitis in drinking water or AA I, by gavage. After seven months, renal morphology was studied using conventional haematoxylin and eosin and immunohistochemistry for ribosomal p-S6 protein. Plant extracts (cumulative AA approximately 1.8 g/kg b.w.) were tolerated and caused no gross pathology or renal histopathological change, with only faint diffuse p-S6 protein (except in the papilla) as in controls. Cumulative AA I (150 mg/kg b.w. given over 3 days) was also tolerated for seven months by all recipients, without gross pathology or kidney tumours. However, p-S6 protein over-expression was consistent particularly within the renal papilla. In one case given AA I, intense p-S6 protein staining of a proximal tubule fragment crucially matched the pre-neoplastic histology in an adjacent kidney section. We briefly discuss these findings, which compound uncertainty concerning the cause of the renal or upper urinary tract tumours of the Balkan endemic nephropathy. PMID:28326270
Tuncer, D; Yazici, A R; Özgünaltay, G; Dayangac, B
The aim of this study was to compare after 24 months the clinical performance of cervical restorations placed with the use of an etch-and-rinse and an all-in-one adhesive. Twenty-four patients with at least one pair of non-carious cervical lesions participated in this study. One hundred and twenty-three cervical lesions were restored (62 etch-and-rinse adhesive, Solobond M; 61 all-in-one adhesive, Futurabond NR). A nanohybrid resin composite, Grandio, was used as the restorative material. Restorations were evaluated according to modified USPHS criteria by two independent examiners. The survival rates of the restorations were calculated by the Kaplan-Meier estimator and log-rank test. The restorations in each category were compared using the Pearson chi-square test, while the performance of restorations at the baseline and at each recall time was evaluated by McNemar's test (p < 0.05). The recall rate of patients was 100%. The retention rates were 82% and 75% at 6 months and 77% and 62% at 12 months for Solobond M and Futurabond NR, respectively. At the 24-month recall, the retention rate was 69% for Solobond M and 49% for Futurabond NR, and this difference was statistically significant (p < 0.05). No statistically significant difference was found for colour match, marginal staining, or marginal adaptation between the adhesives (p > 0.05). None of the restorations had secondary caries, loss of anatomical form, or surface texture changes. Cervical restorations placed with an etch-and-rinse adhesive showed higher retention than an all-in-one adhesive. © 2013 Australian Dental Association.
Yang-Chun, Feng; Zhen-Zhen, Cheng; Yan-Chun, Huang; Xiu-Min, Ma
Abstract The difference of PD-L1 expression between only HPV-positive patients and premalignant cervical lesion patients did not be reported in present studies. And to test the PD-L1 expression in some cervical cell lesion studies using cervical exfoliated cells sample also was ignored. Meanwhile, the PD-L1 expression as a predictive biomarker still existed controversy. So in the study, first to compare the expression of PD-L1 between only HPV-positive patients and premalignant cervical lesion patients, then to research the association between PD-L1 and HPV status, lastly to explore the possible prognostic value for HPV treatment in premalignant cervical lesion patients. Cervical exfoliated cells samples of 54 premalignant cervical lesion patients with HPV16 infection were collected; meanwhile the cervical exfoliated cells samples from 20 healthy women without HPV infection and 20 patients with only HPV16 infection but cervical cytology normal were collected as 2 control groups. Flow-through hybridization and gene chip (FHGC) was used to detect the HPV type, the PD-L1 expression was tested by Flow cytometry analysis, the methylation-sensitive high-resolution melting (MS-HRM) was used to test the HPV16 L1 gene methylation. The 54 premalignant cervical lesion patients were followed up in 18 months to assess the prognostic value of PD-L1 for HPV treatment. The PD-L1 positive cell rate and mean fluorescence intensity of PD-L1 positive cell in premalignant cervical lesion patients with HPV16 infection were higher than 2 control groups. Mean fluorescence intensity of PD-L1 positive cell were increased in 54 cases when existing multiple HPV status and high HPV16-L1 gene methylation (L1 gene methylation more than 50%). High PD-L1 expression (PD-L1 positive cell rate more than 10%), high HPV16-L1 gene methylation, and multiple HPV infection status could prolong the time to clean HPV infection by Kaplan–Meier analysis. Multivariate Cox proportional hazards analysis also
Karunaratne, Kanishka; Ihalagama, Himali; Rohitha, Saman; Molijn, Anco; Gopala, Kusuma; Schmidt, Johannes E; Chen, Jing; Datta, Sanjoy; Mehta, Shailesh
Cervical cancer ranks second among all cancers reported in Sri Lankan women. This study assessed the prevalence and type-distribution of human papillomavirus (HPV) among Sri Lankan women with invasive cervical cancer (ICC) and pre-cancerous lesions. 114 women aged 21 years and above, hospitalized in the National Cancer Institute, Sri Lanka with a diagnosis of ICC or cervical intraepithelial neoplasia (CIN) 2/3 were prospectively enrolled between October 2009 and September 2010 (110430/NCT01221987). The cervical biopsy or excision specimens collected during routine clinical procedures were subjected to histopathological review. DNA was extracted from samples with a confirmed histological diagnosis and was amplified using polymerase chain reaction and HPV DNA was detected using Enzyme Immuno Assay. HPV positive samples were typed using reverse hybridization Line Probe Assay. Of the cervical samples collected, 93.0% (106/114) had a histologically confirmed diagnosis of either ICC (98/106) or CIN 2/3 (8/106). Among all ICC cases, squamous cell carcinoma was diagnosed in the majority of women (81.6% [80/98]). HPV prevalence among ICC cases was 84.7% (83/98). The HPV types most commonly detected in ICC cases with single HPV infection (98.8% [82/83]) were HPV-16 (67.3%) and HPV-18 (9.2%). Infection with multiple HPV types was recorded in a single case (co-infection of HPV-16 and HPV-59). HPV was prevalent in most women with ICC in Sri Lanka; HPV-16 and HPV-18 were the predominantly detected HPV types. An effective prophylactic vaccine against the most prevalent HPV types may help to reduce the burden of ICC disease.
Royse, Kathryn E.; Zhi, Degui; Conner, Michael G.; Clodfelder-Miller, Buffie; Srinivasasainagendra, Vinodh; Vaughan, Laura Kelly; Skibola, Christine F.; Crossman, David K.; Levy, Shawn; Shrestha, Sadeep
Genetic changes occurring in different stages of pre-cancer lesions reflect causal events initiating and promoting the progression to cancer. Co-existing pre-cancerous lesions including low- and high-grade squamous intraepithelial lesion (LGSIL and HGSIL), and adjacent “normal” cervical epithelium from six formalin-fixed paraffin-embedded samples were selected. Tissues from these 18 samples were isolated using laser-capture microdissection, RNA was extracted and sequenced. RNA-sequencing generated 2.4 billion raw reads in 18 samples, of which ~50.1% mapped to known and annotated genes in the human genome. There were 40 genes up-regulated and 3 down-regulated (normal to LGSIL) in at least one-third of the sample pairs (same direction and FDR p < 0.05) including S100A7 and KLK6. Previous studies have shown that S110A7 and KLK7 are up-regulated in several other cancers, whereas CCL18, CFTR, and SLC6A14, also differentially expressed in two samples, are up-regulated specifically in cervical cancer. These differentially expressed genes in normal to LGSIL progression were enriched in pathways related to epithelial cell differentiation, keratinocyte differentiation, peptidase, and extracellular activities. In progression from LGSIL to HGSIL, two genes were up-regulated and five down-regulated in at least two samples. Further investigations using co-existing samples, which account for all internal confounders, will provide insights to better understand progression of cervical pre-cancer. PMID:25505737
Dijkstra, Maaike G; Heideman, Daniëlle A M; de Roy, Sabine C; Rozendaal, Lawrence; Berkhof, Johannes; van Krimpen, Kees; van Groningen, Krijn; Snijders, Peter J F; Meijer, Chris J L M; van Kemenade, Folkert J
Histomorphological grading of cervical intraepithelial neoplasia (CIN) is crucial for clinical management. CIN grading is however subjective and affected by substantial rates of discordance among pathologists, which may lead to overtreatment. To minimise this problem, a histology review of CIN lesions by a consensus panel of pathologists is often used. Diffuse strong p16(INK4a) immunostaining has been proposed to aid the identification of true high-grade cervical lesions (ie, CIN2/3). To assess the value of additional interpretation of p16(INK4a) immunostains for making a more reproducible diagnosis of CIN2/3 lesions. The authors used a series of 406 biopsies of cervical lesions, with known HPV status, stained for both H&E- and p16(INK4a). First, in a randomly selected set of 49 biopsies, we examined the effect of additional interpretation of p16(INK4a) immunostained slides, on the agreement of CIN diagnosis among three pathologists. Second, the full series of samples was used to assess the accuracy of p16(INK4a)-supported lesion grading by a single pathologist, by evaluating the degree of diagnostic agreement with the consensus diagnosis of expert pathologists based on H&E-stained sections only. The study shows that the interobserver agreement between three pathologists for the routine H&E-based diagnosis ranged from fair (weighted kappa 0.44 (95% CI 0.19 to 0.64)) to moderate (weighted kappa 0.66 (95% CI 0.47 to 0.79)). The concordance increased substantially for p16(INK4a)-supported grading (mean weighted kappa 0.80 (95% CI 0.66 to 0.89)). Furthermore, an almost perfect agreement was found between the p16(INK4a)-supported diagnosis of a single pathologist and the consensus diagnosis of an expert pathology panel (kappa 0.88 (95% CI 0.85 to 0.89)). These data demonstrate that additive use of p16(INK4a) immunohistochemistry significantly improves the accuracy of grading CIN lesions by a single pathologist, equalling an expert consensus diagnosis. Hence, the authors
Moretto, S G; Russo, E M A; Carvalho, R C R; De Munck, J; Van Landuyt, K; Peumans, M; Van Meerbeek, B; Cardoso, M V
Despite representing an important component of current dental adhesives, HEMA has been said to negatively influence the long-term stability of adhesion to dentine and enamel. The aim of this randomised clinical trial was to evaluate the 3-year clinical performance of two one-step self-etch adhesives. Thirty patients had 175 non-carious cervical lesions restored with composite (Gradia Direct Anterior, GC) using either the HEMA-rich adhesive Clearfil Tri-S Bond (C3S; Kuraray) or the HEMA-free adhesive G-Bond (GB; GC). The restorations were evaluated by two examiners at baseline, 6, 12, 24 and 36 months regarding retention, caries recurrence, marginal integrity and discoloration and post-operative sensitivity. The data were statistically analysed with GEE and McNemar tests (p<0.05). The recall rate at 6 and 12 months was 100% and decreased to 96.7% at 24 and 36 months. At 3 years, the retention rate was 93.8% for C3S and 98.8% for GB (p=0.14). A pairwise comparison showed no significant differences between the two adhesives for all the parameters evaluated, irrespective of the recall (p>0.05). After 3 years, both adhesives presented an increase in the percentage of clinically acceptable marginal discoloration (C3S: 32.9% and GB: 26.8%) normally associated to clinically acceptable marginal defects (C3S: 35.8% and GB: 26.5%). Only 1 dentine margin of a GB restoration presented a severe marginal defect (1.2%) and 1 C3S restoration presented caries recurrence. The overall 3-year clinical success rate was 92.6% for C3S and 97.6% for GB (p=0.16). Both one-step self-etch adhesives presented an equally favourable clinical effectiveness at 3 years. HEMA is a monomer frequently present in dental adhesives in order to increase their wettability and hydrophilicity. However, this monomer negatively influences hydrolytic stability and durability of the adhesive interface complex. In this 3-year clinical trial no significant difference in bonding effectiveness was noticed between a
Samwel, H; Slappendel, R; Crul, B J; Voerman, V F
In this study, 54 patients suffering from chronic cervicobrachialgia (mean pain duration 7 years) were treated with radiofrequency lesioning of the cervical spinal dorsal root ganglion (RF-DRG). The aim of the study was to investigate whether psychological variables would be predictive for the changes in pain intensity after medical treatment. The following psychological aspects were measured: pain cognitions, negative self-efficacy and catastrophizing, physical and psychosocial dysfunction, and overall distress. The level of catastrophizing before treatment appeared to predict 10% of the changes in pain intensity after treatment. Changes in pain intensity after RF-DRG were positively correlated with changes in psychosocial dysfunction and negative self-efficacy.
Analysis of cytosine-adenine repeats in P1 promoter region of IGF-1 gene in peripheral blood cells and cervical tissue samples of females with cervical intraepithelial lesions and squamous cervical cancer.
Kwasniewski, Wojciech; Gozdzicka-Jozefiak, Anna; Kotarska, Maria; Polak, Grzegorz; Barczynski, Bartlomiej; Broniarczyk, Justyna; Nowak, Witold; Wolun-Cholewa, Maria; Kwasniewska, Anna; Kotarski, Jan
High oncogenic risk human papillomaviruses (HPVs) are closely associated with cancer of the cervix. However, HPV infection alone may not be sufficient to cause cervical cancer, and other factors or cofactors may have a cumulative effect on the risk of progression from cervical HPV infection to cancer. The present study investigates the cytosine‑adenine (CA) repeat polymorphism in the P1 promoter region of the insulin‑like growth factor‑1 (IGF‑1) gene among cervical precancerous and cancer patients and healthy control females. The association between these polymorphisms, tissue and blood serum levels of IGF‑1, and cervical cancer risk and progression is evaluated. The material for analysis consisted of blood cells and postoperative tissues from patients diagnosed with low‑grade squamous intraepithelial lesions (L‑SILs), high‑grade squamous intraepithelial lesions (H‑SILs) and invasive cervical cancer (ICC). A polymerase chain reaction amplification and the sequencing of DNA were used for the identification of (CA)n repeats in the IGF‑1 P1 region and detection of HPV DNA. The blood serum concentration of IGF was determined by enzyme‑linked immunosorbent assay. The identification of the IGF‑1 protein in the cervical tissues was performed by immunohistochemical analysis. The range of the length of the CA repeats in the study DNA was 11 to 21. However, the most common allele length and genotype in the control and study patients from serum and tissues was 19 CA repeats and a homozygous genotype of CA19/19. Statistically significant differences in the concentration of IGF‑1 in the blood serum were observed between H‑SILs and controls, only (p=0.047). However, the concentration of IGF‑1 in the group of females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group of patients with H‑SIL (P=0.041) and ICC (P=0.048) in comparison with the control group. An association was detected between CA repeat length <19 and/or >19, IGF
Analysis of cytosine-adenine repeats in P1 promoter region of IGF-1 gene in peripheral blood cells and cervical tissue samples of females with cervical intraepithelial lesions and squamous cervical cancer
KWASNIEWSKI, WOJCIECH; GOZDZICKA-JOZEFIAK, ANNA; KOTARSKA, MARIA; POLAK, GRZEGORZ; BARCZYNSKI, BARTLOMIEJ; BRONIARCZYK, JUSTYNA; NOWAK, WITOLD; WOLUN-CHOLEWA, MARIA; KWASNIEWSKA, ANNA; KOTARSKI, JAN
High oncogenic risk human papillomaviruses (HPVs) are closely associated with cancer of the cervix. However, HPV infection alone may not be sufficient to cause cervical cancer, and other factors or cofactors may have a cumulative effect on the risk of progression from cervical HPV infection to cancer. The present study investigates the cytosine-adenine (CA) repeat polymorphism in the P1 promoter region of the insulin-like growth factor-1 (IGF-1) gene among cervical precancerous and cancer patients and healthy control females. The association between these polymorphisms, tissue and blood serum levels of IGF-1, and cervical cancer risk and progression is evaluated. The material for analysis consisted of blood cells and postoperative tissues from patients diagnosed with low-grade squamous intraepithelial lesions (L-SILs), high-grade squamous intraepithelial lesions (H-SILs) and invasive cervical cancer (ICC). A polymerase chain reaction amplification and the sequencing of DNA were used for the identification of (CA)n repeats in the IGF-1 P1 region and detection of HPV DNA. The blood serum concentration of IGF was determined by enzyme-linked immunosorbent assay. The identification of the IGF-1 protein in the cervical tissues was performed by immunohistochemical analysis. The range of the length of the CA repeats in the study DNA was 11 to 21. However, the most common allele length and genotype in the control and study patients from serum and tissues was 19 CA repeats and a homozygous genotype of CA19/19. Statistically significant differences in the concentration of IGF-1 in the blood serum were observed between H-SILs and controls, only (p=0.047). However, the concentration of IGF-1 in the group of females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group of patients with H-SIL (P=0.041) and ICC (P=0.048) in comparison with the control group. An association was detected between CA repeat length <19 and/or >19, IGF concentration in blood serum and
Kuang, Fei; Yan, Zhiping; Li, Huili; Feng, Hao
To compare the diagnostic accuracy of routine magnetic resonance imaging (MRI) (T1 WI and T2 WI), diffusion-weighted MRI (DWI), and DCE-MRI (dynamic contrast-enhanced MRI) at 3.0T for differentiation of cervical cancer and benign cervical lesions. A cohort of 75 cervical cancer patients, 26 cervical leiomyoma patients, 22 patients with cervical polyps consecutively underwent pelvic MRI scanning on a 3T MR unit. Two radiologists independently evaluated images at three imaging settings; routine MRI alone, DWI combined with routine MRI (DWI+routine MRI), and DCE-MRI. The apparent diffusion coefficients (ADCs) were calculated from b 0, 600 s/mm(2) and b 0, 1000 s/mm(2). DWI+routine MRI was significantly better than routine MRI and obtained high accuracy (0.95); the diagnostic performance was not significantly different between DWI+routine MRI and DCE-MRI. Reader agreement was excellent for both DWI+routine MRI (κ, 0.90) and DCE-MRI (κ, 0.92). The ADCs of cervical cancer were significantly lower than those of benign cervical lesions at both ADC maps (P = 0.0001). The diagnostic accuracy was not different at both ADC maps (P = 0.375). For differentiation of cervical cancer and benign cervical lesions, unenhanced MRI with combined diffusion-weighted and routine MRI (DWI+routine MRI) at 3T can provide accurate information and may be preferable to DCE. © 2015 Wiley Periodicals, Inc.
Vanya, Melinda; Jakó, Mária; Terhes, Gabriella; Szakács, László; Kaiser, László; Deák, Judit; Bártfai, György
Although the natural history of cervical and oral human papillomavirus infection has been intensively investigated in the past years, the ability of this virus to infect oral and genital mucosae in the same individual and its potential to co-infect both cervical and oral mucosa are still unclear. The aim of the authors was to assess the presence of oropharyngeal human papillomavirus infection in women with cervical lesions in the South-Eastern Hungarian population. The total of 103 women have been included in the study between March 1, 2013 and January 1, 2015. Brushing was used to collect cells from the oropharyngeal mucosa. Human papillomavirus DNA was detected using polymerase chain reaction, and Amplicor line blot test was used for genotyping. Oropharyngeal human papillomavirus infection was detected in 2 cases (3%). The detected genotypes were 31, 40/61 and 73 in the oropharyngeal region. The results indicate that in women with cervical lesions oropharyngeal human papillomavirus infection rarely occurs.
Szesz, Anna; Parreiras, Sibelli; Reis, Alessandra; Loguercio, Alessandro
To identify if selective etching of enamel (SEE) margins improves the retention rates and marginal discoloration of cervical composite restorations in non-carious cervical lesions (NCCLs) of adult patients. MEDLINE, Scopus, Web of Science, LILACS, BBO Library, Cochrane Library and SIGLE were searched without restrictions, as well as IADR abstracts and gray literature via trial registries. Dissertations and theses were searched using the ProQuest Dissertations and Periódicos Capes Theses databases. We included randomized clinical trials that compared the clinical effectiveness of SEE using the self-etch adhesive for direct composite resin restorations in NCCLs in the permanent dentition. After removal of duplicates, 2689 articles were identified. Following screening of abstracts, 10 studies remained in the qualitative synthesis. Seven were considered to be at "low" risk of bias. The report of the studies varied from 1 to 5 years. Except for one-year follow-up, there was a significantly lower marginal discoloration and marginal adaptation during all follow-up periods. Significantly less loss of retention of restorations at the 3-year follow-up was observed with the selective enamel etching technique. Selective enamel prior to application of self-etch adhesive systems in NCCLs might improve clinical performance of resin-composite cervical restorations, although further long-term research is required to confirm this. Selective enamel etching prior to application of self-etch adhesive systems in NCCLs can produce composite restorations with higher longevity. Copyright © 2016 Elsevier Ltd. All rights reserved.
Zhao, Zhi-Mei; Pan, Xiong-Fei; Lv, Si-Han; Xie, Yao; Zhang, Shao-Kai; Qiao, You-Lin; Qi, Xiao-Rong; Yang, Chun-Xia; Zhao, Fang-Hui
The overall survival of patients with cervical cancer has improved due to detection at an early stage and availability of comprehensive treatments in China. As patients' lives prolonged, it is important to understand their health-related quality of life (QoL) during and after treatment. We used the EQ-5D questionnaire to assess QoL of 194 patients with cervical lesions at Sichuan University West China Second Hospital between May 2010 and January 2011. Patients were surveyed before primary treatment and at 1, 3, and 6 months after primary treatment. Results showed a consistent decline in EQ-5D scores in the spectrum of cervical lesions at each time point after treatment (all P < 0.05). For patients with precursor lesions, there was an increasing trend along the timeline of treatment (P < 0.01). For patients with early-stage cervical cancer, EQ-5D scores declined in the first month (P = 0.01) and gradually increased to higher levels at 6 months post-treatment than those before treatment (P < 0.01). EQ-5D scores followed a similar trend in patients with advanced cervical cancer (P = 0.04), though they did not statistically rebound after 6 months (0.84 ± 0.19 vs. 0.86 ± 0.11, P = 0.62). Regarding advanced cervical cancer, EQ-5D scores for women above 40 years of age appeared to recover more rapidly and reached higher levels than those for women below 40 years (P = 0.03). Caution and extra care are recommended in the early period of cervical cancer treatment given the slight deterioration in the QoL, and in particular, for younger cervical cancer patients. Our study implies that health care providers may need to improve the health-related QoL of cervical cancer patients. PMID:24698497
Cardozo, Mônica Testoni; Furtado, Kelly Silva; De Conti, Aline; de Oliveira Andrade, Fábia; Fernandes, Laura Helena Gasparini; Campos, Adriana; Scolastici, Clarissa; Moreno, Fernando Salvador
The hepatocellular carcinoma occupies the third position in the ranking of the most lethal cancers worldwide. Given the poor prognosis, adoption of preventive strategies is necessary. We have reported that β-ionone (βI) exhibits chemoprotective activity in hepatocarcinogenesis, specifically in the development of persistent pre-neoplastic lesions (pPNLs) and in remodeling pre-neoplastic lesions (rPNLs). In this study, Wistar rats were submitted to the resistant hepatocyte model and treated with corn oil (CO) [0.25ml/100g body weight (b.w.); control group] or βI (16mg/100g b.w.; βI group) during initial promotion stage to assess possible βI's targets. Five animals were not submitted to RH model or any treatment (N group). Analyses of global hepatic gene expression showed that most of the genes that were differentially expressed between CO and N groups or between βI and CO groups encoded cellular receptors (24.81% and 37.5%, respectively). Thus, we validated the genes encoding the nuclear receptors Rxrα, Rarβ and Coup-Tf1 in microdissected tissue. No significant differences in the expression of Rxrα and Rarβ were observed when comparing CO and N groups. However, we observed an increase (P<0.05) in Rxrα and Rarβ expression in pPNLs and rPNLs in βI group compared to CO group, respectively. Coup-Tf1 showed increased (P<0.05) expression in CO group when compared to N group. On the other hand βI group exhibited a reduced expression of Coup-Tf1 in pPNLs and rPNLs compared to CO group (P<0.05). We demonstrate that Rxrα, Rarβ and Coup-Tf1 are molecular targets that may underlie βI's chemopreventive activity during the early stages of hepatocarcinogenesis.
Vilchez, José R; Torres-Moreno, Daniel; Martínez-Senac, María M; Trujillo-Santos, Javier; Conesa-Zamora, Pablo
Squamous intraepithelial lesions (SIL) and cervical cancer are primary due to suboptimal host-dependent immune response against human papillomavirus (HPV). Natural killer cells (NK) are innate-immune response components against virus and tumors. We studied whether the null allele of NKG2C NK cell receptor could be associated with low-grade (LSIL) to high-grade SIL (HSIL) transition or likelihood of HPV infection. Eight-hundred and sixty-seven subjects (263 LSIL, 309 HSIL and 295 controls) were genotyped for NKG2C using a novel multiplex PCR protocol. HPV genotype information was obtained from the cases. NKG2C genotype distributions in LSIL were WT/WT: 69.2%, WT/null: 26.2% and null/null: 4.6%; whereas in HSIL were WT/WT: 65.4%, WT/null: 28.5% and null/null: 6.1% and no statistical differences were observed (LSIL vs. HSIL p=0.541; LSIL vs. controls p=0.230; HSIL vs. controls p=0.624) nor when restricting to HPV positive, HR-HPV nor co-infection. This study demonstrates that NKG2Cnull does not seem to constitute a risk factor for HPV-induced cervical lesions. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Kone, Elsa S; Balili, Avenir D; Paparisto, Piro D; Ceka, Xheladin R; Petrela, Elizana D
Background: Cervical cytology is the best single method for large screening of the population in identifying precancerous lesions of the uterine cervix. Aim: To estimate the frequency of human papillomavirus (HPV) positivity in a group of Albanian women, the prevalence of vaginal coinfections, and the relationship of coinfections with HPV, as well as their role in metaplasia or cervical intraepithelial lesions (CIN). Materials and Methods: In this retrospective study, 2075 vaginal smears were examined. The Papanicolaou stain was used for all slides. The New Bethesda System 2001 was used for the interpretations of the smears. Data analysis was completed using the Statistical Package for the Social Sciences version 19.0. Results: Prevalence of HPV positivity was 43.9% with an average age of 35.48 ± 9.27 years. Candida coinfection resulted in 57.8% of HPV positive women with a significant relationship between them. Gardnerella coinfection resulted in 36 (23%), mixed flora in 34 (8%), and Trichomonas vaginalis in 50% of HPV positive woman. Among the women with positive HPV, 19% had CIN, 8% had metaplasia, and 1% had metaplasia and CIN; 9% of the women with HPV had CIN1 and one of the coinfections. Conclusions: There is a strong relationship between CIN1 and HPV positivity as well as between CIN1 and coinfections. HPV infection is a major factor contributing to metaplasia, and bacterial coinfections in HPV positive women have a statistically significant impact in the development of metaplasia. PMID:28182076
Urquiza, Mauricio; Guevara, Tatiana; Sanchez, Ricardo; Vanegas, Magnolia; Patarroyo, Manuel E
Anti-human papillomavirus (HPV) antibody detection is promising technique for detecting women at risk of suffering cervical cancer, since potentially oncogenic, persistent, long-term HPV-infections elicit an antibody response which is rarely detected in transitory HPV-infection patients. We have identified a non-variable C-terminus L1-peptide, belonging to an alpha-helix surface exposed on L1-protein, specifically recognized by antibodies from HPV-associated cervical lesion patients. This peptide tested against 313 sera presented higher reactivity with antibodies from cervical cancer (OD mean 0.43+/-0.13) or cervical lesion patients (OD mean 0.41+/-0.17) than antibodies from normal cytology patients (OD mean 0.17+/-0.03). High-risk HPV-infected patients presented higher antibody reactivity (OD mean 0.36+/-0.17) than high-risk HPV-non-infected patients (OD mean 0.22+/-0.11). This peptide showed 88.36% sensitivity, 99.39% specificity and 94.21% correct classification of high risk-HPV cervical lesion or cervical cancer patients. This peptide should be taken into account for designing serological screening or diagnostic tests for use in a clinical scenario.
Figueiredo, Priscila Garcia; Sarian, Luis Otávio; Tambascia, Julia Kawamura; Simões, José Antônio; Rabelo-Santos, Silvia Helena; Discacciati, Michelle Garcia; Derchain, Sophie
The relation between the detection of clue cells in cervical smears of women with CIN and the expression of COX-2 in these lesions were determined. Samples from 228 women, treated due to CIN and who underwent cervical conization, were obtained. Hybrid Capture II and Pap smear samples were collected immediately before performing conization. Pathological diagnoses were 11 (5%) normal cervix, 35 (15%) CIN1, 31 (14%) CIN2, and 151 (66%) CIN3. COX-2 immunoreactivity grading on the pathological specimens was based on the German ImmunoReactive score. In cervical smears, 20 fields (40x) were examined, each of them with a minimum count of 10 epithelial cells. When 20% or more of clue cells were detected the sample was considered positive for clue cells. The prevalence of clue cells was similar across histological strata (P = 0.42). Although the expression of COX-2 did not differ in lesions with varying severities (P = 0.24), there was a negative association between the expression of COX-2 and the presence of clue cells in Pap smear (OR = 0.4; 95% CI = 0.2-0.9): only 12% of women with moderate and strong expression of COX-2 had clue cells in their smears, contrasted to 22% of those with negative and weak expression of COX-2. HPV infection was associated in a borderline manner to the expression of COX-2 (P = 0.04; OR = 2.3 95% CI = 1.0-5.4). The reduced expression of COX-2 in CIN specimens may suggest that clue cells interfere with the inflammatory component of the carcinogenic process that lead to CIN.
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
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
... uterine lining and the fallopian tubes, resulting in pelvic inflammatory disease (PID), an infection of the female reproductive organs that can cause fertility problems if left untreated. Cervicitis can also ... incidentally during a routine pelvic exam and Pap test and may not require ...
Memiah, Peter; Makokha, Violet; Mbuthia, Wangeci; Kiiru, Grace Wanjiku; Agbor, Solomon; Odhiambo, Francesca; Ojoo, Sylvia; Mbizo, Justice; Muhula, Samuel; Mahasi, Gabriel; Biadgilign, Sibhatu
Cervical cancer is the second most common cancer among women worldwide. Infection with the human immunodeficiency virus (HIV) and its related immunosuppression are associated with an increased risk of prevalent, incident, and persistent squamous intraepithelial lesions (SILs) of the cervix. The objective of the study was to describe the prevalence and predictors of high-risk HPV and cervical cancer to support the need for strengthening cervical cancer screening programs for HIV infected women in Kenya. A cross sectional study was conducted in a hospital in Central Kenya, Kiambu district. The study population constituted of HIV positive women attending the ART treatment clinic. A total of 715 HIV positive women initiated on Antiretroviral Therapy (ART) were enrolled in this study. About 359 (52.1%) were less than 40 years of age and 644 (90.3%) of the patients were widowed. About 642 (92.6%) of the HIV infected women were in follow-up period of ≥ 1 year. The outcome/prognosis of the patients undergoing ICC was 3 cured, 5 good and 4 poor respectively. In a multivariable ordinal logistic regression analysis showed that for a one-unit decrease of CD4, we expect 1.23 log odds of increasing the severity of cervical cancer (B = 1.23, P < 0.0 15), given that all of the other variables in the model are held constant. In conclusion screening of all HIV infected women, who are under HIV care and treatment, enrolling patients on HAART with higher CD4 counts is recommended to see the net effect of HAART response.
Chen, Jinmiao; Xue, Yuezhen; Poidinger, Michael; Lim, Thimothy; Chew, Sung Hock; Pang, Chai Ling; Abastado, Jean-Pierre; Thierry, Françoise
Two classes of Human papillomaviruses (HPV) infect the anogenital track: high risk viruses that are associated with risk of cervical cancer and low risk types that drive development of benign lesions, such as condylomas. In the present study, we established quantitative transcriptional maps of the viral genome in clinical lesions associated with high risk HPV16 or low risk HPV6b. Marked qualitative and quantitative changes in the HPV16 transcriptome were associated with progression from low to high grade lesions. Specific transcripts encoding essential regulatory proteins such as E7, E2, E1^E4 and E5 were identified. We also identified intrinsic differences between the HPV6b-associated condyloma transcript map and that of the HPV16-associated low grade CIN specifically regarding promoter usage. Characterization and quantification of HPV transcripts in patient samples thus establish the impact of viral transcriptional regulation on the status of HPV-associated lesions and may therefore help in defining new biologically-relevant prognosis markers. Copyright © 2014 Elsevier Inc. All rights reserved.
Oliveira, Micheline de Lucena; Amorim, Melania Maria Ramos de; Souza, Paulo Roberto Eleutério de; Albuquerque, Lúcia Cristina Bezerra de; Brandão, Lucas André Cavalcanti; Guimarães, Rafael Lima
This study compares the detection rates of Chlamydia trachomatis by two techniques, direct immunofluorescence (IMF) and real time polymerase chain reaction (PCR), in patients with and without intra-epithelial cervical lesions (SIL) in Recife. We conducted a transversal study involving 35 women with SIL and 35 without SIL attended at Ambulatório Especializado da Mulher, Recife, Brazil. They were tested for Chlamydia trachomatis using two techniques, direct IMF or real time PCR. The rates of Chlamydia trachomatis detection were compared and the association with intra-epithelial cervical lesions was determined using the chi-square test at a 5% level of significance. Concordance between the tests was evaluated using kappa. The global prevalence of Chlamydia infection was 47.1% by direct IMF and 58.6% by real time PCR. A significant association was observed between Chlamydia diagnosis and presence of intra-epithelial cervical lesions, with about 80% positive results by direct IMF and 77.1% by real time PCR. However, the detected rate of infection with Chlamydia trachomatis was significantly greater in patients without intra-epithelial cervical lesions tested by real time PCR (40%) when compared to direct IMF (14.3%). The concordance between the tests was weak, with a kappa coefficient of 0.4. Both real time PCR and direct IMF detected elevated rates of Chlamydia infection in patients with intra-epithelial cervical lesions (80%) but the tests were discordant when patients without cervical lesions were tested, possibly because sensitivity of real time PCR is greater.
Background Since the mid-1990s, there have been growing efforts to prevent cervical cancer in less-developed countries through the development of innovative screening approaches such as visual inspection of the cervix associated with same day management of cervical lesions with cryotherapy or loop electrosurgical excision procedure (LEEP). In the past, promising cancer screening interventions have been widely promoted despite incomplete evidence, only to become the subject of intense controversies about ensuing net health benefit. Because the efficacy and effectiveness of the new protocols for global cervical cancer screening have not been well characterized yet, and as a contribution to the evaluation of the balance between the benefits and risks of these protocols, we reviewed the literature on the safety of cryotherapy and LEEP for cervical intraepithelial neoplasia (CIN) in low- and middle-income countries. Methods We searched 12 databases (Medline, Google Scholar, Scopus, Cochrane Library, Web of Science, OCLC, PAIS International Database, WHO Global Health Library, CINAHL, Science.gov, NYAM Grey Literature Report, and POPLINE) for original research published between January 1995 and April 2009. Both peer-reviewed publications and items of "grey" literature were retrieved; no language restriction was applied. We calculated the median (minimum, maximum) reported rate for each harm considered. Because of limitations and heterogeneity in the data, no formal meta-analysis was performed. Results The search identified 32 articles that reported safety data from 24 cryotherapy and LEEP studies. The combined sample consisted of 6,902 women treated by cryotherapy and 4,524 women treated by LEEP. Most studies were conducted in reference or research settings in Asia and Africa. Short-term harms of cryotherapy and LEEP appeared to be similar to those described in the literature from high-income countries. Information was sparse on HIV-related harms and long
Chamot, Eric; Kristensen, Sibylle; Stringer, Jeffrey S A; Mwanahamuntu, Mulindi H
Since the mid-1990 s, there have been growing efforts to prevent cervical cancer in less-developed countries through the development of innovative screening approaches such as visual inspection of the cervix associated with same day management of cervical lesions with cryotherapy or loop electrosurgical excision procedure (LEEP). In the past, promising cancer screening interventions have been widely promoted despite incomplete evidence, only to become the subject of intense controversies about ensuing net health benefit. Because the efficacy and effectiveness of the new protocols for global cervical cancer screening have not been well characterized yet, and as a contribution to the evaluation of the balance between the benefits and risks of these protocols, we reviewed the literature on the safety of cryotherapy and LEEP for cervical intraepithelial neoplasia (CIN) in low- and middle-income countries. We searched 12 databases (Medline, Google Scholar, Scopus, Cochrane Library, Web of Science, OCLC, PAIS International Database, WHO Global Health Library, CINAHL, Science.gov, NYAM Grey Literature Report, and POPLINE) for original research published between January 1995 and April 2009. Both peer-reviewed publications and items of "grey" literature were retrieved; no language restriction was applied. We calculated the median (minimum, maximum) reported rate for each harm considered. Because of limitations and heterogeneity in the data, no formal meta-analysis was performed. The search identified 32 articles that reported safety data from 24 cryotherapy and LEEP studies. The combined sample consisted of 6,902 women treated by cryotherapy and 4,524 women treated by LEEP. Most studies were conducted in reference or research settings in Asia and Africa. Short-term harms of cryotherapy and LEEP appeared to be similar to those described in the literature from high-income countries. Information was sparse on HIV-related harms and long-term reproductive outcomes of treatment
Graillon, T; Pech-Gourg, G; Adetchessi, T; Metellus, P; Dufour, H; Fuentes, S
Klippel-Feil syndrome (KFS) is defined as a congenital fusion of at least two cervical vertebrae. Patients with KFS are known to be at high risk for spinal cord injury in case of cervical trauma even with weak kinetic. We report the case of a patient with C4-C5 and C6-C7 congenital fusion, harbouring C5-C6 post-traumatic spinal cord injury, associated with an odontoid fracture type 2 of Anderson and D'Alonzo classification following a motorbike accident.
Antuña, S A; Méndez, J G; Cincunegui, J A; López-Fanjul, J C
A case of cervical spine metastasis from an extraocular sebaceous carcinoma of the scalp is presented. Anterior decompression and fusion were performed and resulted in complete relief of symptoms. Postoperatively the primary tumor behaved in a very aggressive manner, with visceral metastases leading to the death of the patient in a few weeks.
Souho, Tiatou; El Fatemi, Hinde; Karim, Safae; El Rhazi, Karima; Bouchikhi, Chahrazed; Banani, Abdelaziz; Melhouf, Moulay Abdelilah; Benlemlih, Mohamed; Bennani, Bahia
Objectives To determine the distribution of cervical high-risk human papillomavirus genotypes and their association to cellular abnormalities in women from Fez and its neighborhood. Methods Women attending the Hassan II University Hospital for cervical pap smears were recruited after an informed consent. Interviews and two cervical samples were performed for each woman. Cervical samples were used for cytological analysis and HPV DNA detection. HPV was typed using a method based on multiplex PCR with fluorescently labeled specific primers followed by capillary electrophoresis. The study was approved by the ethics committee of the Faculty of Medicine and Pharmacy of Fez. Results The HPV prevalence in the studied population was 43.1% and the most prevalent types were HPV 53 (23 cases); HPV 16 (20 cases); HPV 35 (18 cases); HPV 51 (10 cases) and HPV 56 (7 cases). From the 619 confirmed pap smears, 20% were abnormal. The cytological abnormalities were significantly associated to HPV infection, women age, number of pregnancies and parity (p < 0.05). Conclusion More attention should be given to HPV in Morocco because it represents an important public health concern. The distribution of carcinogenic HPV types in the studied population is different from the data in other regions but epidemiological studies in other Moroccan regions are required. PMID:26731415
Fleck, Steffen Kristian; Langner, Soenke; Baldauf, Joerg; Kirsch, Michael; Rosenstengel, Christian; Schroeder, Henry W
The awareness of traumatic craniocervical artery injuries has increased over the last years, and the detection rate varies in published trauma series. These injuries are often associated with cervical spinal and cranial trauma. The purpose of this prospective study was to determine the frequency and injury characteristics of blunt traumatic cervical artery injuries in patients suffering from cervical spine injuries by using a standardized CT angiography (CTA) protocol of the craniocervical vessels. Over a period of 32 months (February 2006 to September 2008), we prospectively evaluated 53 patients with osseous cervical spine injuries. Of these, 41 patients were screened for blunt craniocervical vessel injuries using CT angiography in 718 consecutive patients requiring a whole-body trauma CT due to the mechanism of their injury and injury patterns. All examinations were performed using a 16-row multi-slice computed tomography (Sensation 16, Siemens, Erlangen, Germany). Initially, a scan of the neurocranium angulated in orbito-meatal orientation was acquired. Then, a CT angiography of the craniocervical vessels with 40 ml of iodinated contrast agent (flow 4 ml/s; 40 ml saline flush, flow 4 ml/s) was performed starting at the level of Th2 up to the roof of the lateral ventricles. The scan was started using bolus tracking. Finally, a contrast-enhanced spiral thoraco-abdominal scan was performed with a delay of 20 s after administering a second contrast bolus of 60 ml. Besides, 11 patients with already detected isolated cervical spine injury, who were not initially involved in the whole-body trauma imaging protocol, underwent a secondary CT angiography with 60 ml of contrast agent (flow 4 ml/s; 40 ml saline flush, flow 4 ml/s), starting at the level of Th2 up to the roof of the lateral ventricles. The craniocervical vessels were analyzed in the source images, with the use of maximum-intensity projections and curved multi-planar reconstructions. Alternatively, a duplex
Kulkarni, Padmaja Ramesh; Rani, Hephzibah; Vimalambike, Manjunath Gubbanna; Ravishankar, Sunila
The incidence and mortality of cervical cancer remains high in India even after sixty years of introduction of the Pap smear (cervical cytology) which is an effective means of identifying preinvasive lesions of carcinoma cervix. The morbidity and mortality due to cervical cancer has come down drastically in countries with well established screening programmes at national level. This study aims at screening women for cervical cancer opportunistically during their visit to hospital and to study various types of neoplastic and non-neoplastic lesions of the cervix by cervical smear study (Pap smear study). In the present study, a total of 350 cervical smears were studied. The age of patients ranged from 19 years to 80 years with mean age being 37.5 years. Out of 350 cases, the diagnosis of neoplasia was given in 43 cases and 258 cases were diagnosed as inflammatory smears. Forty-cases were normal and 9 cases were inadequate to evaluate. Forty-three patients who were found to have neoplastic lesions on cytology were referred for further investigations like colposcopy and biopsy to confirm the diagnosis and avail proper treatment. Limitation of the present study was small sample size as all female patients aged between 20 and 60 years visiting hospital were not included in the screening, other screening tests like VIA (visual inspection with acetic acid test) and HPV DNA (human papilloma virus) tests were not done. Until the time centrally organised screening programmes for cervical cancer are established in India, arrangements should be made for hospital based opportunistic screening for all women attending hospital. The cost effectiveness of different screening tests for cervical cancer should be evaluated.
Hirai, Takashi; Yoshii, Toshitaka; Iwanami, Akio; Takeuchi, Kazuhiro; Mori, Kanji; Yamada, Tsuyoshi; Wada, Kanichiro; Koda, Masao; Matsuyama, Yukihiro; Takeshita, Katsushi; Abematsu, Masahiko; Haro, Hirotaka; Watanabe, Masahiko; Watanabe, Kei; Ozawa, Hiroshi; Kanno, Haruo; Imagama, Shiro; Fujibayashi, Shunsuke; Yamazaki, Masashi; Matsumoto, Morio; Nakamura, Masaya; Okawa, Atsushi; Kawaguchi, Yoshiharu
Ossification of the posterior longitudinal ligament (OPLL) can cause severe and irreversible paralysis in not only the cervical spine but also the thoracolumbar spine. To date, however, the prevalence and distribution of OPLL in the whole spine has not been precisely evaluated in patients with cervical OPLL. Therefore, we conducted a multi-center study to comprehensively evaluate the prevalence and distribution of OPLL using multi-detector computed tomography (CT) images in the whole spine and to analyze what factors predict the presence of ossified lesions in the thoracolumbar spine in patients who were diagnosed with cervical OPLL by plain X-ray. Three hundred and twenty-two patients with a diagnosis of cervical OPLL underwent CT imaging of the whole spine. The sum of the levels in which OPLL was present in the whole spine was defined as the OP-index and used to evaluate the extent of ossification. The distribution of OPLL in the whole spine was compared between male and female subjects. In addition, a multiple regression model was used to ascertain related factors that affected the OP-index. Among patients with cervical OPLL, women tended to have more ossified lesions in the thoracolumbar spine than did men. A multiple regression model revealed that the OP-index was significantly correlated with the cervical OP-index, sex (female), and body mass index. Furthermore, the prevalence of thoracolumbar OPLL in patients with a cervical OP-index ≥ 10 was 7.8 times greater than that in patients with a cervical OP-index ≤ 5. The results of this study reveal that the extent of OPLL in the whole spine is significantly associated with the extent of cervical OPLL, female sex, and obesity. PMID:27548354
Nieves-Ramirez, Miriam Enriqueta; Partida-Rodriguez, Oswaldo; Alegre-Crespo, Pedro Eduardo; Tapia-Lugo, Maria del Carmen; Perez-Rodriguez, Martha Esthela
Development of cervical cancer is a long process of abnormal cancerous cell growth in the cervix and is primarily the result of infection with specific high-risk types of human papillomavirus (HPV). The cytokines tumor necrosis factor α (TNFα) and lymphotoxin α (LTA) have an important role in all stages of cervical cancer and have the ability to induce the regression or promote the development of human tumors. Biologically important single-nucleotide polymorphisms (SNPs) occur within the TNFα and LTA genes. Therefore, the purpose of this study was to investigate the SNPs in the TNFα promoter region (-163, -238, -244, -308, -376, -857, -863, and -1031) and in the first intron of LTA (+252) in women with precursor lesions of cervical cancer. Overall, we studied 396 women from Mexico City. A total of 191 patients with HPV infection and precursor cervical lesions were subdivided in two groups: those with low-grade squamous intraepithelial lesions (n = 132) and those with high-grade squamous intraepithelial lesions (n = 59). Women (n = 205) negative for HPV and without cervical lesions were also included in the study. DNA was extracted from peripheral white blood cells and from cervical samples, and detection of biallelic polymorphisms of TNFα and LTA was performed using the polymerase chain reaction-sequence-specific oligonucleotide probe and restriction fragment length polymorphism techniques, respectively. We demonstrated that risk is associated with the genotype G/A (odds ratio = 2.48) and that protection is associated with the genotype G/G of SNP TNFα -376 (odds ratio = 0.37). PMID:22190997
Lane, Michael A.; White, Todd E.; Coutts, Marcella A.; Jones, Alex L.; Sandhu, Milapjit S.; Bloom, David C.; Bolser, Donald C.; Yates, Bill J.; Fuller, David D.; Reier, Paul J.
While monosynaptic bulbospinal projections to phrenic motoneurons have been extensively described, little is known about the organization of phrenic premotor neurons in the adult rat spinal cord. As interneurons may play an important role in normal breathing and recovery following spinal cord injury, the present study has used anterograde and transneuronal retrograde tracing to study their distribution and synaptic relations. Exclusive unilateral, first-order labeling of the phrenic motoneuron pool with pseudorabies virus demonstrated a substantial number of second-order, bilaterally-distributed cervical interneurons predominantly in the dorsal horn and around the central canal. Combined transneuronal and anterograde tracing revealed ventral respiratory column projections to pre-phrenic interneurons suggesting some propriospinal relays exist between medullary neurons and the phrenic nucleus. Dual-labeling studies with pseudorabies virus recombinants also showed pre-phrenic interneurons integrated with either contralateral phrenic or intercostal motoneuron pools. The stability of interneuronal pseudorabies virus labeling patterns following lateral cervical hemisection was then addressed. Except for fewer infected contralateral interneurons at the level of the central canal, the number and distribution of phrenic-associated interneurons was not significantly altered two weeks post-hemisection (i.e. when the earliest post-injury recovery of phrenic activity has been reported). These results demonstrate a heterogeneous population of phrenic-related interneurons. Their connectivity and relative stability after cervical hemisection raises speculation for potentially diverse roles in modulating phrenic function normally and post-injury. PMID:18924146
Gage, Julia C.; Rodriguez, Ana Cecilia; Schiffman, Mark; Adadevoh, Sydney; Alvarez Larraondo, Manuel J.; Chumworathayi, Bandit; Lejarza, Sandra Vargas; Araya, Luis Villegas; Garcia, Francisco; Budihas, Scott R.; Long, Rodney; Katki, Hormuzd A.; Herrero, Rolando; Burk, Robert D.; Jeronimo, Jose
Objectives To estimate efficacy of a visual triage of human papillomavirus (HPV)– positive women to either immediate cryotherapy or referral if not treatable (eg, invasive cancer, large precancers). Methods We evaluated visual triage in the HPV-positive women aged 25 to 55 years from the 10,000-woman Guanacaste Cohort Study (n = 552). Twelve Peruvian midwives and 5 international gynecologists assessed treatability by cryotherapy using digitized high-resolution cervical images taken at enrollment. The reference standard of treatability was determined by 2 lead gynecologists from the entire 7-year follow-up of the women. Women diagnosed with histologic cervical intraepithelial neoplasia grade 2 or worse or 5-year persistence of carcinogenic HPV infection were defined as needing treatment. Results Midwives and gynecologists judged 30.8% and 41.2% of women not treatable by cryotherapy, respectively (P < 0.01). Among 149 women needing treatment, midwives and gynecologists correctly identified 57.5% and 63.8% (P = 0.07 for difference) of 71 women judged not treatable by the lead gynecologists and 77.6% and 59.7% (P < 0.01 for difference) of 78 women judged treatable by cryotherapy. The proportion of women judged not treatable by a reviewer varied widely and ranged from 18.6%to 61.1%. Interrater agreement was poor with mean pairwise overall agreement of 71.4% and 66.3% and κ ’s of 0.33 and 0.30 for midwives and gynecologists, respectively. Conclusions In future “screen-and-treat” cervical cancer prevention programs using HPV testing and cryotherapy, practitioners will visually triage HPV-positive women. The suboptimal performance of visual triage suggests that screen-and-treat programs using cryotherapy might be insufficient for treating precancerous lesions. Improved, low-technology triage methods and/or improved safe and low-technology treatment options are needed. PMID:19509579
Xu, Dong; Xu, Hai-Miao; Li, Ming-Kui; Chen, Li-Yu; Wang, Li-Jing
The aim of the study was to investigate the feasibility and value of clinical application of fine-needle aspiration histological biopsy via ultrasound-guided thyroid nodule and enlarged cervical lymph node fine-needle aspiration histological biopsy. Fine-needle aspiration cytological and histological biopsies and surgical treatments were performed on 982 patients with thyroid nodule and 1435 patients with enlarged cervical lymph nodes. A comparative study of the histological and cytological examination results and post-surgical etiology results was subsequently conducted. Among the 982 thyroid nodule patients, the acquisition rates were 89.8% (882/982) for fine-needle aspiration histological biopsy and 96.2% (945/982) for cytological biopsy, while among the 1435 patients with enlarged cervical lymph nodes, the acquisition rate for fine-needle aspiration cytological biopsy was slightly higher than that for histological biopsy, with values of 95.7% (1374/1435) and 91.4% (1312/1435), respectively. For the thyroid nodule patients, when the acquired histological and cytological biopsy results were compared with the post-surgical etiology results, the sensitivity, specificity, and accuracy of the histological results were 98.5%, 100%, and 98.9%, respectively, whereas those of the cytological results were 86.8%, 82.9%, and 85.6%, respectively; the differences between the 2 biopsy methods were statistically significant (P < 0.05). For the patients with enlarged cervical lymph nodes, when the acquired histological and cytological biopsy results were compared with the post-surgical etiology results, the sensitivity, specificity, and accuracy of the histological results were 96.3%, 99.8%, and 97.6%, respectively, whereas the those of the cytological results were 76.8%, 92.1%, and 82.2%, respectively; again, the differences between the 2 methods were statistically significant (P < 0.05). In conclusion, Fine-needle aspiration histological biopsy is a reliable and highly
Fokom-Domgue, Joël; Vassilakos, Pierre; Petignat, Patrick
The World Health Organization guidelines for screening and management of cervical precancerous lesions updated in 2013 made an emphasis on the use of the 'screen-and-treat' approach for cervical cancer prevention. In order to facilitate scaling-up in low income settings, most of these screen-and-treat strategies do not involve confirmatory biopsy. This yields a certain rate of overtreatment. In other words, a majority of people undergoing screen-and-treat intervention who are treated does not necessarily benefit from the treatment. Therefore, the issue of potential short term and long term complications of the recommended treatment procedures (cryotherapy and Loop Electrosurgical Excision Procedure) arises. This question has seldom been studied in resource poor countries, particularly in Sub-Saharan Africa where Human Immunodeficiency Virus infection is rampant in an epidemic fashion and where the procreative capacities are socially rewarding for women. We draw the attention of the scientific community and policy makers to the fact that the lack of evidence supporting the safety of these treatment procedures in African populations may have an impact on the acceptability of these strategies and therefore on the effectiveness of screening programs. Copyright © 2014 Elsevier Inc. All rights reserved.
HASIM, AYSHAMGUL; ALI, MAYINUER; MAMTIMIN, BATUR; MA, JUN-QI; LI, QIAO-ZHI; ABUDULA, ABULIZI
1H nuclear magnetic resonance (NMR)-based metabonomics has been used to characterize the metabolic profiles of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC). Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to model the systematic variation related to patients with CIN or CSCC with healthy controls. Potential metabolic biomarkers were identified using database comparisons, and the one-way analysis of variance (ANOVA) test was used to examine the significance of the metabolites. Compared with plasma obtained from the healthy controls, plasma from patients with CIN had higher levels of very-low density lipoprotein (VLDL), acetone, unsaturated lipid and carnitine, together with lower levels of creatine, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine, glycine, acetylcysteine, myo-inositol, choline and glycoprotein. Plasma from patients with CSCC had higher levels of acetate and formate, together with lower levels of creatine, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine and tyrosine compared with the plasma of the healthy controls. In addition, compared with the plasma of patients with CIN, the plasma of CSCC patients had higher levels of acetate, formate, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine, tyrosine, acetylcysteine, myo-inositol, glycoprotein, α-glucose and β-glucose, together with lower levels of acetone, unsaturated lipid and carnitine. Moreover, the profiles showed high feasibility and specificity by statistical analysis with OPLS-DA compared to the Thinprep cytology test (TCT) by setting the histopathological outcome as standard. The metabolic profile obtained for cervical cancer is significant, even for the precancerous disease. This suggests a systemic metabolic response to cancer, which may be used to identify potential early diagnostic biomarkers of the cancer and to establish
Weinmann, Sheila; Naleway, Allison; Swamy, Geeta; Krishnarajah, Girishanthy; Arondekar, Bhakti; Fernandez, Jovelle; Myers, Evan
To examine whether surgical procedures involving the uterine cervix were associated with pregnancy outcomes, including preterm birth, low birth weight, cesarean delivery and pregnancy loss. Population-based observational study nested in retrospective matched cohort. Kaiser Permanente Northwest integrated health plan in Oregon/Washington, U.S.A. Female health plan members age 14-53 years with documented pregnancies from 1998-2009. Women with prior excisional and ablative cervical surgical procedures (N = 322) were compared to women unexposed to cervical procedures (N = 4,307) and, separately, to those having undergone only diagnostic/biopsy procedures (N = 847). Using log-linear regression models, we examined risk of adverse pregnancy outcomes in relation to prior excisional or ablative cervical surgical procedures. We stratified excisional procedures by excision thickness. We evaluated for confounding by age, body mass index, race, smoking history, previous preterm birth, and parity. We found a positive association between excisional treatment > = 1.0 cm and the outcomes preterm birth and low birth weight (preterm birth unadjusted risk ratio [RR] = 2.15, 95% confidence interval [CI] 1.16-3.98 for excisions ≥1.0 cm compared to unexposed women), particularly in women who delivered within one year of surgery (RR = 3.26, 95% CI 1.41-7.53). There was no clear association between excisional treatment and cesarean delivery, and treated women did not have a substantially higher risk of dysfunctional labor. Ablative treatment was not associated with low birth weight, preterm birth, or cesarean delivery but was associated with pregnancy loss (RR = 1.43, 95% CI 1.05-1.93 vs. unexposed women). Analyses using the diagnostic procedures comparison group produced similar results. Women with > = 1.0 cm excisional treatment had elevated risk of preterm birth and low birth weight when compared to unexposed women and women with cervical diagnostic procedures. This suggests that
Naleway, Allison; Swamy, Geeta; Krishnarajah, Girishanthy; Arondekar, Bhakti; Fernandez, Jovelle; Myers, Evan
Objective To examine whether surgical procedures involving the uterine cervix were associated with pregnancy outcomes, including preterm birth, low birth weight, cesarean delivery and pregnancy loss. Design Population-based observational study nested in retrospective matched cohort Setting Kaiser Permanente Northwest integrated health plan in Oregon/Washington, U.S.A. Population Female health plan members age 14–53 years with documented pregnancies from 1998–2009. Women with prior excisional and ablative cervical surgical procedures (N = 322) were compared to women unexposed to cervical procedures (N = 4,307) and, separately, to those having undergone only diagnostic/biopsy procedures (N = 847). Methods Using log-linear regression models, we examined risk of adverse pregnancy outcomes in relation to prior excisional or ablative cervical surgical procedures. We stratified excisional procedures by excision thickness. We evaluated for confounding by age, body mass index, race, smoking history, previous preterm birth, and parity. Results We found a positive association between excisional treatment > = 1.0 cm and the outcomes preterm birth and low birth weight (preterm birth unadjusted risk ratio [RR] = 2.15, 95% confidence interval [CI] 1.16–3.98 for excisions ≥1.0 cm compared to unexposed women), particularly in women who delivered within one year of surgery (RR = 3.26, 95% CI 1.41–7.53). There was no clear association between excisional treatment and cesarean delivery, and treated women did not have a substantially higher risk of dysfunctional labor. Ablative treatment was not associated with low birth weight, preterm birth, or cesarean delivery but was associated with pregnancy loss (RR = 1.43, 95% CI 1.05–1.93 vs. unexposed women). Analyses using the diagnostic procedures comparison group produced similar results. Conclusion Women with > = 1.0 cm excisional treatment had elevated risk of preterm birth and low birth weight when compared to unexposed
Song, Y S; Kee, S H; Kim, J W; Park, N H; Kang, S B; Chang, W H; Lee, H P
Geographic specificity of nucleotide sequence variations in the coding and noncoding regions of HPV 16 genome has been reported. Little has been known, however, regarding whether these naturally occurring sequence variations of HPV 16 may result in marked differences in biological properties, such as oncogenic potential. This study was performed to identify sequence variants in the HPV 16 E7 gene derived from Korean women with cervical cancerous and noncancerous lesions, and to assess the association between the sequence variant and the cervical cancer. We examined E7 variants of HPV 16 in a total of 157 patients with no cervical disease (NCD, n = 87) or cervical neoplasia (cervical intraepithelial neoplasia 3, n = 21; cervical carcinoma, n = 49), using the nested polymerase chain reaction (PCR) and the PCR-directed sequencing methods with outer consensus and inner type-specific primers. Forty-two (NCD, n = 9; CIN 3, n = 6; cervical carcinoma, n = 27) of 157 cervical samples contained HPV 16 E7 DNA, but only 8 had prototype sequences. Four variants of the HPV 16 E7 gene were identified. The variant with a single nucleotide change at position 647 (A --> G, Asn --> Ser) was found in about 60% of DNA samples with HPV 16. The second most common variant, found in 16.7% of cases, had three silent mutations at positions 732 (T --> C), 789 (T --> C), and 795 (T --> G). Two other variants were detected, one in a patient with cervical cancer and the other in a patient with no cervical disease. One had a single nucleotide change at position 666 (G --> A) and the other had one silent mutation at position 796 (T --> C). The most common variant in Korea has a change of nucleotide affecting the predicted amino acid related with high antigenicity and binding to retinoblastoma protein. There was a statistically significant trend for this variant to be more frequently detected in cancerous lesions of the uterine cervix than in noncancerous lesions. These data suggest that naturally
Chigbu, Chibuike O; Onyebuchi, Azubuike K
To compare the effectiveness of cryotherapy and loop electrosurgical excision procedure without colposcopy (visual LEEP) in treating cervical lesions detected through visual inspection with acetic acid (VIA). In rural southeast Nigeria, women with VIA-positive lesions who were eligible for ablative treatment were selected to undergo immediate cryotherapy with nitrous oxide. Women with VIA-positive lesions who were not eligible for ablative treatment were selected to undergo visual LEEP at the same visit. A portable diathermy machine was used for LEEP. Participants were re-evaluated 6 months later using VIA. The main outcome measures included persistent VIA positivity at 6 months, duration of procedure, second clinic visits for complications, and patient acceptability. In total, 304 women completed the study. Persistent VIA-positivity rates, duration of procedure, second clinic visits for complications, and patient acceptability were similar in the 2 groups. Visual LEEP and cryotherapy have similar efficacy and patient acceptability in see-and-treat management of VIA-positive cervical lesions. In see-and-treat VIA-based cervical cancer prevention programs in low-resource countries, visual LEEP can be used to treat women who do not meet the criteria for ablative treatment. This would increase the treatment coverage of women with VIA-positive lesions and improve program efficiency. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
Alatise, O I; Babalola, O O; Omoniyi-Esan, G O; Lawal, O O; Adesunkanmi, A R; Agbakwuru, E A
The aim of this prospective case controlled study was to evaluate the tissue levels of selenium in patients with cases of fibroadenoma, cancer of the breast and in the controls in order to relate them to the occurrence of breast diseases. Consecutive consenting patients who had histologically confirmed breast cancer and fibroadenoma attending the General surgical outpatients departments of Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, were recruited for the study. One gram of core disease breast tissues was taken for Selenium level estimation. There were 127 female subjects;. 95 (74.8%) cases of fibroadenoma and 32 (25.2%) of breast cancer. While breast cancer was common on the left, fibroadenoma was more common on the right breast (? = 8.994; p=0.011). The median tissue level of selenium in patients with fibroadenoma was 0.0272 mg/g with a range of 0.0124 to 0.0576 mg/g and that of the cancer patients was 0.0178 mg/g with a range 0.0072 to 0.0436 mg/g. These were statistically significantly different ( p=0.001). Factors affecting tissue selenium level include age (p<0.001), overall stage of breast cancer (p<0.001), maximum length of breast mass (p=0.023), previous delivery (p=0.004), age at last confinement (p=0.007), parity (p<0.001), oestrogen receptor (ER) status (p<0.001) and progesterone receptor (PR) status (p=0.021). Tissue selenium was lower in breast cancer than in fibroadenoma; Tissue selenium inhibits carcinogenesis; low tissue level of selenium therefore may be a factor in the development of breast cancer.
Giovannini, M; Ardizzone, S
Accurate staging of rectal and anal carcinoma is crucial for planning surgery and indicating adjuvant therapy. Although, computed tomography and magnetic resonance imaging are very sensitive in detecting metastatic disease, the local staging of rectal cancer with these techniques has been disappointing. Endorectal ultrasound (ERUS) and anal endosonography (AE) remain the most accurate methods for staging rectal and anal cancer. Anal endosonography is also of value in evaluating perianal sepsis: it can assist the surgeon in planning the surgical strategy by delineating the anatomy of fistula tracts, and can aid in puncturing abscesses in the operating room. Continued research and development has made the instrumentation for ERUS and AE more accurate and user-friendly. New techniques that have contributed significantly to the evolution of ERUS include three-dimensional ERUS, high-frequency miniprobes, transrectal ultrasound-guided biopsy techniques and hydrogen peroxide-enhanced endosonography. Further improvements can be expected from contrast enhancement with microbubbles and colour Doppler imaging. In this new millennium, new developments in ERUS and anal endosonography, such as tri-dimensional ERUS and anal endosonography and radial electronic probing, widen the role of ERUS in the staging of rectal and anal carcinoma, as well as for perianal inflammatory conditions.
Jyothi, KN; Annapurna, S; Kumar, Anil S; Venugopal, P; Jayashankara, CM
Objectives: To evaluate and compare the clinical performance of Giomer (Beautifil II) and RMGIC (Fuji II LC) in noncarious cervical lesions. Materials and Methods: Thirty-two subjects with one or two pairs of noncarious cervical lesions were included in the study. Each pair of lesion was restored with either giomer or RMGIC assigned randomly. Clinical evaluation of restorations was done using USPHS criteria. Data was formulated in a predesigned format and subjected to statistical analysis using the chi square test. Results: Statistically significant difference was found between RMGIC and Giomer with respect to surface roughness with P value <0.001. Conclusion: Giomer showed superior surface finish compared to RMGIC. Both Giomer and RMGIC showed equal retention ability. PMID:22144814
González-López, Sergio; Martínez-Silva, María G; Hernández-Hernández, Dulce M; Aguilar-Lemarroy, Adriana; Jave-Suárez, Luis Felipe
The Official Mexican Norm for the prevention, treatment and control of Cervical Cancer (CC) indicates that the Papanicolau (Pap) is the procedure for the detection of this neoplasia; therefore, it is of interest to know the prevalence of suspected cases by this technique in Mexican population. In this study, we show the diagnosed cases in the State of Jalisco, México. A retrospective study was made to the samples that arrived for their analysis to the Laboratorio Regional de Citología Exfoliativa (LARCE), of the Instituto Mexicano del Seguro Social (IMSS) in Guadalajara, Jalisco. We considered all cases from January 2010 to December 2012. We analyzed 188 095 cases, from which 5.3 % had a diagnosis of low dysplasia, 0.18 % of moderated dysplasia and 0.05 % of high dysplasia. Microinvasive and invasive cancer showed a low frequency (0.03 %). The frequency of abnormal findings identified by vaginal cervical cytology is relatively low. The number of inadequate and limited samples for cytological assessment is high; there is a high proportion of women attending for the first time in life to cytology evaluation in older age groups.
Bueno, Caroline Tanski; Dornelles da Silva, Cláudia Maria; Barcellos, Regina Bones; da Silva, Juliana; Dos Santos, Carla Rossana; Menezes, João Evangelista Sampaio; Menezes, Honório Sampaio; Rossetti, Maria Lucia Rosa
The aim of this study was to evaluate the association between the frequency of micronuclei (MN) and the cellular changes detected in the conventional Papanicolaou test. One hundred and seventy-four Papanicolaou test smears with cellular changes were examined. MN screening was done in cytopathological smears by counting 1,000 cervical cells in a light microscope. MN frequencies were significantly higher in the group with cellular changes compared to the control group (p < 0.001). The mean MN frequencies were 0.95 ± 1.12 (mean ± SD) in the control group (n = 223), 2.98 ± 1.20 in individuals with atypical squamous cells of undetermined significance (ASC-US) (n = 50), 4.04 ± 1.45 in cervical intraepithelial neoplasia (CIN) I (n = 52), 5.97 ± 1.83 in CIN II (n = 30), 7.29 ± 1.55 in CIN III (n = 17) and 8.64 ± 1.55 in invasive cancer (n = 25). These findings suggest that MN monitoring should be included as an additional criterion for the early detection of cytogenetic damage in routine examinations. This monitoring should be done in the same smear as used for cytopathological examination. More specific and systematic studies are necessary to confirm this proposal.
Bueno, Caroline Tanski; Dornelles da Silva, Cláudia Maria; Barcellos, Regina Bones; da Silva, Juliana; dos Santos, Carla Rossana; Menezes, João Evangelista Sampaio; Menezes, Honório Sampaio; Rossetti, Maria Lucia Rosa
The aim of this study was to evaluate the association between the frequency of micronuclei (MN) and the cellular changes detected in the conventional Papanicolaou test. One hundred and seventy-four Papanicolaou test smears with cellular changes were examined. MN screening was done in cytopathological smears by counting 1,000 cervical cells in a light microscope. MN frequencies were significantly higher in the group with cellular changes compared to the control group (p < 0.001). The mean MN frequencies were 0.95 ± 1.12 (mean ± SD) in the control group (n = 223), 2.98 ± 1.20 in individuals with atypical squamous cells of undetermined significance (ASC-US) (n = 50), 4.04 ± 1.45 in cervical intraepithelial neoplasia (CIN) I (n = 52), 5.97 ± 1.83 in CIN II (n = 30), 7.29 ± 1.55 in CIN III (n = 17) and 8.64 ± 1.55 in invasive cancer (n = 25). These findings suggest that MN monitoring should be included as an additional criterion for the early detection of cytogenetic damage in routine examinations. This monitoring should be done in the same smear as used for cytopathological examination. More specific and systematic studies are necessary to confirm this proposal. PMID:25249771
Oliveira, Bmb; Ulbaldini, Alm; Sato, F; Baesso, M L; Bento, A C; Andrade, Lhc; Lima, S M; Pascotto, R C
The purpose of this study was to evaluate the chemical bonds of a self-etch 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) adhesive to natural noncarious cervical lesions (NCCLs) and compare them with those occurring in sclerotic dentin in artificially prepared defects (APDs). Four human teeth with natural NCCLs on the buccal surface were selected. Artificial defects matching the natural lesions were prepared on the lingual surface of the same teeth serving as control. Micro-Raman (MR) spectroscopy was used to quantify mineral content in natural NCCLs and in APDs. Fourier transform infrared-photoacoustic spectroscopy (FTIR-PAS) readouts were taken before and after adhesive application to analyze the protein matrix/mineral (M:M) ratio and chemical interactions between 10-MDP adhesive and dentin. The MR and FTIR-PAS spectra collected from natural NCCLs demonstrated a larger area of the band (961 cm(-1), PO4) and lower M:M ratio, respectively, characterizing a hypermineralized dentin, compared with APDs. FTIR-PAS demonstrated emergence of a peak (1179 cm(-1), P=O) in spectra after adhesive treatment, demonstrating a more intense chemical interaction in natural NCCLs. The results demonstrated that chemical bonding of 10-MDP adhesive to natural NCCLs is more intense, due to the hypermineralized surface, and suggest that it is unnecessary to remove the hypermineralized layer with burs, as this may decrease the chemical bonding potential of 10-MDP.
Igarashi, Yuriko; Yoshida, Satoru; Kanazawa, Eisaku
Non-carious cervical lesions (NCCLs) were examined in 6541 extracted human teeth and classified based on the morphology of the lesions. As a result, NCCLs were found on 38.7% of teeth (41.6% on maxillary teeth and 36.0% on mandibular teeth), and were most frequent on canines and first premolars. According to the new method of classification, the morphology of NCCLs was classified both by the surface contour (SC) and by the cross-sectional contour (CC). Three types of NCCLs appeared to be dominant. The causes of these NCCLs were discussed based on their morphologies, positions where these NCCLs were frequently found, and the results of previous studies. NCCLs with a horizontal oval SC and a round CC (Type I), which were frequent on the labial surfaces of maxillary canines and buccal surfaces of maxillary first premolars, may be associated with wear by friction and chemical degradation. NCCLs with a vertical oval SC and a round CC (Type II), which were frequent on the lingual surfaces of mandibular incisors and canines, might be mainly related to chemical degradation. NCCLs with a horizontal oval SC and a wedge shape CC (Type III), which were extensively found on the buccal surfaces of maxillary premolars, had formed most probably due to wear by friction and microstructural loss by stress. This new method can classify the morphology of NCCLs more precisely and deduce the mechanisms of the formation of NCCLs more clearly than former methods.
Kefala, Maria; Kottaridi, Christine; Spathis, Aris; Gouloumi, Alina-Roxani; Pouliakis, Abraham; Pappas, Asimakis; Sioulas, Vasileios; Chrelias, Charalambos; Karakitsos, Petros; Panayiotides, Ioannis
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
Rabelo-Santos, Silvia Helena; Derchain, Sophie Françoise Mauricette; Villa, Luísa Lina; Costa, Maria Cecília; Sarian, Luis Otávio Zanatta; do Amaral Westin, Maria Cristina; Kornegay, Janet; Zeferino, Luiz Carlos
This study was designed to analyze whether specific human papillomavirus (HPV) genotypes may predict histologic outcomes in women with glandular abnormalities in their cervical smears. Of the 160 women included, 111 were diagnosed with atypical glandular cells, 35 had both atypical glandular cells and high-grade squamous intraepithelial lesions, whereas 14 women had AIS, in 1 case associated with high-grade squamous intraepithelial lesions. All women underwent colposcopic examinations and biopsy was performed in 129/160 (80.6%). Thirty-one women (19.3%) were considered negative for neoplasia and scheduled for follow-up. All specimens were tested for 27 HPV genotypes by Roche's polymerase chain reaction-reverse line blot assay. Histologic diagnoses were either cervical intraepithelial neoplasia or invasive carcinoma in 75 (58%) women, and negative for neoplasia in 54 (42%). The overall prevalence of HPV was 43%. HPV 16 was the most prevalent type followed by HPV 18. HPV 16 was significantly associated with squamous and glandular neoplasia and HPV 18 with glandular neoplasia. In women with cervical intraepithelial neoplasia 2 or 3, 11 different HPV genotypes were found, whereas in those who had invasive glandular or invasive carcinoma HPV 16 and HPV 18 were found predominantly. The detection of HPV 16 in women with glandular abnormalities in cervical smears did not help differentiating squamous from glandular lesions. However, the detection of HPV 53 in abnormal smears can predict squamous neoplasia, whereas HPV 18 can predict glandular neoplasia as histologic diagnoses.
Freitas, Luciana Bueno; Chen, Zigui; Muqui, Elaine Freire; Boldrini, Neide Aparecida Tosato; Miranda, Angélica Espinosa; Spano, Liliana Cruz; Burk, Robert D
HPV16 accounts for 50-70% of cervical cancer cases worldwide. Characterization of HPV16 variants previously indicated that they differ in risks for viral persistence, progression to cervical precancer and malignant cancer. The aim of this study was to examine the association of severity of disease with HPV16 variants identified in specimens (n = 281) obtained from a Cervical Pathology and Colposcopy outpatient clinic in the University Hospital of Espírito Santo State, Southeastern Brazil, from April 2010 to November 2011. All cytologic and histologic diagnoses were determined prior to definitive treatment. The DNA was isolated using QIAamp DNA Mini Kit and HPV was detected by amplification with PGMY09/11 primers and positive samples were genotyped by RFLP analyses and reverse line blot. The genomes of the HPV16 positive samples were sequenced, from which variant lineages were determined. Chi2 statistics was performed to test the association of HPV16 variants between case and control groups. The prevalence of HR-HPV types in
Wang, Hye-Young; Park, Sunyoung; Lee, Dongsup; Kim, Sunghyun; Kim, Geehyuk; Park, Kwang Hwa; Lee, Hyeyoung
Human papillomavirus (HPV) infection is a major cause of premalignant dysplasia and cervical cancer. There are no data on the prevalence of genotype-specific HPV infection assessed by HPV E6/E7 mRNA in women representative of the Korean population across a broad age range. A total of 630 women aged 17-90 years were enrolled in this study. ThinPrep liquid-based cytology samples were evaluated using the CervicGen HPV RT-qDx assay, which detects 16 high-risk (HR) HPV genotypes (set 1: HPV 16, 31, 33, 35, 52, and 58; set 2: HPV 18, 39, 45, 51, 59, and 68; and set 3: HPV 53, 56, 66, and 69). The overall prevalence of HPV infection was 33.2% (n=209), and oncogenic high-risk HPV was detected in 75.9% (n=107) of 141 women with high-grade cervical lesions. HPV 16 was the most common HPV genotype among women with high-grade cervical lesions and histologically confirmed cervical intraepithelial neoplasia grade 2 and above (CIN2+) in the Republic of Korea (41.6%). Among women aged over 30 years, 182/329 (55%) had invasive cervical cancer and 135 (74%) of these were infected with oncogenic HR-HPV types (in particular 25% with HPV 16). Among patients diagnosed with CIN2+, the positivity rate of HR-HPV was the highest in women aged 40-49 years. These results suggest that the determination of specific HPV genotypes is very important for evaluating the potential impact of preventive measures, including the use of prophylactic vaccines, on reducing the burden of cervical cancer. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Anaya-Prado, Roberto; Norzgaray-Ibarra, Fabiola Geovanna; Bravo-Cuéllar, Alejandro; Pérez-Avila, Carlos Eduardo; Schadegg-Peña, Daniel; Anaya-Fernández, Michelle M
Introducción: se ha demostrado que la glicoproteína TREM-1 pertenece a la superfamilia de las inmunoglobulinas que induce la secreción de varias citocinas proinflamatorias. El objetivo de este trabajo fue medir la expresión de TREM-1 en pacientes con cáncer cervical. Métodos: en este estudio transversal analítico incluimos 4 grupos de pacientes: GI: mujeres con lesión intraepitelial (LI) escamosa de bajo grado (n = 15 p/g); GII: pacientes con LI escamosa de alto grado (n = 9 p/g); GIII: pacientes con cáncer cervical invasor (n = 9 p/g), y GIV: pacientes sanas (n = 15 p/g). En todas las pacientes se midió la expresión de TREM-1 y el Índice Medio de Fluorescencia (IMF) en neutrófilos y monocitos, así como los niveles de leucocitos, neutrófilos y monocitos. Usamos t de Student para muestras independientes. Para estas mismas variables, aplicamos prueba de suma de rangos de Mann-Whitney, ANOVA y Turkey. Para las variables cualitativas se utilizó la prueba de Chi cuadrada. Resultados: los porcentaje de expresión de TREM-1 en neutrófilos y monocitos, además del IMF en neutrófilos en los 4 grupos, no fue significativamente diferente. El IMF de TREM-1 en monocitos fue significativamente diferente al comparar el grupo II y grupo III frente al grupo IV (p < 0.02). Tampoco hubo diferencia significativa al comparar los valores promedio de leucocitos, neutrófilos y monocitos en los diferentes grupos. Conclusión: este estudio documenta una mayor expresión de TREM-1 en monocitos de pacientes con cáncer avanzado.
Background Human Papillomavirus (HPV) is considered as a necessary, but not sufficient, cause of cervical cancer. In this study, we aimed to assess the prevalence of HPV in a series of pre-malignant and malignant cervical lesion cases, to identify the virus genotypes, and to assess their distribution pattern according to lesion type, age range, and other considered variables. The samples were submitted to histopathological revision examination and analysed by polymerase chain reaction (PCR) for the presence of HPV DNA, followed by HPV typing by dot blot hybridisation. Findings Of the analysed samples, 53.7% showed pre-malignant cervical lesions, and 46.3% presented with cervical cancer. Most cancer samples (84.1%) were classified as invasive carcinoma. The mean age of these cancer patients was 47.3 years. The overall HPV prevalence was 82.4% in patients with pre-malignant lesions and 92.0% in the cancer patients. HPV 16 was the most prevalent type, followed by HPV 18 and 58, including both single and double infections. Double infection was detected in 11.6% of the samples, and the most common combination was HPV 16+18. Conclusions Cervical cancer appears to occur in women in a lower age range in the studied area, compared to the situation in other Brazilian regions. Furthermore, among the patients with CIN 3 and those with cancer, we observed a higher proportion of married women, women with more than one sexual partner, smokers, and individuals with less than an elementary education, relative to their counterparts. Findings The overall HPV prevalence was 82.4% in patients with pre-malignant lesions and 92.0% in the cervical cancer patients from Northeast Brazil. HPV 16 was the most prevalent type, followed by HPV 18 and 58. The most common double infection was HPV 16+18. Cervical cancer appears to occur in women in a lower age range in the Northeast Brazil. Among the patients with CIN 3 and those with cancer, we observed a higher proportion of married women, women
Nieminen, Pekka; Lönnberg, Stefan; Malila, Nea; Hakama, Matti; Pokhrel, Arun; Laurila, Pekka; Tarkkanen, Jussi; Anttila, Ahti
Objective To compare the detection rates of precancerous and cancerous cervical lesions by human papillomavirus (HPV) DNA testing and by conventional cytology screening. Design Prospective randomised trial. Two cohorts were followed over one screening round of five years, screened initially by primary HPV DNA testing or by primary Pap test. Setting Population based programme for cervical cancer screening in Finland. Participants Women aged 25-65 years invited for screening in 2003-07 (101 678 in HPV arm; 101 747 in conventional cytology arm). Intervention Women were randomly allocated (1:1) to primary HPV DNA screening followed by cytology triage if they had positive results, or to primary cytology screening. Screening method was disclosed at the screening visit. Trial personnel involved were aware of all test results. Main outcome measures Cumulative detection rates of cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), and invasive cervical cancer before the second screening (after five years) or before 31 December 2008. Lesions detected at screening and during the five year interval were included. Results 1010 and 701 precancerous or cancerous lesions were detected during an average follow-up of 3.6 years in the HPV and cytology arms, respectively. Among invited women, the hazard ratio was 1.53 (95% confidence interval l.28 to 1.84) for CIN grade 1, 1.54 (1.33 to 1.78) for CIN 2, 1.32 (1.09 to 1.59) for CIN 3 or AIS, and 0.81 (0.48 to 1.37) for cervical cancer. In 25-34 year old participants, the cumulative hazard (or cumulative detection rate) was 0.0057 (0.0045 to 0.0072) for HPV screening versus 0.0046 (0.0035 to 0.0059) for conventional screening; corresponding data for women aged 35 years and older were 0.0022 (0.0019 to 0.0026) and 0.0017 (0.0014 to 0.0021), respectively. Conclusions Primary HPV DNA screening detects more cervical lesions than primary cytology within one screening round of five years. Even if the detection rate of
Background Cervical cancer ranks third in prevalence and fourth as cause of death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the disease. Persistent infection with high-risk HPV types is a necessary condition for the development of pre-invasive and invasive cervical neoplasia. Currently, over 100 HPV types have been identified, but HPV16 and 18 are recognized as the mayor culprits in cervical carcinogenesis. Our objective was to assess the relationships between single- (ST) and multiple-type (MT) HPV infections with patients’ age and lesion pathological status. Methods 328 patients with either squamous or glandular intraepithelial or invasive cervical lesion were selected. All subjects were tested for HPV genotypes with reverse hybridization for 21 high- (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections was compared across histological types and age strata. Results 287 (87%) women had at least one HPV type detected and 149 (52%) had MT infections. The most prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive cases), followed by HPV58, 52, 31, 35 and 33. HPV18, in single or multiple infections, occurred in 23 cases (8% of hr-HPV cases). Almost all glandular lesions were associated with HPV16 and 18 alone. Multiple infections were significantly more prevalent in squamous than in glandular lesion for HPV16 and 18 (P = 0.04 and 0.03 respectively). The prevalence of MT infections followed a bimodal distribution; peaking in women younger 29 years and in those aged 50 to 59. Conclusions Our data indicate that prevention strategies for pre-invasive and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV types. It is clear to us that in young women, prophylaxis must cover a large amalgam of HPV types beyond classic HPV16 and 18. PMID:24751127
Resende, Leandro Santos de Araújo; Rabelo-Santos, Sílvia Helena; Sarian, Luís Otávio; Figueiredo Alves, Rosane Ribeiro; Ribeiro, Andréa Alves; Zeferino, Luiz Carlos; Derchain, Sophie
Cervical cancer ranks third in prevalence and fourth as cause of death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the disease. Persistent infection with high-risk HPV types is a necessary condition for the development of pre-invasive and invasive cervical neoplasia. Currently, over 100 HPV types have been identified, but HPV16 and 18 are recognized as the mayor culprits in cervical carcinogenesis. Our objective was to assess the relationships between single- (ST) and multiple-type (MT) HPV infections with patients' age and lesion pathological status. 328 patients with either squamous or glandular intraepithelial or invasive cervical lesion were selected. All subjects were tested for HPV genotypes with reverse hybridization for 21 high- (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections was compared across histological types and age strata. 287 (87%) women had at least one HPV type detected and 149 (52%) had MT infections. The most prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive cases), followed by HPV58, 52, 31, 35 and 33. HPV18, in single or multiple infections, occurred in 23 cases (8% of hr-HPV cases). Almost all glandular lesions were associated with HPV16 and 18 alone. Multiple infections were significantly more prevalent in squamous than in glandular lesion for HPV16 and 18 (P = 0.04 and 0.03 respectively). The prevalence of MT infections followed a bimodal distribution; peaking in women younger 29 years and in those aged 50 to 59. Our data indicate that prevention strategies for pre-invasive and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV types. It is clear to us that in young women, prophylaxis must cover a large amalgam of HPV types beyond classic HPV16 and 18.
Roth, Patrick; Weller, Michael
Leptomeningeal dissemination of tumor cells, also referred to as neoplastic meningitis, is most frequently seen in patients with late-stage cancer and mostly associated with a poor prognosis. Basically, neoplastic meningitis may affect all patients with a malignant tumor but is most common in patients affected by lung cancer, breast carcinoma, melanoma or hematologic neoplasms such as lymphoma and leukemia. Controlled clinical trials are largely lacking which results in various non-standardized treatment regimens. The presence of solid tumor manifestations in the CNS as well as the extracranial tumor load defines the most appropriate treatment approach. Radiation therapy, systemic chemotherapy and intrathecal treatment must be considered. For each patient, the individual situation needs to be carefully evaluated to determine the potential benefit as well as putative side effects associated with any therapy. A moderate survival benefit and particularly relief from pain and neurological deficits are the main treatment goals. Here, we summarize the management of patients with neoplastic meningitis and review the available treatment options.
Zhong, Pingping; Li, Jifeng; Gu, Yiqun; Liu, Yu; Wang, Aichun; Sun, Yunfei; Lu, Lijuan
Objective: To determine the association between the expression of p16 and Ki-67 and cervical lesions, and to evaluate the role of p16 and Ki-67 as prognostic markers for persistent high risk human papillomavirus (hr-HPV) infection. Methods: Totally 1,154 cases of cervical biopsies were enrolled, 331 cases with negative for dysplasia (NEG), 462 with cervical intraepithelial neoplasia 1 (CIN1), 176 with CIN2, 163 with CIN3 and 22 with cervical squamous cell carcinoma (SCC). Furthermore, 283 women with CIN1 were recruited into 12-month follow-up, and HPV specific gene detection by polymerase chain reaction was used to detect hr-HPV of cervical secretions at 6-month-interval for 12-month follow-up period. 40 women were infected with persistent hr-HPV, 182 with transient infection and 61 unfected with hr-HPV. The expression of p16 and Ki-67 were evaluated by immunohistochemical method. The immunostaining results of p16 and Ki-67 were classified into four categories: negative, 1+, 2+ and 3+. Results: There was significant increase in the expression of p16 (P < 0.001) and Ki-67 (P < 0.001) from NEG to SCC. The expression of Ki-67 (P < 0.001) but not p16 (P = 0.254) significantly increased in CIN2, CIN3. Ratio of p16 (P = 0.215) and Ki-67 (P = 0.495) positivity were not correlated with persistent hr-HPV infection. Conclusion: P16 and Ki-67 can improve the diagnostic accuracy of cervical lesions but can not predict persistent hr-HPV infection with CIN1. PMID:26045807
Zhong, Pingping; Li, Jifeng; Gu, Yiqun; Liu, Yu; Wang, Aichun; Sun, Yunfei; Lu, Lijuan
To determine the association between the expression of p16 and Ki-67 and cervical lesions, and to evaluate the role of p16 and Ki-67 as prognostic markers for persistent high risk human papillomavirus (hr-HPV) infection. Totally 1,154 cases of cervical biopsies were enrolled, 331 cases with negative for dysplasia (NEG), 462 with cervical intraepithelial neoplasia 1 (CIN1), 176 with CIN2, 163 with CIN3 and 22 with cervical squamous cell carcinoma (SCC). Furthermore, 283 women with CIN1 were recruited into 12-month follow-up, and HPV specific gene detection by polymerase chain reaction was used to detect hr-HPV of cervical secretions at 6-month-interval for 12-month follow-up period. 40 women were infected with persistent hr-HPV, 182 with transient infection and 61 unfected with hr-HPV. The expression of p16 and Ki-67 were evaluated by immunohistochemical method. The immunostaining results of p16 and Ki-67 were classified into four categories: negative, 1+, 2+ and 3+. There was significant increase in the expression of p16 (P<0.001) and Ki-67 (P<0.001) from NEG to SCC. The expression of Ki-67 (P<0.001) but not p16 (P=0.254) significantly increased in CIN2, CIN3. Ratio of p16 (P=0.215) and Ki-67 (P=0.495) positivity were not correlated with persistent hr-HPV infection. P16 and Ki-67 can improve the diagnostic accuracy of cervical lesions but can not predict persistent hr-HPV infection with CIN1.
Ye, Jing; Cheng, Bei; Cheng, Yi-Fan; Yao, Ye-Li; Xie, Xing; Lu, Wei-Guo; Cheng, Xiao-Dong
Histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by normal or mildly abnormal cytology is recommended for conservative follow-up, with no separated management. In this study, we assessed the triage value of human papillomavirus (HPV) 16/18 genotyping in 273 patients with LSIL/CIN1. HPV16/18 genotyping was performed at baseline and follow-up was at 6-monthly intervals for up to 2 years. At each follow-up, women positive for cytology or high-risk HPV (hrHPV) were referred for colposcopy. Enrollment cytology, HPV16/18 genotyping, and questionnaire-obtained factors were linked to the 2-year cumulative progression rate. Univariate and multivariate analyses were performed taking into account time-to-event with Cox proportional hazard regression. The results showed that 190 cases (69.6%) regressed, 37 (13.6%) persisted, and 46 (16.8%) progressed. HPV16/18 positivity (hazard ratio (HR), 2.708; 95% confidence interval (CI), 1.432-5.121; P=0.002) is significantly associated with higher 2-year cumulative progression rate. Sub-analysis by enrollment cytology and age restricted the positive association among patients preceded by mildly abnormal cytology and aged 30 years or older. Immediate treatment is a rational recommendation for the high-risk subgroup, when good compliance is not assured.
Lin, Kuei-You; Hsu, Ying-Shuo; Young, Yi-Ho
This study utilized a combined ocular vestibular-evoked myogenic potential (oVEMP) and cervical VEMP (cVEMP) test in children with benign paroxysmal vertigo (BPV) to investigate whether the upper or lower brainstem is more frequently affected in BPV children. Fifteen BPV children aged 4-14 years, and 15 age- and sex-matched healthy children were enrolled. All subjects underwent pure tone audiometry, stabilometry, and a combined oVEMP and cVEMP test using acoustic stimulation. All BPV patients displayed normal hearing and clear oVEMPs. However, 11 (73%) of 15 BPV patients had delayed cVEMPs, showing significant difference when compared with 100% normal cVEMPs in healthy children. The sway path and sway area in stabilometry were significantly different between BPV and healthy children, regardless of whether their eyes were open or closed. However, neither the sway path nor sway area correlated significantly with cVEMP results. Normal oVEMPs in BPV children indicate an intact vestibulo-ocular reflex pathway, which travels through the upper brainstem. In contrast, delayed cVEMPs in BPV children reflect a retrolabyrinthine lesion along the sacculo-collic reflex pathway, which descends via the lower brainstem. Hence, the lower brainstem is more frequently affected than the upper brainstem in children with BPV. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
Ye, Jing; Cheng, Bei; Cheng, Yi-fan; Yao, Ye-li; Xie, Xing; Lu, Wei-guo; Cheng, Xiao-dong
Histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by normal or mildly abnormal cytology is recommended for conservative follow-up, with no separated management. In this study, we assessed the triage value of human papillomavirus (HPV) 16/18 genotyping in 273 patients with LSIL/CIN1. HPV16/18 genotyping was performed at baseline and follow-up was at 6-monthly intervals for up to 2 years. At each follow-up, women positive for cytology or high-risk HPV (hrHPV) were referred for colposcopy. Enrollment cytology, HPV16/18 genotyping, and questionnaire-obtained factors were linked to the 2-year cumulative progression rate. Univariate and multivariate analyses were performed taking into account time-to-event with Cox proportional hazard regression. The results showed that 190 cases (69.6%) regressed, 37 (13.6%) persisted, and 46 (16.8%) progressed. HPV16/18 positivity (hazard ratio (HR), 2.708; 95% confidence interval (CI), 1.432–5.121; P=0.002) is significantly associated with higher 2-year cumulative progression rate. Sub-analysis by enrollment cytology and age restricted the positive association among patients preceded by mildly abnormal cytology and aged 30 years or older. Immediate treatment is a rational recommendation for the high-risk subgroup, when good compliance is not assured. PMID:28271660
Reis, Alessandra; Loguercio, Alessandro D
This study compared the clinical performance of a microhybrid resin composite to lined Class V restorations or to those restorations without a flowable resin composite over a 24-month period. Nineteen patients with at least 2 pairs of equivalent cervical erosion/attrition/abfraction lesions, under occlusion, were enrolled in this study. A total of 74 restorations were placed, half for each group (Single-Bond + Filtek-Flow + Filtek Z250 or Single-Bond + Filtek Z250). According to the manufacturers' instructions, 2 calibrated operators placed all restorations. Two other independent examiners evaluated the restorations at baseline and after 24 months, according to the USPHS criteria and modified criteria for color match. The classic alpha score was divided into A1 for "not detectable" and A2 for "slightly discernible" filling. Statistical analysis was conducted using Fisher's exact test (alpha=0.05). For each group, 8 restorations were lost after 24 months (retention rate of 89.2%). All the restorations showed a trend toward dark yellowing after 24 months (color match A2).
Albuquerque, Nadine Luísa Guimarães; de Souza, André Mattos Brito; de Moraes, Maria Denise Rodrigues; Mendonça, Juliano Sartori; Rodrigues, Lidiany Karla Azevedo; Santiago, Sérgio Lima
The aim of this study was to evaluate the efficiency of oxalic acid (BisBlock) on restorations of non-carious cervical lesions. One operator placed 90 restorations randomly divided into two groups in 20 patients under cotton rolls isolation: Control Group-two-step etch-and-rinse adhesive technique; and Experimental Group-two-step etch-and-rinse adhesive technique with oxalic acid pretreatment after acid-etched dentin. The restorative adhesive system used was XP Bond/Durafill. The restorations were directly assessed by two independent examiners, using the modified United States Public Health Service (USPHS) criteria at the baseline and 4 years. Data were statistically analyzed using the Fisher and McNemar tests (p < 0.05). Fifteen patients (75%) were available for recall after 4 years. The McNemar test detected significant differences within the Experimental Group between the baseline and 4-year evaluations for retention (p < 0.05). For the Control Group, there was no significant difference (p > 0.05) between the periods. The Fisher test showed no statistically significant difference between the groups for all other criteria (p > 0.05). After 4 years of service, the use of oxalic acid did not influence the clinical performance of restorations when it was used under composite resin restorations.
Jiang, Shanghai; Kang, Deyong; Xu, Meifang; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin
Gastric polyps can be broadly defined as luminal lesions projecting above the plane of the mucosal surface. They are generally divided into non-neoplastic and neoplastic polyps. Accurate diagnosis of neoplastic polyps is important because of their well-known relationship with gastric cancer. Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) is one of the most important recent inventions in biological imaging. In this study, we used MPM to image the microstructure of gastric polyps, including fundic gland polyps, hyperplastic polyps, inflammatory fibroid polyps and adenomas, then compared with gold-standard hematoxylin- eosin(H-E)-stained histopathology. MPM images showed that different gastric polyps have different gland architecture and cell morphology. Dilated, elongated or branch-like hyperplastic polyps are arranged by columnar epithelial cells. Inflammatory fibroid polyps are composed of small, thin-walled blood vessels surrounded by short spindle cells. Fundic glands polyps are lined by parietal cells and chief cells, admixed with normal glands. Gastric adenomas are generally composed of tubules or villi of dysplastic epithelium, which usually show some degree of intestinal-type differentiation toward absorptive cells, goblet cells, endocrine cells. Our results demonstrated that MPM can be used to identify non- neoplastic and neoplastic gastric polyps without the need of any staining procedure.
Cortés-Gutiérrez, E I; Leal-Elizondo, E; Cerda-Flores, R M; Leal-Garza, C H
To evaluate Ag(+)-stained (Ag(+)-NOR) polymorphism in four groups of patients with various grades of cervical lesions and in a control group. Forty-five women were selected, diagnosed and classified on the bases of the Pap smear and colposcopy/biopsy at Hospital de Ginecologia y Obstetricia del Instituto Mexicano del Seguro Social in Monterrey, Mexico. Five categories were considered: (1) inflammatory, (2) low grade squamous intraepithelial lesions (LSILs), (3) high grade squamous intraepithelial lesions (HSILs), (4) invasive cervical cancer, and (5) normal. The cervical smears were stained by the Ag(+)-NOR method. One hundred cells per slide were counted and classified according to the polymorphism of Ag(+)-NOR dots: typical (spherical) and atypical (large, kidney shaped and clustered). The four shapes of Ag(+)-NORs were quantified by percentage and transformed using the arcsine root procedure. Statistical analysis showed a significant decrease in spherical shape according to neoplastic development. The three atypical shapes showed a significant increase in patients with HSIL and invasive carcinoma in respect to LSIL. Principal components analysis grouped the data at five locations in the plane formed by the first two principal components according to the diagnosis. These findings suggest the potential diagnostic and prognostic value of the determination of Ag(+)-NOR polymorphism in cervical cytology studies.
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
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
Pennazio, Marco; Rondonotti, Emanuele; de Franchis, Roberto
Until recently, diagnosis and management of small-bowel tumors were delayed by the difficulty of access to the small bowel and the poor diagnostic capabilities of the available diagnostic techniques. An array of new methods has recently been developed, increasing the possibility of detecting these tumors at an earlier stage. Capsule endoscopy (CE) appears to be an ideal tool to recognize the presence of neoplastic lesions along this organ, since it is non-invasive and enables the entire small bowel to be visualized. High-quality images of the small-bowel mucosa may be captured and small and flat lesions recognized, without exposure to radiation. Recent studies on a large population of patients undergoing CE have reported small-bowel tumor frequency only slightly above that reported in previous surgical series (range, 1.6%-2.4%) and have also confirmed that the main clinical indication to CE in patients with small-bowel tumors is obscure gastrointestinal (GI) bleeding. The majority of tumors identified by CE are malignant; many were unsuspected and not found by other methods. However, it remains difficult to identify pathology and tumor type based on the lesion's endoscopic appearance. Despite its limitations, CE provides crucial information leading in most cases to changes in subsequent patient management. Whether the use of CE in combination with other new diagnostic (MRI or multidetector CT enterography) and therapeutic (Push-and-pull enteroscopy) techniques will lead to earlier diagnosis and treatment of these neoplasms, ultimately resulting in a survival advantage and in cost savings, remains to be determined through carefully-designed studies.
Matsuda, Katsuya; Miura, Shiro; Kurashige, Tomomi; Suzuki, Keiji; Kondo, Hisayoshi; Ihara, Makoto; Nakajima, Hisayoshi; Masuzaki, Hideaki; Nakashima, Masahiro
Aims A defective DNA damage response can result in genomic instability (GIN) and lead to transformation to cancer. As p53-binding protein 1 (53BP1) localizes at the sites of DNA double strand breaks (DSBs) and rapidly forms nuclear foci (NF), the presence of 53BP1 NF can be considered to be an indicator of endogenous DSBs reflecting GIN. Our aim was to analyse the presence of DSBs by immunofluorescence for 53BP1 expression in a series of cervical lesions, to evaluate the significance of GIN during carcinogenesis. Methods and results A total of 80 archival cervical tissue samples, including 11 normal, 16 cervical intraepithelial neoplasia (CIN)1, 15 CIN2, 24 CIN3 and 14 squamous cell carcinoma samples, were analysed for 53BP1 NF, human papillomavirus (HPV) infection, and p16INK4a overexpression. The number of 53BP1 NF in cervical cells appeared to increase with progression during carcinogenesis. The distribution of 53BP1 NF was similar to that of the punctate HPV signals as determined by in-situ hybridization and also to p16INK4a overexpression in CIN, suggesting an association with viral infection and replication stress. Conclusions Immunofluorescence analysis of 53BP1 expression can be a useful tool with which to estimate the level of GIN. During cervical carcinogenesis, GIN may allow further accumulation of genomic alterations, causing progression to invasive cancer. PMID:22034884
Hariri, Susan; Bennett, Nancy M; Niccolai, Linda M; Schafer, Sean; Park, Ina U; Bloch, Karen C; Unger, Elizabeth R; Whitney, Erin; Julian, Pamela; Scahill, Mary W; Abdullah, Nasreen; Levine, Diane; Johnson, Michelle L; Steinau, Martin; Markowitz, Lauri E
Prevention of pre-invasive cervical lesions is an important benefit of HPV vaccines, but demonstrating impact on these lesions is impeded by changes in cervical cancer screening. Monitoring vaccine-types associated with lesions can help distinguish vaccine impact from screening effects. We examined trends in prevalence of HPV 16/18 types detected in cervical intraepithelial neoplasia 2, 3, and adenocarcinoma in situ (CIN2+) among women diagnosed with CIN2+ from 2008 to 2012 by vaccination status. We estimated vaccine effectiveness against HPV 16/18-attributable CIN2+ among women who received ≥1 dose by increasing time intervals between date of first vaccination and the screening test that led to detection of CIN2+ lesion. Data are from a population-based sentinel surveillance system to monitor HPV vaccine impact on type-specific CIN2+ among adult female residents of five catchment areas in California, Connecticut, New York, Oregon, and Tennessee. Vaccination and cervical cancer screening information was retrieved. Archived diagnostic specimens were obtained from reporting laboratories for HPV DNA typing. From 2008 to 2012, prevalence of HPV 16/18 in CIN2+ lesions statistically significantly decreased from 53.6% to 28.4% among women who received at least one dose (Ptrend<.001) but not among unvaccinated women (57.1% vs 52.5%; Ptrend=.08) or women with unknown vaccination status (55.0% vs 50.5%; Ptrend=.71). Estimated vaccine effectiveness for prevention of HPV 16/18-attributable CIN2+ was 21% (95% CI: 1-37), 49% (95% CI: 28-64), and 72% (95% CI: 45-86) in women who initiated vaccination 25-36 months, 37-48 months, and >48 months prior to the screening test that led to CIN2+ diagnosis. Population-based data from the United States indicate significant reductions in CIN2+ lesions attributable to types targeted by the vaccines and increasing HPV vaccine effectiveness with increasing interval between first vaccination and earliest detection of cervical disease
Aguilar-Lemarroy, Adriana; Vallejo-Ruiz, Verónica; Cortés-Gutiérrez, Elva I; Salgado-Bernabé, Manuel Eduardo; Ramos-González, Norma Patricia; Ortega-Cervantes, Laura; Arias-Flores, Rafael; Medina-Díaz, Irma M; Hernández-Garza, Fernando; Santos-López, Gerardo; Piña-Sánchez, Patricia
The prevalence and genotype distribution of human papillomavirus (HPV) provides the basis for designing HPV prevention programs. The prevalence rates of type-specific HPV and coinfections in samples of Mexican women were investigated in 822 women aged 18-87 years. HPV detection was performed using a Linear Array™ genotyping test. HPV infection was found in 12.4% of controls, 46.3% of those with cervical intraepithelial neoplasia 1, and 100% of those with cervical intraepithelial neoplasia 3 or cervical cancer. HPV 16 was the most prevalent type in all diagnosis groups. The HPV types most frequently found in cervical cancers were 16, 18, 45, 52, 58, and 39; HPV types 16, 62, 51, 84, 18, 53, and CP6108 were the most prevalent in control women. Considering HPV-positive samples only, coinfections occurred most often in controls (63%) and were less frequent in those with cervical cancer (26%). The most frequent viral types in coinfections with HPV 16 in control women were HPV 62, 51, and 84; in women with cervical cancers, HPV 18, 39, and 70 were most common. In conclusion, in addition to HPV types 16 and 18, types 45, 39, 58, 52, and 71 were found in cervical cancers in Mexican women (78%); among them, only 65% were attributable to HPV types 16 and 18. Therefore, it is necessary to consider these viral types in the design of new vaccines, and to determine whether certain HPV types coinfecting with HPV 16 in precursor lesions determine tumor progression or regression.
A Comparison of 3 Ways of Conventional Pap Smear, Liquid-Based Cytology and Colposcopy vs Cervical Biopsy for Early Diagnosis of Premalignant Lesions or Cervical Cancer in Women with Abnormal Conventional Pap Test.
Karimi-Zarchi, Mojgan; Peighmbari, Fateme; Karimi, Neda; Rohi, Mitra; Chiti, Zohre
The most cost effective method of prevention and detection of cervical cancer is the Pap smear. In abnormal Pap smear, colposcopy, endocervical curettage and biopsy will be done. Gold standard method in detecting cervical lesion is biopsy. Now in two ways conventional Pap smear and liquid base are routine diagnostic technique in Iran and given easily and cost-effectiveness of this method in the detection of cervical lesions to determine the sensitivity the objective of this study was compare three methods of Pap smear and colposcopy in detection of any lesion to gold standard biopsy in the positive ASC cases who referred to gynecologic Oncology Clinic of shahid Sadoughi University of Medical Science. This study is a descriptive analytic in 2009-2010 years on 150 cases of patients with Atypical Squamose Cell (ASC) results in previous pap smear ,conventional pap smear, liquid based pap smear, colposcopy and cervical biopsy had been done for all patient and finally data were analyzed with chi-square statistical test on spss ver 16 saftware. Average age of patients in this study was, 42 ± 9.9 year and reason for referring patients in 35.4% of cases was due to follow-up of abnormal results of previous Pap smear, in 30% bleeding, 12% Pain and 2.6% percent of cases was checking-up. In final results of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy any of the methods conventional and liquid based Pap smear and colposcopy were compared with cervical biopsy as a gold standard. The conventional Pap smear method had a sensitivity 51%, specificity 66.6%, PPV 96%, NPV was 8% and accuracy was 92%, about the liquid base Pap smear method, sensitivity was 55.3%, specificity was 77.7%, PPV was 97.5%, NPV was 10% and accuracy was 56/6%. About the colposcopy, sensitivity was70/9 % specificity 44/4%, PPV was 95.2%, NPV was 8/8% and accuracy was 69.3%. The relationship between sensitivity results of conventional Pap smear and
Xu, Huihui; Lin, Aifen; Shao, Xiujuan; Shi, Weiwu; Zhang, Yang; Yan, Weihua
Currently, clinical data for primary HPV screening alone are lacking in China. Here, we evaluate cervical cancer screening with primary HPV genotyping, as well as possible future screening strategy. Overall, high-risk HPV (hrHPV) prevalence was 18.2% among hospital-based population in Taizhou area. For cervical intraepithelial neoplasia 2 or worse (CIN2+), the sensitivity of primary hrHPV genotyping strategy and current cervical cancer screening strategy were 93.5%, and 71.1%, respectively; whereas the specificity was 17.5%, and 62.4%, respectively. Current cervical screening strategy had slightly higher positive predictive values (28.4%) for CIN2+ than hrHPV genotyping strategy (21.9%), whereas primary hrHPV genotyping strategy demonstrated higher negative predictive values (94.7%) than current cervical screening strategy (91.1%). Compared to HPV35/39/45/51/56/59/66/68 genotypes, the odds ratios (OR) for CIN2+ in HPV16/18/31/33/52/58 infection women were 3.2 (95% confidence interval [CI] 2.3-4.1). Primary hrHPV genotyping strategy provides a better predictive value than HPV16/18 genotyping alone in guiding the clinical management of the current cervical cancer screening. HPV testing without adjunctive cytology may be sufficiently sensitive for primary cervical cancer screening.
Xu, Huihui; Lin, Aifen; Shao, Xiujuan; Shi, Weiwu; Zhang, Yang; Yan, Weihua
Currently, clinical data for primary HPV screening alone are lacking in China. Here, we evaluate cervical cancer screening with primary HPV genotyping, as well as possible future screening strategy. Overall, high-risk HPV (hrHPV) prevalence was 18.2% among hospital-based population in Taizhou area. For cervical intraepithelial neoplasia 2 or worse (CIN2+), the sensitivity of primary hrHPV genotyping strategy and current cervical cancer screening strategy were 93.5%, and 71.1%, respectively; whereas the specificity was 17.5%, and 62.4%, respectively. Current cervical screening strategy had slightly higher positive predictive values (28.4%) for CIN2+ than hrHPV genotyping strategy (21.9%), whereas primary hrHPV genotyping strategy demonstrated higher negative predictive values (94.7%) than current cervical screening strategy (91.1%). Compared to HPV35/39/45/51/56/59/66/68 genotypes, the odds ratios (OR) for CIN2+ in HPV16/18/31/33/52/58 infection women were 3.2 (95% confidence interval [CI] 2.3-4.1). Primary hrHPV genotyping strategy provides a better predictive value than HPV16/18 genotyping alone in guiding the clinical management of the current cervical cancer screening. HPV testing without adjunctive cytology may be sufficiently sensitive for primary cervical cancer screening. PMID:27626178
Gurgel, Ana Pavla Almeida Diniz; Chagas, Bárbara Simas; do Amaral, Carolina Maria Medeiros; Albuquerque, Eugênia Maria Bezerra; Serra, Ivi Gonçalves Soares Santos; Silva Neto, Jacinto da Costa; Muniz, Maria Tereza Cartaxo; de Freitas, Antonio Carlos
The aim of this study was to examine the prevalence and genetic variability of the capsid L1 gene of rare HPV genotypes that were found in the cervical lesions of women from North-East Brazil. A total number of 263 patients were included in this study. HPV detection was performed using PCR followed by direct sequencing of MY09/11, as well as type-specific PCR to detect the Alpha-9 species. Epitope prediction was performed to determine whether or not the genetic variants are inserted in B-cell and T-cell epitopes. The prevalence of rare HPV types in cervical lesions was found to be 9.47%. The rare HPV genotypes that were detected were HPV-53, 54, 56, 61, 62, 66, 70, and 81. The genetic variability in the L1 gene of rare HPV types involved thirty nucleotide changes, eight of which were detected for the first time in this study. Moreover, some of these variants are embedded in B-cell or T-cell epitope regions. The results of this research suggest that rare HPV types might be involved in cervical lesions and some of these variants can be found in B-cell and T-cell epitopes. Data on the prevalence and variability of rare HPV types will assist in clarifying the role of these viruses in carcinogenesis. PMID:23865057
Gurgel, Ana Pavla Almeida Diniz; Chagas, Bárbara Simas; do Amaral, Carolina Maria Medeiros; Albuquerque, Eugênia Maria Bezerra; Serra, Ivi Gonçalves Soares Santos; Silva Neto, Jacinto da Costa; Muniz, Maria Tereza Cartaxo; de Freitas, Antonio Carlos
The aim of this study was to examine the prevalence and genetic variability of the capsid L1 gene of rare HPV genotypes that were found in the cervical lesions of women from North-East Brazil. A total number of 263 patients were included in this study. HPV detection was performed using PCR followed by direct sequencing of MY09/11, as well as type-specific PCR to detect the Alpha-9 species. Epitope prediction was performed to determine whether or not the genetic variants are inserted in B-cell and T-cell epitopes. The prevalence of rare HPV types in cervical lesions was found to be 9.47%. The rare HPV genotypes that were detected were HPV-53, 54, 56, 61, 62, 66, 70, and 81. The genetic variability in the L1 gene of rare HPV types involved thirty nucleotide changes, eight of which were detected for the first time in this study. Moreover, some of these variants are embedded in B-cell or T-cell epitope regions. The results of this research suggest that rare HPV types might be involved in cervical lesions and some of these variants can be found in B-cell and T-cell epitopes. Data on the prevalence and variability of rare HPV types will assist in clarifying the role of these viruses in carcinogenesis.
Bernstein, A; Vitner, S; Webber, J M
A new autocollection tampon device for obtaining material for cervical cytologic testing was compared with cervical scraping and endocervical aspiration in order to evaluate the cytodiagnostic results. In 1428 cases there proved to be a 94% correlation between these methods. In addition, both smears were compared in a group of patients known to have neoplastic disease of the cervix. In evaluating cervical cancer both techniques detected 100% of the cases. However, the smears, both regular and tampon, were able to diagnose only 96.5% and 89% of grade 3 lesions and 86% and 81% of grades 1 and 2 lesions, respectively. False negative results occurred in 8.2% of the regular smears and 15% of the tampon smear group. These preliminary data, if confirmed by more broad and in-depth studies, suggest the new autocollection tampon may be a useful tool for mass cervical screening.
Fabrizii, Markus; Moinfar, Farid; Jelinek, Herbert F; Karperien, Audrey; Ahammer, Helmut
Cervical intraepithelial neoplasias (CIN) represent precursor lesions of cervical cancer. These neoplastic lesions are traditionally subdivided into three categories CIN 1, CIN 2, and CIN 3, using microscopical criteria. The relation between grades of cervical intraepithelial neoplasia (CIN) and its fractal dimension was investigated to establish a basis for an objective diagnosis using the method proposed. Classical evaluation of the tissue samples was performed by an experienced gynecologic pathologist. Tissue samples were scanned and saved as digital images using Aperio scanner and software. After image segmentation the box counting method as well as multifractal methods were applied to determine the relation between fractal dimension and grades of CIN. A total of 46 images were used to compare the pathologist's neoplasia grades with the predicted groups obtained by fractal methods. Significant or highly significant differences between all grades of CIN could be found. The confusion matrix, comparing between pathologist's grading and predicted group by fractal methods showed a match of 87.1%. Multifractal spectra were able to differentiate between normal epithelium and low grade as well as high grade neoplasia. Fractal dimension can be considered to be an objective parameter to grade cervical intraepithelial neoplasia.
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.
Sherman, Mark E; Wang, Sophia S; Tarone, Robert; Rich, Laurie; Schiffman, Mark
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.
Tagle, Diana K Jiménez; Sotelo, Daniel Hernández; Illades-Aguiar, Berenice; Leyva-Vazquez, Marco A; Alfaro, Eugenia Flores; Coronel, Yaneth Castro; Hernández, Oscar del Moral; Romero, Luz del Carmen Alarcón
The aim of this study was to determine the correlation between expression of HPV16 E6, p53 and p21 proteins and the physical state of HPV16 in cervical cytologies without squamous intraepithelial lesions (Non-SIL) and with low grade squamous intraepithelial lesions (LSIL), both with HPV16 infection. 101 liquid-based cytological samples were analyzed. 50 samples were without squamous intraepithelial lesions (Non-IL) and 51 samples of low grade squamous intraepithelial lesions (LSIL), both with HPV16 infection. HPV16 infection was determined by PCR-RFLP, and the physical state of HPV16 by in situ hybridization with tyramide-amplification. The expression of E6, p53 and p21 proteins was evaluated by immunocytochemistry. The expression of HPV16 E6 protein was significantly higher in LSIL that in Non-SIL samples (p=0.006). We found a significant correlation between E6 expression and the physical state of HPV16 in Non-SIL (p=0.049). Our results suggest that high expression of E6 in LSIL is an early event of cervical carcinogenesis and perhaps can be used as an early marker. PMID:24482706
Romeed, Shihab A; Malik, Raheel; Dunne, Stephen M
Non-carious cervical tooth lesions for many decades were attributed to the effects of abrasion and erosion mainly through toothbrush trauma, abrasive toothpaste, and erosive acids. However, though the above may be involved, more recently a biomechanical theory for the formation of these lesions has arisen, and the term abfraction was coined. The aim of this study was to investigate the biomechanics of abfraction lesions in upper canine teeth under axial and lateral loading conditions using a three-dimensional finite element analysis. An extracted human upper canine tooth was scanned by μCT machine (Skyscan, Belgium). These μCT scans were segmented, reconstructed, and meshed using ScanIP (Simpleware, Exeter, UK) to create a three-dimensional finite element model. A 100 N load was applied axially at the incisal edge and laterally at 45° midpalatally to the long axis of the canine tooth. Separately, 200 N axial and non-axial loads were applied simultaneously to the tooth. It was found that stresses were concentrated at the CEJ in all scenarios. Lateral loading produced maximum stresses greater than axial loading, and pulp tissues, however, experienced minimum levels of stresses. This study has contributed towards the understanding of the aetiology of non-carious cervical lesions which is a key in their clinical management.
Tagle, Diana K Jiménez; Sotelo, Daniel Hernández; Illades-Aguiar, Berenice; Leyva-Vazquez, Marco A; Alfaro, Eugenia Flores; Coronel, Yaneth Castro; Hernández, Oscar Del Moral; Romero, Luz Del Carmen Alarcón
The aim of this study was to determine the correlation between expression of HPV16 E6, p53 and p21 proteins and the physical state of HPV16 in cervical cytologies without squamous intraepithelial lesions (Non-SIL) and with low grade squamous intraepithelial lesions (LSIL), both with HPV16 infection. 101 liquid-based cytological samples were analyzed. 50 samples were without squamous intraepithelial lesions (Non-IL) and 51 samples of low grade squamous intraepithelial lesions (LSIL), both with HPV16 infection. HPV16 infection was determined by PCR-RFLP, and the physical state of HPV16 by in situ hybridization with tyramide-amplification. The expression of E6, p53 and p21 proteins was evaluated by immunocytochemistry. The expression of HPV16 E6 protein was significantly higher in LSIL that in Non-SIL samples (p=0.006). We found a significant correlation between E6 expression and the physical state of HPV16 in Non-SIL (p=0.049). Our results suggest that high expression of E6 in LSIL is an early event of cervical carcinogenesis and perhaps can be used as an early marker.
Kaplan, M H
Human retroviral infections result in significant neoplastic disease. Human T cell lymphotropic virus I (HTLV-I), the first human retrovirus to be discovered, is associated with the development of acute T cell leukemia with characteristic hypercalcemia and skin lesions after many years of chronic infection of CD4+ cells. HTLV-I also produces myelopathy. A minor T cell immunodeficiency occurs in HTLV-I acute T cell leukemia with associated strongyloidiasis and Pneumocystis carinii pneumonia. Human T cell lymphotropic virus II (HTLV-II) is found to be endemic in Amerindians and intravenous drug users (IVDUs) and has been linked to some cases of hairy-cell leukemia. HTLV-II infects the CD8+ population, with significant cell-associated viremia. Clinical neurological disease is rare, with one patient with myelopathy having been described. Immunodeficiency does not seem to occur. Human immunodeficiency virus 1 (HIV-1) produces aggressive large cell and Burkitt's lymphoma in as many as 10% of HIV-1-infected patients. More than 20% of homosexual men infected with HIV-1 develop Kaposi's sarcoma (KS). The pathogenesis of KS is better understood through studying KS-like cell lines that induce angiogenic factors. In some patients HIV-1 and HTLV-I or HTLV-II infections occur concomitantly. HIV-1 accelerates the tumorigenesis of HTLV-I and produces unusual skin diseases when combined with HTLV-II. Immunodeficiency occurs in all HIV-1-infected patients.
Up-regulation of lipocalin 2 is associated with high-risk human papillomavirus and grade of cervical lesion at baseline but does not predict outcomes of infections or incident cervical intraepithelial neoplasia.
Syrjänen, Stina; Naud, Paulo; Sarian, Luis; Derchain, Sophie; Roteli-Martins, Cecilia; Tatti, Silvio; Branca, Margerita; Erzen, Mojca; Hammes, Luciano S; Costa, Silvano; Longatto-Filho, Adhemar; Syrjänen, Kari
Our objective was to assess whether neutrophil gelatinase-associated lipocalin (NGAL)/lipocalin 2 (LCN2) expression in cervical human papillomavirus (HPV) lesions has implications on the outcome of HPV infections or disease progression. Cervical biopsy specimens from 225 women in the Latin American Screening study were analyzed for NGAL/LCN2 expression using immunohistochemical analysis, to assess associations with cervical intraepithelial neoplasia (CIN) grade, high-risk HPV, and in predicting outcomes of high-risk (HR)-HPV infections. Expression of NGAL/LCN2 increased with lesion grade (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.53-9.71; P = .001). Up-regulation was also related to HR-HPV detection (OR, 2.21; 95% CI, 1.15-4.24; P = .016) and showed a linear relationship to HR-HPV load (P = .002). NGAL/LCN2 expression was of no value in predicting the outcomes of HR-HPV infections or the surrogate end points (incident CIN 1+ and CIN 2+) of progressive disease. Because the SV40 large T antigen is a powerful up-regulator of this lipocalin, up-regulation of NGAL/LCN2 in CIN is probably induced by HR-HPV E6 oncoprotein, most likely by eliminating its normal transcription repression exerted by wild-type p53.
Yang, J; Cai, D; Wang, F; He, D; Ma, L; Jin, Y; Que, K
This study investigated the prevalence, risk factors and association of occlusive wear with non-carious cervical lesions (NCCLs) in the general Chinese population. A total of 1320 subjects were recruited, and multistage and random sampling methods of survey spots were performed. All age groups comprised similar numbers of participants and equal numbers of males and females. Each subject completed a structured interview, and all teeth of each subject were examined by a practitioner to determine NCCLs and occlusive wear. Binary logistic regression was conducted by analysing the association of risk factors with the occurrence of NCCLs. Bivariate correlation analysis was performed by determining the association of NCCLs dimension or depth with the range of occlusive wear facets. Clinical assessment showed that the overall prevalence of subjects diagnosed with NCCLs was 63%. The proportion of subjects or teeth with NCCLs significantly increased with age. Pre-molars were the most commonly affected teeth. Single variables and interactive effects of variables associated with the occurrence of NCCLs include the following: age group, intensity of toothbrushing, frequency of fresh fruit consumption and interactive effect between intensity of toothbrushing and frequency of fresh fruit consumption. A weak positive correlation of the grading index was found between NCCLs dimension, size or depth and range of occlusive wear facets. This study reported the higher prevalence of NCCLs in the general Chinese population. Implementation of a combined strategy to reduce risk factors of NCCLs could be more effective than individual techniques; meanwhile, the occurrence of NCCL could be related to the wear degree of occlusive defects in the population studied. © 2016 John Wiley & Sons Ltd.
Bomfim, Rafael Aiello; Crosato, Edgard; Mazzilli, Luiz Eugênio Nigro; Frias, Antonio Carlos
This study evaluates the prevalence and risk factors of non-carious cervical lesions (NCCLs) in a Brazilian population of workers exposed and non-exposed to acid mists and chemical products. One hundred workers (46 exposed and 54 non-exposed) were evaluated in a Centro de Referência em Saúde do Trabalhador - CEREST (Worker's Health Reference Center). The workers responded to questionnaires regarding their personal information and about alcohol consumption and tobacco use. A clinical examination was conducted to evaluate the presence of NCCLs, according to WHO parameters. Statistical analyses were performed by unconditional logistic regression and multiple linear regression, with the critical level of p < 0.05. NCCLs were significantly associated with age groups (18-34, 35-44, 45-68 years). The unconditional logistic regression showed that the presence of NCCLs was better explained by age group (OR = 4.04; CI 95% 1.77-9.22) and occupational exposure to acid mists and chemical products (OR = 3.84; CI 95% 1.10-13.49), whereas the linear multiple regression revealed that NCCLs were better explained by years of smoking (p = 0.01) and age group (p = 0.04). The prevalence of NCCLs in the study population was particularly high (76.84%), and the risk factors for NCCLs were age, exposure to acid mists and smoking habit. Controlling risk factors through preventive and educative measures, allied to the use of personal protective equipment to prevent the occupational exposure to acid mists, may contribute to minimizing the prevalence of NCCLs.
Kostopoulou, E; Samara, M; Kollia, P; Zacharouli, K; Mademtzis, I; Daponte, A; Messinis, I E; Koukoulis, G
p16 is one extensively studied marker in gynecological pathology. However, its routine application in the diagnosis of squamous intraepithelial lesions of the uterine cervix may present difficulties for the general pathologist. The aim of the present study was to examine a series of 100 cervical biopsies/LEEP specimens, with detailed HPV-typing, for patterns of p16 immunoreactivity and possible correlations with morphology and HPV types. Four patterns of immunopositivity were recognized, according to the distribution of positively stained cells, and these correlated to lesion grade. A review of the pertinent literature concerning p16 immunoreactivity in squamous intraepithelial lesions and nonneoplastic epithelia of the uterine cervix is included in an effort to summarize the existing data and the remaining questions at both the practical and theoretical level.
Benevolo, Maria; Mottolese, Marcella; Marandino, Ferdinando; Vocaturo, Giuseppe; Sindico, Roberto; Piperno, Giulia; Mariani, Luciano; Sperduti, Isabella; Canalini, Paola; Donnorso, Raffaele P; Vocaturo, Amina
The p16(INK4a) is a cyclin-dependent kinase inhibitor that decelerates the cell cycle by inactivating the cyclin-dependent kinases involved in the phosphorylation of the retinoblastoma protein (RB). Expression of E6 and E7 oncogenes of high-risk (HR) human papillomavirus (HPV), affecting the RB-p16 pathway, leads to p16 upregulation. Although it is widely reported that p16 is overexpressed in a high percentage of preneoplastic lesions and in almost all carcinomas of the uterine cervix, protein upregulation and its correlation with HPV infection in low-grade lesions is still being debated. In this study, we investigated in parallel, p16 expression and HPV infection in 100 cervical biopsies (17 normal tissues, 54 CIN1, 10 CIN2, 11 CIN3, eight invasive squamous cancers). Results obtained demonstrated that none of the 17 normal cervical tissues, evaluated by immunohistochemistry, presented p16 positivity whereas, starting from CIN1 (31%) to CIN2 (90%), CIN3 (100%) and carcinomas (100%), a constant and significant increase of protein overexpression (P<0.0001) was observed. In addition, p16 overexpression consistently showed elevated sensitivity (84%) and specificity (98%) in detecting HR-HPV infection with a high positive predictive value (97%) and negative predictive value (86%). Of interest, 93% of the p16-positive CIN1 were also HR-HPV infected. Our findings confirmed that p16 overexpression is associated to high-grade precancerous lesions and cervical carcinomas, and further demonstrated that immunohistochemical evaluation of p16 may be a useful biomarker in identifying HR-HPV-infected low-grade lesions.
Chen, Qing; Du, Hui; Pretorius, Robert G; Wang, Chun; Yang, Bin; Wang, Guixiang; Tang, Jinlong; Belinson, Jerome L; Wu, Ruifang
The aim of the study was to determine whether p16 positive/cervical intraepithelial neoplasia (CIN) 2, 3, and cancer (p16 + CIN 2/3+) detected by colposcopy-directed or random biopsy differ by age, referral cytology, human papillomavirus (HPV) 16, and lesion size. Data from the Shenzhen Cervical Cancer Screening Trial II where, at colposcopy, women who had directed and random cervical biopsies were reviewed to find women with CIN 2, 3, or cancer; 227 such women identified had their paraffin-embedded tissue blocks recut, reviewed, and then immune stained for p16. Data were analyzed by χ, Fisher exact test, and linear regression. After histopathologic review and p16 staining of CIN 2, 175 women were diagnosed with p16 + CIN 2/3+. When compared with those diagnosed by colposcopy-directed biopsy (n = 138), those diagnosed by random biopsy (n = 37) were more likely to have Cytology-Lo (cytology of negative, atypical squamous cells of undetermined significance, or low-grade squamous intraepithelial lesion; p = .07), less likely to have HPV 16 (p = .041), more likely to be 51 years or older (p = .022), and more likely to have 1 quadrant lesions (p < .001). Logistic regression analysis showed p16 + CIN 2/3+ diagnosed by random biopsy was predicted by 1 quadrant lesions (p < .0001) and age of 51 years or older (p = .03) but not by Cytology-Lo (p = .71) nor HPV 16 (p = .26). Women with p16 + CIN 2/3+ diagnosed by random biopsy are older and less likely to have HPV 16; hence, CIN diagnosed by random biopsy may not be as virulent as CIN diagnosed by colposcopy-directed biopsy. Regardless, we advise that CIN diagnosed by random biopsy be viewed like CIN diagnosed by colposcopy-directed biopsy.
Frega, A; Manzara, F; Schimberni, M; Guarino, A; Catalano, A; Bianchi, P; Marziani, R; Cozza, G; Milazzo, G N; French, D; Caserta, D
The increased use of the intrauterine contraception (IUC) in female population and its probable relationship with cervical squamous intraepithelial lesions and cervical cancer make necessary clarify the possible interaction between the device and the pre-neoplastic lesions. Seven hundred and eighty-nine patients users of IUC and 1491 patients ever users of IUC were followed every 6 months for 3 years. Each clinical control included Papanicolau test, colposcopy, HPV-DNA test and HPV-mRNA test. Also, in patients IUC users we analyzed the type of device, years of use and average age. Cytological sampling, histological examination, HPV-DNA test and HPV-mRNA test showed that there are not significantly differences between patients with or without IUC. None difference arose regarding persistence and progression between patients IUC users and IUC no users, for this reason, intrauterine contraception does not seem to be a co-causal factor in the possible development of cervical cancer.
Zonta, Marco Antonio; Monteiro, Jussimara; Santos Jr, Gildo; Pignatari, Antonio Carlos Campos
Carcinoma of the head and neck is the 6th cause of death by cancer in the world. In recent decades the human papillomavirus (HPV) has been implicated in the etiology of this disease. To characterize the types of HPV detected in the oral mucosa in women with cytological abnormalities suggesting intraepithelial squamous lesions in the uterine cervix. Four-hundred-nine cervical-vaginal and oral pap-smears of women interned in a Female Prison in São Paulo were examined. The relationship between cervical and oral lesion was analyzed by PCR/RFLP and DNA sequencing. Of 27 (6.67%) specimens showing cervical cytological abnormalities suggesting LSIL and HSIL, 22 (81.48%) had oncogenic high-risk HPV infection, of which HPV 59 was the most prevalent. Three (11.1%) samples showed cytological changes suggesting mild dysplasia in the oral cavity. Our study suggests an association between carcinoma of the oral cavity and HPV infection, regardless of the virus type.
Munmany, M; Marimon, L; Cardona, M; Nonell, R; Juiz, M; Astudillo, R; Ordi, J; Torné, A; Del Pino, M
To evaluate whether colposcopic measurement of the lesion size at diagnosis and/or human papillomavirus (HPV) genotyping can predict the absence of dysplasia in a large loop excision of the transformation zone (LLETZ) specimen in women treated for squamous intraepithelial lesions/cervical intraepithelial neoplasia (SIL/CIN). Prospective observational study. Tertiary university hospital. A cohort of 116 women who underwent LLETZ because of biopsy-proven low-grade SIL/CIN that had persisted for 2 years, or because of a high-grade SIL/CIN diagnosed in the referral visit and squamocolumnar junction completely visible (types 1 or 2, according to the International Federation of Cervical Pathology and Colposcopy, IFCPC). After LLETZ the women were classified by histology into the study group (absence of SIL/CIN in the surgical specimen, 28/116, 24.1%) and the control group (SIL/CIN in the LLETZ specimen, 88/116, 75.9%). The size of the lesion determined in the diagnostic colposcopy and the HPV genotype were evaluated in all women. The lesion size was significantly smaller in the study group (25.7 ± 37.8 versus 84.5 ± 81.7 mm(2) ; P < 0.001). A lesion size of ≤12 mm(2) and HPV types other than 16 or 18 were associated with an absence of SIL/CIN in the LLETZ specimen (P < 0.001 and P = 0.016, respectively). On multivariate analysis only a lesion size of ≤12 mm(2) predicted the absence of SIL/CIN (odds ratio, OR 10.6; 95% confidence interval, 95% CI 3.6-30.6; P < 0.001). A lesion size of ≤12 mm(2) had a specificity of 90.9% (95% CI 83.0-95.3%) and a negative predictive value of 86.0% (95% CI 77.5-91.6%) to predict the absence of SIL/CIN in the surgical specimen. Small lesion size in diagnostic colposcopy could predict the absence of SIL/CIN in the LLETZ specimen. Colposcopy measurement of lesion size prior to LLETZ may avoid unnecessary treatment. Small lesion size in colposcopic evaluation might predict the absence of SIL/CIN in an LLETZ specimen. © 2016 Royal
Dray, Michael; Russell, Peter; Dalrymple, Chris; Wallman, Neil; Angus, George; Leong, Adelyn; Carter, Jonathan; Cheerala, Bharathi
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
Kuo, K-T; Chang, H-C; Hsiao, C-H; Lin, M-C
It is generally assumed that similar pathways are involved in human papillomavirus (HPV) induced pathogenesis of cervical squamous intraepithelial lesions (SILs) and cancers and a subset of conjunctival intraepithelial neoplasm (CIN)-that the malignancies or pre-cancerous lesions arise through HPV oncoproteins E6 and E7, which disrupt the pathways of p53 and the product of the retinoblastoma (Rb) gene and, in turn, increase the protein product of gene p16INK4 through the mechanism of positive feedback. Several cell cycle molecules are detected to test this hypothesis. Nine cases of CIN and eight non-CIN cases were analysed for the expression of Ki-67, pRb, p53, and p16INK4 via immunohistochemistry. Nine cases of cervical high grade squamous intraepithelial lesion (HSIL), and 10 cases of cervical low grade squamous intraepithelial lesion (LSIL) were included for stain control of p16INK4a, and comparison of p16INK4a expression to CIN cases. A nested polymerase chain reaction and a genechip HPV typing were used to detect HPV infection and types in the CIN and non-CIN samples HPV positivity was demonstrated in all of the CIN lesions but in none of the non-CIN lesions. The Ki-67 proliferative index (Ki-67 PI) was statistically higher in the CIN group than the non-CIN group; however, there were no differences of expression of pRb and p53 between the two groups and no expression of p16INK4 in all cases. All nine cases of HSIL, and seven out of 10 cases of LSIL used for stain control were immunoreactive for p16INK4a. There were statistically significant differences in overexpression of p16INK4a between the CINs and SILs The Ki-67 proliferative index may be a sensitive marker for CIN lesions and these results, with significant differences in overexpression of p16INK4a between CINs and SILs, may provide new evidence that HPV related mucosal dysplasia in different anatomical locations may lead to dissimilar molecular pathways.
Carns, Bhavini; Fadare, Oluwole
Studies evaluating the routine Papanicolaou (Pap) test have traditionally used as the reference gold standard, the diagnoses on the follow-up histologic samples. Since the latter are typically obtained days to weeks after the Pap test, the accuracy of the resultant comparison may be affected by interim factors, such as regression of human papillomavirus, new lesion acquisitions or colposcopy-associated variability. A subset of our clinicians have routinely obtained cervical cytology samples immediately prior to their colposcopic procedures, which presented a unique opportunity to re-evaluate the test performance of liquid-based cervical cytology in detecting the most clinically significant lesions (i.e. cervical intraepithelial neoplasia 2 or worse: CIN2+), using as gold standard, diagnoses on cervical biopsies that were essentially obtained simultaneously. For each patient, cytohistologic non-correlation between the Pap test and biopsy was considered to be present when either modality displayed a high-grade squamous intraepithelial lesion (HGSIL)/CIN2+ while the other displayed a less severe lesion. Therefore, HGSIL/CIN2+ was present in both the Pap test and biopsy in true positives, and absent in both modalities in true negatives. In false positives, the Pap test showed HGSIL while the biopsy showed less than a CIN2+. In false negatives, Pap tests displaying less than a HGSIL were associated with biopsies displaying CIN2+. Combinations associated with "atypical" interpretations were excluded. A cytohistologic non-correlation was present in 17 (4.8%) of the 356 combinations reviewed. The non-correlation was attributed, by virtue of having the less severe interpretation, to the Pap test in all 17 cases. There were 17, 322, 0, and 17 true positives, true negatives, false positives and false negatives respectively. The sensitivity, specificity, positive predictive value and negative predictive value of the Pap test, at a diagnostic threshold of HGSIL, in identifying
Swangvaree, Sukumarn Sanersak; Kongkaew, Phon; Ngamkham, Jarunya
Cervical cancer is the most important female gynecological cancer, the second leading cause of cancer mortality in women worldwide and the second most common cancer in Thai women. The major cause of cervical cancer is persistent infection of human papillomavirus (HPV), leading to abnormal epithelial lesions, with progression to precancerous and invasive cancer. This study was conducted to investigate the frequency and type distribution of HPV in Thai women who had abnormal cytology. HPV detection from FFPE confirmed abnormal of high grade cervical intraepithelial lesions were for SPF-10-Innogenic Line Probe Assay. HPV-positivity was detected in 320/355 cases (90.14%) and HPV-negativity in 35/355 (9.86%). HPV-positive was found 147/320 cases (41.4%) of single infection, whereas 173/320 cases (48.7%) showed the multiple HPV infection. The most common seven types were HPV-16, -52, -18, -11, -51, -31 and -33, in that order. HPV 16 and 18, the important oncogenic HPV type, were observed in 64.8% of HSIL cases. Interestingly, a high proportion of multiple infections was found in this study and more than ten types could be detected in one case. Therefore, HPV infection screening program in women is essential, particularly in Thailand. Effective primary and secondary prevention campaigns that reinforce HPV screening for HPV detection and typing may be decrease the incidence and mortality of cervical cancer in the future and may lead to significantly improve the quality of life in Thai women.
Barut, Mert Ulaş; Kale, Ahmet; Kuyumcuoğlu, Umur; Bozkurt, Murat; Ağaçayak, Elif; Özekinci, Server; Gul, Talip
Background This study aimed to examine the positive and negative predictive value in the diagnosis of premalignant and malignant lesions of cervical colposcopy, the sensitivity and specificity of smear, and to evaluate the correlation with histopathology of abnormal cytology and colposcopy. Material/Methods The criteria for inclusion of patients with unhealthy cervix in the study were: Erosion, Chronic cervicitis, and Healed lacerations, Hypertrophied cervix, bleeding on touch, suspicious growth/ulcer/polyp on the cervix, and abnormal discharges from the cervix. Women with frank carcinoma cervix, pregnant females, patients with bleeding per vaginum at the time of examination, and those who had used vaginal medications, vaginal contraceptives or douches in the last 48 h of examination were excluded from the study. Demographic analysis was performed for 450 patients who were admitted to the clinic. Sensitivity, specificity, positive predictive value and negative predictive values of patients to identify cervical pathologies of smear and colposcopy were histopathologically calculated. The statistical software package SPSS 15.0 (SPSS Inc., Chicago, IL, USA) and Spearman‘s and Chi-Square tests were used for statistical analysis. Results Sensitivity, specificity, PPD and NDP of smear were 0.57%, 0.76%, 0.26%, 0.92% respectively. Sensitivity, specificity, PPD and NDP of colposcopy were 0.92%, 0.67%, 0.52%, 0.96% respectively. A statistically significant correlation was found between abnormal cytology and histopathology, and abnormal colposcopy finding and histopathology. Conclusions Women with clinical diagnosis of unhealthy cervix should be evaluated by cytology to detect any premalignant or malignant lesions. It was concluded that Pap smear, colposcopy and histopathology should be collectively evaluated to evaluate cervical findings in low socio-economic regions. PMID:26655816
Barut, Mert Ulaş; Kale, Ahmet; Kuyumcuoğlu, Umur; Bozkurt, Murat; Ağaçayak, Elif; Özekinci, Server; Gül, Talip
BACKGROUND This study aimed to examine the positive and negative predictive value in the diagnosis of premalignant and malignant lesions of cervical colposcopy, the sensitivity and specificity of smear, and to evaluate the correlation with histopathology of abnormal cytology and colposcopy. MATERIAL AND METHODS The criteria for inclusion of patients with unhealthy cervix in the study were: Erosion, Chronic cervicitis, and Healed lacerations, Hypertrophied cervix, bleeding on touch, suspicious growth/ulcer/polyp on the cervix, and abnormal discharges from the cervix. Women with frank carcinoma cervix, pregnant females, patients with bleeding per vaginum at the time of examination, and those who had used vaginal medications, vaginal contraceptives or douches in the last 48 h of examination were excluded from the study. Demographic analysis was performed for 450 patients who were admitted to the clinic. Sensitivity, specificity, positive predictive value and negative predictive values of patients to identify cervical pathologies of smear and colposcopy were histopathologically calculated. The statistical software package SPSS 15.0 (SPSS Inc., Chicago, IL, USA) and Spearman's and Chi-Square tests were used for statistical analysis. RESULTS Sensitivity, specificity, PPD and NDP of smear were 0.57%, 0.76%, 0.26%, 0.92% respectively. Sensitivity, specificity, PPD and NDP of colposcopy were 0.92%, 0.67%, 0.52%, 0.96% respectively. A statistically significant correlation was found between abnormal cytology and histopathology, and abnormal colposcopy finding and histopathology. CONCLUSIONS Women with clinical diagnosis of unhealthy cervix should be evaluated by cytology to detect any premalignant or malignant lesions. It was concluded that Pap smear, colposcopy and histopathology should be collectively evaluated to evaluate cervical findings in low socio-economic regions.
Gimenes, Fabrícia; Souza, Raquel Pantarotto; de Abreu, André Luelsdorf Pimenta; Pereira, Monalisa Wolski; Consolaro, Marcia Edilaine Lopes; da Silva, Vânia Ramos Sela
The persistence of high-risk oncogenic human papillomavirus (HR-HPV) infection and its integration into the host genome are key steps in the induction of malignant alterations. c-MYC chromosome region is a frequent localization for HPV insertion that has been observed in chromosome band 8q24 by fluorescence in situ hybridization (FISH). We report the HPV viral integration and amplification patterns of the c-MYC gene in cytological smears with FISH as a potential biomarker for the progression of squamous intraepithelial lesions (SIL). HPV detection and genotyping by polymerase chain reaction (PCR) and FISH analysis by "Vysis Cervical FISH Probe" kit (ABBOTT Molecular Inc.) were performed in 37 cervical samples including 8 NILM, 7 ASC-US, 7 LSIL, 3 ASC-H, 7 HSIL and 5 SCC. The results show concordance between FISH and PCR techniques for HPV detection. The majority of the samples contained HR-HPV, the majority being -16 and -18 genotypes. HPV integration as determined by FISH was most frequent in high-risk lesions. The c-MYC gene amplification was found only in HPV-positive samples and was detected primarily in high-risk lesions and in cells with an integrated form of HPV. HPV integration and c-MYC gene amplification detected by FISH could be an important biomarker for use in clinical practice to determine SIL with a risk of progression.
Franz, P; Swoboda, H; Quint, C
Non-neoplastic disorders of the salivary glands are divided into the following groups: malformations, salivary gland cysts, sialadenosis, sialolithiasis, sialadenitis, HIV-associated salivary gland disease, oncocytosis and necrotizing sialometaplasia (salivary gland infarction). Clinically, an etiological classification of sialadenitis is mandatory. Sialadenosis is distinguishable from sialadenitis by its clinical, radiological, and morphological characteristics. Non-neoplastic cysts make up about 6% of diseases of the salivary glands. Mucoceles represent the majority of these cysts (75%). HIV-associated salivary gland disease includes lymphoepithelial lesions and cysts involving the salivary gland tissue and/or intraglandular lymph nodes, and Sjögren's syndrome-like conditions, diffuse interstitial lymphocytosis syndrome, and other reported lesions of the major salivary glands. The diagnosis, differential diagnosis, symptoms and treatment of different non-neoplastic salivary gland disorders are discussed.
Parikh, Neil; Perl, Daniel; Lee, Michelle H.; Shah, Brijen; Young, Yuki; Chang, Shannon S.; Shukla, Richa; Polydorides, Alexandros D.; Moshier, Erin; Godbold, James; Zhou, Elinor; Mitchaml, Josephine; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila
High-resolution microendoscopy (HRME) is a low-cost, “optical biopsy” technology that allows for subcellular imaging. The purpose of this study was to determine the in vivo diagnostic accuracy of the HRME for the differentiation of neoplastic from non-neoplastic colorectal polyps and compare it to that of high-definition white-light endoscopy (WLE) with histopathology as the gold standard. Three endoscopists prospectively detected a total of 171 polyps from 94 patients that were then imaged by HRME and classified in real-time as neoplastic (adenomatous, cancer) or non-neoplastic (normal, hyperplastic, inflammatory). HRME had a significantly higher accuracy (94%), specificity (95%), and positive predictive value (87%) for the determination of neoplastic colorectal polyps compared to WLE (65%, 39%, and 55%, respectively). When looking at small colorectal polyps (less than 10 mm), HRME continued to significantly outperform WLE in terms of accuracy (95% vs. 64%), specificity (98% vs. 40%) and positive predictive value (92% vs. 55%). These trends continued when evaluating diminutive polyps (less than 5 mm) as HRME's accuracy (95%), specificity (98%), and positive predictive value (93%) were all significantly greater than their WLE counterparts (62%, 41%, and 53%, respectively). In conclusion, this in vivo study demonstrates that HRME can be a very effective modality in the differentiation of neoplastic and non-neoplastic colorectal polyps. A combination of standard white-light colonoscopy for polyp detection and HRME for polyp classification has the potential to truly allow the endoscopist to selectively determine which lesions can be left in situ, which lesions can simply be discarded, and which lesions need formal histopathologic analysis. PMID:24296752
Leite, Paulo Macêdo de Oliveira; Tafuri, Luciene; Costa, Maria Zélia de Oliveira; Lima, Maria Inês de Miranda; Simões, Renata Toscano
Objective To evaluate the expressions of biomarkers p16 and Ki-67 in low-grade (LG) or high-grade (HG) lesions, and to relate them to risk factors and the recurrence of these lesions. Methods A retrospective case-control study of 86 patients with LG and HG lesions who underwent a loop electrosurgical excision procedure (LEEP) between 1999 and 2004. The control group was composed of 69 women with no recurrence, and the study group, of 17 patients with recurrence. All patients were followed-up over a two-year period after surgery, and screened every six months, including cytology and colposcopy. Biopsy samples collected from LEEP were submitted to immunohistochemical analysis for p16 and Ki-67. The statistical analysis was performed using the Statistical Package for the Social Sciences software (SPSS, IBM-SPSS, Inc., Chicago, IL, US), with a significant p < 0.05. Results The biomarkers p16 and Ki-67, separately or combined, showed no relation to recurrence on the total analysis. However, evaluating specifically HG lesions, the positive expression (2+ and 3+) of p16/Ki-67 was associated with recurrence (0.010). In addition, p16 isolated was also more expressive in HG lesions (2+ and 3 + , p = 0.018), but it was unrelated to recurrence. Conclusion Proteins p16 and Ki-67, both isolated and combined, are not reliable primary markers for the recurrence of cervical lesions in the majority of LG lesions. However, analyzing only the group with prior diagnosis of HG lesions, the expressions of p16 and of p16/Ki-67 were associated with recurrence, and they may be useful in monitoring these cases. Thieme-Revinter Publicações Ltda Rio de Janeiro, Brazil.
Sørbye, Sveinung Wergeland; Arbyn, Marc; Fismen, Silje; Gutteberg, Tore Jarl; Mortensen, Elin Synnøve
Background In Norway, women with low-grade squamous intraepithelial lesions (LSIL) are followed up after six months in order to decide whether they should undergo further follow-up or be referred back to the screening interval of three years. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures. Materials and Methods At the University Hospital of North Norway, repeat cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in triage of women with ASC-US and LSIL. In this study, women with LSIL cytology in the period 2005–2008 were included (n = 522). Two triage methods were evaluated in two separate groups: repeat cytology only (n = 225) and HPV mRNA testing in addition to repeat cytology (n = 297). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as the study endpoint. Results Of 522 women with LSIL, 207 had biopsies and 125 of them had CIN2+. The sensitivity and specificity of repeat cytology (ASC-US or worse) were 85.7% (95% confidence interval (CI): 72.1, 92.2) and 54.4 % (95% CI: 46.9, 61.9), respectively. The sensitivity and specificity of the HPV mRNA test were 94.2% (95% CI: 88.7, 99.7) and 86.0% (95% CI: 81.5, 90.5), respectively. The PPV of repeat cytology was 38.4% (95% CI: 29.9, 46.9) compared to 67.0% (95% CI: 57.7, 76.4) of the HPV mRNA test. Conclusion HPV mRNA testing was more sensitive and specific than repeat cytology in triage of women with LSIL cytology. In addition, the HPV mRNA test showed higher PPV. These data indicate that the HPV mRNA test is a better triage test for women with LSIL than repeat cytology. PMID:21918682
Sopracordevole, F; Cadorin, L; Muffato, G; De Benetti, L; Parin, A
The Authors have correlated 39 cervical diagnostic biopsies for squamous intraepithelial lesions (SILs) with correspective Papanicolau smears (PS), with relation to the presence or the absence of HPV of oncogenic type (HPV-one) detected by in situ hybridization (ISH). Agreement between cytological and histological diagnosis was present in 14 of 16 cases with detectable HPV-one and only in 12 of 23 cases without detectable HPV-one at ISH. The importance of the HPV type in the SILs with relation to the diagnostic accuracy of Papanicolaou smears has been discussed.
Chogovadze, N K; Dzhugeli, M K; Kachechiladze, M G; Burkadze, G M
Morphological diagnosis of cervical intraepithelial neoplastic (CIN) lesions sometimes requires an additional study of molecular markers. Cyclin D1 is a key regulatory protein, which regulates cell cycle progression from G1 to S phase. Disruption of G1/S regulatory mechanisms is basic mechanism of HPV mediated malignant transformation of cervical epithelium. The aim of the research was to study the peculiarities of cyclin D1 protein expression in reproductive and menopausal women with cervical hyperkeratosis. We examined cyclin D1 protein expression in 381 reproductive and 233 menopausal women with cyto-colposcopically detected and histologically proved hyperkeratosis, using immunohistochemical method. Monoclonal ready to use (RTU) antibody against cyclin D1 antigen (Dako) was used. Cyclin D1 positivity in ≤50% of cells considered as low and in ≥50% - as high expression. High expression of cyclin D1 was present in CIN1 of 93,3% reproductive and 66,7% menopausal women, whilst in CINII the high expression was revealed in 53,3% and 43,8% respectively. The weak expression of cyclin D1 was present in only one cases of CINIII, other CINIII cases were all negative. The expression of cyclin D1 protein in cervical intraepithelial neoplastic lesions is not regular, however the overexpression of cyclin D1 is almost always present in CIN1 of reproductive women, in which it might be considered as an additional diagnostic marker.
Gu, Ying; Ma, Chenyun; Zou, Jue; Zhu, Yi; Yang, Rong; Xu, Yan; Zhang, Yu
A complete understanding of the natural history of infection with high-risk human papillomaviruses (HPVs) in cervical cancer requires data from regional and ethnic studies. The prevalence of high-risk HPVs was evaluated retrospectively in 2040 patients with cervicitis, 239 with cervical intraepithelial neoplasia grade 1 (CIN1), 242 with CIN2/3, and 42 patients with invasive squamous cell carcinoma (SCC) based on data from patients who visited our hospital between May 2013 and May 2015. The rates of high-risk HPV infection in patients with cervicitis, CIN1, CIN2/3, and invasive SCC were 40.8%, 74.9%, 70.2%, and 83.3%, respectively. The three most dominant HPV genotypes were HPV16, 58, and 52. HPV16 and HPV58 positivity in cervicitis, CIN1, CIN2/3, and SCC patients were 20.9% and 16.4%, 19.0% and 20.1%, 44.1% and 23.5%, and 60.0% and 31.4%, respectively. Compared to cervicitis, the odds ratios (ORs) for CIN2/3 in HPV16- and HPV58-positive patients were 2.99 (95% confidence interval [CI]: 1.32-4.33) and 1.56 (1.11-3.21), respectively; for SCC, the corresponding values were 5.68 (2.31-7.893) and 2.33 (1.41-3.87). Further identifying of carcinogenic HPVs and a fully aware of regional differences in HPV genotype distribution are tasks of top priority for cervical cancer control and prevention.
Fantini, Jacopo; Sartori, Arianna; Manganotti, Paolo
The radiological finding of multiple calcified brain lesions is atypical for brain metastases and in absence of a clear evidence of disseminated neoplastic disease the differential diagnosis may be difficult. Calcified brain metastases (CBM) are rarely encountered in clinical practice and they mostly arise from lung, breast and gastrointestinal primitive tumours. Only one case of uterine cervical carcinoma (UCC) with CBM has been reported so far. We describe the case of a 41-year-old Caucasian woman with a history of hysterectomy and bilateral salpingo-oophorectomy for UCC 3 years prior to observation and no evidence of neoplastic recurrence that developed cystic CBM. Owing to their peculiar radiological appearance, lesions were initially misidentified as neurocysticercosis, the most common parasitic infection of the central nervous system. We offer the reader some important teaching points for the differential diagnosis and discuss the rarity of our case. 2017 BMJ Publishing Group Ltd.
Hoover, Jason M; Wenger, Doris E; Eckel, Laurence J; Krauss, William E
The authors present the case of a 56-year-old right hand-dominant woman who was referred for chronic neck pain and a second opinion regarding a cervical lesion. The patient's pain was localized to the subaxial spine in the midline. She reported a subjective sense of intermittent left arm weakness manifesting as difficulty manipulating small objects with her hands and fingers. She also reported paresthesias and numbness in the left hand. Physical and neurological examinations demonstrated no abnormal findings except for a positive Tinel sign over the left median nerve at the wrist. Electromyography demonstrated bilateral carpal tunnel syndrome with no cervical radiculopathy. Cervical spine imaging demonstrated multilevel degenerative disc disease and a pneumatocyst of the C-5 vertebral body. The alignment of the cervical spine was normal. A review of the patient's cervical imaging studies obtained in 1995, 2007, 2008, and 2010 demonstrated that the pneumatocyst was not present in 1995 but was present in 2007. The lesion had not changed in appearance since 2007. At an outside institution, multilevel fusion of the cervical spine was recommended to treat the pneumatocyst prior to evaluation at the authors' institution. The authors, however, did not think that the pneumatocyst was the cause of the patient's neck pain, and cervical pneumatocysts typically have a benign course. As such, the authors recommended conservative management and repeated MR imaging in 6 months. Splinting was used to treat the patient's carpal tunnel syndrome.
[Immigration from countries with a strong migratory pressure and participation in cervical cancer screening program in the Local Health Unit 2, Umbria Region. Impact on the probability of high-grade lesions and cervical cancer].
Vallesi, Giuseppe; Bietta, Carla; Marri, Maria; Petrella, Marco
to measure the risk of having serious lesions and cervical cancer for immigrant women, by evaluating the impact of their lack of participation in the previous rounds. retrospective study. archive of the screening programme of Local Health Unit 2, Umbria. People subjected to the study: those adhering to the last round (2008- 2010) and belonging to an age group potentially capable of participating in all the previous rounds (1999-2007). positivity to Pap test; lesions that require colposcopy (AGCH,AGCUS,ASCH, HSIL); tumours (squamous cell carcinomas and adenocarcinomas). 1.7% of the women were positive to the Pap test, 0.7% presented lesions with the immediate need for colposcopy, and 0.039% were diagnosed with cancer. The percentage of women who resulted either positive to the Pap test, or presenting lesions requiring colposcopy or with cancer, is significantly higher among those who come from poor countries. Furthermore, participation in previous rounds has proven to be protective with reference to the above-mentioned markers. the independent weight of several risk factors has emerged and consequently the need to promote with particular commitment the participation in screening of women coming from poor countries.
Yang-chun, Feng; Yuan, Zhang; Cheng-ming, Liu; Yan-chun, Huang; Xiu-min, Ma
Abstract Human papillomavirus (HPV) L1 gene methylation deeply involved in the progression and heterogeneity of cervical cell epithelial lesions. The DNA ploidy also represented the early lesions of cervical cell, and it was associated with different HPV infection status in different ethnic women. So, the research was to explore whether it was possible that HPV L1 gene methylation and HPV infection status as the risk factors to lead to the differences of cervical epithelial cells’ lesions in different ethnics women. The flow-through hybridization and gene chip for HPV genotypes test, general characteristics, and cervical exfoliated cell samples were collected from 94 Uygur and 79 Han women with HPV-16 infection. The cases were divided into the single HPV-16 (sHPV-16) infection group and multiple HPV-16 (mHPV-16) infection group in each ethnic women. The DNA ploidy was analyzed by flow cytometry, and the methylation-sensitive high resolution melting (MS-HRM) was used to test the HPV-16 L1 gene methylation, the results of methylation was segmented into mild methylation, moderate methylation, and severe methylation groups. Multifactor logistic analysis explored the relation between DNA heteroploid and HPV-16 infection status, HPV-16 L1 gene methylation in different ethnic women. The higher proportion of mHPV-16 infection in Uygur than Han women (61.7% vs 38.0%). L1 gene methylation had statistic difference between single and mHPV-16 infection under the same ethnic women. The proportion of DNA heteroploid had statistic difference between different HPV-16 infection status or different L1 gene methylation grades in Han or Uygur women. Both L1 gene methylation and HPV infection status were the risk factors of DNA heteroploid. Compared to the sHPV-16 infection, the odds ratio (OR) of mHPV-16 infection were 4.409 (CI: 1.398–13.910) and 3.279 (CI: 1.069–10.060) in Han and Uygur women. Compared the mild L1 gene methylation, the OR of moderate L1 gene methylation were 3
Cui, Ning-hua; Zhang, Shuai; Wang, Chen; Zheng, Fang
To assess the associations of P16INK4a methylation status with low-grade squamous intra-epithelial lesion (LSIL), high-grade squamous intra-epithelial lesion (HSIL), cervical cancer (CC) and their clinicopathological features, a meta-analysis with 29 eligible studies was conducted. Pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were estimated to assess the strength of the associations. Heterogeneity, sensitivity of pooled results and publication bias were also evaluated. Overall, there was an increasing trend of P16INK4a hypermethylation rates among LSIL (21.4%), HSIL (30.9%) and CC (35.0%) specimens. P16INK4a hypermethylation was significantly associated with the increased risk of LSIL, HSIL and CC, with the pooled ORs of 3.26 (95% CI: 1.86-5.71), 5.80 (95% CI: 3.80-8.84) and 12.17 (95% CI: 5.86-25.27), respectively. A significant association was also found between P16INK4a hypermethylation and smoking habit (OR = 3.88, 95% CI: 2.13-7.08). Taken together, meta-analysis results support P16INK4a hypermethylation as an epigenetic marker for the progression of cervical carcinogenesis. PMID:27669738
Background Previous studies have either investigated the relationship of HPV with oral cancer or the prevalence of HPV on the oral cavity. The purpose of this investigation was to study the prevalence of HPV in oral cavity of women with oral sex practices and cervical lesions. Methods Forty six (46) non-smokers and non-alcoholic patients attended the "Clínica de Displasias" of "Ciudad Juarez" were sampled. This population had a CIN diagnosis sometime between the previous six months. On previous consent they filled out a questionnaire related to their oral sex practices. Afterwards one swab from cheeks and another from palate/gum were taken; PCR was used to determine generic HPV, HPV16 and HPV18. Results Seventy two percent (72%) of the patients stated to have oral sex practices regularly which all of them were positive to HPV either in oral mucus, palate/gum or both. The total of the given results showed that 35% had HPV16; among those distributed in 26% with regular oral sex practices and 9% stated as never practiced oral sex. An association was found between oral HPV16 positivity and progression to cervical CIN advanced lesions. On the other hand HPV18 was not detected. The frequency of HPV16 was higher in buccal mucosa (23%) versus palate/gum (16%). Conclusions This study suggests that buccal HPV16 infection is associated with CIN progression. PMID:21129222
von Knebel Doeberitz, Magnus; Reuschenbach, Miriam; Schmidt, Dietmar; Bergeron, Christine
Biomarkers indicating the initiation of neoplastic transformation processes in human papillomavirus (HPV)-infected epithelial cells are moving into the focus of cancer prevention research, particularly for anogenital cancer, including cancer of the uterine cervix. Based on the in-depth understanding of the molecular events leading to neoplastic transformation of HPV-infected human cells, the cyclin-dependent kinase inhibitor p16(INK4a) turned out to be substantially overexpressed in virtually all HPV-transformed cells. This finding opened novel avenues in diagnostic histopathology to substantially improve the diagnostic accuracy of cervical cancer and its precursor lesions. Furthermore, it provides a novel technical platform to substantially improve the accuracy of cytology-based cancer early-detection programs. Here, we review the molecular background and the current evidence for the clinical utility of the p16(INK4a) biomarker for HPV-related cancers, and cervical cancer prevention in particular.
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
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
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
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.
Limiting factors for cytopathological diagnosis of high-grade squamous intraepithelial lesions: a cytohistological correlation between findings in cervical smears and loop electrical excision procedure.
Pinto AP, Alvaro P; Tuon, Felipe F B; Torres, Luiz Fernando Bleggi; Collaço, Luiz Martins
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.
Vega-Peña, Arianna; Illades-Aguiar, Berenice; Flores-Alfaro, Eugenia; López-Bayghen, Esther; Leyva-Vázquez, Marco Antonio; Castañeda-Saucedo, Eduardo; Alarcón-Romero, Luz Del Carmen
Background: Low-grade squamous intraepithelial lesions (LSIL) are the earliest lesions of the uterine cervix, the persistence and integration of high-risk human papillomavirus (HR-HPV) as type 16, which promotes the development of more aggressive lesions. Aim: To select more aggressive lesions with tendency to progress to invasive cervical cancer. Materials and Methods: A total of 75 cytological specimens in liquid base (Liqui-PREP) were analyzed: 25 specimens were with no signs of SIL (NSIL) and without HPV; 25 NSIL with HPV-16, and 25 with both LSIL and HPV-16. The expression of Ki-67, telomerase, and viral E6 was evaluated by immunocytochemistry; and the detection of viral DNA was done by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLPs) for genotyping or sequencing of HPV-16. The physical state of HPV-16 was evaluated by in situ hybridization with amplification with tyramide. Results: Of the total group, 58.6% had LSIL associated with persistence and of these 59.3% was associated with integrated state of HPV as intense expression of E6, Ki-67 (P = 0.013, P = 0.055) has except for the expression of telomerase present a non-significant association (P<0.341). Conclusions: Overexpression of E6 and Ki-67 is associated with the integration of HPV-16, favoring viral persistence, and increasing the risk of progression in women with NSIL and LSIL. PMID:24648664
Ritter, André V; Heymann, Harald O; Swift, Edward J; Sturdevant, John R; Wilder, Aldridge D
This randomized clinical trial compared the performance of an all-in-one adhesive (iBond) applied in sclerotic and non-sclerotic non-carious cervical lesions with that of a three-step etch-prime-bond adhesive (Gluma Solid Bond, SB). One-hundred and five lesions were randomly assigned to four groups according to adhesive, sclerosis scale and technique: 1) SB applied to lesions with sclerosis scale 1 and 2 (n=26); 2) iBond applied to lesions with sclerosis scale 1 and 2 (n=28); 3) iBond applied to lesions with sclerosis scale 3 and 4 (n=25) and 4) iBond applied with prior acid-etching to lesions with sclerosis scale 3 and 4 (n=26). A microfilled composite (Durafill VS) was used as the restorative material. The restorations were evaluated for retention, color match, marginal adaptation, anatomic form, cavosurface margin discoloration, secondary caries, pre- and post-operative sensitivity, surface texture and fracture at insertion (baseline), 6, 18 months and at 3 years using modified USPHS evaluation criteria (Alfa=excellent; Bravo=clinically acceptable; Charlie=clinically unacceptable). There was a high percentage of Bravo scores for marginal adaptation (4%-32%) and marginal discoloration (18%-60%) in Groups 2, 3 and 4, but all groups had <5% Charlie scores at 6 months and <10% Charlie scores at 18 months for retention and marginal discoloration, respectively. However, it should be noted that 13% of the restorations in Group 4 were not retained at three years.
Cao, Lanqing; Sun, Ping-Li; Yao, Min; Chen, Shifan; Gao, Hongwen
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.
Erasmus, M A; Turner, P V; Nykamp, S G; Widowski, T M
Three experiments were conducted to assess brain damage resulting from percussive bolt shooting and cervical dislocation by crushing (neck crushing) in turkey hens (mean [se] bodyweight 11.4 [0.1] kg); percussive bolt shooting and blunt trauma in turkey toms (13.1 [0.2] kg); and percussive bolt shooting, blunt trauma and cervical dislocation by stretching (neck stretching) in broiler turkeys (3.9 [0.3] kg). Brain and skull damage were assessed using macroscopic and microscopic evaluations and CT. Macroscopic subcutaneous haemorrhage was significantly greater with the percussive bolt in all three experiments (hens P=0.01, toms P=0.02, broilers P=0.0003), and skull fractures were more severe for toms (P<0.0001) and broilers (P=0.03) killed with the percussive bolt versus blunt trauma. In a subsample of turkeys, microscopic brain damage was present in all turkeys killed by percussive bolt shooting (five hens, 10 toms and four broilers) and blunt trauma (nine toms and three broilers), but only in one of four turkeys killed by neck crushing and one of four turkeys killed by neck stretching. Percussive bolt shooting and blunt trauma most likely caused death by directly disrupting brain function, whereas neck stretching and neck crushing probably resulted in death from cerebral hypoxia and ischaemia.
Broaddus, V. Courtney; Everitt, Jeffrey I.; Black, Brad; Kane, Agnes B.
Exposure to asbestos fibers is associated with non-neoplastic pleural diseases including plaques, fibrosis, and benign effusions, as well as with diffuse malignant pleural mesothelioma. Translocation and retention of fibers are fundamental processes in understanding the interactions between the dose and dimensions of fibers retained at this anatomic site and the subsequent pathological reactions. The initial interaction of fibers with target cells in the pleura has been studied in cellular models in vitro and in experimental studies in vivo. The proposed biological mechanisms responsible for non-neoplastic and neoplastic pleural diseases and the physical and chemical properties of asbestos fibers relevant to these mechanisms are critically reviewed. Understanding mechanisms of asbestos fiber toxicity may help us anticipate the problems from future exposures both to asbestos and to novel fibrous materials such as nanotubes. Gaps in our understanding have been outlined as guides for future research. PMID:21534088
Vici, P; Pizzuti, L; Mariani, L; Zampa, G; Santini, D; Di Lauro, L; Gamucci, T; Natoli, C; Marchetti, P; Barba, M; Maugeri-Saccà, M; Sergi, D; Tomao, F; Vizza, E; Di Filippo, S; Paolini, F; Curzio, G; Corrado, G; Michelotti, A; Sanguineti, G; Giordano, A; De Maria, R; Venuti, A
ABSTRACT Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease. PMID:27063030
Zhang, Q; Hu, S Y; Feng, R M; Dong, L; Chen, F; Zhang, X; Pan, Q J; Ma, J F; Shi, S D; Zhao, F H; Qiao, Y L
Objective: To evaluate the 15 years changing trends of prevalence of high risk HPV (HR-HPV) infection and the risks of cervical cancer and precancerous lesions (CIN2+ ) among a Chinese rural population. Methods: The screening cohort with 1 997 women aged 35 to 45 years old was built in 1999 in Xiangyuan County, Shanxi province (SPOCCS-I) and followed up by cytology and HR-HPV testing in the years of 2005, 2010, and 2014. The changes of HR-HPV prevalence and the risks of cervical precancerous lesions with CIN2+ as the endpoints were analyzed during the past 15 years. Results: The detection rates of HPV infection and CIN2+ were 15.7%-22.3% and 1.1%-4.3% for the baseline visit and the other 3 follow-ups, respectively. The cumulative risk of CIN2+ in HR-HPV positive women at baseline was significantly higher than HR-HPV negative women (P<0.01) during the 15-year follow-up. The risk of CIN2+ in the four-times HPV positive group was 40.0%, while the group with four-times negative HPV results was 0.6% (Adjusted RR = 55.0, 95% CI: 11.3 to 268.4). Conclusions: The prevalence of HR-HPV infection and CIN2+ lesions were high in Xiangyuan county during the 15 years. HR-HPV positivity elevated the risk of CIN2+ compared to women whose HR-HPV test was negative. The risks of CIN2+ incidence in 6 years were low among women with negative HR-HPV test. The risk of CIN2+ increased with the numbers of HPV infection events. The screening interval could be extended to 5-6 years.
Tadros, Talaat; Herring-Bailey, Gina; Birdsong, George; Mosunjac, Marina; Flowers, Lisa; Nguyen, Minh Ly
Abstract Our objective was to evaluate the progression and regression of cervical dysplasia in human immunodeficiency virus (HIV)-positive women during the late antiretroviral era. Risk factors as well as outcomes after treatment of cancerous or precancerous lesions were examined. This is a longitudinal retrospective review of cervical Pap tests performed on HIV-infected women with an intact cervix between 2004 and 2011. Subjects needed over two Pap tests for at least 2 years of follow-up. Progression was defined as those who developed a squamous intraepithelial lesion (SIL), atypical glandular cells (AGC), had low-grade SIL (LSIL) followed by atypical squamous cells-cannot exclude high-grade SIL (ASC-H) or high-grade SIL (HSIL), or cancer. Regression was defined as an initial SIL with two or more subsequent normal Pap tests. Persistence was defined as having an SIL without progression or regression. High-risk human papillomavirus (HPV) testing started in 2006 on atypical squamous cells of undetermined significance (ASCUS) Pap tests. AGC at enrollment were excluded from progression analysis. Of 1,445 screened, 383 patients had over two Pap tests for a 2-year period. Of those, 309 had an intact cervix. The median age was 40 years and CD4+ cell count was 277 cells/mL. Four had AGC at enrollment. A quarter had persistently normal Pap tests, 64 (31%) regressed, and 50 (24%) progressed. Four developed cancer. The only risk factor associated with progression was CD4 count. In those with treated lesions, 24 (59%) had negative Pap tests at the end of follow-up. More studies are needed to evaluate follow-up strategies of LSIL patients, potentially combined with HPV testing. Guidelines for HIV-seropositive women who are in care, have improved CD4, and have persistently negative Pap tests could likely lengthen the follow-up interval. PMID:25693769
Kang, Yoon-Jung; Lewis, Hazel; Smith, Megan A; Simonella, Leonardo; Neal, Harold; Bromhead, Collette; Canfell, Karen
New Zealand initiated HPV vaccination in 2008, and has attained 3-dose coverage of ~50 % in 12-13 year old girls. Due to the success of program initiatives in Māori girls, higher coverage rates of ~60 % have been achieved in this group. We have previously reported a benchmark overall pre-vaccination prevalence of oncogenic HPV infection in high grade cervical lesions in New Zealand. The current extended analysis provides separate pre-vaccination benchmark prevalence for Māori and non-Māori women. The National Cervical Screening Programme Register (NCSP-R) was used to identify any woman aged 20-69 years of age with an index high grade cytology report from 2009-2011. Extended recruitment was performed until 2012 in clinics with a high proportion of Māori women. Ethnicity status was based on self-reported information by participating women through phone contact supplemented by recordings on the study questionnaire (the NCSP-R was not used to extract ethnicity status). A total of 730 women consented to participate and had a valid HPV test result; 418 of these had histologically-confirmed cervical intraepithelial neoplasia (CIN) 2/3 lesions (149 Māori, 269 non-Māori). The prevalence of any cervical oncogenic HPV infection, HPV16, and HPV18 was calculated in women with CIN2/3. In confirmed CIN2/3, the prevalence of any oncogenic HPV, HPV16 and HPV18 was 96 % (95 % CI:91-99 %), 54 % (95 % CI:46-63 %), 11 % (95 % CI:7-18 %) in Māori and 96 % (95 % CI:93-98 %), 54 % (95 % CI:48-60 %), 11 % (95 % CI:7-15 %) in non-Māori women, respectively. Age-specific patterns of infection for HPV16/18 in confirmed CIN2/3 differed between the two groups (Pinteraction = 0.02), with a lower prevalence in younger vs. older Māori women (57 % in 20-29 years vs 75 % in 40-69 years) but a higher prevalence in younger vs. older non-Māori women (70 % in 20-29 years vs 49 % in 40-69 years); the difference in the age-specific patterns of infection for HPV16/18 was not significant either
Dedhia, Kavita; Chi, David H
We present the case of a 10-year-old boy with the sudden onset of a large, painless left neck mass. Findings on magnetic resonance imaging (MRI) and fine needle aspiration (FNA) biopsy suggest a cystic lesion, most likely of thymic origin. Cervical thymic cysts are a rare form of cervical mass, which are easily overlooked in the differential diagnosis of children presenting with painless neck masses. A combination of CT and MRI investigations can be helpful in differentiating thymic cysts from other congenital and neoplastic masses, but the definitive diagnosis of thymic cyst requires histopathological documentation of thymic tissue. Surgical excision is considered the management of choice for thymic cysts, and no cases of postoperative recurrence have been reported. PMID:28191377
Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing
A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations.
Herfs, Michael; Crum, Christopher P
Since the discovery of human papillomavirus (HPV) type 16 in early 80s, the link between HPV and cervical cancer has been established with certainty, a function of the discovery and cloning of a range of HPV types associated with both cancer precursors (cervical intraepithelial neoplasia or CIN) and carcinomas and extensive epidemiologic, clinical, pathologic, and experimental data. These accumulated results have culminated in new paradigms of cancer prevention through screening and triage. Despite this, the management of women with CIN is still suboptimal and the overtreatment of these conditions still occurs, largely due to the lack of clarity regarding which precancerous lesions are most likely to progress in grade. Recently, a discrete population of cuboidal cells was discovered at the cervical squamocolumnar junction, the anatomic site where the large majority of HPV-related (pre)neoplastic lesions develop. These cells seem to be embryonic in nature and participate both in benign metaplasias and the initial phase of precancer development. This review summarizes the historical evolution of precursor management, assesses the potential role of this and other discoveries in segregating lower from higher-risk precursors, and examines their potential impact on the management of women with real or potential cervical cancer precursors.
Aili, Aixingzi; Hasim, Ayshamgul; Kelimu, Alimujiang; Guo, Xia; Mamtimin, Batur; Abudula, Abuliz; Upur, Halmurat
Riboflavin deficiency can cause a variety of metabolic problems that lead to skin and mucosal disorders. Limited evidence suggests that high intake of riboflavin may reduce overall risks of cancer. However, association of this deficiency with cervical cancer and precancerous lesions are still not definitively known. In this study, we characterized the relationship between plasma and tissue riboflavin levels and C20orf54 protein expression in patients with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) as well as the relationship of these levels with human papillomavirus virus 16, 18 (HPV16/18) infections. High-performance liquid chromatography (HPLC) was used to measure blood riboflavin levels in patients with CIN and CSCC, and an enzyme-linked immunosorbent assay (ELISA) was used to determine tissue riboflavin levels in patients with CSCC and matched normal mucous epithelia. The expression of C20orf54 in fresh CSCC and matched tissues were detected by qRT-PCR and western blot, respectively. And it was further confirmed by immunohistochemistry (IHC) with formalin-fixed, paraffin-embedded CIN and CSCC. An HPV genotyping chip was used to analyze HPV infection and typing. The results showed that patients with CIN and CSCC had decreased plasma riboflavin levels as compared with normal controls. There was also significantly decreased riboflavin in tissues from CSCC patients, when compared with normal cervical epithelia. C20orf54 expression were significantly up-regulated in CSCC compared to matched control on both mRNA and protein level. Tissue riboflavin levels were significantly lower in HPV16/18 positive tissue compared with HPV16/18-negative tissue, and an inverse association was found between tissue riboflavin levels and C20orf54 mRNA and protein expression in CSCC. Additionally, C20orf54 was significantly correlated with tumor stages. In conclusion, C20orf54 tend to play a protective role in Uyghur cervical carcinogenesis of
Kelimu, Alimujiang; Guo, Xia; Mamtimin, Batur; Abudula, Abuliz; Upur, Halmurat
Riboflavin deficiency can cause a variety of metabolic problems that lead to skin and mucosal disorders. Limited evidence suggests that high intake of riboflavin may reduce overall risks of cancer. However, association of this deficiency with cervical cancer and precancerous lesions are still not definitively known. In this study, we characterized the relationship between plasma and tissue riboflavin levels and C20orf54 protein expression in patients with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) as well as the relationship of these levels with human papillomavirus virus 16, 18 (HPV16/18) infections. High-performance liquid chromatography (HPLC) was used to measure blood riboflavin levels in patients with CIN and CSCC, and an enzyme-linked immunosorbent assay (ELISA) was used to determine tissue riboflavin levels in patients with CSCC and matched normal mucous epithelia. The expression of C20orf54 in fresh CSCC and matched tissues were detected by qRT-PCR and western blot, respectively. And it was further confirmed by immunohistochemistry (IHC) with formalin-fixed, paraffin-embedded CIN and CSCC. An HPV genotyping chip was used to analyze HPV infection and typing. The results showed that patients with CIN and CSCC had decreased plasma riboflavin levels as compared with normal controls. There was also significantly decreased riboflavin in tissues from CSCC patients, when compared with normal cervical epithelia. C20orf54 expression were significantly up-regulated in CSCC compared to matched control on both mRNA and protein level. Tissue riboflavin levels were significantly lower in HPV16/18 positive tissue compared with HPV16/18-negative tissue, and an inverse association was found between tissue riboflavin levels and C20orf54 mRNA and protein expression in CSCC. Additionally, C20orf54 was significantly correlated with tumor stages. In conclusion, C20orf54 tend to play a protective role in Uyghur cervical carcinogenesis of
Hudelist, Gernot; Manavi, Mahmood; Pischinger, Kerstin I D; Watkins-Riedel, Thomas; Singer, Christian F; Kubista, E; Czerwenka, Klaus F
Human papillomavirus (HPV) infection is the most important event in the malignant transformation of human cervical epithelium. Several high-risk (HR-)HPV subtypes have been identified, which lead to CIN and subsequently to invasive carcinoma. The reason for this phenomenon is still unknown, but it seems to be related to the physical state of HPV DNA. Digene HC II test was used to identify HR- and/or low-risk (LR-)HPV infections in cervical swabs of 275 women attending our clinic for routine cytological screening and/or colposcopy because of an abnormal Pap smear comprising low-grade squamous intraepithelial lesions (LGSIL) and high-grade SIL (HGSIL). Specific HR (16, 18, 31, 33, 52b, 58) and LR (6, 11) subtypes were characterized in cervical biopsies of 10 women with benign cellular changes and of 68 women with CIN I-III by the PCR-restriction enzyme method. The physical state of HPV DNA (episomal, mixed and integrated form) was analyzed by bi-dimensional (2D)-gel electrophoresis. In addition, mRNA expression of E6/E7 genes was analyzed by RT-PCR. Furthermore, the relative virus load was determined in nine selected cases. The physical state and transcriptional activity of HPV DNA were then correlated to histopathological results. LR-HPV infection [27 cases (9.8%)] and HR-HPV infection [121 cases (44%)] of cervical swabs were clearly correlated to the degree of SIL. Further HPV typing in cervical biopsies of 78 women showed that HPV6 and 11 were restricted to benign cellular changes, CIN I and II, whereas HPV16 and 18 were observed predominantly in CIN III/CIS (P=0.01). No clear distribution pattern was observed for HPV31, 33, 52b and 58. Expression of HPV E6 and E7 transcripts was uniformly correlated with the different physical state of HPV DNA. Analyzing the physical state of these HPV subtypes, HPV6 and 11 could only be detected as an episomal form, independent of SIL grade. In normal epithelium and in CIN I and II, HPV16 and 18 were exclusively found in the
López-Romero, Ricardo; Marrero-Rodríguez, Daniel; Romero-Morelos, Pablo; Villegas, Vanessa; Valdivia, Alejandra; Arreola, Hugo; Huerta-Padilla, Víctor; Salcedo, Mauricio
Cervical cancer (CC) is a multifactorial disease associated to genetic, environmental and epigenetic factors, being the infection by human papillomavirus the main etiologic agent. Additionally, the alteration in the expression of transcription factors has been considered of importance for the development of this tumor. HOX genes encode a group of transcription factors involved in cellular proliferation and differentiation processes during the development of embryonic structures in vertebrates; their aberrant expression is associated with tumorigenesis and metastasis. A range of evidence suggests a role for HOX genes in the development of cervical neoplastic cell. Studies in CC cell lines, primary tumors and premalignant lesions have suggested the involvement of HOXA1, HOXC5, C6, C8 and C10, HOXD9 and HOXD13 in the process of cervical carcinogenesis. Also, the de novo expression of genes HOXB2, B4, B13 and HOXC11-C13 appears to be involved in the process of malignant transformation of cervical epithelial cell. These data would allow to open a field in search of new molecular markers in cervical cancer and the development of new therapeutic strategies for this malignancy.
Hongo, Yu; Onoue, Hiroyuki; Takeshima, Shinichi; Kamakura, Keiko; Kaida, Ken-Ichi
We report a case of a 67 year-old man with bilateral sensory ataxia of the upper extremities. He was diagnosed as having ANCA-related angitis and Sjögren syndrome at age 60. On admission to our hospital at age 67, he presented with severe sensory ataxia in his upper extremities, while his lower extremity neurological symptoms were limited to the absence of tendon reflexes. Cervical MRI showed an increased T2 signal intensity in an area limited to the bilateral cuneate fasciculus. Serum levels of vitamin B12 and folic acid were normal. Plasma homocysteine, serum and urine methylmalonic acid were also normal. Eight-week intramuscular administration of vitamin B12 did not improve either his disorder or the MRI findings. His sensory ataxia might be attributed to Sjögren syndrome-associated ganglionopathy at the cervical level, and the MRI findings might reflect centripetal Wallerian degeneration in the cuneate fasciculus. Gracilis fasciculus are well-known as vulnerable regions in Sjögren-associated myelopathy, whereas cervical myelopathy, limited to cuneate fascicules, can emerge as Sjögren-associated disorders.
Gallo Reynoso, S; Candelaria Hernández, M G
Non-neoplastic colon polyps are benign lesions with normal histology components, we present our experience with colonoscopy polypectomy in 10 years. We resected 187 polyps in 96 patients (50 males) with medium age of 49.3 years and range 2-82. Most common indication was hemorrhage (37%) taking out the hyperplastic polyps who were found in asymptomatic patients with the highest frequency (41%). Juvenile polyps follows with 25%. 71% polyps were unique but hamaetomatous polyps of Peutz-Jeghers syndrome were multiple (39%). Juvenile (retention) polyps were found among the youngest patients (average 13.2 years) and frequently had hemorrhage (21-25). Lipomas were found in elder patients (range 52.5 years). We had no major complications with hemorrhage or mortality, minor complications were found in 3.09%.
Seval, Mehmet Murat; Cavkaytar, Sabri; Atak, Zeliha; Guresci, Servet
Endometriosis of the uterine cervix is a rare lesion that is generally asymptomatic in gynaecological practice. We present a case with postcoital bleeding due to a cervical mass mimicking cervical polyp or fibroma which was histologically proven as cervical endometriosis later. Cervical endometriosis should be considered in the differential diagnosis of cervical masses with postcoital bleeding. PMID:23376669
Seval, Mehmet Murat; Cavkaytar, Sabri; Atak, Zeliha; Guresci, Servet
Endometriosis of the uterine cervix is a rare lesion that is generally asymptomatic in gynaecological practice. We present a case with postcoital bleeding due to a cervical mass mimicking cervical polyp or fibroma which was histologically proven as cervical endometriosis later. Cervical endometriosis should be considered in the differential diagnosis of cervical masses with postcoital bleeding.
Visioli, Carmen Beatriz; Crocetti, Emanuele; Zappa, Marco; Iossa, Anna; Andersson, Karin Louise; Bulgaresi, Paolo; Alfieri, Antonia; Amunni, Gianni
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.
Femiano, Felice; Femiano, Rossella; Lanza, Alessandro; Lanza, Michele; Perillo, Letizia
This study compares sensitivity reduction after dental restoration with and without prior diode laser (DL) irradiation for cervical dentine hypersensitivity (CDH) from non-carious cervical lesions (NCCLs) unresponsive to desensitizing agents. Eighty-eight teeth of 28 subjects (21 females; age 23-64 years), with CDH from NCCL were included in this study. NCCLs of each oral quadrant were randomized in two groups (study group (SG)) to estimate the sensitivity reduction after dental restoration (SG-1) compared with the DL irradiation used prior to restoration placement (SG-2). The subjects were asked to rate the sensitivity experienced during air stimulation using a visual analog scale before (baseline), immediately after, and at 6 and 12 months from restoration. The outcomes showed a significant reduction of discomfort compared to baseline for NCCLs of SG-2 with the decrease of 78.5, 78.9, and 78.1 % immediately and at 6 and 12 months after restoration, respectively; in comparison with the decrease of 70.1, 67, and 65.3 % for NCCLs of SG-1 immediately and at 6 and 12 months after restoration, respectively; and compared to baseline. The DL irradiation prior to dental restoration can further improve the painful symptomatology of CDH from NCCL unresponsive to desensitizing agents.
Kaale, Bertel Rune; Krakenes, Jostein; Albrektsen, Grethe; Wester, Knut
In the present study, we compared magnetic resonance imaging (MRI) findings of soft tissue structures in the upper cervical spine between whiplash-associated disorder (WAD) patients and population-based control persons, and examined whether MRI-verified abnormalities in WAD patients were related to accident-related factors hypothesized to be of importance for severity of injury. A total of 92 whiplash patients and 30 control persons, randomly drawn, were included. Information on the accident-related factors (i.e., head position and impact direction) was obtained by a questionnaire that was answered within 1 week after the accident. The MRI examination was performed 2-9 (mean 6) years after the accident. Focus was on MRI abnormalities of the alar and the transverse ligaments, and the tectorial and posterior atlanto-occipital membranes, graded 0-3. For all neck structures, the whiplash patients had more high-grade lesions (grade 2 or 3) than the control persons (Chi-square test, p < 0.055). An abnormal alar ligament was most common (66.3% graded 2 or 3). Whiplash patients who had been sitting with their head/neck turned to one side at the moment of collision more often had high-grade lesions of the alar and transverse ligaments (p < 0.001, p = 0.040, respectively). Severe injuries to the transverse ligament and the posterior atlanto-occipital membrane were more common in front than in rear end collisions (p < 0.001, p = 0.001, respectively). In conclusion, the difference in MRI-verified lesions between WAD patients and control persons, and in particular the association with head position and impact direction at time of accident, indicate that these lesions are caused by the whiplash trauma.
Jansen, Kathrin U
Cervical cancer and precancerous lesions of the genital tract are a major threat to women's health worldwide. Although the introduction of screening tests to detect cervical cancer and its precursor lesions has reduced overall cervical cancer rates in the developed world, the approach was largely unsuccessful for developing countries, primarily due to a lack of appropriate infrastructures and high costs. Annually, 470,000 cervical cancer cases are diagnosed worldwide, of which 80% occur in developing countries. Despite advances in treatment of cervical cancer, approximately half of the women afflicted with the disease will die. Over 20 years of dedicated research has provided conclusive evidence that a subset of human papillomaviruses are the aetiological agents for cervical cancer. Finding a viral origin for this disease provided the basis to fight cervical cancer using prophylactic or therapeutic vaccination. Both vaccine approaches are reviewed here, with an emphasis on recent clinical data.
Iordanishvili, A K; Chernyj, D A; Jankovskij, V V; Orlov, A K; Drobkova, K O
The article is devoted to gerontostomatological and gender-specific prevalence of non-carious lesions of the hard tissue of teeth in adults. The paper presents data of epidemiological study on prevalence of non-carious lesions of dental hard tissues (high abrasion, erosion, wedge-shaped defects, hyperesthesia). Allocated to four age groups: young adults surveyed--from 22 to 39 years; middle ages--from 40 to 59 years; older--from 60 to 74 years of age; senile age--from 75 to 87 years. To determine the frequency of occurrence of different forms of non-carious lesions of the hard tissue of teeth we have used the following: general scientific and special methods: poll, dental examination, groupings, statistical and mathematical methods of processing sample. We have ranked low incidence of non-carious lesions of the hard tissue of the teeth in the sample surveyed: high abrasion, erosion, wedge-shaped defects of solid tissues, hyperesthesia. The features of clinical course of non-carious lesions have been determined. In particular a rare combined lesion of the teeth with advanced erasibility, wedge defects and erosion has been noted. Significant combination of the pathological processes of the hard tissue of teeth with their hyperesthesia has been found. Features of different forms of non-carious lesions of the hard tissue of teeth in different age periods of life have been determined. Noted that older people, due to non-carious esions of the hard tissue of teeth were more likely to require medical intervention aimed at addressing the ncreased sensitivity and loss of hard tissue of teeth by dental therapeutic activities or dental prosthetics.
Background Women with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL). Methods Peripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL. Results No significant differences were found between genotype frequencies at loci −819, -1082, and −1352. Individuals carrying at least one copy of risk allele A of polymorphism −592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A. Conclusions The −592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease. PMID:23148667