Correlation between standardized uptake value and apparent diffusion coefficient of neoplastic lesions evaluated with whole-body simultaneous hybrid PET/MRI.

PubMed

Rakheja, Rajan; Chandarana, Hersh; DeMello, Linda; Jackson, Kimberly; Geppert, Christian; Faul, David; Glielmi, Christopher; Friedman, Kent P

2013-11-01

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

Neoplastic Multifocal Skin Lesions: Biology, Etiology, and Targeted Therapies for Nonmelanoma Skin Cancers.

PubMed

Fernandes, Ana R; Santos, Ana C; Sanchez-Lopez, Elena; Kovačević, Andjekla B; Espina, Marta; Calpena, Ana C; Veiga, Francisco J; Garcia, Maria L; Souto, Eliana B

2018-01-01

Neoplastic skin lesions are multifocal, diffuse skin infiltrations of particular relevance in the differential diagnosis of ulcerative, nodular, or crusting skin lesions. Nonmelanoma skin cancers (NMSCs), namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and also actinic keratosis (AK), are the most common malignant tumors in humans. BCCs do not proliferate rapidly and most of the times do not metastasize, while SCCs are more infiltrative, metastatic, and destructive. AKs are precursor lesions of cutaneous SCCs. The classical therapy of NMSCs makes use of photodynamic therapy associated with chemotherapeutics. With improved understanding of the pathological mechanisms of tumor initiation, progression, and differentiation, a case is made towards the use of targeted chemotherapy with the intent to reduce the cytotoxicity of classical treatments. The present review aims to describe the current state of the art on the knowledge of NMSC, including its risks factors, oncogenes, and skin carcinogenesis, discussing the classical therapy against new therapeutic options. © 2017 S. Karger AG, Basel.

Gonadotropin-Dependent Precocious Puberty: Neoplastic Causes and Endocrine Considerations

PubMed Central

2011-01-01

Premature activation of the hypothalamic-pituitary-gonadal (HPG) axis manifests as gonadotropin-dependent precocious puberty. The mechanisms behind HPG activation are complex and a clear etiology for early activation is often not elucidated. Though collectively uncommon, the neoplastic and developmental causes of gonadotropin-dependent precocious puberty are very important to consider, as a delay in diagnosis may lead to adverse patient outcomes. The intent of the current paper is to review the neoplastic and developmental causes of gonadotropin-dependent precocious puberty. We discuss the common CNS lesions and human chorionic gonadotropin-secreting tumors that cause sexual precocity, review the relationship between therapeutic radiation and gonadotropin-dependent precocious puberty, and finally, provide an overview of the therapies available for height preservation in this unique patient population. PMID:21603196

Screening colonoscopy for the detection of neoplastic lesions in asymptomatic HIV-infected subjects.

PubMed

Bini, E J; Green, B; Poles, M A

2009-08-01

Although non-AIDS defining malignancies are rapidly increasing as HIV-infected subjects live longer, little is know about the results of screening for colonic neoplasms (adenomatous polyps and adenocarcinomas) in this population. We conducted a screening colonoscopy study to determine the prevalence of colonic neoplasms in 136 asymptomatic HIV-infected subjects >or=50 years of age and 272 asymptomatic uninfected control subjects matched for age, sex, and family history of colorectal cancer. Advanced neoplasms were defined as adenomas >or=10 mm or any adenoma, regardless of size, with villous histology, high-grade dysplasia, or adenocarcinoma. The prevalence of neoplastic lesions was significantly higher in HIV-infected subjects than in control subjects (62.5% vs 41.2%, p<0.001), and remained highly significant after adjustment for potential confounding variables (odds ratio = 3.00; 95% confidence interval, 1.83 to 4.93). Among patients with colorectal adenocarcinoma, HIV-infected subjects were significantly younger (52.4 (SD 1.3) vs 60.3 (SD 4.0) years, p = 0.002) and were more likely to have advanced cancers (stage III or IV) than control subjects (60.0% vs 16.7%, p = 0.24). Of HIV-infected subjects with advanced neoplasms proximal to the splenic flexure, distal neoplastic lesions were absent in 88.9% of individuals and these would have been missed by flexible sigmoidoscopy. HIV-infected subjects have a higher prevalence of colonic neoplasms, and adenocarcinomas develop at a younger age and are more advanced than in uninfected subjects. Our findings suggest that screening colonoscopy should be offered to HIV-infected subjects, but the age of initiation and the optimal frequency of screening require further study.

[Microsatellite instability and human papilloma virus genotypes in preneoplastic and neoplastic uterine cervix lesions].

PubMed

Roa S, Juan Carlos; Martínez S, Ricardo; Montenegro, Sonia; Roa E, Iván; Capurro V, Italo; Ibacache S, Gilda; Melo A, Angélica

2007-01-01

The association between some specific human papilloma virus (HPV) types and cervix cancer is well known. However, the genetic conditions that favor the development of cervical cancer are less well known. To determine the presence of satellite instability (MSI) in preneoplastic and neoplastic lesions of the cervix and correlate these findings with HPV genotypes. Biopsy samples of cervical lesions were studied. Sixteen had low grade lesions, 22 had high grade lesions and 28 had an epidermoid cancer. Viral types were identified with polymerase chain reaction, dot-blot hybridization and restriction fragment length polymorphism. MSI was determined using a panel of eight highly informative microsatellites. Microsatellite instability in at least one locus was observed in 91, 56 and 69% of low grade lesions, high grade lesions and epidermoid carcinomas, respectively. MSI-High grade, MSI-Low grade instability and microsatellite stability were observed in 5, 60 and 46% of samples, respectively. Two of three samples with high grade instability had HPV 52 genotype. Other viral subtypes had frequencies that ranged from 78% to 100%, with the exception of HPV16 that was present in only 53% of samples with low grade instability. Two thirds of biopsy samples from cervical lesions had MSI, mechanism that can be involved in the first stages of cervical carcinogenesis. The low frequency of high grade instability, its association with HPV52 and the low frequency of HPV16 in samples with low grade instability, suggest different coadjutant mechanisms in cervical carcinogenesis.

Effects of Training and Feedback on Accuracy of Predicting Rectosigmoid Neoplastic Lesions and Selection of Surveillance Intervals by Endoscopists Performing Optical Diagnosis of Diminutive Polyps.

PubMed

Vleugels, Jasper L A; Dijkgraaf, Marcel G W; Hazewinkel, Yark; Wanders, Linda K; Fockens, Paul; Dekker, Evelien

2018-05-01

Real-time differentiation of diminutive polyps (1-5 mm) during endoscopy could replace histopathology analysis. According to guidelines, implementation of optical diagnosis into routine practice would require it to identify rectosigmoid neoplastic lesions with a negative predictive value (NPV) of more than 90%, using histologic findings as a reference, and agreement with histology-based surveillance intervals for more than 90% of cases. We performed a prospective study with 39 endoscopists accredited to perform colonoscopies on participants with positive results from fecal immunochemical tests in the Bowel Cancer Screening Program at 13 centers in the Netherlands. Endoscopists were trained in optical diagnosis using a validated module (Workgroup serrAted polypS and Polyposis). After meeting predefined performance thresholds in the training program, the endoscopists started a 1-year program (continuation phase) in which they performed narrow band imaging analyses during colonoscopies of participants in the screening program and predicted histological findings with confidence levels. The endoscopists were randomly assigned to groups that received feedback or no feedback on the accuracy of their predictions. Primary outcome measures were endoscopists' abilities to identify rectosigmoid neoplastic lesions (using histology as a reference) with NPVs of 90% or more, and selecting surveillance intervals that agreed with those determined by histology for at least 90% of cases. Of 39 endoscopists initially trained, 27 (69%) completed the training program. During the continuation phase, these 27 endoscopists performed 3144 colonoscopies in which 4504 diminutive polyps were removed. The endoscopists identified neoplastic lesions with a pooled NPV of 90.8% (95% confidence interval 88.6-92.6); their proposed surveillance intervals agreed with those determined by histologic analysis for 95.4% of cases (95% confidence interval 94.0-96.6). Findings did not differ between the group

Identification of non-neoplastic and neoplastic gastric polyps using multiphoton microscopy

NASA Astrophysics Data System (ADS)

Jiang, Shanghai; Kang, Deyong; Xu, Meifang; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

2012-12-01

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.

Mucinous expression in benign and neoplastic glandular lesions of the uterine cervix.

PubMed

Baker, Allyson C; Eltoum, Isam; Curry, Rebecca O; Stockard, Cecil R; Manne, Upender; Grizzle, William E; Chhieng, David

2006-10-01

Mucins are glycoproteins produced by both normal and neoplastic glandular epithelial cells including endocervix. To determine the expression of mucins in uterine cervical glandular lesions and whether mucin expression correlates with the nature and origin of the glandular lesions. Antibodies to MUC1, MUC2, MUC4, and MUC5AC were applied on 52 cases including 14 endocervical adenocarcinomas (including 4 adenosquamous carcinomas), 9 endometrial carcinomas (8 endometrioid adenocarcinomas and 1 adenosquamous carcinoma), 8 adenocarcinoma in situ (AIS), 2 glandular dysplasias, 6 tubal metaplasias, 10 microglandular hyperplasias, and 3 normal endocervix. The presence of any staining was considered positive. All benign endocervical epithelia, including tubal metaplasia and microglandular hyperplasia, expressed MUC1, MUC4, and MUC5AC but not MUC2. Almost all endocervical AIS and carcinomas and all endometrial adenocarcinomas expressed MUC1; the exceptions were 2 cases of endocervical adenocarcinoma and 1 case of adenosquamous carcinoma of the endocervix. MUC2 staining was noted in 25%, 40%, and 22% of AIS, endocervical adenocarcinomas, and endometrial adenocarcinomas, respectively. About 38% of AIS, 75% of endocervical adenocarcinomas, and 44% of endometrial adenocarcinomas expressed MUC4. Half of AIS, most of endocervical adenocarcinomas, and 22% of endometrial adenocarcinomas expressed MUC5AC. The difference in MUC4 and MUC5AC expression between benign endocervical lesions and AIS and the difference in MUC5AC expression between endocervical and endometrial neoplasms were statistically significant. Mucin expressions differed among benign endocervical lesions and AIS and among endocervical and endometrial malignancies. These results suggest that mucin staining may potentially be helpful in differentiating various uterine cervical glandular lesions.

B-mode ultrasound examination of canine mammary gland neoplastic lesions of small size (diameter < 2 cm).

PubMed

Vannozzi, Iacopo; Tesi, Matteo; Zangheri, Marta; Innocenti, Viola Maria; Rota, Alessandra; Citi, Simonetta; Poli, Alessandro

2018-06-01

Ultrasonography is a valuable tool for the evaluation of neoplastic lesions in the dog and there is a growing interest in the use of this technique for the stadiation of canine mammary tumours. An accurate assessment of small sized nodules facilitates the stadiation of the mammary lesions and helps the clinician in the choice of the most indicated surgical therapy. The aim of this study was to identify those ultrasound criteria that may be useful in discriminating between benign and malignant lesions of small size (diameter smaller than 2 cm). Sixty-two nodules, < 2 cm in larger diameter, belonging to thirty-five bitches presented between January 2012 and February 2014 were evaluated. Tumours were observed by conventional ultrasound and assessed for: shape (regular-irregular), limit (defined-ill-defined), margins (regular-irregular), echogenicity (hypoechoic-isoechoic-hyperecoic), echotexture (homogeneus-heterogeneus), presence of hyperecoic halo, distal acoustic enhancement or shadowing and surrounding tissue alterations. Among the alterations in surrounding tissues, the disruption of the glandular tissue and the increase in echogenicity of the peritumoral tissues were assessed. Thereafter, bitches were subjected to mastectomy and nodules were evaluated histologically. None of the ultasound criteria considered in the current study showed a statistically significant relation with malignancy, except for the presence of alterations in the tissue surrounding the nodules. According to our results, this characteristic may indicate malignancy, however its subjectivity may affect the applicability in clinical practice. In conclusions, conventional ultrasound in bitches had a limited ability in discriminating benign and malignant mammary gland neoplastic lesions of small size (diameter < 2 cm).

Promotional effects of CO2 laser on neoplastic lesions in hamsters

NASA Astrophysics Data System (ADS)

Kingsbury, Jeffrey S.; Margarone, Joseph E., III; Satchidanand, S.; Liebow, Charles

1991-06-01

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.

Extra-prostatic transgene-associated neoplastic lesions in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice.

PubMed

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

2015-02-01

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. © 2014 by The Author(s).

[Non-neoplastic enlargement of salivary glands: clinico-histologic analysis].

PubMed

González Guevara, Martha Beatriz; Torres Tejero, Marco Antonio; Martínez Mata, Guillermo

2005-01-01

We carried out a retrospective study on non-neoplastic enlargement of the salivary glands at the Oral Histopathology Diagnostic Center of the Autonomous Metropolitan University at Xochimilco (UAM-Xochimilco) in Mexico during a period of 24 years (1979-2003). From 5,625 biopsies received and analyzed, a total of 461 (8.2%) were non-neoplastic enlargement of the salivary glands; for each case, we registered demographic data as well as clinic characteristics. These lesions were characterized as a heterogeneous group of pathologic entities among which we included local, obstructive, infectious, and immunopathologic lesions. The most frequent lesion was the extravasation cyst in 341 (74%) cases, followed by chronic sialoadenitis and Sjögren's syndrome with 54 (11.7%) and 41 (8.8%) cases, respectively, and at a lesser percentage mucous retention cyst, sialosis, benign lymphoepithelial lesions and those related with sialolytes. Females were affected more frequently; mean age was second to third life decades. These lesions were most frequently localized on inferior labial mucosa.

Confocal laser endomicroscopy and ultrasound endoscopy during the same endoscopic session for diagnosis and staging of gastric neoplastic lesions.

PubMed

Gheorghe, C; Iacob, R; Dumbrava, Mona; Becheanu, G; Ionescu, M

2009-01-01

Confocal LASER endomicroscopy (CLE) is a newly developed endoscopic technique which allows subsurface in vivo histological assessment during ongoing endoscopy and targeted biopsies. Ultrasound endoscopy (EUS) is a useful tool in staging upper GI malignant lesions. We describe for the first time the use of both techniques during the same endoscopic session, in a pilot study, in order to increase the diagnostic yield of histological assessment and provide the staging of the gastric neoplastic lesions thus decreasing the time to therapeutic decision. CLE has been performed with the Pentax EG-3870CIK confocal endomicroscope after a 5 ml intravenous 10% fluorescein injection; EUS has been performed subsequently, during the same endoscopic Propofol sedation session, using a standard radial EUS-scope. Eleven patients have been investigated, 4 females, 7 males, mean age 59.7 +/- 12.3 years. The indication of CLE/EUS exploration was the presence of a gastric polypoid lesion in 37% of cases, atypical gastric ulcer in 27% of patients, gastric lymphoma 18%, suspicion of gastric cancer recurrence after resection 9% and infiltrating type gastric cancer 9%. Histological assessment after targeted biopsy has established the diagnosis of gastric adenocarcinoma in 55% of cases, gastric lymphoma in 18% of cases, gastric adenoma, gastric GIST and gastric foveolar hyperplasia in 9% of cases respectively. CLE has allowed targeted biopsies in 81.8% of cases. In 2 patients - one case with suspected recurrent gastric cancer after surgery and one case of gastric lymphoma, CLE has indicated normal gastric mucosa. The EUS evaluation has shown TO lesion in two cases, T1 in 3 cases, T2 in 3 cases, T3 in one case. The EUS evaluation showed in one gastric lymphoma patient a lesion interesting the mucosa and submucosa with regional adenopathy and a submucosal lesion with regional adenopathy in the other gastric lymphoma case. The therapeutic decision was surgery in 73% of cases, chemotherapy and

Lymphoproliferative lung disorders: a radiologic-pathologic overview. Part II: Neoplastic disorders.

PubMed

Restrepo, Carlos S; Carrillo, Jorge; Rosado de Christenson, Melissa; Ojeda Leon, Paulina; Lucia Rivera, Aura; Koss, Micheal N

2013-12-01

Lymphoproliferative pulmonary neoplasms can occur as primary pulmonary lymphomas or because of secondary pulmonary involvement. Neoplastic disorders may be difficult to differentiate from reactive pulmonary lymphoproliferative disorders, and immunohistochemical evaluation is often required to differentiate the 2 types of lesions. Neoplastic lymphoproliferative disorders are monoclonal lesions. Most affected patients present with systemic complaints, and imaging findings typically include nodules, masses, and lymphadenopathy. Primary pulmonary lymphomas are rare and account for less than 4% of the lymphomas that arise in extranodal sites. Secondary pulmonary lymphomas can affect the lung via hematogenous dissemination or by secondary involvement from tumor in adjacent or contiguous sites. Neoplastic lymphoproliferative lesions also include leukemia and plasma cell neoplasms. Posttransplantation lymphoproliferative disorders constitute a special type of lymphoid proliferation occurring in the setting of the chronic immunosuppression required for solid organ and bone marrow transplantation. Copyright © 2013 Elsevier Inc. All rights reserved.

Linked color imaging reduces the miss rate of neoplastic lesions in the right colon: a randomized tandem colonoscopy study.

PubMed

Paggi, Silvia; Mogavero, Giuseppe; Amato, Arnaldo; Rondonotti, Emanuele; Andrealli, Alida; Imperiali, Gianni; Lenoci, Nicoletta; Mandelli, Giovanna; Terreni, Natalia; Conforti, Francesco Simone; Conte, Dario; Spinzi, Giancarlo; Radaelli, Franco

2018-04-01

 Linked color imaging (LCI) is a newly developed image-enhancing endoscopy technology that provides bright endoscopic images and increases color contrast. We investigated whether LCI improves the detection of neoplastic lesions in the right colon when compared with high definition white-light imaging (WLI).  Consecutive patients undergoing colonoscopy were randomized (1:1) after cecal intubation into right colon inspection at first pass by LCI or by WLI. At the hepatic flexure, the scope was reintroduced to the cecum under LCI and a second right colon inspection was performed under WLI in previously LCI-scoped patients (LCI-WLI group) and vice versa (WLI-LCI group). Lesions detected on first- and second-pass examinations were used to calculate detection and miss rates, respectively. The primary outcome was the right colon adenoma miss rate.  Of the 600 patients enrolled, 142 had at least one adenoma in the right colon, with similar right colon adenoma detection rates (r-ADR) in the two groups (22.7 % in LCI-WLI and 24.7 % in WLI-LCI). At per-polyp analysis, double inspection of the right colon in the LCI-WLI and WLI-LCI groups resulted in an 11.8 % and 30.6 % adenoma miss rate, respectively ( P  < 0.001). No significant difference in miss rate was found for advanced adenomas or sessile serrated lesions. At per-patient analysis, at least one adenoma was identified in the second pass only (incremental ADR) in 2 of 300 patients (0.7 %) in the LCI - WLI group and in 13 of 300 patients (4.3 %) in the WLI - LCI group ( P  = 0.01).  LCI could reduce the miss rate of neoplastic lesions in the right colon. © Georg Thieme Verlag KG Stuttgart · New York.

Prox1-Heterozygosis Sensitizes the Pancreas to Oncogenic Kras-Induced Neoplastic Transformation.

PubMed

Drosos, Yiannis; Neale, Geoffrey; Ye, Jianming; Paul, Leena; Kuliyev, Emin; Maitra, Anirban; Means, Anna L; Washington, M Kay; Rehg, Jerold; Finkelstein, David B; Sosa-Pineda, Beatriz

2016-03-01

The current paradigm of pancreatic neoplastic transformation proposes an initial step whereby acinar cells convert into acinar-to-ductal metaplasias, followed by progression of these lesions into neoplasias under sustained oncogenic activity and inflammation. Understanding the molecular mechanisms driving these processes is crucial to the early diagnostic and prevention of pancreatic cancer. Emerging evidence indicates that transcription factors that control exocrine pancreatic development could have either, protective or facilitating roles in the formation of preneoplasias and neoplasias in the pancreas. We previously identified that the homeodomain transcription factor Prox1 is a novel regulator of mouse exocrine pancreas development. Here we investigated whether Prox1 function participates in early neoplastic transformation using in vivo, in vitro and in silico approaches. We found that Prox1 expression is transiently re-activated in acinar cells undergoing dedifferentiation and acinar-to-ductal metaplastic conversion. In contrast, Prox1 expression is largely absent in neoplasias and tumors in the pancreas of mice and humans. We also uncovered that Prox1-heterozygosis markedly increases the formation of acinar-to-ductal-metaplasias and early neoplasias, and enhances features associated with inflammation, in mouse pancreatic tissues expressing oncogenic Kras. Furthermore, we discovered that Prox1-heterozygosis increases tissue damage and delays recovery from inflammation in pancreata of mice injected with caerulein. These results are the first demonstration that Prox1 activity protects pancreatic cells from acute tissue damage and early neoplastic transformation. Additional data in our study indicate that this novel role of Prox1 involves suppression of pathways associated with inflammatory responses and cell invasiveness. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Acinar cell cystadenoma of the pancreas: a benign neoplasm or non-neoplastic ballooning of acinar and ductal epithelium?

PubMed

Singhi, Aatur D; Norwood, Stephanie; Liu, Ta-Chiang; Sharma, Rajni; Wolfgang, Christopher L; Schulick, Richard D; Zeh, Herbert J; Hruban, Ralph H

2013-09-01

Acinar cell cystadenoma (ACA) of the pancreas was initially described as a non-neoplastic cyst of the pancreas and, at that time, referred to as "acinar cystic transformation." In subsequent studies, these lesions were given the designation of "-oma," despite the relative lack of evidence supporting a neoplastic process. To characterize these lesions further, we examined the clinical, pathologic, and immunohistochemical features of 8 ACAs. The majority of patients were female (7 of 8, 88%) and ranged in age from 18 to 57 years (mean, 43 y). Grossly, the cysts involved the head (n=5), body (n=1), or the entire pancreas (n=2). ACAs were either multilocular (n=4) or unilocular (n=4) and ranged in size from 1.8 to 15 cm (mean, 6.8 cm). Histologically, multilocular ACAs were lined by patches of acinar and ductal epithelium. Immunolabeling, including double-labeling for cytokeratin 19 and chymotrypsin, highlighted the patchy pattern of the ductal and acinar cells lining the cysts. In some areas, the cysts with patches of acinar and ductal differentiation formed larger locules with incomplete septa as they appeared to fuse with other cysts. In contrast, the unilocular cases were lined by 1 to 2 cell layers of acinar cells with little intervening ductal epithelium. Nuclear atypia, mitotic figures, necrosis, infiltrative growth, and associated invasive carcinoma were absent in all cases. In addition, we assessed the clonal versus polyclonal nature of ACAs, occurring in women, using X-chromosome inactivation analysis of the human androgen receptor (AR) gene. Five of 7 cases were informative and demonstrated a random X-chromosome inactivation pattern. Clinical follow-up information was available for all patients, and follow-up ranged from 10 months to 7.8 years (mean, 3.6 y), with no evidence of recurrence or malignant transformation. We hypothesize that early lesions are marked by acinar dilatation that expands into and incorporates smaller ductules and later larger ducts

Non-Whipple Operations in the Management of Benign, Premalignant and Early Cancerous Duodenal Lesions.

PubMed

Papalampros, Alexandros; Moris, Demetrios; Petrou, Athanasios; Dimitrokallis, Nikolaos; Karavokyros, Ioannis; Schizas, Dimitrios; Delladetsima, Ioanna; Pappas, Theodore N; Felekouras, Evangelos

2017-03-01

We reviewed our 20-year experience with non-Whipple operations (pancreas-preserving duodenectomy and transduodenal ampullectomy) for the treatment of benign, premalignant or early-stage malignant duodenal lesions. Twenty-four patients who underwent non-Whipple operations between January 1996 and December 2015 were identified from an institutional database and retrospectively analyzed. Between 1996 and 2015, 10 patients underwent pancreas-preserving duodenectomy and 14 patients underwent transduodenal ampullectomy. The mean follow-up was 25.8 months (range=6-54 months) and no patient was lost to follow-up. Eighteen patients had preoperative diagnosis of duodenal adenomatosis, three patients had preoperative diagnosis of duodenal adenocarcinoma, one had a bleeding polyp and two had localized inflammation. Average operative time was 145 min (range=127-168 min) for transduodenal ampullectomy and 183 min (range=173-200 min) for pancreas-preserving duodenectomy (p<0.05). The estimated blood loss for transduodenal ampullectomy was 85 vs. 125 ml for pancreas-preserving duodenectomy (p<0.05). Early postoperative complications were noted in 13 cases (54.17%). There were no postoperative (90-day) deaths observed in this series and there were no recurrences during follow-up for the patients operated on with neoplastic lesions. For carefully selected patients, transduodenal ampullectomy and pancreas-preserving duodenectomy may be used in place of the Whipple operation for benign and occasionally early-stage malignant (Tis and T1) duodenal and ampullary disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Differential diagnosis of well-differentiated squamous cell carcinoma from non-neoplastic oral mucosal lesions: New cytopathologic evaluation method dependent on keratinization-related parameters but not nuclear atypism.

PubMed

Hara, Hitoshi; Misawa, Tsuneo; Ishii, Eri; Nakagawa, Miki; Koshiishi, Saki; Amemiya, Kenji; Oyama, Toshio; Tominaga, Kazuya; Cheng, Jun; Tanaka, Akio; Saku, Takashi

2017-05-01

The cytology of oral squamous cell carcinoma (SCC) is challenging because oral SCC cells tend to be well differentiated and lack nuclear atypia, often resulting in a false negative diagnosis. The purpose of this study was to establish practical cytological parameters specific to oral SCCs. We reviewed 123 cases of malignancy and 53 of non-neoplastic lesions of the oral mucosa, which had been diagnosed using both cytology and histopathology specimens. From those, we selected 12 SCC and 4 CIS cases that had initially been categorized as NILM to ASC-H with the Bethesda system, as well as 4 non-neoplastic samples categorized as LSIL or ASC-H as controls, and compared their characteristic findings. After careful examinations, we highlighted five cytological parameters, as described in Results. Those 20 cytology samples were then reevaluated by 4 independent examiners using the Bethesda system as well as the 5 parameters. Five cytological features, (i) concentric arrangement of orangeophilic cells (indicating keratin pearls), (ii) large number of orangeophilic cells, (iii) bizarre-shaped orangeophilic cells without nuclear atypia, (iv) keratoglobules, and (v) uneven filamentous cytoplasm, were found to be significant parameters. All malignant cases contained at least one of those parameters, while none were observed in the four non-neoplastic cases with nuclear atypia. In reevaluations, the Bethesda system did not help the screeners distinguish oral SCCs from non-neoplastic lesions, while use of the five parameters enabled them to make a diagnosis of SCC. Recognition of the present five parameters is useful for oral SCC cytology. Diagn. Cytopathol. 2017;45:406-417. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Can endoscopic ultrasonography differentiate nonneoplastic from neoplastic gallbladder polyps?

PubMed

Akatsu, Tomotaka; Aiura, Koichi; Shimazu, Motohide; Ueda, Masakazu; Wakabayashi, Go; Tanabe, Minoru; Kawachi, Shigeyuki; Kitajima, Masaki

2006-02-01

The present study aimed to clarify the endoscopic ultrasonography (EUS) features of nonneoplastic (cholesterol polyps and adenomyomatosis) and neoplastic (adenoma and adenocarcinoma) gallbladder polyps and to evaluate the effectiveness and limitation of EUS in the differential diagnosis of these lesions. We retrospectively compared EUS images with histologic findings in 29 surgical cases with gallbladder polyps with a diameter of 10 to 20 mm. Those cases were indicated for surgery based on the findings of a sessile appearance, a solitary lesion, low echogenicity, and/or a lobulated surface. Six of 10 cholesterol polyps were atypically seen as partially or completely hypoechoic due to predominant proliferation of glandular epithelia. Nine of 10 cholesterol polyps demonstrated an aggregation of hyperechoic spots, which represented multiple granules of cholesterosis. All adenomyomatoses (n = 10) showed multiple microcysts, which corresponded to proliferated Rokitansky-Aschoff sinuses. However, three of nine neoplastic lesions (three adenomas and six adenocarcinomas) showed one of these signs due to concomitant cholesterosis (n = 2) or proliferated Rokitansky-Aschoff sinuses (n = 1). In conclusion, 69% (20/29) of gallbladder polyps larger than 10 mm that were preoperatively suspected of malignancy were nonneoplastic. An aggregation of hyperechoic spots and multiple microcysts are considered to be important predictive factors for cholesterol polyps and adenomyomatosis, respectively. However, we should caution that these findings can also occur in neoplastic polyps when they contain a concomitant nonneoplastic component (cholesterosis or proliferated Rokitansky-Aschoff sinuses).

Proposed Terminology and Classification of Pre-Malignant Neoplastic Conditions: A Consensus Proposal.

PubMed

Valent, Peter; Akin, Cem; Arock, Michel; Bock, Christoph; George, Tracy I; Galli, Stephen J; Gotlib, Jason; Haferlach, Torsten; Hoermann, Gregor; Hermine, Olivier; Jäger, Ulrich; Kenner, Lukas; Kreipe, Hans; Majeti, Ravindra; Metcalfe, Dean D; Orfao, Alberto; Reiter, Andreas; Sperr, Wolfgang R; Staber, Philipp B; Sotlar, Karl; Schiffer, Charles; Superti-Furga, Giulio; Horny, Hans-Peter

2017-12-01

Cancer evolution is a step-wise non-linear process that may start early in life or later in adulthood, and includes pre-malignant (indolent) and malignant phases. Early somatic changes may not be detectable or are found by chance in apparently healthy individuals. The same lesions may be detected in pre-malignant clonal conditions. In some patients, these lesions may never become relevant clinically whereas in others, they act together with additional pro-oncogenic hits and thereby contribute to the formation of an overt malignancy. Although some pre-malignant stages of a malignancy have been characterized, no global system to define and to classify these conditions is available. To discuss open issues related to pre-malignant phases of neoplastic disorders, a working conference was organized in Vienna in August 2015. The outcomes of this conference are summarized herein and include a basic proposal for a nomenclature and classification of pre-malignant conditions. This proposal should assist in the communication among patients, physicians and scientists, which is critical as genome-sequencing will soon be offered widely for early cancer-detection. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Hypothalamic beta-endorphin neurons suppress preneoplastic and neoplastic lesions development in 1,2-dimethylhydrazine induced rat colon cancer model.

PubMed

Murugan, Sengottuvelan; Dave, Yatee; Rakhit, Ankush; Sarkar, Dipak K

2017-01-01

In recent years, experimental studies demonstrated negative impacts of impaired body stress response on colonic pathologies. In this study, we tested if reducing body stress response by the use of β-endorphin (BEP) neuronal transplants in the hypothalamus suppresses pre-neoplastic and neoplastic lesions. Colon cancer was induced by injecting 1,2-dimethylhydrazine (DMH) for sixteen weeks in Sprague Dawley rats with BEP neuron transplants or control neuron transplants, and their colonic histopathologies, colon tissue levels of pro-inflammatory cytokines and epithelial-mesenchymal transition (EMT) proteins and splenic levels of cytotoxic proteins were measured. Our results revealed that DMH induced tumors in colon at 100% incidence in control rats but failed to induce colonic tumors in 70% of animal with BEP neuronal transplants. The mean volume of tumor at the colon was smaller in BEP neurons transplanted rats than those in controls. Histopathologies of colon tissues revealed that BEP neurons transplanted animals had lesser tissue lesions such as aberrant crypt foci (ACF) and adenocarcinoma development in the colon than those in control groups. Immunohistochemical and western blot analyses identified reduced expression of Ki-67, TNF-α and NF-κB nuclear translocation in colonic tissues of BEP neurons transplanted rats than those in controls. BEP neurons transplanted rats also showed reduced expressions of transcription factors linked to EMT like Snail, Twist, and N-cadherin, but increased the levels of an epithelial cell marker E-cadherin in colon tissue. Furthermore, splenic NK cells cytolytic proteins such as perforin, granzyme B and IFN-γ levels in BEP neurons transplanted rats were higher than those in control rats. These data suggest that BEP neuron transplants suppress the growth and progression of colonic tumors possibly by decreasing inflammatory mileu and EMT via activation of innate immune responses.

A first immunohistochemistry study of transketolase and transketolase-like 1 expression in canine hyperplastic and neoplastic mammary lesions.

PubMed

Burrai, Giovanni Pietro; Tanca, Alessandro; Cubeddu, Tiziana; Abbondio, Marcello; Polinas, Marta; Addis, Maria Filippa; Antuofermo, Elisabetta

2017-01-31

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.

Prevalence of cervical neoplastic lesions and Human Papilloma Virus infection in Egypt: National Cervical Cancer Screening Project

PubMed Central

Abd El All, Howayda S; Refaat, Amany; Dandash, Khadiga

2007-01-01

Background 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. Methods 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). Results 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

Histopathological Study of Central Nervous System Lesions: Emphasizing Association of Neoplasms with ABO Blood Groups.

PubMed

Kumarguru, B N; Pallavi, P; Sunila; Manjunath, G V; Vasan, T S; Rajalakshmi, B R

2017-04-01

The Central Nervous System (CNS) lesions show considerable geographic and racial variations with respect to the incidence and the pattern of distribution of lesions. The ABO blood status is a readily accessible factor in genetic constitution of the patients. It has been shown to be associated with many diseases. But the influence of blood group status on the pathogenesis of brain tumours is still unclear. To study various histopathological patterns of CNS lesions and to evaluate the association of CNS tumours with the distribution of ABO blood groups in documented cases. In the present study, 147 cases were analyzed. It was an analytical type of study, done at JSS Medical College, Mysore, over a period of 2 years and 8 months from January 2009 to August 2011. Histopathology slides were routinely stained by Haematoxylin and Eosin (H&E) stain. Special stains were performed in selected cases. Blood group of the patients and the control group were documented. Blood group distribution pattern was assessed in relation to histopathological diagnosis of various CNS tumours. Histopathological diagnosis of 147 cases included neoplastic lesions (84.35%) and non-neoplastic lesions (15.64%). Neoplastic lesions (84.35%) constituted the majority, which included neuroepithelial tumours (29.25%) as predominant pattern. Non-neoplastic lesions constituted only 15.64%, which included inflammatory lesion (8.16%) as the predominant pattern. ABO blood group data was available in 92 cases (84.4%) of neoplastic lesions, which included 71 cases (48.29%) of primary CNS neoplasms categorized according to WHO grades. The control group constituted 21,067 healthy voluntary donors. Blood group O was the most frequent blood group in neoplastic lesions (40.21%) and primary CNS neoplasms categorized according to WHO grades (45.07%). The association between the CNS neoplasms and ABO blood groups was not statistically significant (p = 0.055). But a definite change in the pattern of distribution of ABO

Three Cases of Intravascular Large B-Cell Lymphoma Detected in a Biopsy of Skin Lesions.

PubMed

Arai, Takashi; Kato, Yukihiko; Funaki, Maki; Shimamura, Sanae; Yokogawa, Naoto; Sugii, Syoji; Tsuboi, Ryoji

2016-01-01

Intravascular large B-cell lymphoma (IVL) is a rare subtype of extranodal malignant lymphoma. The proliferation of neoplastic B cells within small blood vessels causes eruptions and other symptoms in a variety of organs. The random skin biopsy is useful for diagnosing this condition in its early stages. In order to assess the diagnostic utility of this method, we examined 3 cases with the aim of comparing the occurrence of tumor cells in lesional and healthy-looking skin by performing a random skin biopsy of 32 separate sites. Our findings from the total of 32 biopsy specimens collected from the 3 cases indicated that 16 of the 17 sites on the lesional skin and 1 of the 15 sites on the healthy-looking skin were positive for neoplastic cells. This finding suggested that IVL cells occurred more frequently in the lesional skin than in the healthy-looking skin. © 2016 S. Karger AG, Basel.

Diagnostic accuracy of pit pattern and vascular pattern analyses in colorectal lesions.

PubMed

Wada, Yoshiki; Kashida, Hiroshi; Kudo, Shin-ei; Misawa, Masashi; Ikehara, Nobunao; Hamatani, Shigeharu

2010-07-01

The aim of this prospective study is to compare the usefulness of magnifying narrow band imaging (NBI) and magnifying chromoendoscopy in the diagnosis of colorectal lesions. The subjects were 1185 patients who underwent a complete colonoscopic examination and endoscopic or surgical treatment, from January 2006 to February 2008. A total of 1473 lesions were evaluated (53 hyperplastic polyps, 1317 adenomas, 103 submucosally invasive cancers). The digital images with NBI or chromoendoscopy were recorded and diagnosed independently from each other by two endoscopists who were blinded to the final pathological diagnosis. We could differentiate between neoplastic and non-neoplastic lesions with sensitivity of 88.9%, specificity of 98.5% and accuracy of 98.2% according to the vascular pattern. By recognizing an irregular or sparse pattern with NBI, massively invasive submucosal cancer could be diagnosed with the sensitivity and specificity of 94.9% and 76.0%. Using chromoendoscopy, we could differentiate between neoplastic and non-neoplastic lesions with sensitivity of 86.8% and specificity of 99.2%. We were able to differentiate between massively invasive cancers and slightly invasive cancers using the pit patterns with sensitivity of 89.7% and specificity of 88.0%. The specificity was superior to that of NBI colonoscopy. Both NBI and chromoendoscopy can be useful for distinguishing between neoplastic and non-neoplastic lesions. In the diagnosis of submucosal cancer, pit pattern diagnosis was slightly superior to vascular pattern diagnosis. It is desirable to perform chromoendoscopy in addition to NBI for distinguishing between slightly and massively invasive submucosal cancer lesions and determining the treatment.

Large contribution of human papillomavirus in vaginal neoplastic lesions: a worldwide study in 597 samples.

PubMed

Alemany, L; Saunier, M; Tinoco, L; Quirós, B; Alvarado-Cabrero, I; Alejo, M; Joura, E A; Maldonado, P; Klaustermeier, J; Salmerón, J; Bergeron, C; Petry, K U; Guimerà, N; Clavero, O; Murillo, R; Clavel, C; Wain, V; Geraets, D T; Jach, R; Cross, P; Carrilho, C; Molina, C; Shin, H R; Mandys, V; Nowakowski, A M; Vidal, A; Lombardi, L; Kitchener, H; Sica, A R; Magaña-León, C; Pawlita, M; Quint, W; Bravo, I G; Muñoz, N; de Sanjosé, S; Bosch, F X

2014-11-01

This work describes the human papillomavirus (HPV) prevalence and the HPV type distribution in a large series of vaginal intraepithelial neoplasia (VAIN) grades 2/3 and vaginal cancer worldwide. We analysed 189 VAIN 2/3 and 408 invasive vaginal cancer cases collected from 31 countries from 1986 to 2011. After histopathological evaluation of sectioned formalin-fixed paraffin-embedded samples, HPV DNA detection and typing was performed using the SPF-10/DNA enzyme immunoassay (DEIA)/LiPA25 system (version 1). A subset of 146 vaginal cancers was tested for p16(INK4a) expression, a cellular surrogate marker for HPV transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance. HPV DNA was detected in 74% (95% confidence interval (CI): 70-78%) of invasive cancers and in 96% (95% CI: 92-98%) of VAIN 2/3. Among cancers, the highest detection rates were observed in warty-basaloid subtype of squamous cell carcinomas, and in younger ages. Concerning the type-specific distribution, HPV16 was the most frequently type detected in both precancerous and cancerous lesions (59%). p16(INK4a) overexpression was found in 87% of HPV DNA positive vaginal cancer cases. HPV was identified in a large proportion of invasive vaginal cancers and in almost all VAIN 2/3. HPV16 was the most common type detected. A large impact in the reduction of the burden of vaginal neoplastic lesions is expected among vaccinated cohorts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinicopathological importance of Papanicolaou smears for the diagnosis of premalignant and malignant lesions of the cervix.

PubMed

Bukhari, Mulazim Hussain; Saba, Kanwal; Qamar, Samina; Majeed, Muhammad Muddasar; Niazi, Shahida; Naeem, Samina

2012-01-01

Premalignant and malignant lesions are not uncommon in Pakistani women, especially in the older age-groups This study was conducted to determine the clinicopathological importance of conventional Papanicolaou (Pap) smears for the diagnosis of premalignant and malignant lesions of the cervix. Pap smears of 1000 women were examined from January 2007 to June 2009. Only cases with neoplastic cytology were included. The overall frequency of normal, inadequate, neoplastic, and infective smears was 50%, 1.8%, 10.2%, and 38.3%, respectively. Most of the patients (67%) were in the postmenopausal age-group, with the mean age being 44.7±15.63 years. The commonest clinical signs/symptoms seen among the 102 patients with neoplastic gynecological lesions were vaginal discharge and abnormal bleeding (93/102;(91.2% and 62/102;60.7%). Of the 102 cases with neoplastic lesions 46 patients (45%) had low-grade squamous cell intraepithelial lesions (LSILs), 22 (21.5%) had high-grade squamous cell intraepithelial lesions (HSILs), 14 (13.7%) had squamous cell carcinoma, and 6 (5.8%) showed features of adenocarcinoma. Ten (9.8%) cases showed cytology of atypical squamous cells of undetermined significance (ASCUS) and four (3.9%) cases had atypical glandular cells of undetermined significance (AGUS). We conclude that cervical smear examination is well suited for diagnosing neoplastic disease. It is clear that cervical neoplastic lesions are becoming a problem in Pakistan.

Ultrasonographic Differentiation Between Nodular Hyperplasia and Neoplastic Follicular-Patterned Lesions of the Thyroid Gland.

PubMed

Song, Yong Sub; Kim, Ji-Hoon; Na, Dong Gyu; Min, Hye Sook; Won, Jae-Kyung; Yun, Tae Jin; Choi, Seung Hong; Sohn, Chul-Ho

2016-08-01

We evaluate the gray-scale ultrasonographic characteristics that differentiate between nodular hyperplasia (NH) and neoplastic follicular-patterned lesions (NFPLs) of the thyroid gland. Ultrasonographic features of 750 patients with 832 thyroid nodules (NH, n = 361; or NFPLs, follicular adenoma, n = 123; follicular carcinoma, n = 159; and follicular variant papillary carcinoma, n = 189) were analyzed. Except for echogenicity, over two-thirds of the cases of NH and NFPLs share the ultrasonographic characteristics of solid internal content, a well-defined smooth margin and round-to-ovoid shape. Independent predictors for NH were non-solid internal content (sensitivity 27.1%, specificity 90.2%), isoechogenicity (sensitivity 69.5%, specificity 63.5%) and an ill-defined margin (sensitivity 18.8%, specificity 94.5%). Independent predictors for NFPLs were hypoechogenicity (sensitivity 60.5%, specificity 70.4%), marked hypoechogenicity (sensitivity 2.8%, specificity 99.4%) and taller-than-wide shape (sensitivity 6.6%, specificity 98.1%). Although NH and NFPLs commonly share ultrasonographic characteristics, non-solid internal content and ill-defined margin are specific to NH and marked hypoechogenicity and taller-than-wide shape are specific to NFPLs. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Clinicopathological importance of Papanicolaou smears for the diagnosis of premalignant and malignant lesions of the cervix

PubMed Central

Bukhari, Mulazim Hussain; Saba, Kanwal; Qamar, Samina; Majeed, Muhammad Muddasar; Niazi, Shahida; Naeem, Samina

2012-01-01

Background: Premalignant and malignant lesions are not uncommon in Pakistani women, especially in the older age-groups Aim: This study was conducted to determine the clinicopathological importance of conventional Papanicolaou (Pap) smears for the diagnosis of premalignant and malignant lesions of the cervix. Materials and Methods: Pap smears of 1000 women were examined from January 2007 to June 2009. Only cases with neoplastic cytology were included. Results: The overall frequency of normal, inadequate, neoplastic, and infective smears was 50%, 1.8%, 10.2%, and 38.3%, respectively. Most of the patients (67%) were in the postmenopausal age-group, with the mean age being 44.7±15.63 years. The commonest clinical signs/symptoms seen among the 102 patients with neoplastic gynecological lesions were vaginal discharge and abnormal bleeding (93/102;(91.2% and 62/102;60.7%). Of the 102 cases with neoplastic lesions 46 patients (45%) had low-grade squamous cell intraepithelial lesions (LSILs), 22 (21.5%) had high-grade squamous cell intraepithelial lesions (HSILs), 14 (13.7%) had squamous cell carcinoma, and 6 (5.8%) showed features of adenocarcinoma. Ten (9.8%) cases showed cytology of atypical squamous cells of undetermined significance (ASCUS) and four (3.9%) cases had atypical glandular cells of undetermined significance (AGUS). Conclusion: We conclude that cervical smear examination is well suited for diagnosing neoplastic disease. It is clear that cervical neoplastic lesions are becoming a problem in Pakistan. PMID:22438612

A rare neoplastic growth on the ear lobe.

PubMed

Rovere, R K; Hilgert, S F; da Costa, P Camara; de Lima, A S

2014-01-01

We report a case of an 83-year-old previously healthy female patient presenting with a swiftly evolving erythematous violaceous, infiltrative, ulcerated onion like mass with hyperkeratotic surface on the left ear lobe. The lesion was excised and resulted as an atypical fibroxanthoma, an extremely rare neoplastic growth, being a superficial variant of pleomorphic malignant fibrous histiocytoma. A brief review of dia-gnosis, treatment and prognosis is discussed.

Epidemiological survey of oral lesions in children and adolescents in a Brazilian population.

PubMed

Pessôa, Camila Porto; Alves, Técia Daltro Borges; dos Santos, Nilton César Nogueira; dos Santos, Heloísa Laís Rosário; Azevedo, Alana de Cássia Silva; dos Santos, Jean Nunes; Oliveira, Márcio Campos

2015-11-01

To identify the most frequent oral lesions in children and adolescents in Reference Units of Oral Lesions of Public Universities of Bahia, Brazil, in the period between 1996 and 2010, and estimate the association between socio-demographic factors and type of oral lesions found. Cross-sectional study using secondary data obtained from medical records, records of requests and reports of biopsies from patients aged between 0 and 19 years treated in Reference Units of Oral Lesions of Public Universities in Bahia, Brazil, in the period between 1996 and 2010. For data analysis, we used descriptive analysis of the variables, bivariate analysis by calculating the prevalence ratios (PR) to assess the association between oral lesions and gender, age and skin color, and the analysis of potential modifying and confounding effects by logistic regression modeling. To calculate the p-value of associations, we used the chi-square test, and p<0.05 was considered statistically significant. There were 360 records of patients between 0 and 19 years (8.7% of total records). The results revealed 72 different types of lesions. The most prevalent lesions were mucoceles (14.2%), fibroma (5.6%) and pyogenic granuloma (5.3%). The variable "age" was the only socio-demographic characteristics among those analyzed that showed a statistically significant association with both neoplastic and non-neoplastic lesions, according to bivariate analysis, considering the rates adjusted for potential confounders. Neoplastic lesions appeared more often in the age group 0-9 years, while the non-neoplastic lesions were more prevalent in individuals 10-19 years. There was no effect modification noted in the predictive models analyzed. The study identified the existence of a broad range of oral lesions affecting children and adolescents. Most of the lesions found were of the non-neoplastic type. The age of individuals was associated with the type of oral lesion found. Copyright © 2015 Elsevier Ireland Ltd

Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes.

PubMed

Suliman, Salwa; Mustafa, Kamal; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Osdal, Tereza; Hamza, Amani O; Sun, Yang; Parajuli, Himalaya; Waag, Thilo; Nickel, Joachim; Johannessen, Anne Christine; McCormack, Emmet; Costea, Daniela Elena

2016-07-01

This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOK(Luc)) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOK(Luc) previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOK(Luc) + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOK(Luc) both in vitro in 3D-OT and in vivo in xenografts formed by DOK(Luc) alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOK(Luc) + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOK(Luc), while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

DIAGNOSTIC CRITERIA FOR PROLIFERATIVE THYROID LESIONS IN BONY FISHES

EPA Science Inventory

Thyroid proliferative lesions are rather common in bony fishes but disagreement exists in the fish pathology community concerning diagnostic criteria for hyperplastic versus neoplastic lesions. To simplify the diagnosis of proliferative thyroid lesions and to reduce confusion reg...

Assessment of different excitation wavelengths for photodetecting neoplastic urothelial lesions by laser-induced autofluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Anidjar, Maurice; Cussenot, Oliver; Avrillier, Sigrid; Ettori, Dominique; Teillac, Pierre; Le Duc, Alain

1996-04-01

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.

CINtec PLUS immunocytochemistry as a tool for the cytologic diagnosis of glandular lesions of the cervix uteri.

PubMed

Ravarino, Alberto; Nemolato, Sonia; Macciocu, Elena; Fraschini, Matteo; Senes, Giancarlo; Faa, Gavino; Negri, Giovanni

2012-11-01

Cytologic findings of glandular lesions of the cervix uteri are often difficult to evaluate. We studied the usefulness of CINtec PLUS p16/Ki-67 double stain (mtm laboratories, Heidelberg, Germany) for the diagnosis of glandular lesions. The study included 47 abnormal results on liquid-based cytologic tests with a subsequent histologic diagnosis of adenocarcinoma in situ or with early invasion, and 16 samples with negative results on follow-up. All samples were stained with CINtec PLUS p16/Ki-67 double stain. Of the neoplastic samples, 7 were excluded because of insufficient residual cellularity or loss of neoplastic cells. Of the samples that were adequate, 92.5% were stained with CINtec PLUS, whereas 7.5% were judged inconclusive. All inconclusive cases were at least 3 years old. Of the 16 negative samples, 15 (93.8%) stained negative and only 1 (6.2%) showed several positive clusters of cells. Our study shows that CINtec PLUS is a robust and useful tool for the diagnosis of glandular lesions of the cervix uteri.

KRAS Mutation and Epithelial-Macrophage Interplay in Pancreatic Neoplastic Transformation.

PubMed

Bishehsari, Faraz; Zhang, Lijuan; Barlass, Usman; Preite, Nailliw; Turturro, Sanja; Najor, Matthew S; Shetuni, Brandon B; Zayas, Janet P; Mahdavinia, Mahboobeh; Abukhdeir, Abde M; Keshavarzian, Ali

2018-05-14

Pancreatic ductal adenocarcinoma (PDA) is characterized by epithelial mutations in KRAS and prominent tumor-associated inflammation, including macrophage infiltration. But knowledge of early interactions between neoplastic epithelium and macrophages in PDA carcinogenesis is limited. Using a pancreatic organoid model, we found that the expression of mutant KRAS in organoids increased i) ductal to acinar gene expression ratios, ii) epithelial cells proliferation, and iii) colony formation capacity in vitro, and endowed pancreatic cells with the ability to generate neoplastic tumors in vivo. KRAS mutations induced a pro-tumorigenic phenotype in macrophages. Altered macrophages decreased epithelial Pigment Epithelial Derived Factor (PEDF) expression and induced a cancerous phenotype. We validated our findings using annotated patient samples from The Cancer Genome Atlas (TCGA) as well as in our human PDA specimens. Epithelium-macrophage cross talk occurs early in pancreatic carcinogenesis where KRAS directly induces cancer-related phenotypes in epithelium, and also promotes a pro-tumorigenic phenotype in macrophages, in turn augmenting neoplastic growth. This article is protected by copyright. All rights reserved. © 2018 UICC.

Differentiating neoplastic from benign lesions of the pancreas: translational techniques.

PubMed

Khalid, Asif

2009-11-01

There has been substantial recent progress in our ability to image and sample the pancreas leading to the improved recognition of benign and premalignant conditions of the pancreas such as autoimmune pancreatitis (AIP) and mucinous lesions (mucinous cystic neoplasms [MCN] and intraductal papillary mucinous neoplasms [IPMN]), respectively. Clinically relevant and difficult situations that continue to be faced in this context include differentiating MCN and IPMN from nonmucinous pancreatic cysts, the early detection of malignant degeneration in MCN and IPMN, and accurate differentiation between pancreatic cancer and inflammatory masses, especially AIP. These challenges arise primarily due to the less than perfect sensitivity for malignancy utilizing cytological samples obtained via EUS and ERCP. Aspirates from pancreatic cysts are often paucicellular further limiting the accuracy of cytology. One approach to improve the diagnostic yield from these very small samples is through the use of molecular techniques. Because the development of pancreatic cancer and malignant degeneration in MCN and IPMN is associated with well studied genetic insults including oncogene activation (eg, k-ras), tumor suppressor gene losses (eg, p53, p16, and DPC4), and genome maintenance gene mutations (eg, BRCA2 and telomerase), detecting these molecular abnormalities may aid in improving our diagnostic accuracy. A number of studies have shown the utility of testing clinical samples from pancreatic lesions and bile duct strictures for these molecular markers of malignancy to differentiate between cancer and inflammation. The information from these studies will be discussed with emphasis on how to use this information in clinical practice.

Clinical monitoring of early caries lesions using cross polarization optical coherence tomography

NASA Astrophysics Data System (ADS)

Fried, Daniel; Staninec, Michal; Darling, Cynthia L.; Chan, Kenneth H.; Pelzner, Roger B.

New methods are needed for the nondestructive measurement of tooth demineralization and remineralization and to monitor the progression of incipient caries lesions (tooth decay) for effective nonsurgical intervention and to evaluate the performance of anti-caries treatments such as chemical treatments or laser irradiation. Studies have shown that optical coherence tomography (OCT) has great potential to fulfill this role, since it can be used to measure the depth and severity of early lesions with an axial resolution exceeding 10-μm. It is easy to apply in vivo and it can be used to image the convoluted topography of tooth occlusal surfaces. In this paper we present early results from two clinical studies underway to measure the effect of fluoride intervention on early lesions. CP-OCT was used to monitor early lesions on enamel and root surfaces before and after intervention with fluoride varnish. The lesion depth and internal structure were resolved for all the lesions examined and some lesions had well defined surface zones of lower reflectivity that may be indicative of arrested lesions. Changes were also noted in the structure of some of the lesions after fluoride intervention.

A Microbiomic Analysis in African Americans with Colonic Lesions Reveals Streptococcus sp.VT162 as a Marker of Neoplastic Transformation

PubMed Central

Brim, Hassan; Yooseph, Shibu; Lee, Edward; Sherif, Zaki A.; Abbas, Muneer; Laiyemo, Adeyinka O.; Varma, Sudhir; Torralba, Manolito; Dowd, Scot E.; Nelson, Karen E.; Pathmasiri, Wimal; Sumner, Susan; de Vos, Willem; Liang, Qiaoyi; Yu, Jun; Zoetendal, Erwin; Ashktorab, Hassan

2017-01-01

Increasing evidence suggests a role of the gut microbiota in colorectal carcinogenesis (CRC). To detect bacterial markers of colorectal cancer in African Americans a metabolomic analysis was performed on fecal water extracts. DNA from stool samples of adenoma and healthy subjects and from colon cancer and matched normal tissues was analyzed to determine the microbiota composition (using 16S rDNA) and genomic content (metagenomics). Metagenomic functions with discriminative power between healthy and neoplastic specimens were established. Quantitative Polymerase Chain Reaction (q-PCR) using primers and probes specific to Streptococcus sp. VT_162 were used to validate this bacterium association with neoplastic transformation in stool samples from two independent cohorts of African Americans and Chinese patients with colorectal lesions. The metabolomic analysis of adenomas revealed low amino acids content. The microbiota in both cancer vs. normal tissues and adenoma vs. normal stool samples were different at the 16S rRNA gene level. Cross-mapping of metagenomic data led to 9 markers with significant discriminative power between normal and diseased specimens. These markers identified with Streptococcus sp. VT_162. Q-PCR data showed a statistically significant presence of this bacterium in advanced adenoma and cancer samples in an independent cohort of CRC patients. We defined metagenomic functions from Streptococcus sp. VT_162 with discriminative power among cancers vs. matched normal and adenomas vs. healthy subjects’ stools. Streptococcus sp. VT_162 specific 16S rDNA was validated in an independent cohort. These findings might facilitate non-invasive screening for colorectal cancer. PMID:29120399

Felis catus papillomavirus types 1 and 4 are rarely present in neoplastic and inflammatory oral lesions of cats.

PubMed

Munday, John S; French, Adrienne F

2015-06-01

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.

The flavonoid chrysin attenuates colorectal pathological remodeling reducing the number and severity of pre-neoplastic lesions in rats exposed to the carcinogen 1,2-dimethylhydrazine.

PubMed

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

2013-05-01

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.

The utility of magnetic resonance imaging in the diagnosis and management of pediatric benign ovarian lesions.

PubMed

Emil, Sherif; Youssef, Fouad; Arbash, Ghaidaa; Baird, Robert; Laberge, Jean-Martin; Puligandla, Pramod; Albuquerque, Pedro

2018-01-31

The utility of magnetic resonance imaging (MRI) in the diagnosis and management of pediatric ovarian lesions has not been well defined. A retrospective review of all girls who underwent MRI evaluation of ovarian masses during the period 2009-2015 was performed. The accuracy of MRI was evaluated by comparing results with surgical findings, pathology reports, and subsequent imaging. The influence of the MRI on the treatment plan was specifically explored. Eighteen girls, 12-17years of age, underwent 27 MRIs, subsequent to ultrasound identification of ovarian lesions. Of 9 neoplastic lesions diagnosed on MRI, 8 (89%) were confirmed by surgical and pathological findings. Of 18 functional lesions, 17 (94.4%) were confirmed pathologically or by resolution on subsequent imaging. Twenty MRI exams (74%) directly influenced the treatment plan, by leading to appropriate operative intervention in 9 and appropriate observation in 11. The extent of ovarian resection was guided by MRI findings in 8 of 9 (89%) neoplastic lesions. For characterizing lesions as neoplastic, the sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of MRI were 89%, 94%, 94%, 89%, and 93% respectively. MRI can differentiate functional from neoplastic pediatric ovarian masses, and guide ovarian resection in appropriate cases. II. Copyright © 2018. Published by Elsevier Inc.

Cell-block procedure in endoscopic ultrasound-guided-fine-needle-aspiration of gastrointestinal solid neoplastic lesions

PubMed Central

Ieni, Antonio; Barresi, Valeria; Todaro, Paolo; Caruso, Rosario Alberto; Tuccari, Giovanni

2015-01-01

In the present review we have analyzed the clinical applications of endoscopic ultrasound-guided-fine-needle-aspiration (EUS-FNA) and the methodological aspects obtained by cell-block procedure (CBP) in the diagnostic approach to the gastrointestinal neoplastic pathology. CBP showed numerous advantages in comparison to the cytologic routine smears; in particular, better preservation of cell architecture, achievement of routine haematoxylin-eosin staining equivalent to histological slides and possibility to perform immunohistochemistry or molecular analyses represented the most evident reasons to choose this method. Moreover, by this approach, the differential diagnosis of solid gastrointestinal neoplasias may be more easily achieved and the background of contaminant non-neoplastic gastrointestinal avoided. Finally, biological samples collected by EUS-FNA CBP-assisted should be investigated in order to identify and quantify further potential molecular markers. PMID:26322154

Genetic biomarkers for neoplastic colorectal cancer in peripheral lymphocytes.

PubMed

Ionescu, Mirela; Ciocirlan, Mihai; Ionescu, Cristina; Becheanu, Gabriel; Gologan, Serban; Teiusanu, Adriana; Arbanas, Tudor; Mircea, Diculescu

2011-04-01

Loss of genomic stability appears as a key step in colorectal carcinogenesis. Micronucleus (MN) designates a chromosome fragment or an entire chromosme which lags behind mitosis. MN may be noticed as an additional nucleus within the cytoplasm cell during the intermediate mitosis phases. We tested the hypothesis that MN and its related anomalies may be associated with the presence of neoplastic colorectal lesions. Peripheral blood lymphocytes were cultured and microscopically examined. The frequency of micronuclei (FMN) and the presence of nucleoplasmic bridges (NPB) in binucleated cells were compared in patients with of without colorectal neoplastic lesions. We included 45 patients undergoing colonoscopy, 23 males and 22 females, with a median age of 59. 17 patients had polyps, 11 colorectal cancer (CRC) and 17 had a normal colonoscopy. The FMN was significantly higher in women than in men (8.14 vs 4.17, p=0.008); NPB were significantly less frequent in patients with advanced adenomas (>10mm or vilous) or CRC (p=0.044) when compared with patients with normal colonoscopy, hiperplastic polyps or non-advanced adenomas. Micronuclei are more frequent in women, but its frequency was not significantly different in patients with advanced adenomas or CRC. Null or low frequency values for nucleoplasmic bridges presence in peripheral lymphocyte may be predictive for advanced adenomas and colorectal cancer.

Genetic Biomarkers for Neoplastic Colorectal Cancer in Peripheral Lymphocytes

PubMed Central

Ionescu, Mirela; Ciocirlan, Mihai; Ionescu, Cristina; Becheanu, Gabriel; Gologan, Serban; Teiusanu, Adriana; Arbanas, Tudor; Mircea, Diculescu

2011-01-01

ABSTRACT Background: Loss of genomic stability appears as a key step in colorectal carcinogenesis. Micronucleus (MN) designates a chromosome fragment or an entire chromosme which lags behind mitosis. MN may be noticed as an additional nucleus within the cytoplasm cell during the intermediate mitosis phases. We tested the hypothesis that MN and its related anomalies may be associated with the presence of neoplastic colorectal lesions. Method: Peripheral blood lymphocytes were cultured and microscopically examined. The frequency of micronuclei (FMN) and the presence of nucleoplasmic bridges (NPB) in binucleated cells were compared in patients with of without colorectal neoplastic lesions. Results: We included 45 patients undergoing colonoscopy, 23 males and 22 females, with a median age of 59. 17 patients had polyps, 11 colorectal cancer (CRC) and 17 had a normal colonoscopy. The FMN was significantly higher in women than in men (8.14 vs 4.17, p=0.008); NPB were significantly less frequent in patients with advanced adenomas (>10mm or vilous) or CRC (p=0.044) when compared with patients with normal colonoscopy, hiperplastic polyps or non-advanced adenomas. Conclusion: Micronuclei are more frequent in women, but its frequency was not significantly different in patients with advanced adenomas or CRC. Null or low frequency values for nucleoplasmic bridges presence in peripheral lymphocyte may be predictive for advanced adenomas and colorectal cancer. PMID:22205889

Multispectral near-IR reflectance imaging of simulated early occlusal lesions: Variation of lesion contrast with lesion depth and severity

PubMed Central

Simon, Jacob C.; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

2014-01-01

Background and Objectives Early demineralization appears with high contrast at near-IR wavelengths due to a ten to twenty fold difference in the magnitude of light scattering between sound and demineralized enamel. Water absorption in the near-IR has a significant effect on the lesion contrast and the highest contrast has been measured in spectral regions with higher water absorption. The purpose of this study was to determine how the lesion contrast changes with lesion severity and depth for different spectral regions in the near-IR and compare that range of contrast with visible reflectance and fluorescence. Materials and Methods Forty-four human molars were used in this in vitro study. Teeth were painted with an acid-resistant varnish, leaving a 4×4 mm window on the occlusal surface of each tooth exposed for demineralization. Artificial lesions were produced in the unprotected windows after 12–48 hr exposure to a demineralizing solution at pH-4.5. Near-IR reflectance images were acquired over several near-IR spectral distributions, visible light reflectance, and fluorescence with 405-nm excitation and detection at wavelengths greater than 500-nm. Crossed polarizers were used for reflectance measurements to reduce interference from specular reflectance. Cross polarization optical coherence tomography (CP-OCT) was used to non-destructively assess the depth and severity of demineralization in each sample window. Matching two dimensional CP-OCT images of the lesion depth and integrated reflectivity were compared with the reflectance and fluorescence images to determine how accurately the variation in the lesion contrast represents the variation in the lesion severity. Results Artificial lesions appear more uniform on tooth surfaces exposed to an acid challenge at visible wavelengths than they do in the near-IR. Measurements of the lesion depth and severity using CP-OCT show that the lesion severity varies markedly across the sample windows and that the lesion

Non-Neoplastic and Neoplastic Pleural Endpoints Following Fiber Exposure

PubMed Central

Broaddus, V. Courtney; Everitt, Jeffrey I.; Black, Brad; Kane, Agnes B.

2011-01-01

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

Differential diagnosis of a neoplastic condition in a prehistoric juvenile individual from La Falda site, Northwest Argentina.

PubMed

Arrieta, Mario A; Mendonça, Osvaldo J; Bordach, María A

2018-06-01

Bone neoplasms or tumors are of great interest for paleopathological studies due to their close relationship with health and survivorship as well as for their epidemiologic and demographic relevance. However, the identification of these lesions in archaeological specimens is very uncommon. The aim of this paper is to report the case of skeleton R5 E#1 from the prehistoric cemetery La Falda, in the Northwest region of Argentina. During the osteopathological analysis of the skeletal series, proliferative lesions in several bones of the skeleton of a 7-10-year-old juvenile were observed (i.e., both scapulae; left clavicle, humerus, and ulna, both os coxae, femora, and fibulae, and right foot bones). Age-at-death estimation, location and distribution pattern, and morphological appearances of the lesions indicated that this juvenile suffered from a neoplastic condition. A comprehensive differential diagnosis was carried out, suggesting that these lesions were compatible with hereditary multiple osteochondromas. However, Ewing's sarcoma was not definitively ruled out as a probable diagnosis. Thus, this work adds new evidence to the existence of neoplastic conditions in the prehistoric populations of the Americas, and it contributes original data to perform a differential diagnosis for multiple proliferative lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

[Aseptic process validation and stability study of an injectable preparation of fructose (5%)-glycerol (10%) as part of a hospital clinical research program on endoscopic curative treatment for early epithelial neoplastic lesions of the gastrointestinal tract].

PubMed

Tall, M L; Salmon, D; Diouf, E; Drai, J; Filali, S; Lépilliez, V; Pioche, M; Laleye, D; Dhelens, C; Ponchon, T; Pivot, C; Pirot, F

2015-03-01

As part of a hospital clinical research program on endoscopic curative treatment for early epithelial neoplastic lesions of the gastrointestinal tract, a new hospital sterile and non-pyrogenic preparation of fructose (5%)-glycerol (10%) was realized. Under pharmaceutical legislation, the provision of this hospital preparation involves of aseptic process validation and achieve a stability study. After the aseptic process validation with Mediafill Test, the preparation was made under aseptic conditions associated with a sterilizing filtration according to the good practices preparation. Prepared flexible bags (100mL of solution) were stored for one year in a climatic chamber (25±2°C). To assess stability, the physicochemical controls (fructose concentration, glycerol concentration, hydroxy-methyl-5 furfural [5-HMF] concentration, sodium concentration, pH measure, osmolality and sub-visible particles count) and microbiological (bioburden, bacterial endotoxin and sterility) were performed at regular intervals for one year. Neither significant decrease of fructose concentration, glycerol concentration and sodium concentration nor pH, 5-HMF, osmolality variations out of specifications were observed for one year. The sub-visible particles count, the bacterial endotoxin and sterility were in accordance with the European pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. The hospital preparation was stable over one year at 25±2°C, ensuring safe administration in humans within the framework of this clinical research. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Noninvasive Assessment of Early Dental Lesion Using a Dual-Contrast Photoacoustic Tomography

PubMed Central

Cheng, Renxiang; Shao, Jiaojiao; Gao, Xiaoxiang; Tao, Chao; Ge, Jiuyu; Liu, Xiaojun

2016-01-01

Dental hard tissue lesions, including caries, cracked-tooth, etc., are the most prevalent diseases of people worldwide. Dental lesions and correlative diseases greatly decrease the life quality of patients throughout their lifetime. It is still hard to noninvasively detect these dental lesions in their early stages. Photoacoustic imaging is an emerging hybrid technology combining the high spatial resolution of ultrasound in deep tissue with the rich optical contrasts. In this study, a dual-contrast photoacoustic tomography is applied to detect the early dental lesions. One contrast, named B-mode, is related to the optical absorption. It is good at providing the sharp image about the morphological and macro-structural features of the teeth. Another contrast, named S-mode, is associated with the micro-structural and mechanical properties of the hard tissue. It is sensitive to the change of tissue properties induced by the early dental lesions. Experiments show that the comprehensive analysis of dual-contrast information can provide reliable information of the early dental lesions. Moreover, the imaging parameter of S-mode is device-independent and it could measure tissue properties quantitatively. We expect that the proposed scheme could be beneficial for improving safety, accuracy and sensitivity of the clinical diagnosis of the dental lesion. PMID:26902394

Noninvasive Assessment of Early Dental Lesion Using a Dual-Contrast Photoacoustic Tomography

NASA Astrophysics Data System (ADS)

Cheng, Renxiang; Shao, Jiaojiao; Gao, Xiaoxiang; Tao, Chao; Ge, Jiuyu; Liu, Xiaojun

2016-02-01

Dental hard tissue lesions, including caries, cracked-tooth, etc., are the most prevalent diseases of people worldwide. Dental lesions and correlative diseases greatly decrease the life quality of patients throughout their lifetime. It is still hard to noninvasively detect these dental lesions in their early stages. Photoacoustic imaging is an emerging hybrid technology combining the high spatial resolution of ultrasound in deep tissue with the rich optical contrasts. In this study, a dual-contrast photoacoustic tomography is applied to detect the early dental lesions. One contrast, named B-mode, is related to the optical absorption. It is good at providing the sharp image about the morphological and macro-structural features of the teeth. Another contrast, named S-mode, is associated with the micro-structural and mechanical properties of the hard tissue. It is sensitive to the change of tissue properties induced by the early dental lesions. Experiments show that the comprehensive analysis of dual-contrast information can provide reliable information of the early dental lesions. Moreover, the imaging parameter of S-mode is device-independent and it could measure tissue properties quantitatively. We expect that the proposed scheme could be beneficial for improving safety, accuracy and sensitivity of the clinical diagnosis of the dental lesion.

Eosinophils as a marker for invasion in vulvar squamous neoplastic lesions.

PubMed

Spiegel, Gregory W

2002-04-01

A study of eosinophils directed against vulvar neoplastic squamous epithelium was undertaken to determine whether there were thresholds per high-power field (hpf) or 10 hpf that were a marker for invasion. The presence of stromal and intraepithelial eosinophils in 33 cases of vulvar grade 3 squamous intraepithelial neoplasia (carcinoma in situ) (VIN 3) was compared with that in 38 cases of vulvar invasive carcinoma with any degree of invasion (ISC). In both incisional biopsy and excisional specimens, the presence of >3 eosinophils per high-power field (eos/hpf) and the presence of >or=5 eosinophils per 10 high-power fields (eos/10 hpf) were both significantly associated with invasion, and the presence of >or=20 eos/hpf and/or >50 eos/10 hpf was limited to cases with invasion. The presence of eosinophils within the neoplastic squamous epithelium was also limited to cases with invasion. The author proposes: 1) eosinophil counts in vulvar incisional biopsy specimens of >3/hpf and/or >or=5/10 hpf warrant a note of caution that invasion may be present even when none is identified by conventional criteria; 2) eosinophil counts of >3/hpf and/or >or=5/10 hpf in excisional specimens should raise the suspicion of invasion in cases in which only VIN 3 is identified in the initial sections, and warrant additional sections and/or levels to search for invasion; 3) the above eosinophil counts provide supportive evidence for invasion in cases with equivocal invasion by conventional criteria; and 4) the presence of >or=20 eos/hpf and/or >50 eos/10 hpf, and the presence of intraepithelial eosinophils in conjunction with >3 eos/hpf and >or=5 eos/10 hpf is virtually diagnostic of invasion.

Prevalence, location and concurrent diseases of ultrasonographic cyst-like lesions of abdominal lymph nodes in dogs.

PubMed

Liotta, A; Billen, F; Heimann, M; Hamaide, A; Rizza, M; Etienne, A L; Bolen, G

2017-04-01

Lymph nodal cyst-like lesions are occasionally identified during abdominal ultrasound in dogs. However, a study evaluating their prevalence and clinical significance is lacking. The aim of this observational cross-sectional study was to evaluate prevalence, most common location and concurrent diseases of cyst-like lymph nodes detected during abdominal ultrasound. Affected lymph nodes, patient signalment and concurrent diseases of dogs with cyst-like lymph nodal lesions having undergone abdominal ultrasound over a one-year period were recorded. Twenty-three affected lymph nodes were observed in 17/553 dogs (prevalence=3 per cent). The most commonly affected was the lumbar lymphocenter (7/23), followed by the coeliac (6/23), the cranial mesenteric (5/23) and the iliosacral (5/23). Twenty-three concurrent diseases were diagnosed in 17 dogs, among which 16/23 were non-neoplastic (70 per cent). The most common concurrent disease was renal insufficiency (8/23), followed by neoplasia (7/23), gastroenteropathy (3/23), benign prostatic disease (2/23), pancreatitis (1/23), peritonitis (1/23) and neurological disease (1/23). No statistical correlation existed between cyst-like lymph nodal lesion and a specific neoplastic or non-neoplastic disease. In conclusion, in the present study, cyst-like lymph nodal lesions have a low prevalence, involve different lymphocenters and were found in dogs affected by different diseases, including both non-neoplastic and neoplastic aetiologies. British Veterinary Association.

[Value of narrow band imaging endoscopy in detection of early laryngeal squamous cell carcinoma].

PubMed

Staníková, L; Kučová, H; Walderová, R; Zeleník, K; Šatanková, J; Komínek, P

2015-01-01

Narrow band imaging (NBI) is an endoscopic method using filtered wavelengths in detection of microvascular abnormalities associated with preneoplastic and neoplastic changes of the mucosa. The aim of the study is to evaluate the value of NBI endoscopy in the dia-gnosis of laryngeal precancerous and early stages of cancerous lesions and to investigate impact of NBI method in prehistological diagnostics in vivo. One hundred patients were enrolled in the study and their larynx was investigated using white light HD endoscopy and narrow band imaging between 6/ 2013- 10/ 2014. Indication criteria included chronic laryngitis, hoarseness for more than three weeks or macroscopic laryngeal lesion. Features of mucosal lesions were evaluated by white light endoscopy and afterwards were compared with intra-epithelial papillary capillary loop changes, viewed using NBI endoscopy. Suspicious lesions (leukoplakia, exophytic tumors, recurrent respiratory papillomatosis and/ or malignant type of vascular network by NBI endoscopy) were evaluated by histological analysis, results were compared with prehistological NBI dia-gnosis. Using NBI endoscopy, larger demarcation of pathological mucosal features than in white light visualization were recorded in 32/ 100 (32.0%) lesions, in 4/ 100 (4.0%) cases even new lesions were detected only by NBI endoscopy. 63/ 100 (63.0%) suspected lesions were evaluated histologically -  malign changes (carcinoma in situ or invasive carcinoma) were observed in 25/ 63 (39.7%). Prehistological diagnostics of malignant lesions using NBI endoscopy were in agreement with results of histological examination in 23/ 25 (92.0%) cases. The sensitivity of NBI in detecting malignant lesions was 89.3%, specificity of this method was 94.9%. NBI endoscopy is a promising optical technique enabling in vivo differentiation of superficial neoplastic lesions. These results suggest endoscopic NBI may be useful in the early detection of laryngeal cancer and precancerous

An improved high order texture features extraction method with application to pathological diagnosis of colon lesions for CT colonography

NASA Astrophysics Data System (ADS)

Song, Bowen; Zhang, Guopeng; Lu, Hongbing; Wang, Huafeng; Han, Fangfang; Zhu, Wei; Liang, Zhengrong

2014-03-01

Differentiation of colon lesions according to underlying pathology, e.g., neoplastic and non-neoplastic, is of fundamental importance for patient management. Image intensity based textural features have been recognized as a useful biomarker for the differentiation task. In this paper, we introduce high order texture features, beyond the intensity, such as gradient and curvature, for that task. Based on the Haralick texture analysis method, we introduce a virtual pathological method to explore the utility of texture features from high order differentiations, i.e., gradient and curvature, of the image intensity distribution. The texture features were validated on database consisting of 148 colon lesions, of which 35 are non-neoplastic lesions, using the random forest classifier and the merit of area under the curve (AUC) of the receiver operating characteristics. The results show that after applying the high order features, the AUC was improved from 0.8069 to 0.8544 in differentiating non-neoplastic lesion from neoplastic ones, e.g., hyperplastic polyps from tubular adenomas, tubulovillous adenomas and adenocarcinomas. The experimental results demonstrated that texture features from the higher order images can significantly improve the classification accuracy in pathological differentiation of colorectal lesions. The gain in differentiation capability shall increase the potential of computed tomography (CT) colonography for colorectal cancer screening by not only detecting polyps but also classifying them from optimal polyp management for the best outcome in personalized medicine.

Vital-dye-enhanced multimodal imaging of neoplastic progression in a mouse model of oral carcinogenesis

NASA Astrophysics Data System (ADS)

Hellebust, Anne; Rosbach, Kelsey; Wu, Jessica Keren; Nguyen, Jennifer; Gillenwater, Ann; Vigneswaran, Nadarajah; Richards-Kortum, Rebecca

2013-12-01

In this longitudinal study, a mouse model of 4-nitroquinoline 1-oxide chemically induced tongue carcinogenesis was used to assess the ability of optical imaging with exogenous and endogenous contrast to detect neoplastic lesions in a heterogeneous mucosal surface. Widefield autofluorescence and fluorescence images of intact 2-NBDG-stained and proflavine-stained tissues were acquired at multiple time points in the carcinogenesis process. Confocal fluorescence images of transverse fresh tissue slices from the same specimens were acquired to investigate how changes in tissue microarchitecture affect widefield fluorescence images of intact tissue. Widefield images were analyzed to develop and evaluate an algorithm to delineate areas of dysplasia and cancer. A classification algorithm for the presence of neoplasia based on the mean fluorescence intensity of 2-NBDG staining and the standard deviation of the fluorescence intensity of proflavine staining was found to separate moderate dysplasia, severe dysplasia, and cancer from non-neoplastic regions of interest with 91% sensitivity and specificity. Results suggest this combination of noninvasive optical imaging modalities can be used in vivo to discriminate non-neoplastic from neoplastic tissue in this model with the potential to translate this technology to the clinic.

Benign Pediatric Salivary Gland Lesions.

PubMed

Carlson, Eric R; Ord, Robert A

2016-02-01

Salivary gland lesions are rare in pediatric patients. In addition, the types of salivary gland tumors are different in their distribution in specific sites in the major and minor salivary glands in children compared with adults. This article reviews benign neoplastic and nonneoplastic salivary gland disorders in pediatric patients to help clinicians to develop an orderly differential diagnosis that will lead to expedient treatment of pediatric patients with salivary gland lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Necrotizing lymphocytic folliculitis: the early lesion of acne necrotica (varioliformis).

PubMed

Kossard, S; Collins, A; McCrossin, I

1987-05-01

Skin biopsy specimens from four patients who had recurrent bouts of lesions conforming to the clinical description of acne necrotica were studied. The pathologic findings were dominated by lymphocytic inflammation around centrally placed follicles evolving to follicular necrosis that extended to the perifollicular epidermis and dermis. Early lesions showed the development of multiple individual necrotic keratinocytes within the follicular sheath and adjacent epidermis with lymphocytic exocytosis. Later lesions showed more intense necrosis and scale crust obscuring the central target but were still dominated by a peripheral lymphocytic infiltrate. The early pathologic findings of acne necrotica (varioliformis) are represented by a necrotizing lymphocytic folliculitis and differ from the pattern seen in association with nonspecific excoriations, acute bacterial folliculitis, classic comedogenic acne, or acnitis.

Diagnostic criteria for proliferative hepatic lesions in brown bullhead Ameiurus nebulosus

USGS Publications Warehouse

Blazer, V.S.; Fournie, J.W.; Wolf, J.C.; Wolfe, M.J.

2006-01-01

Brown bullhead Ameiurus nebulosus is used as indicator species for contaminant effects at areas of concern (AOC) in the Great Lakes and other areas. One of the beneficial use impairments at numerous AOC is 'fish tumors and other deformities'. An impairment occurs when the prevalence of fish tumors and other deformities exceeds those at unimpacted or control sites or when survey data confirm the presence of neoplastic or preneoplastic liver lesions in bullhead or white sucker Catostomus commersonii. Numerous surveys have been conducted over the years assessing neoplasia in these fishes, both liver and skin tumors. However, a major problem in comparing the results has been a lack of consistent criteria for evaluating histological changes in bullhead livers. As individual AOC develop and implement remedial action plans, realistic and attainable delisting targets need to be specified. For this to occur and be consistent from site to site there must be standardization of the criteria being used to evaluate specific impairments. In this report, specific diagnostic criteria are provided for both non-neoplastic and neoplastic proliferative hepatocellular and biliary lesions. These criteria should assist fish pathologists in describing and categorizing proliferative liver lesions from brown bullhead. ?? Inter-Research 2006.

Adenomatous Polyposis Coli-Mediated Accumulation of Abasic DNA Lesions Lead to Cigarette Smoke Condensate-Induced Neoplastic Transformation of Normal Breast Epithelial Cells1

PubMed Central

Jaiswal, Aruna S; Panda, Harekrushna; Pampo, Christine A; Siemann, Dietmar W; Gairola, C Gary; Hromas, Robert; Narayan, Satya

2013-01-01

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

Viral Oncolytic Therapeutics for Neoplastic Meningitis

DTIC Science & Technology

2012-07-01

will in due course approach DOD for approval of the animal protocol. 15. SUBJECT TERMS Viral oncolysis, neoplastic meningitis , cell lines, HSV-1...proposed study is to develop novel, safe and efficient therapy for neoplastic meningitis – that of HSV-1 oncolysis. The viral genome is genetically...1 AD_________________ Award Number: W81XWH-11-1-0388 TITLE: Viral Oncolytic Therapeutics for Neoplastic

Plasma Cholesterol–Induced Lesion Networks Activated before Regression of Early, Mature, and Advanced Atherosclerosis

PubMed Central

Björkegren, Johan L. M.; Hägg, Sara; Jain, Rajeev K.; Cedergren, Cecilia; Shang, Ming-Mei; Rossignoli, Aránzazu; Takolander, Rabbe; Melander, Olle; Hamsten, Anders; Michoel, Tom; Skogsberg, Josefin

2014-01-01

Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (≥80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr−/−Apob 100/100 Mttp flox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions. PMID:24586211

Anti-angiogenic drug loaded liposomes: Nanotherapy for early atherosclerotic lesions in mice

PubMed Central

Pont, Isabel; Calatayud-Pascual, Aracely; López-Castellano, Alicia; Albelda, Elena P.; García-España, Enrique; Martí-Bonmatí, Luis; Frias, Juan C.

2018-01-01

Fumagillin-loaded liposomes were injected into ApoE-KO mice. The animals were divided into several groups to test the efficacy of this anti-angiogenic drug for early treatment of atherosclerotic lesions. Statistical analysis of the lesions revealed a decrease in the lesion size after 5 weeks of treatment. PMID:29338009

Altered growth pattern, not altered growth per se, is the hallmark of early lesions preceding cancer development.

PubMed

Doratiotto, S; Marongiu, F; Faedda, S; Pani, P; Laconi, E

2009-01-01

Many human solid cancers arise from focal proliferative lesions that long precede the overt clinical appearance of the disease. The available evidence supports the notion that cancer precursor lesions are clonal in origin, and this notion forms the basis for most of the current theories on the pathogenesis of neoplastic disease. In contrast, far less attention has been devoted to the analysis of the phenotypic property that serves to define these focal lesions, i.e. their altered growth pattern. In fact, the latter is often considered a mere morphological by-product of clonal growth, with no specific relevance in the process. In the following study, evidence will be presented to support the concept that focal growth pattern is an inherent property of altered cells, independent of clonal growth; furthermore, it will be discussed how such a property, far from being merely descriptive, might indeed play a fundamental role in the sequence of events leading to the development of cancer. Within this paradigm, the earliest steps of neoplasia should be considered and analysed as defects in the mechanisms of tissue pattern formation.

[Detection of early neoplasia in Barrett's oesophagus: focus attention on index endoscopy in short-segment-Barrett's oesophagus with random biopsies].

PubMed

Behrens, A; Pech, O; Wuthnow, E; Manner, H; Pohl, J; May, A; Ell, C

2015-06-01

Detecting early neoplasias in Barrett's oesophagus (BE) is challenging. Recent publications have been focusing on improving the detection of such lesions during Barrett's surveillance. However in a recently published Danish register study calculating the risk for cancer-development in BE two-thirds of the diagnosed tumors were identified during the first examination or in the first year. This means that index endoscopy might be more effective than surveillance in detecting early neoplasia in BE.  In the period from January 2010 to April 2011, all patients who consecutively presented with a diagnosis of early neoplastic changes in BE were recorded prospectively. The analysis included data for 121 patients. In patients with short-segment BE (SSBE), neoplasia was only diagnosed in 6 % of cases in the surveillance examination, compared with 44 % of cases in long-segment BE (LSBE). The neoplastic lesion was identified visually in 43 patients (36 %) during the external EGD. Type II tumours were detected in 40 % (39/98) and were correctly assessed as neoplastic in 25 % of cases (24/98). 1. in patients with SSBE almost all early tumours are diagnosed by index endoscopy and not by Barrett's surveillance; 2. around 40 % of all early neoplasias are endoscopically invisible and are only diagnosed using four-quadrant biopsies; 3. the macroscopic tumour type has a substantial influence on the detection rate for neoplasia. If efforts to increase the detection rate for early neoplasia in BE are focused solely on the Barrett's surveillance method, then only a minority of patients - 20 % in the present group - will benefit from the measure. German clinical trials register, DRKS00 004 168. © Georg Thieme Verlag KG Stuttgart · New York.

Sweet-spot training for early esophageal cancer detection

NASA Astrophysics Data System (ADS)

van der Sommen, Fons; Zinger, Svitlana; Schoon, Erik J.; de With, Peter H. N.

2016-03-01

Over the past decade, the imaging tools for endoscopists have improved drastically. This has enabled physicians to visually inspect the intestinal tissue for early signs of malignant lesions. Besides this, recent studies show the feasibility of supportive image analysis for endoscopists, but the analysis problem is typically approached as a segmentation task where binary ground truth is employed. In this study, we show that the detection of early cancerous tissue in the gastrointestinal tract cannot be approached as a binary segmentation problem and it is crucial and clinically relevant to involve multiple experts for annotating early lesions. By employing the so-called sweet spot for training purposes as a metric, a much better detection performance can be achieved. Furthermore, a multi-expert-based ground truth, i.e. a golden standard, enables an improved validation of the resulting delineations. For this purpose, besides the sweet spot we also propose another novel metric, the Jaccard Golden Standard (JIGS) that can handle multiple ground-truth annotations. Our experiments involving these new metrics and based on the golden standard show that the performance of a detection algorithm of early neoplastic lesions in Barrett's esophagus can be increased significantly, demonstrating a 10 percent point increase in the resulting F1 detection score.

Neoplastic Meningitis from Solid Tumors: New Diagnostic and Therapeutic Approaches

PubMed Central

Zustovich, Fable; Farina, Patrizia; Della Puppa, Alessandro; Manara, Renzo; Cecchin, Diego; Brunello, Antonella; Cappetta, Alessandro; Zagonel, Vittorina

2011-01-01

Neoplastic meningitis is a result of the spread of malignant cells to the leptomeninges and subarachnoid space and their dissemination within the cerebrospinal fluid. This event occurs in 4%–15% of all patients with solid tumors and represents an important prognostic factor for poor survival. Neoplastic meningitis should be diagnosed in the early stages of disease to prevent important neurological deficits and to provide the most appropriate treatment. Despite new diagnostic approaches developed in recent years, such as positron emission tomography–computed tomography and new biological markers, the combination of magnetic resonance imaging without and with gadolinium enhancement and cytology still has the greatest diagnostic sensitivity. Recently, no new randomized studies comparing intrathecal (i.t.) with systemic treatment have been performed, yet there have been a few small phase II studies and case reports about new molecularly targeted substances whose successful i.t. or systemic application has been reported. Trastuzumab, gefitinib, and sorafenib are examples of possible future treatments for neoplastic meningitis, in order to better individualize therapy thus allowing better outcomes. In this review, we analyze the most recent and interesting developments on diagnostic and therapeutic approaches. PMID:21795431

Detection of Early-Stage Oral Cancer Lesions: A Survey of California Dental Hygienists.

PubMed

Barao, Dayna M Hashimoto; Essex, Gwen; Lazar, Ann A; Rowe, Dorothy J

2016-12-01

Purpose: To assess dental hygienists' knowledge of early-stage oral cancer lesions and their practices, attitudes, barriers, and facilitators related to early detection. Methods: A 20-item survey containing images of oral lesions and related multiple-choice questions was distributed electronically by the California Dental Hygienists' Association to all dental hygienists whose email addresses were in their database. Response frequencies were calculated per survey item. Logistic regression analysis was used to explore associations. Results: Seven hundred fifty-one dental hygienists responded, yielding a 12% response rate. Respondents' correct identification of the six images of oral lesions varied from 40%-97%. Most respondents reported conducting oral cancer examinations (OCE) at every dental hygiene appointment and performing palpation during OCE. Regions of the mouth varied regarding the frequency of palpation. Lymph node palpation was considered the most commonly omitted step. Those who conducted palpations were 3.3 (95% CI: 1.4 to 7.9, p=0.006) times more likely to report that they knew someone with oral cancer and had detected oral cancer lesions than those who did not. Knowing a person with a history of oral cancer and previously detecting a cancerous lesion were also reported as factors encouraging respondents to bring suspicious lesions to the attention of the dentist. Discouraging factors were mostly related to the dentist' behavior, such as not referring a suspicious lesion for biopsy that the respondent identified. Conclusion: Detection of early-stage oral cancer lesions by dental hygienists may be enhanced through more extensive education of visual appearances of lesions and the importance of palpation in a comprehensive OCE. Copyright © 2016 The American Dental Hygienists’ Association.

Retrospective review of pediatric oral lesions from a dental school biopsy service.

PubMed

Shah, Suhani K; Le, Mary C; Carpenter, William M

2009-01-01

This report presents a review of the results from 5457 biopsies of patients, 0-16 years of age, received over 15 years at the University of the Pacific School of Dentistry (Pacific Oral and Maxillofacial Pathology Laboratory). To carry out the largest and most up to date U.S. survey of oral specimens from children. The computerized data was retrieved and compiled for age and diagnoses. The lesions were divided by the MIND classification system into 1) Metabolic 2) Inflammatory 3) Neoplastic and 4) Developmental. Inflammatory lesions formed the largest group of biopsies (2758, 51%) followed by Developmental conditions (1928, 35%) and Neoplasms (734, 13%). Dentigerous cysts were the most common lesions, followed by the mucous retention phenomenon (mucocele). The 15 most frequently occurring lesions accounted for 80% of all biopsies. Eight malignancies and 22 benign aggressive tumors were also included. 1. Pathoses increase with age. 2. Results from our study are similar to most of the other studies. 3. More serious pathoses occur in some countries where there is limited access to care, resulting in patients seeking care only when symptomatic. 4. Oral malignancies are rare, but as with any malignancy, early diagnosis renders a more favorable prognosis.

Role of Fine Needle Aspiration Cytology in the Diagnosis of Skin and Superficial Soft Tissue Lesions: A Study of 510 Cases.

PubMed

Bhowmik, Abhijit; Mallick Sinha, Mamata Guha; Barman, Dilip Chandra

2015-01-01

Diseases of the skin and superficial subcutaneous soft tissues present with a wide array of lesions ranging from nonspecific dermatoses and inflammatory lesions to frank neoplasms. Though cytopathology is an excellent diagnostic tool in routine dermatologic practice, studies relating to histopathological and cytological correlation are sparse. The aim of this study was to analyze the concordance rate between cytological and histopathological diagnosis of skin and superficial soft tissue lesions. We retrospectively studied 510 consecutive fine needle aspiration cytology findings of cases from North Bengal Medical College and Hospital and correlated their diagnoses based upon cytological and histopathological grounds. Out of the 510 cases studied, 253 were non neoplastic lesions and 257 were neoplastic. A high degree of concordance was observed (100% for malignant and 96.15% for benign lesions) when these two diagnostic modalities were compared. Histopathological correlation was possible in all malignant, 52/189 (27.51%) of benign and 27/253 (10.67%) of non-neoplastic lesions. Sensitivity and specificity of diagnoses were 95.31% and 97.6%, respectively. It can be safely concluded that fine needle aspiration cytology is a rapid, reliable and fairly accurate tool for initial triage and treatment of skin and superficial soft tissue lesions.

Targeting Premalignant Lesions - Implications for Early Breast Cancer Detection and Intervention

DTIC Science & Technology

2017-04-01

lesions. Peptide conjugated AgNP were injected intravenously in mice and mammary glands were isolated and analyzed for nanoparticle accumulation by silver ...Furthermore, these probes will be used to develop targeted therapeutic nanoparticles for early intervention in breast cancer. 2. KEYWORDS...cancer (Months 18-24) (To be done) Specific Aim 3: Target premalignant lesions utilizing peptide-conjugated nanoparticles to prevent/delay

Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions.

PubMed

Albéniz, Eduardo; Pellisé, María; Gimeno García, Antonio Z; Lucendo, Alfredo José; Alonso Aguirre, Pedro A; Herreros de Tejada, Alberto; Álvarez, Marco Antonio; Fraile, María; Herráiz Bayod, Maite; López Rosés, Leopoldo; Martínez Ares, David; Ono, Akiko; Parra Blanco, Adolfo; Redondo, Eduardo; Sánchez Yagüe, Andrés; Soto, Santiago; Díaz Tasende, José; Montes Díaz, Marta; Téllez, Manuel Rodríguez; García, Orlando; Zuñiga Ripa, Alba; Hernández Conde, Marta; Alberca de Las Parras, Fernando; Gargallo, Carla; Saperas, Esteban; Navas, Miguel Muñoz; Gordillo, Javier; Ramos Zabala, Felipe; Echevarría, José Manuel; Bustamante, Marco; González Haba, Mariano; González Huix, Ferrán; González Suárez, Begoña; Vila Costas, Juan José; Guarner Argente, Carlos; Múgica, Fernando; Cobián, Julyssa; Rodríguez Sánchez, Joaquín; López Viedma, Bartolomé; Pin, Noel; Marín Gabriel, José Carlos; Nogales, Óscar; de la Peña, Joaquín; Navajas León, Francisco Javier; León Brito, Helena; Remedios, David; Esteban, José Miguel; Barquero, David; Martínez Cara, Juan Gabriel; Martínez Alcalá, Felipe; Fernández Urién, Ignacio; Valdivielso, Eduardo

2018-03-01

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Characterization of oral precancerous lesions based on higher-harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Lin, Chen-Yu; Lin, Chih-Feng; Sun, Chi-Kuang

2013-03-01

It is generally accepted that oral cancer arises in the presence of oral precancerous lesions. However, the clinical courses of these lesions are quite unpredictable, and a fundamental enigma remains that when and how these lesions turn to malignant growth. Characterization of these potentially malignant lesions is thus important and could serve as early indicators of this neoplastic transformation process, potentially facilitates the treatment outcome and improves the survival rate. Higher harmonic generation microscope (HGM), providing images with a <500nm lateral resolution at a 300μm penetration depth without leaving photodamages in the tissues, was used for this purpose. Oral cavity biopsies were obtained from 18 patients with clinical suspected oral precancerous lesions scheduled for surgical biopsy. HGM images were compared with histological images to determine the results. By visualization of subtle cellular and morphological changes, the preliminary result of this HGM image discloses excellent consistency with traditional histolopathology studies, without the need for fixation, sectioning and staining. More specifically speaking, the keratin thickness was found to be increased comparing with normal adjacent controls. In some cases, variations in cell size, nuclear size and increased nuclear/cytoplasmic ratio, and increased size of nucleoli were identified, indicating different stages of malignant transformation. These results together indicated that HGM provides the capability to characterize features of oral precancerous lesions as well as oral cancer progression, and holds the greatest potential as an ideal tool for clinical screening and surveillance of suspicious oral lesions.

Tumor and tumor-like lesions of perilimbal conjunctiva in laboratory dogs.

PubMed

Hargis, A M; Lee, A C; Thomassen, R W

1978-11-01

Review of records of 1,680 research colony Beagles revealed proliferative and neoplastic lesions in the nasal or temporal limbal conjunctiva of 8 male and 6 famale dogs. The mean age at observation was 5.2 years. The lesions ranged from acanthosis and squamous cell carcinoma of the conjunctival epithelium to vascular ectasia, hemangioma, and invasive hemangiosarcoma of the underlying lamina propria. The lesions developed under circumstances that suggested solar radiation was involved in the pathogenesis.

Evaluation of Calretinin expression in Ameloblastoma and Non-Neoplastic Odontogenic Cysts - An immunohistochemical study.

PubMed

D'Silva, Shaloom; Sumathi, M K; Balaji, N; Shetty, Nisha K N; Pramod, K M; Cheeramelil, Jacob

2013-12-01

Calretinin a 29-kDa calcium binding protein is expressed widely in normal human tissue and tumours including amelobastoma. The objective of this study was to determine calretinin expression in heamatoxylin and eosin diagnosed cases of ameloblastoma and non-neoplastic odontogenic cysts. The lining epithelium in 3 cases of radicular cysts, 5 cases of odontogenic keratocysts, 5 cases of dentigerous cysts and 11 cases of ameloblastomas were examined for expression of calretinin. No positive epithelial staining was observed in radicular and dentigerous cysts. In comparison, however 100% of cases of ameloblastomas and 40% of cases of odontogenic karatocysts showed positive calretinin expression. Calretinin may be a specific immunohistochemical marker for ameloblastoma. If there is any possible relation between calretinin expression and neural origin of the odontogenic epithelium and its neoplastic transformation and if calretinin could be used as an early marker to predict the tendency of neoplastic change of odontogenic epithelium could be answered through further researches. How to cite this article: D'Silva S, Sumathi MK, Balaji N, Shetty NK, Pramod KM, Cheeramelil J. Evaluation of Calretinin expression in Ameloblastoma and Non-Neoplastic Odontogenic Cysts - An immunohistochemical study. J Int Oral Health 2013; 5(6):42-8 .

Thermophotonic lock-in imaging of early demineralized and carious lesions in human teeth

NASA Astrophysics Data System (ADS)

Tabatabaei, Nima; Mandelis, Andreas; Amaechi, Bennett Tochukwu

2011-07-01

As an extension of frequency-domain photothermal radiometry, a novel dental-imaging modality, thermophotonic lock-in imaging (TPLI), is introduced. This methodology uses photothermal wave principles and is capable of detecting early carious lesions and cracks on occlusal and approximal surfaces as well as early caries induced by artificial demineralizing solutions. The increased light scattering and absorption within early carious lesions increases the thermal-wave amplitude and shifts the thermal-wave centroid, producing contrast between the carious lesion and the intact enamel in both amplitude and phase images. Samples with artificial and natural occlusal and approximal caries were examined in this study. Thermophotonic effective detection depth is controlled by the modulation frequency according to the well-known concept of thermal diffusion length. TPLI phase images are emissivity normalized and therefore insensitive to the presence of stains. Amplitude images, on the other hand, provide integrated information from deeper enamel regions. It is concluded that the results of our noninvasive, noncontacting imaging methodology exhibit higher sensitivity to very early demineralization than dental radiographs and are in agreement with the destructive transverse microradiography mineral density profiles.

Genetic polymorphisms and protein expression of P53 and BRCA1 in preneoplastic and neoplastic rat mammary glands.

PubMed

Al-Dhaheri, Wafa; Hassouna, Imam; Karam, Sherif M

2018-05-01

Breast cancer is the most common type of cancer and the leading cause of cancer-related deaths among women in the United Arab Emirates and worldwide. Although many factors contribute to the high incidence of breast cancer, a considerable number of cases are related to environmental factors. In the present study, breast cancer was induced in female rats using a single dose, 80 mg/kg body wt, of the environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The aim of the present study, was to characterize some of the molecular changes that occur during breast cancer development in the DMBA-treated rat model. Mammary gland tissues of control and DMBA-treated rats were processed for: i) immunohistochemical probing using anti-BRCA1 antibody to characterize and correlate the localization of this cell cycle protein during progression to cancer, ii) western blotting to analyze the alteration of p53 protein expression in preneoplastic and neoplastic lesions of the mammary glands, and iii) polymerase chain reactions using primers specific for BRCA1 and P53 genes followed by single stranded conformational polymorphism (SSCP) or restriction fragment length polymorphism (RFLP) assays to detect possible mutations in these genes during development of breast cancer. Microscopic examination revealed a wide range of preneoplastic and neoplastic lesions providing a sequence representing the multistep process of breast cancer formation in DMBA-treated rats. Probing for BRCA1 protein revealed a gradual defect in its translocation from the cytoplasm to the nucleus during breast cancer progression. In control rats, BRCA1 was present in the nuclei of terminal duct epithelial cells. However, in the preneoplastic lesions, BRCA1 was localized in both the cytoplasm and nuclei of the epithelial duct cells. In all malignant lesions, BRCA1 was mostly found in the cytoplasm. Western blotting revealed initial downregulation in the expression of p53 protein during breast cancer

Oral precancerous lesions: Problems of early detection and oral cancer prevention

NASA Astrophysics Data System (ADS)

Gileva, Olga S.; Libik, Tatiana V.; Danilov, Konstantin V.

2016-08-01

The study presents the results of the research in the structure, local and systemic risk factors, peculiarities of the clinical manifestation, and quality of primary diagnosis of precancerous oral mucosa lesions (OMLs). In the study a wide range of OMLs and high (25.4%) proportion of oral precancerous lesions (OPLs) in their structure was indicated. The high percentage of different diagnostic errors and the lack of oncological awareness of dental practitioners, as well as the sharp necessity of inclusion of precancer/cancer early detection techniques into their daily practice were noted. The effectiveness of chemilumenescence system of early OPLs and oral cancer detection was demonstrated, the prospects of infrared thermography as a diagnostic tool were also discussed.

Capsule endoscopy in neoplastic diseases

PubMed Central

Pennazio, Marco; Rondonotti, Emanuele; de Franchis, Roberto

2008-01-01

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. PMID:18785274

Enhanced G2 chromatid radiosensitivity, an early stage in the neoplastic transformation of human epidermal keratinocytes in culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gantt, R.; Sanford, K.K.; Parshad, R.

1987-03-01

A deficiency in DNA repair, manifest as enhanced chromatid radiosensitivity during the G2 phase of the cell cycle, together with a proliferative stimulus such as that provided by active oncogenes may be necessary and sufficient for the malignant neoplastic transformation of human keratinocytes in culture. Normal epidermal keratinocytes established as continuous cell lines by transfection with pSV3-neo or infection with adeno 12-SV40 hybrid virus developed enhanced G2 chromatid radiosensitivity after 18 passages in culture. In contrast to cells from primary or secondary culture, these cells could be transformed to malignant neoplastic cells by infection with Kirsten murine sarcoma virus containingmore » the Ki-ras oncogene or in one line by the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine; both of these agents produced a marked proliferative response. Cytological heterogeneity and karyotypic instability characterized the cells during their progression to neoplasia. These results are interpreted in terms of a mechanism for neoplastic transformation.« less

Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin Haiyan; Department of Gastroenterology and Hepatology, Yanbian University Hospital, Yanji, Jilin; Yamamoto, Naoki

2007-12-28

Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor {gamma} activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions bymore » down-regulating TGF{beta}1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.« less

Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet.

PubMed

Jin, Haiyan; Yamamoto, Naoki; Uchida, Koichi; Terai, Shuji; Sakaida, Isao

2007-12-28

Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor gamma activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions by down-regulating TGFbeta1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.

The efficacy of real-time colour Doppler flow imaging on endoscopic ultrasonography for differential diagnosis between neoplastic and non-neoplastic gallbladder polyps.

PubMed

Kim, Su Young; Cho, Jae Hee; Kim, Eui Joo; Chung, Dong Hae; Kim, Kun Kuk; Park, Yeon Ho; Kim, Yeon Suk

2018-05-01

We evaluated the usefulness of real-time colour Doppler flow (CDF) endoscopic ultrasonography (EUS) for differentiating neoplastic gallbladder (GB) polyps from non-neoplastic polyps. Between August 2014 and December 2016, a total of 233 patients with GB polyps who underwent real-time CDF-EUS were consecutively enrolled in this prospective study. CDF imaging was subjectively categorized for each patient as: strong CDF pattern, weak CDF pattern and no CDF pattern. Of the 233 patients, 115 underwent surgical resection. Of these, there were 90 cases of non-neoplastic GB polyps and 23 cases of neoplastic GB polyps. In a multivariate analysis, a strong CDF pattern was the most significant predictive factor for neoplastic polyps; sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 52.2 %, 79.4 %, 38.7 %, 86.9 % and 73.9 %, respectively. Solitary polyp and polyp size were associated with an increased risk of neoplasm. The presence of a strong CDF pattern as well as solitary and larger polyps on EUS may be predictive of neoplastic GB polyps. As real-time CDF-EUS poses no danger to the patient and requires no additional equipment, it is likely to become a supplemental tool for the differential diagnosis of GB polyps. • Differential diagnosis between neoplastic polyps and non-neoplastic polyps of GB is limited. • The use of real-time CDF-EUS was convenient, with high agreement between operators. • The real-time CDF-EUS is helpful in differential diagnosis of GB polyps.

Spectrum of intra-thoracic lesion detected by computed tomography guided fine needle aspiration biopsy.

PubMed

Naqvi, Hanna; Edhi, Muhammad Muzzammil; Aslam, Hafiz Muhammad; Faridi, Naveen

2013-02-12

Fine needle aspiration biopsy (FNAB) is a rapid, sensitive and inexpensive procedure for diagnosing benign and malignant palpable lesions. For lesions that are not palpable or deep seated, FNAB can be performed under the guidance of radiological imaging. Our basic objective was to evaluate the spectrum of intrathoracic lesions by using Computed Tomography guided fine needle aspiration biopsy and evaluate its diagnostic yield. It was a retrospective study carried out in the Department of Histopathology, Liaquat National Hospital and Medical College, during the months of August 2011 and August 2012. All patients with pulmonary, mediastinal or paravertebral mass who underwent CT guided intrathoracic biopsy were included in this study. Fine needle aspiration biopsies were performed in the Radiology Department and specimen retrieved was sent in 10% buffered Formalin to the Histopathology Department. All the data was entered and analyzed through SPSS 19.0. A total of 130 cases were evaluated, out of which 108 (83.1%) were pulmonary, 16 (12.3%) were mediastinal and 6 (4.6%) were paravertebral. Conclusive biopsies were possible in 113 cases, while 17 biopsies were inconclusive. In those that showed a conclusive diagnosis, 83.1% were neoplastic and 16.9% were non neoplastic. Of the neoplastic cases, 27 (20.8%) were adenocarcinomas, followed by squamous cell carcinomas (15.4%) and large cell carcinoma, not otherwise specified, (12.3%). CT guided fine needle aspiration biopsy is a reliable tool for examination of intrathoracic lesions, with a high rate of conclusive diagnosis.

Detection of oral early cancerous lesion by using polarization-sensitive optical coherence tomography: mice model

NASA Astrophysics Data System (ADS)

Lee, Hong-Yi; Chen, Ping-Hsien; Lee, Tzu-Han; Chang, Kuo-Wei; Kuo, Wen-Chuan

2018-02-01

Oral cancer is the 11th most common cancer worldwide, especially in a male adult. The median age of death in oral cancer was 55 years, 10-20 years earlier than other cancers. Presently, oral cancer is often found in late stage, because the lesion is often flat in early stage and is difficult to diagnose under traditional white light imaging. The only definitive method for determining cancer is an invasive biopsy and then using histology examination. How to detect precancerous lesions or early malignant lesions is an important issue for improving prognosis of oral cancer. Optical coherence tomography (OCT) is a new optical tool for diagnosing early malignant lesions in the skin or gastrointestinal tract recently. Here we report a new method for detecting precancerous or early malignant oral lesions by using swept source polarization-sensitive optical coherence tomography (PS-OCT) with center-wavelength 1310 nm, bandwidth 110 nm and 100 kHz swept rate. We used all single-mode fiber design to detect the change of birefringence information in the epithelium structure. This system has an advantage that enables measurement of backscattered intensity and birefringence simultaneously with only one A-scan per transverse location. In preliminary result, we computed the slope of the every A-scan signal in tissue part using a linear-curve fitting in backscattered intensity and birefringence on the enface. In this research, we used an oral cancer mice model for observing the change of structure and birefringence properties in different stages of oral cancer mice. We presented the parametric enface imaging that can detect the early oral malignant lesions.

Induction of proliferative lesions of the uterus, testes, and liver in swiss mice given repeated injections of sodium arsenate: possible estrogenic mode of action.

PubMed

Waalkes, M P; Keefer, L K; Diwan, B A

2000-07-01

Inorganic arsenic (As) is a human carcinogen but has not been unequivocally proven carcinogenic in rodents. For instance, one older study indicates that repeated iv injections of sodium arsenate might induce lymphomas in Swiss mice (58% incidence) (Osswald and Goerttler, Verh. Dtsch. Ges. Pathol. 55, 289-293, 1971), but it was considered inadequate for critical evaluation of carcinogenic potential largely because of issues in experimental design. Therefore, we studied repeated iv sodium arsenate injection and neoplastic response in male and female Swiss mice. Groups (n = 25) of mice received sodium arsenate (0.5 mg/kg, iv) or saline (control) once/week for 20 weeks and were observed for a total of 96 weeks when the study ended. Differences in survival and body weights were unremarkable. In females, arsenate induced marked increases in the incidence and severity of cystic hyperplasia of the uterus compared against controls. Arsenate also was associated with a rare adenocarcinoma of the uterus. Hyperplastic uterine epithelium from arsenate-exposed animals showed strong positive immunostaining for the proliferating cell nuclear antigen (PCNA). There was also an upregulation of estrogen receptor (ER) immunoreactive protein in the early lesions of uterine luminal and glandular hyperplasia, although a progressive decrease in its expression was seen in the severe hyperplastic or neoplastic epithelium. In common with the preneoplastic and neoplastic gynecological lesions in humans, the levels of immunoreactive inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine-containing proteins were greater in the uterine hyperplastic epidermis and their intensity was positively correlated with the severity of the lesions. Arsenate-induced uterine hyperplastic lesions also showed a strong upregulation of cyclin D1, an estrogen-associated gene product essential for progression through the G1 phase of the cell cycle. In other tissues, arsenate increased testicular interstitial cell

A cavernous sinus lesion clinically responsive to steroids.

PubMed

Ruff, M W; Carabenciov, I D; Johnson, D R; Pollock, B E; Parisi, J E; Klaas, J P

2018-04-20

Tolosa Hunt syndrome (THS) is characterized by painful ophthalmoplegia secondary to idiopathic granulomatous inflammation of the cavernous sinus. The characteristic finding on MRI is an enhancing T1 isointense and T2 hypo- or hyperintense cavernous sinus mass lesion, which may result in focal narrowing of the ipsilateral internal carotid artery. Although the incidence is quite rare, it is a common diagnostic consideration in cases that present with multiple cranial neuropathies. However, the differential diagnosis for a unilateral cavernous sinus lesion in adults is broad and includes neoplastic, inflammatory (such as sarcoidosis and immunoglobulin G4-related disease [IgG4-RD]), infectious etiologies (such as syphilis and leprosy), as well as vascular lesions. We describe a patient presenting with neurologic symptoms referable to a persistent unilateral cavernous sinus MRI abnormality, initially thought to be consistent with Tolosa-Hunt syndrome, that was clinically but not radiographically responsive to steroids. Following reevaluation due to the presence of new symptoms, pathology revealed that the abnormality was most consistent with chordoma, a rare skull based tumor. In patients with a presumed diagnosis of Tolosa-Hunt syndrome, close clinical and radiographic follow-up is imperative, with early consideration for biopsy in patients that fail to respond to treatment both clinically and radiographically. Copyright © 2018 Elsevier Ltd. All rights reserved.

Viral Oncolytic Therapeutics for Neoplastic Meningitis

DTIC Science & Technology

2013-07-01

SUBTITLE 5a. CONTRACT NUMBER Viral Oncolytic Therapeutics for Neoplastic Meningitis 5b. GRANT NUMBER W81XWH-11-1-0388 5c. PROGRAM ELEMENT NUMBER... viral and cellular kinetics with bioluminescence and PET are being written up for publication. 15. SUBJECT TERMS Neoplastic meningitis , mouse...model of meningeal metastases, breast cancer, bioluminescence, MRI, viral oncolysis, HSV- 1. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

The Spinal Instability Neoplastic Score: Impact on Oncologic Decision-Making.

PubMed

Versteeg, Anne L; Verlaan, Jorrit-Jan; Sahgal, Arjun; Mendel, Ehud; Quraishi, Nasir A; Fourney, Daryl R; Fisher, Charles G

2016-10-15

Systematic literature review. To address the following questions in a systematic literature review: 1. How is spinal neoplastic instability defined or classified in the literature before and after the introduction of the Spinal Instability Neoplastic Score (SINS)? 2. How has SINS affected daily clinical practice? 3. Can SINS be used as a prognostic tool? Spinal neoplastic-related instability was defined in 2010 and simultaneously SINS was introduced as a novel tool with criteria agreed upon by expert consensus to assess the degree of spinal stability. PubMed, Embase, and clinical trial databases were searched with the key words "spinal neoplasm," "spinal instability," "spinal instability neoplastic score," and synonyms. Studies describing spinal neoplastic-related instability were eligible for inclusion. Primary outcomes included studies describing and/or defining neoplastic-related instability, SINS, and studies using SINS as a prognostic factor. The search identified 1414 articles, of which 51 met the inclusion criteria. No precise definition or validated assessment tool was used specific to spinal neoplastic-related instability prior to the introduction of SINS. Since the publication of SINS in 2010, the vast majority of the literature regarding spinal instability has used SINS to assess or describe instability. Twelve studies specifically investigated the prognostic value of SINS in patients who underwent radiotherapy or surgery. No consensus could be determined regarding the definition, assessment, or reporting of neoplastic-related instability before introduction of SINS. Defining spinal neoplastic-related instability and the introduction of SINS have led to improved uniform reporting within the spinal neoplastic literature. Currently, the prognostic value of SINS is controversial. N/A.

COX-2 expression in canine anal sac adenocarcinomas and in non-neoplastic canine anal sacs.

PubMed

Knudsen, C S; Williams, A; Brearley, M J; Demetriou, J L

2013-09-01

Anal sac adenocarcinoma (ASAC) is a clinically significant canine neoplasm characterized by early lymphatic invasion. Up-regulation of cyclooxygenase isoform 2 (COX-2) has been confirmed in several animal and human neoplastic tissues. The aim of the current study was primarily to evaluate COX-2 expression in canine ASAC and compare it to COX-2 expression in non-neoplastic canine anal sac tissue using immunohistochemistry with scoring for percentage positivity and intensity. Twenty-five ASAC samples and 22 normal anal sacs were available for evaluation. All canine ASAC samples and the normal anal sac tissues stained positively for COX-2. However, while normal anal sac tissue showed strong staining of the ductal epithelial cells, ASAC samples showed staining of the neoplastic glandular epithelial cells, with varying percentage positivity and intensity between ASAC samples. COX-2 immunoreactivity of ASAC samples was of low intensity in 52% and high in 12% of the cases; the remaining samples were of intermediate intensity. Seventy-six per cent of the ASAC had over 50% of the neoplastic glandular cells staining positive. These results confirm that COX-2 is expressed in the neoplastic glandular epithelial cells in canine ASAC and suggest a potential role for COX-2 inhibitors in the management of ASAC. Furthermore, the results indicate that COX-2 is expressed in ductal epithelial cells of the normal anal sac. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neoplastic Bone Marrow Niche: Hematopoietic and Mesenchymal Stem Cells

PubMed Central

Saki, Najmaldin; Abroun, Saeid; Farshdousti Hagh, Majid; Asgharei, Farahnaz

2011-01-01

The neoplastic niche comprises complex interactions between multiple cell types and molecules requiring cell-cell signaling as well as local secretion. These niches are important for both the maintenance of cancer stem cells and the induction of neoplastic cells survival and proliferation. Each niche contains a population of tumor stem cells supported by a closely associated vascular bed comprising mesenchyme-derived cells and extracellular matrix. Targeting cancer stem cells and neoplastic niche may provide new therapies to eradicate tumors. Much progress has been very recently made in the understanding of the cellular and molecular interactions in the microenvironment of neoplastic niches. This review article provides an overview of the neoplastic niches in the bone marrow. In addition to highlighting recent advances in the field, we will also discuss components of the niche and their signaling pathways. PMID:23508881

Periosteal pseudotumor in complex total knee arthroplasty resembling a neoplastic process.

PubMed

Chowdhry, Madhav; Dipane, Matthew V; McPherson, Edward J

2018-05-18

This case report describes in detail an erosive distal diaphyseal pseudotumor that occurred 6 years after a complex endoprosthetic hinge total knee arthroplasty (TKA). A female patient had conversion of a knee fusion to an endoprosthetic hinge TKA at the age of 62. At her scheduled 6-year follow-up, she presented with mild distal thigh pain and radiographs showing a 6-7 cm erosive lytic diaphyseal lesion that looked very suspicious for a neoplastic process. An en bloc resection of the distal femur and femoral endoprosthesis was performed. Histologic review showed the mass to be a pseudotumor with the wear debris emanating from within the femoral canal due to distal stem loosening. We deduce that mechanized stem abrasion created microscopic titanium alloy particles that escaped via a small diaphyseal crack and stimulated an inflammatory response resulting in a periosteal erosive pseudotumor. The main lesson of this report is that, in the face of a joint replacement surgery of the knee, pseudotumor formation is a more likely diagnosis than a neoplastic process when encountering an expanding bony mass. Thus, a biopsy prior to en bloc resection, would be our recommended course of action any time a suspicious mass is encountered close to a TKA.

BENIGN TUMORS AND TUMOR-LIKE LESIONS OF THE PANCREAS

PubMed Central

Basturk, Olca; Askan, Gokce

2017-01-01

Synopsis The pancreas is a complex organ that may give rise to large number of neoplasms and non-neoplastic lesions. This article will focus on benign neoplasms such as serous neoplasms as well as tumor-like (pseudotumoral) lesions that may be mistaken for neoplasm not only by clinicians and radiologists, but also by pathologists. The family of pancreatic pseudotumors, by a loosely defined conception of that term, includes a variety of lesions including heterotopia, hamartoma, and lipomatous pseudohypertrophy. Autoimmue pancreatitis (covered in chronic pancreatitis chapter) and paraduodenal (“groove”) pancreatitis may also lead to pseudotumor formation. Knowledge of these entities will help in making an accurate diagnosis. PMID:27926363

Spectrum of intra-thoracic lesion detected by computed tomography guided fine needle aspiration biopsy

PubMed Central

2013-01-01

Background Fine needle aspiration biopsy (FNAB) is a rapid, sensitive and inexpensive procedure for diagnosing benign and malignant palpable lesions. For lesions that are not palpable or deep seated, FNAB can be performed under the guidance of radiological imaging. Our basic objective was to evaluate the spectrum of intrathoracic lesions by using Computed Tomography guided fine needle aspiration biopsy and evaluate its diagnostic yield. Methodology It was a retrospective study carried out in the Department of Histopathology, Liaquat National Hospital and Medical College, during the months of August 2011 and August 2012. All patients with pulmonary, mediastinal or paravertebral mass who underwent CT guided intrathoracic biopsy were included in this study. Fine needle aspiration biopsies were performed in the Radiology Department and specimen retrieved was sent in 10% buffered Formalin to the Histopathology Department. All the data was entered and analyzed through SPSS 19.0. Results A total of 130 cases were evaluated, out of which 108 (83.1%) were pulmonary, 16 (12.3%) were mediastinal and 6 (4.6%) were paravertebral. Conclusive biopsies were possible in 113 cases, while 17 biopsies were inconclusive. In those that showed a conclusive diagnosis, 83.1% were neoplastic and 16.9% were non neoplastic. Of the neoplastic cases, 27 (20.8%) were adenocarcinomas, followed by squamous cell carcinomas (15.4%) and large cell carcinoma, not otherwise specified, (12.3%). Conclusion CT guided fine needle aspiration biopsy is a reliable tool for examination of intrathoracic lesions, with a high rate of conclusive diagnosis. PMID:23402220

Diffusion tensor imaging of early changes in corpus callosum after acute cerebral hemisphere lesions in newborns.

PubMed

Righini, Andrea; Doneda, Chiara; Parazzini, Cecilia; Arrigoni, Filippo; Matta, Ursula; Triulzi, Fabio

2010-11-01

The main purpose was to investigate any early diffusion tensor imaging (DTI) changes in corpus callosum (CC) associated with acute cerebral hemisphere lesions in term newborns. We retrospectively analysed 19 cases of term newborns acutely affected by focal or multi-focal lesions: hypoxic-ischemic encephalopathy, hypoglycaemic encephalopathy, focal ischemic stroke and deep medullary vein associated lesions. DTI was acquired at 1.5 Tesla with dedicated neonatal coil. DTI metrics (apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial λ(∐) and radial λ(⟂) diffusivity) were measured in the hemisphere lesions and in the CC. The control group included seven normal newborns. The following significant differences were found between patients and normal controls in the CC: mean ADC was lower in patients (0.88 SD 0.23 versus 1.18 SD 0.07 μm(2)/s) and so was mean FA (0.50 SD 0.1 versus 0.67 SD 0.05) and mean λ(∐) value (1.61 SD 0.52 versus 2.36 SD 0.14 μm(2)/s). In CC the percentage of ADC always diminished independently of lesion age (with one exception), whereas in hemisphere lesions, it was negative in earlier lesions, but exceeded normal values in the older lesions. CC may undergo early DTI changes in newborns with acute focal or multi-focal hemisphere lesions of different aetiology. Although a direct insult to CC cannot be totally ruled out, DTI changes in CC (in particular λ(∐)) may also be compatible with very early Wallerian degeneration or pre-Wallerian degeneration.

Prenatal Exposure to BPA Alters the Epigenome of the Rat Mammary Gland and Increases the Propensity to Neoplastic Development

PubMed Central

Dhimolea, Eugen; Wadia, Perinaaz R.; Murray, Tessa J.; Settles, Matthew L.; Treitman, Jo D.; Sonnenschein, Carlos; Shioda, Toshi; Soto, Ana M.

2014-01-01

Exposure to environmental estrogens (xenoestrogens) may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA) leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND) 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA) was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments), with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50). BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene expression patterns

Evaluation of autofluorescence and toluidine blue in the differentiation of oral dysplastic and neoplastic lesions from non dysplastic and neoplastic lesions: a cross-sectional study

NASA Astrophysics Data System (ADS)

Petruzzi, Massimo; Lucchese, Alberta; Nardi, Gianna Maria; Lauritano, Dorina; Favia, Gianfranco; Serpico, Rosario; Grassi, Felice Roberto

2014-07-01

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.

Columnar cell lesions and pseudoangiomatous hyperplasia like stroma: is there an epithelial-stromal interaction?

PubMed

Recavarren, Rosemary A; Chivukula, Mamatha; Carter, Gloria; Dabbs, David J

2009-10-10

The significance of association between cancer and its microenvironment has been increasingly recognized. It has been shown in animal models that interaction between neoplastic epithelial cells and adjacent stroma can modulate tumor behavior. Carcinoma associated stromal cells can transform normal epithelial cells into neoplastic cells. In breast, columnar cell lesions are non-obligate precursors of low grade ductal carcinoma in situ. Columnar cell lesions can be seen intimately associated with PASH-like-stroma, a lesion we termed as CCPLS. Our aim is to investigate epithelial-stromal interactions in CCPLS and compare them to PASH without columnar cell lesions in breast core needle biopsies. Normal terminal duct lobular unit (TDLU) epithelium was seen in association with columnar cell lesions as well as PASH. Eight (8) cases of each category were examined by a panel of immunostains: CD117 (C-kit), CD34, CD105, bFGF, AR, ER-beta, MIB-1. We observed a markedly decreased expression of c-kit in columnar cell lesions compared to TDLU-epithelium. CD105 showed a quantitative increase in activated vessels in CCPLS compared to PASH. A subset of CCPLS and PASH were androgen receptor positive. A strong nuclear positivity for ER-beta is observed in the epithelium and stroma of all CCPLS cases. We conclude that (1) activated blood vessels predominate in CCPLS; (2) A molecular alteration is signified by c-kit loss in columnar cell lesions; (3) ER-beta and androgen receptor positivity indicate CCPLS are hormonally responsive lesions. Our study suggests an intimate vascular and hormone dependent epithelial-stromal interaction exists in CCPLS lesions.

Incidence of infusion reactions to anti-neoplastic agents in early phase clinical trials: The MD Anderson Cancer Center experience.

PubMed

Bupathi, Manojkumar; Hajjar, Joud; Bean, Stacie; Fu, Siqing; Hong, David; Karp, Daniel; Stephen, Bettzy; Hess, Kenneth; Meric-Bernstam, Funda; Naing, Aung

2017-02-01

Infusion reactions (IRs) to anti-neoplastic agents require prompt recognition and immediate treatment to avert significant complications. We conducted a retrospective review of the medical records of consecutive patients who received anti-neoplastic therapy in the outpatient treatment center of the Department of Investigational Cancer Therapeutics from January 1, 2013 to November 30, 2013. Of the 597 patients who received treatment, 9 (1.5 %) had IRs (all ≤ grade 2). The most common IRs observed on first occurrence were chills (n = 5), itching, rash, and facial flushing (n = 3 each). There were no IR-related deaths. All the IRs were reversible with appropriate symptomatic treatment and the therapy was completed after temporary cessation of infusion in 7 of the 9 patients. The infusion was stopped in 2 patients due to symptoms suggestive of IgE-mediated allergic reaction and cytokine storm. Five of the 8 patients who were re-challenged with the same therapy developed a similar reaction. However, the infusion was completed in 4 of the 5 patients after administration of intravenous diphenhydramine and/or hydrocortisone, or slowing the rate of infusion. And, subsequent cycles with the same agents were uneventful. IRs to anti-neoplastic agents are rare. Though the clinical presentations are overlapping, most IRs are not IgE-mediated allergic reactions. Appropriate premedication and slow rate of infusion facilitates uneventful administration of the anti-neoplastic agents in subsequent cycles. Further study in a larger cohort of patients to identify biomarkers of hypersensitivity is warranted.

Cervical (pre)neoplastic microenvironment promotes the emergence of tolerogenic dendritic cells via RANKL secretion

PubMed Central

Demoulin, Stéphanie A; Somja, Joan; Duray, Anaëlle; Guénin, Samuel; Roncarati, Patrick; Delvenne, Philippe O; Herfs, Michael F; Hubert, Pascale M

2015-01-01

The progression of genital human papillomavirus (HPV) infections into preneoplastic lesions suggests that infected/malignant cells are not adequately recognized by the immune system. In this study, we demonstrated that cervical/vulvar cancer cells secrete factor(s) that affect both the maturation and function of dendritic cells (DC) leading to a tolerogenic profile. Indeed, DC cocultured with cancer cell lines display both a partially mature phenotype after lipopolysaccharide (LPS) maturation and an altered secretory profile (IL-10high and IL-12p70low). In addition, tumor-converted DC acquire the ability to alter T-cell proliferation and to induce FoxP3+ suppressive T cells from naive CD4+ T cells. Among the immunosuppressive factors implicated in DC alterations in genital (pre)neoplastic microenvironment, we identified receptor activator of nuclear factor kappa-B ligand (RANKL), a TNF family member, as a potential candidate. For the first time, we showed that RANKL expression strongly increases during cervical progression. We also confirmed that RANKL is directly secreted by cancer cells and this expression is not related to HPV viral oncoprotein induction. Interestingly, the addition of osteoprotegerin (OPG) in coculture experiments reduces significantly the inhibition of DC maturation, the release of a tolerogenic cytokine profile (IL-12low IL-10high) and the induction of regulatory T (Treg) cells. Our findings suggest that the use of inhibitory molecules directed against RANKL in cervical/vulvar (pre)neoplastic lesions might prevent alterations of DC functionality and represent an attractive strategy to overcome immune tolerance in such cancers. PMID:26155412

Enhanced Expression of CD13 in Vessels of Inflammatory and Neoplastic Tissues

PubMed Central

Matteo, Paola Di; Arrigoni, Gian Luigi; Alberici, Luca; Corti, Angelo; Gallo-Stampino, Corrado; Traversari, Catia; Doglioni, Claudio; Rizzardi, Gian-Paolo

2011-01-01

Aminopeptidase-N (CD13) is an important target of tumor vasculature-targeting drugs. The authors investigated its expression by immunohistochemistry with three anti-CD13 monoclonal antibodies (WM15, 3D8, and BF10) in normal and pathological human tissues, including 58 normal, 32 inflammatory, and 149 tumor tissue specimens. The three antibodies stained vessels in most neoplastic tissues, interestingly with different patterns. As a matter of fact, WM15 stained almost all intratumor and peritumor capillaries and only partially large vessels, whereas BF10 and 3D8 reacted with arteries and venules and to a lesser extent with capillaries. These antibodies also stained the stroma in about half of neoplastic tissues. In inflammatory lesions, the three antibodies stained vessels and stroma, whereas in normal tissues, they stained a small percentage of blood vessels. Finally, the three antibodies failed to stain endothelial cells of normal colon, whereas they reacted with activated human umbilical vein endothelial cells and with endothelial cells of colon adenocarcinoma vessels. Overall, WM15 was the most specific antibody for angiogenic tumor vessels, suggesting that it may be a good tool for detecting the CD13 form associated with the tumor vasculature. This finding may be relevant for CD13-mediated vascular targeting therapies. PMID:21339174

[Endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) in neoplastic Barrett's esophagus or Barrett early cancer is also economically superior to sole radical endoscopic resection].

PubMed

Wilke, M; Rathmayer, M; Schenker, M; Schepp, W

2016-05-01

Neoplastic changes (mild or high grade intraepithelial neoplasia (L- or HGIEN) or early cancer) in Barrett esophagus are treated with various methods. This study compares clinical-economical aspects of sole stepwise radical endoscopic resection (SRER) against combination treatment with EMR (Endoscopic mucosal resection) and RFA (radiofrequency ablation). Based on clinical data from a randomized controlled trial 1 we developed an economic model for costs of treatment according to the German Hospital Remuneration System (G-DRG). Our calculating incorporated initial treatment costs and the cost of treating complications (both paid via G-DRG). Medical and economically, the treatment with EMR + RFA advantages over sole SRER treatment 1. The successful complete resection or destruction of neoplastic intestinal metaplastic tissue is similar in both procedures. Acute complications (24 vs. 13 % in SRER EMR + RFA) and late complications (88 vs. 13 % in SRER EMR + RFA) are significantly more likely in sole SRER than in the EMR + RFA. While SRER initially appears more cost-effective as a sole therapy, cost levels move significantly above EMR+RFA due to higher complication rates and following procedures costs. Overall, the costs of treatment was € 13 272.11 in the SRER group and € 11 389.33 in the EMR + RFA group. The EMR + RFA group thus achieved a cost advantage of € 1882.78. The study shows that the treatment of neoplastic Barrett esophagus with EMR + RFA is also appropriate in economic terms. © Georg Thieme Verlag KG Stuttgart · New York.

Peripheral Exophytic Oral Lesions: A Clinical Decision Tree

PubMed Central

Safi, Yaser; Jafari, Soudeh

2017-01-01

Diagnosis of peripheral oral exophytic lesions might be quite challenging. This review article aimed to introduce a decision tree for oral exophytic lesions according to their clinical features. General search engines and specialized databases including PubMed, PubMed Central, Medline Plus, EBSCO, Science Direct, Scopus, Embase, and authenticated textbooks were used to find relevant topics by means of keywords such as “oral soft tissue lesion,” “oral tumor like lesion,” “oral mucosal enlargement,” and “oral exophytic lesion.” Related English-language articles published since 1988 to 2016 in both medical and dental journals were appraised. Upon compilation of data, peripheral oral exophytic lesions were categorized into two major groups according to their surface texture: smooth (mesenchymal or nonsquamous epithelium-originated) and rough (squamous epithelium-originated). Lesions with smooth surface were also categorized into three subgroups according to their general frequency: reactive hyperplastic lesions/inflammatory hyperplasia, salivary gland lesions (nonneoplastic and neoplastic), and mesenchymal lesions (benign and malignant neoplasms). In addition, lesions with rough surface were summarized in six more common lesions. In total, 29 entities were organized in the form of a decision tree in order to help clinicians establish a logical diagnosis by a stepwise progression method. PMID:28757870

Spontaneous melanotic lesions in axillary seabream, Pagellus acarne (Risso).

PubMed

Ramos, P; Victor, P; Branco, S

2013-09-01

In this article, we describe spontaneous melanotic lesions in the skin of axillary seabream, Pagellus acarne (Risso), from a defined area of the Portuguese Coast, located in Cabo da Roca and Foz do Arelho. The lesions corresponded to the black pigmentation spots on the skin of the head, fins, lips and conjunctiva and, additionally, black nodules on the skin of the head and lips. In some specimens, the nodular formations in the head changed their anatomical conformation. Histologically, there were melanophores scattered along the basement membrane or forming aggregates in the dermis, infiltrating the subcutaneous tissue but not invading the adjacent muscle tissue. The aim of this study was to characterize the macroscopic and microscopic features of the pigmented lesions. These fish show sessile hyperpigmented lesions (spots) that correspond to proliferative lesions of melanophores in the dermis and nodular lesions that correspond to neoplastic lesions, melanophoromas. The melanophores in such lesions showed high concentration of melanin in the cytoplasm, moderate pleomorphism and compact distribution throughout all of the dermis. © 2013 John Wiley & Sons Ltd.

Autofluorescence guided diagnostic evaluation of suspicious oral mucosal lesions: opportunities, limitations, and pitfalls

NASA Astrophysics Data System (ADS)

Vigneswaran, Nadarajah

2011-03-01

Wide-filed autofluorescence examination is currently considered as a standard of care for screening and diagnostic evaluation of early neoplastic changes of the skin, cervix, lung, bladder, gastrointestinal tract and oral cavity. Naturally occurring fluorophores within the tissue absorb UV and visible light and can re-emit some of this light at longer wavelengths in the form of fluorescence. This non-invasive tissue autofluorescence imaging is used in optical diagnostics, especially in the early detection of cancer. Usually, malignant transformation is associated with thickening of the epithelium, enhanced cellular density due to increased nuclear cytoplasmic ratio which may attenuate the excitation leading to a decrease in collagen autofluorescence. Hence, dysplastic and cancerous tissues often exhibit decreased blue-green autofluorescence and appear darker compared to uninvolved mucosa. Currently, there are three commercially available devices to examine tissue autofluorescence in the oral cavity. In this study we used the oral cancer screening device IdentafiTM 3000 to examine the tissue reflectance and autofluorescence of PML and confounding lesions of the oral cavity. Wide-field autofluorescence imaging enables rapid inspection of large mucosal surfaces, to aid in recognition of suspicious lesions and may also help in discriminate the PML (class 1) from some of the confounding lesions (class II). However, the presence of inflammation or pigments is also associated with loss of stromal autofluorescence, and may give rise to false-positive results with widefield fluorescence imaging. Clinicians who use these autofluorescence based oral cancer screening devices should be aware about the benign oral mucosal lesions that may give false positivity so that unnecessary patient's anxiety and the need for scalpel biopsy can be eliminated.

Local bone marrow renin-angiotensin system in primitive, definitive and neoplastic haematopoiesis.

PubMed

Haznedaroglu, Ibrahim C; Beyazit, Yavuz

2013-03-01

The locally active ligand peptides, mediators, receptors and signalling pathways of the haematopoietic BM (bone marrow) autocrine/paracrine RAS (renin-angiotensin system) affect the essential steps of definitive blood cell production. Haematopoiesis, erythropoiesis, myelopoiesis, formation of monocytic and lymphocytic lineages, thrombopoiesis and other stromal cellular elements are regulated by the local BM RAS. The local BM RAS is present and active even in primitive embryonic haematopoiesis. ACE (angiotensin-converting enzyme) is expressed on the surface of the first endothelial and haematopoietic cells, forming the marrow cavity in the embryo. ACE marks early haematopoietic precursor cells and long-term blood-forming CD34(+) BM cells. The local autocrine tissue BM RAS may also be active in neoplastic haematopoiesis. Critical RAS mediators such as renin, ACE, AngII (angiotensin II) and angiotensinogen have been identified in leukaemic blast cells. The local tissue RAS influences tumour growth and metastases in an autocrine and paracrine fashion via the modulation of numerous carcinogenic events, such as angiogenesis, apoptosis, cellular proliferation, immune responses, cell signalling and extracellular matrix formation. The aim of the present review is to outline the known functions of the local BM RAS within the context of primitive, definitive and neoplastic haematopoiesis. Targeting the actions of local RAS molecules could represent a valuable therapeutic option for the management of neoplastic disorders.

Early childhood caries lesions in preschool children in Kerala, India.

PubMed

Jose, Babu; King, Nigel M

2003-01-01

No data are available on possible risk indicators or the prevalence of caries lesions for preschool children under 4 years of age in Kerala, southern India. Therefore, the aims of this study were: (1) to gather data on caries lesion frequency and distribution; (2) to determine any possible associations with feeding habits and oral health care practices. A sample of 530 children, aged from 8 to 48 months (mean=2.5+/-0.96 years), who attended 13 day care centers were clinically examined for caries lesions using a disposable mouth mirror, tongue spatula, and a torch light. There were 513 dentate children. The caregiver of each child then completed, by interview, a structured questionnaire. Among the group of 252 girls and 278 boys, the dmft was 1.84+/-2.87 with 56% of the children being caries-lesion free. Fifty-nine (12%) were considered to have early childhood caries (ECC), based on the criteria that smooth surface caries lesions on all 4 maxillary incisor teeth indicated severe ECC. Breast-feeding was practiced by 99% of the mothers, and 5% did so exclusively. Generally, breast-feeding was on demand. Statistically significant correlations were found between caries lesions and the child's dental condition, as perceived by the mother or caregiver (P<.0001), the dental status of the caregiver (P=.0417), consumption of snacks (P=.0177), giving of sweets as a reward (P<.0001), cleaning of the child's mouth (P<.0001), oral hygiene status of the child (P<.0001) and low socioeconomic status, as measured by income (P<.0001). From the results of this study of preschool children in Kerala, the groups at high risk from dental caries lesions are: (1) those with poor oral hygiene status; (2) those who consume snacks and are given sweets as rewards; (3) those belonging to a lower socioeconomic class.

Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions

PubMed Central

Hendrickx, Debbie A. E.; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G.; van Eden, Corbert G.; Hol, Elly M.; Hamann, Jörg; Huitinga, Inge

2017-01-01

In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1, and ANO4. Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16, and OLR1, and lipid uptake, such as CHIT1, GPNMB, and CCL18. Except CCL18, these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion. PMID:29312322

Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions.

PubMed

Hendrickx, Debbie A E; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G; van Eden, Corbert G; Hol, Elly M; Hamann, Jörg; Huitinga, Inge

2017-01-01

In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1 , and ANO4 . Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16 , and OLR1 , and lipid uptake, such as CHIT1, GPNMB , and CCL18 . Except CCL18 , these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion.

Spatial distribution of early red lesions is a risk factor for development of vision-threatening diabetic retinopathy.

PubMed

Ometto, Giovanni; Assheton, Phil; Calivá, Francesco; Chudzik, Piotr; Al-Diri, Bashir; Hunter, Andrew; Bek, Toke

2017-12-01

Diabetic retinopathy is characterised by morphological lesions related to disturbances in retinal blood flow. It has previously been shown that the early development of retinal lesions temporal to the fovea may predict the development of treatment-requiring diabetic maculopathy. The aim of this study was to map accurately the area where lesions could predict progression to vision-threatening retinopathy. The predictive value of the location of the earliest red lesions representing haemorrhages and/or microaneurysms was studied by comparing their occurrence in a group of individuals later developing vision-threatening diabetic retinopathy with that in a group matched with respect to diabetes type, age, sex and age of onset of diabetes mellitus who did not develop vision-threatening diabetic retinopathy during a similar observation period. The probability of progression to vision-threatening diabetic retinopathy was higher in a circular area temporal to the fovea, and the occurrence of the first lesions in this area was predictive of the development of vision-threatening diabetic retinopathy. The calculated peak value showed that the risk of progression was 39.5% higher than the average. There was no significant difference in the early distribution of lesions in participants later developing diabetic maculopathy or proliferative diabetic retinopathy. The location of early red lesions in diabetic retinopathy is predictive of whether or not individuals will later develop vision-threatening diabetic retinopathy. This evidence should be incorporated into risk models used to recommend control intervals in screening programmes for diabetic retinopathy.

Role of endoscopic ultrasound-guided fine needle aspiration and ultrasound-guided fine-needle aspiration in diagnosis of cystic pancreatic lesions

PubMed Central

Okasha, Hussein Hassan; Ashry, Mahmoud; Imam, Hala M. K.; Ezzat, Reem; Naguib, Mohamed; Farag, Ali H.; Gemeie, Emad H.; Khattab, Hani M.

2015-01-01

Background and Objective: The addition of fine-needle aspiration (FNA) to different imaging modalities has raised the accuracy for diagnosis of cystic pancreatic lesions. We aim to differentiate benign from neoplastic pancreatic cysts by evaluating cyst fluid carcinoembryonic antigen (CEA), carbohydrate antigen (CA19-9), and amylase levels and cytopathological examination, including mucin stain. Patients and Methods: This prospective study included 77 patients with pancreatic cystic lesions. Ultrasound-FNA (US-FNA) or endoscopic ultrasound-FNA (EUS-FNA) was done according to the accessibility of the lesion. The aspirated specimens were subjected to cytopathological examination (including mucin staining), tumor markers (CEA, CA19-9), and amylase level. Results: Cyst CEA value of 279 or more showed high statistical significance in differentiating mucinous from nonmucinous lesions with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 73%, 60%, 50%, 80%, and 65%, respectively. Cyst amylase could differentiate between neoplastic and nonneoplastic cysts at a level of 1043 with sensitivity of 58%, specificity of 75%, PPV of 73%, NPV of 60%, and accuracy of 66%. CA19-9 could not differentiate between neoplastic and nonneoplastic cysts. Mucin examination showed a sensitivity of 85%, specificity of 95%, PPV of 92%, NPV of 91%, and accuracy of 91% in differentiating mucinous from non-mucinous lesions. Cytopathological examination showed a sensitivity of 81%, specificity of 94%, PPV of 94%, NPV of 83%, and accuracy of 88%. Conclusion: US or EUS-FNA with analysis of cyst CEA level, CA19-9, amylase, mucin stain, and cytopathological examination increases the diagnostic accuracy of cystic pancreatic lesions. PMID:26020048

Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water.

PubMed

Cullen, John M; Ward, Jerrold M; Thompson, Chad M

2016-02-01

Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI) studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality) was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal lesions in rats and mice from the 4 repeated-dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal pathology. The differences in the severity of non-neoplastic lesions also likely contribute to the differential tumor response. © The Author(s) 2015.

Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water

PubMed Central

Cullen, John M.; Ward, Jerrold M.

2015-01-01

Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI) studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality) was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal lesions in rats and mice from the 4 repeated-dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal pathology. The differences in the severity of non-neoplastic lesions also likely contribute to the differential tumor response. PMID:26538584

Surgical pathology of epilepsy-associated non-neoplastic cerebral lesions: a brief introduction with special reference to hippocampal sclerosis and focal cortical dysplasia

PubMed Central

Miyata, Hajime; Hori, Tomokatsu; Vinters, Harry V.

2014-01-01

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

Automated detection of dark and bright lesions in retinal images for early detection of diabetic retinopathy.

PubMed

Akram, Usman M; Khan, Shoab A

2012-10-01

There is an ever-increasing interest in the development of automatic medical diagnosis systems due to the advancement in computing technology and also to improve the service by medical community. The knowledge about health and disease is required for reliable and accurate medical diagnosis. Diabetic Retinopathy (DR) is one of the most common causes of blindness and it can be prevented if detected and treated early. DR has different signs and the most distinctive are microaneurysm and haemorrhage which are dark lesions and hard exudates and cotton wool spots which are bright lesions. Location and structure of blood vessels and optic disk play important role in accurate detection and classification of dark and bright lesions for early detection of DR. In this article, we propose a computer aided system for the early detection of DR. The article presents algorithms for retinal image preprocessing, blood vessel enhancement and segmentation and optic disk localization and detection which eventually lead to detection of different DR lesions using proposed hybrid fuzzy classifier. The developed methods are tested on four different publicly available databases. The presented methods are compared with recently published methods and the results show that presented methods outperform all others.

Alterations in leucocyte subsets and histomorphology in normal-appearing perilesional skin and early and chronic hidradenitis suppurativa lesions.

PubMed

van der Zee, H H; de Ruiter, L; Boer, J; van den Broecke, D G; den Hollander, J C; Laman, J D; Prens, E P

2012-01-01

Current insight into the histopathological course of events during disease progression in hidradenitis suppurativa (HS) is fragmentary. To identify histological alterations and leucocyte subsets in normal-appearing perilesional skin, and early and chronic HS lesions. In this observational study we examined eight perilesional skin samples, and six early and 10 chronic prototypic HS lesions, as well as skin samples from four healthy donors using in situ immunostaining. Perilesional skin showed mild psoriasiform hyperplasia and follicular plugging as well as a low-grade influx of tryptase-positive mast cells, CD3+ T cells, CD138+ plasma cells and factor XIIIa+ dendritic cells. In early HS lesions, neutrophilic abscess formation and influx of mainly macrophages, monocytes and dendritic cells predominated. In chronic disease, the infiltrate expanded with markedly increased frequencies of CD20+ and CD79a+ B cells and CD138+ plasma cells. As in early lesions, free keratin fibres were detected in the dermis and within giant cells. Single detached keratinocytes and strands of follicular epithelium were observed in the dermis, the latter frequently expressing Ki67, indicative of active proliferation. Psoriasiform hyperplasia, follicular plugging and low-grade leucocytic infiltration are already present in normal-appearing perilesional skin. Keratin fibres in the dermis are associated with clinical disease. Early lesions are characterized by neutrophilic abscess formation and influx of mainly histiocytes, and chronic lesions mainly by expansion of B cells and plasma cells in 'pseudo' follicles. Proliferating strands of follicular epithelium may initiate fistula formation. Mast cells are increased in all stages of HS including perilesional skin. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Autofluorescence endoscopy with "real-time" digital image processing in differential diagnostics of selected benign and malignant lesions in the oesophagus.

PubMed

Sieroń-Stołtny, Karolina; Kwiatek, Sebastian; Latos, Wojciech; Kawczyk-Krupka, Aleksandra; Cieślar, Grzegorz; Stanek, Agata; Ziaja, Damian; Bugaj, Andrzej M; Sieroń, Aleksander

2012-03-01

Oesophageal papilloma and Barrett's oesophagus are benign lesions known as risk factors of carcinoma in the oesophagus. Therefore, it is important to diagnose these early changes before neoplastic transformation. Autofluorescence endoscopy is a fast and non-invasive method of imaging of tissues based on the natural fluorescence of endogenous fluorophores. The aim of this study was to prove the diagnostic utility of autofluorescence endoscopy with digital image processing in histological diagnosis of endoscopic findings in the upper digestive tract, primarily in the imaging of oesophageal papilloma. During the retrospective analysis of about 200 endoscopic procedures in the upper digestive tract, 67 cases of benign, precancerous or cancerous changes were found. White light endoscopy (WLE) image, single-channel (red or green) autofluorescence images, as well as green and red fluorescence intensities in two modal fluorescence image and red-to-green (R/G) ratio (Numerical Colour Value, NCV) were correlated with histopathologic results. The NCV analysis in autofluorescence imaging (AFI) showed increased R/G ratio in cancerous changes in 96% vs. 85% in WLE. Simultaneous analysis with digital image processing allowed us to diagnose suspicious tissue as cancerous in all of cases. Barrett's metaplasia was confirmed in 90% vs. 79% (AFI vs. WLE), and 98% in imaging with digital image processing. In benign lesions, WLE allowed us to exclude tissue as malignant in 85%. Using autofluorescence endoscopy R/G ratio was increased in only 10% of benign changes causing the picture to be interpreted as suspicious, but when both methods were used together, 97.5% were cases excluded as malignancies. Mean R/G ratios were estimated to be 2.5 in cancers, 1.25 in Barrett's metaplasia and 0.75 in benign changes and were statistically significant (p=0.04). Autofluorescence imaging is a sensitive method to diagnose precancerous and cancerous early stages of the diseases located in oesophagus

HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions

PubMed Central

TESTI, D.; NARDONE, M.; MELONE, P.; CARDELLI, P.; OTTRIA, L.; ARCURI, C.

2015-01-01

SUMMARY The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%–90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before “sexual puberty”. The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer. PMID:27555904

HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions.

PubMed

Testi, D; Nardone, M; Melone, P; Cardelli, P; Ottria, L; Arcuri, C

2015-01-01

The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%-90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before "sexual puberty". The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer.

DIAGNOSIS OF ENDOCRINE DISEASE: Differentiation of pathologic/neoplastic hypercortisolism (Cushing's syndrome) from physiologic/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing's syndrome).

PubMed

Findling, James W; Raff, Hershel

2017-05-01

Endogenous hypercortisolism (Cushing's syndrome) usually implies the presence of a pathologic condition caused by either an ACTH-secreting neoplasm or autonomous cortisol secretion from a benign or malignant adrenal neoplasm. However, sustained or intermittent hypercortisolism may also accompany many medical disorders that stimulate physiologic/non-neoplastic activation of the HPA axis (formerly known as pseudo-Cushing's syndrome); these two entities may share indistinguishable clinical and biochemical features. A thorough history and physical examination is often the best (and sometimes only) way to exclude pathologic/neoplastic hypercortisolism. The presence of alcoholism, renal failure, poorly controlled diabetes and severe neuropsychiatric disorders should always raise suspicion that the presence of hypercortisolism may be related to physiologic/non-neoplastic Cushing's syndrome. As late-night salivary cortisol and low-dose dexamethasone suppression have good sensitivity and negative predictive value, normal studies exclude Cushing's syndrome of any form. However, these tests have imperfect specificity and additional testing over time with clinical follow-up is often needed. When there is persistent diagnostic uncertainty, secondary tests such as the DDAVP stimulation test and the dexamethasone-CRH test may provide evidence for the presence or absence of an ACTH-secreting tumor. This review will define and characterize the numerous causes of physiologic/non-neoplastic hypercortisolism and provide a rational clinical and biochemical approach to distinguish it from pathologic/neoplastic hypercortisolism (true Cushing's syndrome). © 2017 European Society of Endocrinology.

Embolization of traumatic and non-traumatic peripheral vascular lesions with Onyx.

PubMed

Regine, Renato; Palmieri, Francesco; De Siero, Michele; Rescigno, Antonio; Sica, Vincenzo; Cantarela, Raffaele; Villari, Vincenzo

2015-03-01

The aim of our study is to verify the feasibility and the efficacy of Onyx as embolization agent in the treatment of traumatic and non-traumatic peripheral vascular lesions. In the period between September 2006 and March 2012, we treated with Onyx 26 patients (14 males/12 females; age range, 18-85 years old; mean age, 65 years old), 11 of which with traumatic peripheral vascular lesions and 15 with non-traumatic vascular lesions (9 neoplastic hemorrhagic lesions, 3 arteriovenous malformations (AVMs) and 3 aneurysms). Follow-up controls were performed with clinical examination and by multidetector computed tomography (MDCT) imaging 1, 6, and 12 months after the procedure. All peripheral vascular lesions were embolized with Onyx; 3 patients with aneurysms were treated with Onyx associated with endovascular coils. Four elective and 22 emergency embolization procedures were performed. In all patients, we obtained cessation of bleeding and the complete and permanent embolization of all vascular lesions. Onyx is an effective and safe embolization agent for peripheral vascular lesions.

The pilot study assessing efficacy and versatility of novel therapy for neoplastic ulceration: clinical and microbiological aspects

PubMed Central

Tomaszewska, Elżbieta; Muszyński, Zygmunt; Ciupińska, Maria; Kotlińska-Lemieszek, Aleksandra

2013-01-01

Introduction Neoplastic ulcers are chronic and, most often, irreversible lesions caused by proliferation of tumor cells infiltrating and damaging skin tissues. The treatment of neoplastic ulcers is a very difficult and time-consuming process. So, is very important to find methods of controlling this type of chronic wounds. Aim To evaluate the efficiency of monitored treatment of neoplastic ulcers by means of providing moist wound environment dressings and antiseptic to the group of patients with an advanced stage of tumor, with particular focus on the impact of the treatment applied on the clinical condition of the ulcers; to evaluate the impact of the treatment applied on the dynamics of bacterial flora in neoplastic ulcers, with particular focus on the presence of alarm pathogens; to conduct a risk analysis of the occurrence of local and systemic complications during treatment. Material and methods This was a prospective pilot clinical study of 30 patients with malignant ulcers, 13 male and 17 female aged from 24 to 92 years treated with octenidine antiseptic and dressing set for 3 weeks. The wounds were clinically assessed for the changes of amount of necrotic tissue, exudate level and type, malodour and pain level during treatment. At the baseline and after 3 weeks of treatment, the wounds were swabbed for microbiological assessment. Results The used scheme of treatment is efficient and brings clinical improvement in all treated ulcers. During the 3-week treatment, reduction of necrotic tissue, decrease in the level of exudate, pain and malodour was observed in all patients (p < 0.05). High activity of octenidine against Gram(–) and Gram(+) bacteria was observed. The use of octenidine dihydrochloride correlated with a progressing eradication of multiresistant strains and alarm pathogens (p < 0.001). No serious adverse effects or significant symptoms of intolerance of the applied treatment were observed. PMID:24278081

Comparison of diagnosis of early retinal lesions of diabetic retinopathy between a computer system and human experts.

PubMed

Lee, S C; Lee, E T; Kingsley, R M; Wang, Y; Russell, D; Klein, R; Warn, A

2001-04-01

To investigate whether a computer vision system is comparable with humans in detecting early retinal lesions of diabetic retinopathy using color fundus photographs. A computer system has been developed using image processing and pattern recognition techniques to detect early lesions of diabetic retinopathy (hemorrhages and microaneurysms, hard exudates, and cotton-wool spots). Color fundus photographs obtained from American Indians in Oklahoma were used in developing and testing the system. A set of 369 color fundus slides were used to train the computer system using 3 diagnostic categories: lesions present, questionable, or absent (Y/Q/N). A different set of 428 slides were used to test and evaluate the system, and its diagnostic results were compared with those of 2 human experts-the grader at the University of Wisconsin Fundus Photograph Reading Center (Madison) and a general ophthalmologist. The experiments included comparisons using 3 (Y/Q/N) and 2 diagnostic categories (Y/N) (questionable cases excluded in the latter). In the training phase, the agreement rates, sensitivity, and specificity in detecting the 3 lesions between the retinal specialist and the computer system were all above 90%. The kappa statistics were high (0.75-0.97), indicating excellent agreement between the specialist and the computer system. In the testing phase, the results obtained between the computer system and human experts were consistent with those of the training phase, and they were comparable with those between the human experts. The performance of the computer vision system in diagnosing early retinal lesions was comparable with that of human experts. Therefore, this mobile, electronically easily accessible, and noninvasive computer system, could become a mass screening tool and a clinical aid in diagnosing early lesions of diabetic retinopathy.

Osteoclast-targeting small molecules for the treatment of neoplastic bone metastases.

PubMed

Kawatani, Makoto; Osada, Hiroyuki

2009-11-01

Osteoclasts are highly specialized cells that resorb bone, and their abnormal activity is implicated in a variety of human bone diseases. In neoplastic bone metastasis, the bone destruction caused by osteoclasts is not only associated with the formation and progression of metastatic lesions, but also could contribute to frequent complications such as severe pain and pathological fractures, which greatly diminish the quality of life of patients. Bisphosphonates, potent antiresorptive drugs, have been shown to have efficacy for treating bone metastases in many types of cancer, and the development of various molecularly targeted agents is currently proceeding. Thus, inhibition of osteoclast function is now established as an important treatment strategy for bony metastases. This review focuses on promising small molecules that disrupt osteoclast function and introduces our chemical/biological approach for identifying osteoclast-targeting small molecular inhibitors.

Premalignant lesions in the kidney.

PubMed

Kirkali, Z; Yorukoglu, K

2001-12-07

Renal cell carcinoma (RCC) is the most malignant urologic disease. Different lesions, such as dysplasia in the tubules adjacent to RCC, atypical hyperplasia in the cyst epithelium of von Hippel-Lindau syndrome, and adenoma have been described for a number of years as possible premalignant changes or precursor lesions of RCC. In two recent papers, kidneys adjacent to RCC or removed from other causes were analyzed, and dysplastic lesions were identified and defined in detail. Currently renal intraepithelial neoplasia (RIN) is the proposed term for classification. The criteria for a lesion to be defined as premalignant are (1) morphological similarity; (2) spatial association; (3) development of microinvasive carcinoma; (4) higher frequency, severity, and extent then invasive carcinoma; (5) progression to invasive cancer; and (6) similar genetic alterations. RIN resembles the neoplastic cells of RCC. There is spatial association. Progression to invasive carcinoma is described in experimental cancer models, and in some human renal tumors. Similar molecular alterations are found in some putative premalignant changes. The treatment for RCC is radical or partial nephrectomy. Preneoplastic lesions may remain in the renal remnant in patients treated by partial nephrectomy and may be the source of local recurrences. RIN seems to be a biologic precursor of some RCCs and warrants further investigation. Interpretation and reporting of these lesions would reveal important resources for the biological nature and clinical significance. The management of RIN diagnosed in a renal biopsy and partial nephrectomy needs to be answered.

Facial nerve palsy associated with a cystic lesion of the temporal bone.

PubMed

Kim, Na Hyun; Shin, Seung-Ho

2014-03-01

Facial nerve palsy results in the loss of facial expression and is most commonly caused by a benign, self-limiting inflammatory condition known as Bell palsy. However, there are other conditions that may cause facial paralysis, such as neoplastic conditions of the facial nerve, traumatic nerve injury, and temporal bone lesions. We present a case of facial nerve palsy concurrent with a benign cystic lesion of the temporal bone, adjacent to the tympanic segment of the facial nerve. The patient's symptoms subsided after facial nerve decompression via a transmastoid approach.

Evaluation of a water-soluble bioadhesive patch for photodynamic therapy of vulval lesions.

PubMed

McCarron, Paul A; Donnelly, Ryan F; Zawislak, Agnieszka; Woolfson, A David; Price, John H; McClelland, Raymond

2005-04-11

An innovative bioadhesive patch intended primarily as a vulval drug delivery system and, specifically, as a means to deliver photosensitisers, or their prodrugs, for photodynamic purposes is described. The patch was formulated with a copolymer of methyl vinyl ether and maleic anhydride (PMVE/MA) as a bioadhesive matrix and poly(vinyl chloride) as a drug-impervious backing layer. Adhesive strength to neonate porcine skin, as a model substrate, was evaluated using peel and tensile testing measurements. Acceptabilities of non-drug loaded patches were appraised using human volunteers and visual-analogue scoring devices. An optimal formulation, with water uptake and peel strengths appropriate for vulval drug delivery, was cast from a 20% (w/w) PMVE/MA solution and adhered with a strength of approximately 1.7 Ncm(-2). Patient evaluation demonstrated comfort and firm attachment for up to 4h in mobile patients. Aminolevulinic acid, a commonly used photosensitiser, was formulated into the candidate formulation and applied to vulval intraepithelial neoplastic lesions. Fluorescence under ultraviolet illumination revealed protoporphyrin synthesis. The patch achieves the extended application times obligatory in topical photodynamic therapy of vulval lesions, thereby contributing to potential methods for the eradication of neoplastic lesions in the lower female reproductive tract.

Progress in the detection of neoplastic progress and cancer by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Bakker Schut, Tom C.; Stone, Nicholas; Kendall, Catherine A.; Barr, Hugh; Bruining, Hajo A.; Puppels, Gerwin J.

2000-05-01

Early detection of cancer is important because of the improved survival rates when the cancer is treated early. We study the application of NIR Raman spectroscopy for detection of dysplasia because this technique is sensitive to the small changes in molecular invasive in vivo detection using fiber-optic probes. The result of an in vitro study to detect neoplastic progress of esophageal Barrett's esophageal tissue will be presented. Using multivariate statistics, we developed three different linear discriminant analysis classification models to predict tissue type on the basis of the measured spectrum. Spectra of normal, metaplastic and dysplasia tissue could be discriminated with an accuracy of up to 88 percent. Therefore Raman spectroscopy seems to be a very suitable technique to detect dysplasia in Barrett's esophageal tissue.

ASXL1/EZH2 mutations promote clonal expansion of neoplastic HSC and impair erythropoiesis in PMF.

PubMed

Triviai, Ioanna; Zeschke, Silke; Rentel, Jan; Spanakis, Marios; Scherer, Theo; Gabdoulline, Razif; Panagiota, Victoria; Thol, Felicitas; Heuser, Michael; Stocking, Carol; Kröger, Nicolaus

2018-06-15

Primary myelofibrosis (PMF) is a hematopoietic stem cell (HSC) disease, characterized by aberrant differentiation of all myeloid lineages and profound disruption of the bone marrow niche. PMF samples carry several mutations, but their cell origin and hierarchy in regulating the different waves of clonal and aberrant myeloproliferation from the prime HSC compartment is poorly understood. Genotyping of >2000 colonies from CD133+HSC and progenitors from PMF patients confirmed the complex genetic heterogeneity within the neoplastic population. Notably, mutations in chromatin regulators ASXL1 and/or EZH2 were identified as the first genetic lesions, preceding both JAK2-V617F and CALR mutations, and are thus drivers of clonal myelopoiesis in a PMF subset. HSC from PMF patients with double ASXL1/EZH2 mutations exhibited significantly higher engraftment in immunodeficient mice than those from patients without histone modifier mutations. EZH2 mutations correlate with aberrant erythropoiesis in PMF patients, exemplified by impaired maturation and cell cycle arrest of erythroid progenitors. These data underscore the importance of post-transcriptional modifiers of histones in neoplastic stem cells, whose clonal growth sustains aberrant myelopoiesis and expansion of pre-leukemic clones in PMF.

Embolization of traumatic and non-traumatic peripheral vascular lesions with Onyx

PubMed Central

Regine, Renato; De Siero, Michele; Rescigno, Antonio; Sica, Vincenzo; Cantarela, Raffaele; Villari, Vincenzo

2015-01-01

Purpose The aim of our study is to verify the feasibility and the efficacy of Onyx as embolization agent in the treatment of traumatic and non-traumatic peripheral vascular lesions. Materials and Methods In the period between September 2006 and March 2012, we treated with Onyx 26 patients (14 males/12 females; age range, 18–85 years old; mean age, 65 years old), 11 of which with traumatic peripheral vascular lesions and 15 with non-traumatic vascular lesions (9 neoplastic hemorrhagic lesions, 3 arteriovenous malformations (AVMs) and 3 aneurysms). Follow-up controls were performed with clinical examination and by multidetector computed tomography (MDCT) imaging 1, 6, and 12 months after the procedure. Results All peripheral vascular lesions were embolized with Onyx; 3 patients with aneurysms were treated with Onyx associated with endovascular coils. Four elective and 22 emergency embolization procedures were performed. In all patients, we obtained cessation of bleeding and the complete and permanent embolization of all vascular lesions. Conclusions Onyx is an effective and safe embolization agent for peripheral vascular lesions. PMID:25838923

Identification of early cancerous lesion of esophagus with endoscopic images by hyperspectral image technique (Conference Presentation)

NASA Astrophysics Data System (ADS)

Huang, Shih-Wei; Chen, Shih-Hua; Chen, Weichung; Wu, I.-Chen; Wu, Ming Tsang; Kuo, Chie-Tong; Wang, Hsiang-Chen

2016-03-01

This study presents a method to identify early esophageal cancer within endoscope using hyperspectral imaging technology. The research samples are three kinds of endoscopic images including white light endoscopic, chromoendoscopic, and narrow-band endoscopic images with different stages of pathological changes (normal, dysplasia, dysplasia - esophageal cancer, and esophageal cancer). Research is divided into two parts: first, we analysis the reflectance spectra of endoscopic images with different stages to know the spectral responses by pathological changes. Second, we identified early cancerous lesion of esophagus by principal component analysis (PCA) of the reflectance spectra of endoscopic images. The results of this study show that the identification of early cancerous lesion is possible achieve from three kinds of images. In which the spectral characteristics of NBI endoscopy images of a gray area than those without the existence of the problem the first two, and the trend is very clear. Therefore, if simply to reflect differences in the degree of spectral identification, chromoendoscopic images are suitable samples. The best identification of early esophageal cancer is using the NBI endoscopic images. Based on the results, the use of hyperspectral imaging technology in the early endoscopic esophageal cancer lesion image recognition helps clinicians quickly diagnose. We hope for the future to have a relatively large amount of endoscopic image by establishing a hyperspectral imaging database system developed in this study, so the clinician can take this repository more efficiently preliminary diagnosis.

Correlation of ultrasonographic appearance of lesions and cytologic and histologic diagnoses in splenic aspirates from dogs and cats: 32 cases (2002-2005).

PubMed

Ballegeer, Elizabeth A; Forrest, Lisa J; Dickinson, Ryan M; Schutten, Melissa M; Delaney, Fern A; Young, Karen M

2007-03-01

To determine the accuracy of cytologic diagnosis, compared with histologic diagnosis, in determination of disease in ultrasound-guided fine-needle aspirates of splenic lesions. Retrospective study. Splenic specimens from 29 dogs and 3 cats. Records were searched for dogs and cats that had undergone ultrasound-guided splenic aspiration. Criteria for inclusion were ultrasonographic identification of splenic lesions and cytologic and histologic evaluation of tissue from the same lesion. Cytologic samples were obtained by fine-needle aspiration, and histologic specimens were obtained via surgical biopsy, ultrasound-guided biopsy, or necropsy. Cytologic diagnoses corresponded with histologic diagnoses in 19 of 31 (61.3%) cases and differed in 5 of 31(16.1%) cases, and 1 aspirate was inadequate for evaluation. In 7 of 31 (22.6%) cases, histologic evaluation of tissue architecture was required to distinguish between reactive and neoplastic conditions. On the basis of histologic diagnosis in 14 animals with nonneoplastic conditions, the cytologic diagnosis was correct in 11 cases, not definitive in 2 cases, and incorrect in 1 case. In 17 animals with malignant neoplastic diseases, the cytologic diagnosis was correct in 8 cases, not definitive but consistent with possible neoplasia in 5 cases, and incorrect in 4 cases. Multiple similar-appearing nodules were significantly associated with malignancy, whereas single lesions were more often benign. Ultrasound-guided aspiration of splenic lesions is a minimally invasive tool for obtaining specimens for cytologic evaluation. Although cytologic diagnoses often reflect histologic results, if missampling or incomplete sampling occurs or tissue architecture is required to distinguish between reactive and neoplastic conditions, accurate diagnosis with fine-needle aspiration may not be possible.

Analysis of clonality and HPV infection in benign, hyperplastic, premalignant, and malignant lesions of the vulvar mucosa.

PubMed

Ueda, Yutaka; Enomoto, Takayuki; Miyatake, Takashi; Shroyer, Kenneth R; Yoshizaki, Tatsuo; Kanao, Hiroyuki; Ueno, Yuko; Sun, Hongbo; Nakashima, Ryuichi; Yoshino, Kiyoshi; Kimura, Toshihiro; Haba, Tomoko; Wakasa, Kenichi; Murata, Yuji

2004-08-01

To elucidate the pathogenesis of vulvar carcinomas, we studied clonality and human papillomavirus (HPV) infection in vulvar epithelial diseases. Monoclonal composition was demonstrated in all 9 invasive tumors (squamous cell carcinoma [SCC], 6; basal cell carcinoma, 1; malignant melanoma, 2), 15 of 20 cases of vulvar intraepithelial neoplasia (VIN), 7 of 9 cases of Paget disease, 2 of 6 cases of lichen sclerosus (LS), and 2 of 3 cases of squamous cell hyperplasia (SCH); high-risk type HPV was revealed in 5 of 6 SCCs and 17 of 20 VINs. These observations might imply that a subset of cases of LS and SCH result from a neoplastic proliferation, similar to VINs but not related to infection with high-risk type HPV. In 1 case of SCC with concurrent VIN 3 in an adjacent lesion, both lesions showed the same pattern of X chromosome inactivation and the presence of HPV-16 in episomal and integrated forms, suggesting that monoclonal expansion triggered by high-risk type HPV integration is an early event for carcinogenesis of HPV-associated SCC.

Deficient Repair of Particulate Hexavalent chromium-Induced DNA Double Strand Breaks Leads To Neoplastic Transformation

PubMed Central

Xie, Hong; Wise, Sandra S.; Wise, John. P.

2008-01-01

Hexavalent chromium (Cr(VI)) is a potent respiratory toxicant and carcinogen. The most carcinogenic forms of Cr(VI) are the particulate salts such as lead chromate, which deposit and persist in the respiratory tract after inhalation. We demonstrate here that particulate chromate induces DNA double strand breaks in human lung cells with 0.1, 0.5, and 1 ug/cm2 lead chromate inducing 1.5, 2 and 5 relative increases in the percent of DNA in the comet tail, respectively. These lesions are repaired within 24 h and require Mre11 expression for their repair. Particulate chromate also caused Mre11 to co-localize with gamma-H2A.X and ATM. Failure to repair these breaks with Mre11 induced neoplastic transformation including loss of cell contact inhibition and anchorage independent growth. A 5-day exposure to lead chromate induced loss of cell contact inhibition in a concentration-dependent manner with 0, 0.1, 0.5 and 1 ug/cm2 lead chromate inducing 1, 78 and 103 foci in 20 dishes, respectively. These data indicate that Mre11 is critical to repairing particulate Cr(VI)-induced double strand breaks and preventing Cr(VI)-induced neoplastic transformation. PMID:18023605

Mutant p53 expression in kidney tubules adjacent to renal cell carcinoma: evidence of a precursor lesion.

PubMed

Lai, R; el Dabbagh, L; Mourad, W A

1996-06-01

Neoplastic transformation can be associated with mutations of the p53 gene. This leads to stabilization of its protein product and to its accumulation, which allows immunohistochemical detection. Mutant p53 expression has been seen in many neoplasms, including renal cell carcinoma (RCC). We recently described putative precursor lesions of RCC. The lesions were defined as intratubular epithelial dysplasia (IED) of kidney tubules adjacent to RCC. They were seen in one-third of the cases studied. The findings were based only on light microscopic analysis. We hypothesized that neoplastic transformation would be manifested by mutant p53 expression in the kidney tubules adjacent to RCC and not in nonneoplastic kidneys. Immunohistochemical staining for p53 in 24 cases of RCC with adjacent kidneys was performed. We used the DO-7 monoclonal antibody reactive for the N-terminal of the p53 protein on formalin-fixed paraffin-embedded tissue. Sections from 14 kidneys resected for nonneoplastic conditions were used as controls. Twenty-one (87%) of the 24 cases of RCC had nuclear p53 expression in the tumor cells. This included 14 cases (58%) with intense reactivity and 7 cases (29%) with weaker p53 immunoreactivity. Of the 24 cases of RCC, IED was identified in 13 cases (54%). Immunoreactivity for p53 was focally seen in tubules of all the lesions, as well as in the nonlesional areas. Six of the lesions exhibited intense nuclear staining. The kidneys adjacent to the RCC, with no evidence of IED, showed focally intense positive p53 nuclear staining in four cases. None of the control specimens showed p53 expression. Our findings provide supportive evidence that previously described IED in kidneys adjacent to RCC are most likely precursor lesions of the neoplasm. Aberrant expression of p53 in areas without evidence of IED may suggest that neoplastic transformation manifested by p53 mutation in kidney tubules may be seen before the development of the morphologic features of

Functional Topography of Early Periventricular Brain Lesions in Relation to Cytoarchitectonic Probabilistic Maps

ERIC Educational Resources Information Center

Staudt, Martin; Ticini, Luca F.; Grodd, Wolfgang; Krageloh-Mann, Ingeborg; Karnath, Hans-Otto

2008-01-01

Early periventricular brain lesions can not only cause cerebral palsy, but can also induce a reorganization of language. Here, we asked whether these different functional consequences can be attributed to topographically distinct portions of the periventricular white matter damage. Eight patients with pre- and perinatally acquired left-sided…

Management strategies for neoplastic and vascular brain lesions presenting during pregnancy: A series of 29 patients.

PubMed

Pereira, Celestino Esteves; Lynch, Jose Carlos

2017-01-01

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. 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. 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. 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.

Melanocytic nevi and non-neoplastic hyperpigmentations.

PubMed

Clemente, C

2017-06-01

This is the first of three chapters that will be progressively published on Pathologica as updating activity of the Italian Study Group of Dermatopathology (GISD), Italian Society of Pathology and Cytology (SIAPeC IAP). The first chapter concerns non-neoplastic hyperpigmented skin lesions and nevi, the second will address the topics of dysplastic nevus, borderline and low malignant potential melanocytic proliferations and the third melanoma in its variants and differential diagnoses with a supplement on the immunohistochemistry and molecular support to diagnostic and prognostic definition of nevi and melanomas. Although we believe that great advances were made in the application of ancillary genetic, immunohistochemical and molecular techniques, for the diagnosis and biological characterization of melanocytic tumors the morphology still remains the gold standard. These chapters are not intended as substitutes or even claim to be compared to the numerous and valuable texts that are also recently published, but they want to present, concisely and quickly available, all of those traits that we believe essential to the histopathological evaluation of a melanocytic lesion. No morphological parameter is exclusive and individually sufficient to make the correct diagnosis of nevus or melanoma but to reach a final conclusive and appropriate interpretation a set of morphological characters must be evaluated and compared. I was lucky enough to be able to examine several thousand cases and to draw lessons from each of these increasing my diagnostic experience. I had a great lesson by my teacher and good friend Prof. Martin C. Mihm Jr of Boston, dermato-pathologist with undisputed international reputation, who, with great passion, patience and friendship, transferred me much of his experience and knowledge and for which I always thank him. Special thanks I would like to address Dr. Agostino Crupi, dermatologist, skin-oncologist and brilliant dermatoscopist who taught me how the

Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC.

PubMed

Scarpa, Marco; Scarpa, Melania; Castagliuolo, Ignazio; Erroi, Francesca; Kotsafti, Andromachi; Basato, Silvia; Brun, Paola; D'Incà, Renata; Rugge, Massimo; Angriman, Imerio; Castoro, Carlo

2016-03-01

BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance.

Management strategies for neoplastic and vascular brain lesions presenting during pregnancy: A series of 29 patients

PubMed Central

Pereira, Celestino Esteves; Lynch, Jose Carlos

2017-01-01

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

Orofacial hereditary haemorrhagic telangiectasia: high power diode laser in early and advanced lesion treatment

NASA Astrophysics Data System (ADS)

Tempesta, Angela; Franco, Simonetta; Miccoli, Simona; Suppressa, Patrizia; De Falco, Vincenzo; Crincoli, Vito; Lacaita, Mariagrazia; Giuliani, Michele; Favia, Gianfranco

2014-01-01

Hereditary Haemorrhagic Telangiectasia (HHT) is a muco-cutaneous inherited disease. Symptoms are epistaxis, visceral arterio-venous malformations, multiple muco-cutaneous telangiectasia with the risk of number increasing enlargement, bleeding, and super-infection. The aim of this work is to show the dual Diode Laser efficacy in preventive treatment of Early Lesions (EL < 2mm) and therapeutic treatment of Advanced Lesions (AL < 2mm). 21 patients affected by HHT with 822 muco-cutaneous telangiectatic nodules have been treated in several sessions with local anaesthesia and cooling of treated sites. EL preventive treatment consists of single Laser impulse (fibre 320) in ultrapulsed mode (2 mm single point spot). AL therapeutic treatment consists of repeated Laser impulses in pulsed mode (on 200ms / off 400ms). According to the results, Diode Laser used in pulsed and ultra-pulsed mode is very effective as noninvasive treatment both in early and advanced oral and perioral telangiectasia.

Predictive factors of neoplastic gallbladder polyps: Outcomes of 278 patients.

PubMed

Terzioğlu, Serdar Gökay; Kılıç, Murat Özgür; Sapmaz, Ali; Karaca, Ahmet Serdar

2017-05-01

Distinguishing between neoplastic and nonneoplastic gallbladder polyps (GBPs) in the preoperative workup is of great importance for appropriate treatment. The present study aimed to investigate the characteristics of GBPs and to determine potential predictive factors of neoplastic polyps. The data of 278 patients who were confirmed to have GBPs through laparoscopic cholecystectomy were retrospectively analyzed. Polyps were classified as nonneoplastic and neoplastic GBPs, according to histopathological diagnoses. All clinicopathological characteristics were compared between these two groups. There were 264 (95%) nonneoplastic GBPs and 14 (5%) neoplastic GBPs. In univariate analysis, there were significant differences in age with a cutoff value of 60 years (p=0.002), polyp size (p<0.001), number of polyps (p=0.014), and polyp morphology (p<0.001) between the groups. Multivariate analysis showed that solitary polyp (p<0.001) and sessile morphology (p<0.001) were the independent predictors of neoplastic GBPs. Receiver-operating characteristic curve analysis of three cut-off values of polyp sizes (6, 10, and 15 mm) indicated that a polyp size of 10 mm had the highest area under curve (0.942). Age above 60 years, solitary polyps larger than 1 cm, and sessile morphology are associated with an increased risk of neoplasia in GBP. Therefore, these characteristics should be considered in the management of GBPs to reduce the incidence of unnecessary surgeries and to prevent delays in the treatment of a possible cancer.

Early serum biomarker networks in infants with distinct retinochoroidal lesion status of congenital toxoplasmosis.

PubMed

de Araújo, Thádia Evelyn; Coelho-Dos-Reis, Jordana Grazziela; Béla, Samantha Ribeiro; Carneiro, Ana Carolina Aguiar Vasconcelos; Machado, Anderson Silva; Cardoso, Ludmila Melo; Ribeiro, Ágata Lopes; Dias, Michelle Hallais França; Queiroz Andrade, Gláucia Manzan; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Ferro, Eloisa Amália Vieira; Martins-Filho, Olindo Assis

2017-07-01

The present study characterized the early changes in the serum chemokines/cytokine signatures and networks in infants with congenital-toxoplasmosis/(TOXO) as compared to non-infected-controls/(NI). TOXO were subgrouped according to the retinochoroidal lesion status as no-lesion/(NL), active-lesion/(ARL), active/cicatricial-lesion/(ACRL) and cicatricial-lesion/(CRL). The results showed that TOXO display prominent chemokine production mediated by IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10 and RANTES/CCL5. Additionally, TOXO is accompanied by mixed proinflammatory/regulatory cytokine pattern mediated by IL-6, IFN-γ, IL-4, IL-5 and IL-10. While TNF appears as a putative biomarker for NL and IFN-γ/IL-5 as immunological features for ARL, IL-10 emerges as a relevant mediator in ACRL/CRL. IL-8/CXCL8 and IP-10/CXCL10 are broad-spectrum indicators of ocular disease, whereas TNF is a NL biomarker, IFN-γ and MIG/CXCL9 point out to ARL; and IL-10 is highlighted as a genuine serum biomarker of ACRL/CRL. The network analysis demonstrated a broad chemokine/cytokine crosstalk with divergences in the molecular signatures in patients with different ocular lesions during congenital toxoplasmosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Collaborating with the enemy: function of macrophages in the development of neoplastic disease.

PubMed

Eljaszewicz, Andrzej; Wiese, Małgorzata; Helmin-Basa, Anna; Jankowski, Michal; Gackowska, Lidia; Kubiszewska, Izabela; Kaszewski, Wojciech; Michalkiewicz, Jacek; Zegarski, Wojciech

2013-01-01

Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc.), and support invasion and metastases formation. Tumor-associated macrophages (TAMs), a predominant component of leukocytic infiltrate, "cooperate" with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease.

Persistent erythematous lesion of the vulva: a diagnostic and treatment challenge.

PubMed

Lazaridou, Elizabeth; Fotiadou, Christina; Giannopoulou, Christina; Ioannides, Demetrios

2012-01-01

The painful, erythematous and eroded vulva often proves to be a diagnostic problem both clinically and histologically. Its differential diagnosis includes both non-neoplastic and neoplastic diseases like Bowen's disease and squamous cell carcinoma (SCC). We report the case of a 62-year-old woman diagnosed, after considerable delay, with Bowen's disease of the vulva that eventually progressed to invasive SCC, despite the treatment with imiquimod 5% cream. Our case indicates, on one hand, that dermoscopy could contribute to the accuracy of the pre-operative clinical diagnosis. On the other hand it confirms the fact that treatment of Bowen's disease of the vulva could be rather intriguing. Although imiquimod 5% cream is an effective, non-invasive treatment option for large lesions or poor healing sites, it should be administered with great consideration in carefully selected cases.

Colonic lesion characterization in inflammatory bowel disease: A systematic review and meta-analysis

PubMed Central

Lord, Richard; Burr, Nicholas E; Mohammed, Noor; Subramanian, Venkataraman

2018-01-01

AIM To perform a systematic review and meta-analysis for the diagnostic accuracy of in vivo lesion characterization in colonic inflammatory bowel disease (IBD), using optical imaging techniques, including virtual chromoendoscopy (VCE), dye-based chromoendoscopy (DBC), magnification endoscopy and confocal laser endomicroscopy (CLE). METHODS We searched Medline, Embase and the Cochrane library. We performed a bivariate meta-analysis to calculate the pooled estimate sensitivities, specificities, positive and negative likelihood ratios (+LHR, -LHR), diagnostic odds ratios (DOR), and area under the SROC curve (AUSROC) for each technology group. A subgroup analysis was performed to investigate differences in real-time non-magnified Kudo pit patterns (with VCE and DBC) and real-time CLE. RESULTS We included 22 studies [1491 patients; 4674 polyps, of which 539 (11.5%) were neoplastic]. Real-time CLE had a pooled sensitivity of 91% (95%CI: 66%-98%), specificity of 97% (95%CI: 94%-98%), and an AUSROC of 0.98 (95%CI: 0.97-0.99). Magnification endoscopy had a pooled sensitivity of 90% (95%CI: 77%-96%) and specificity of 87% (95%CI: 81%-91%). VCE had a pooled sensitivity of 86% (95%CI: 62%-95%) and specificity of 87% (95%CI: 72%-95%). DBC had a pooled sensitivity of 67% (95%CI: 44%-84%) and specificity of 86% (95%CI: 72%-94%). CONCLUSION Real-time CLE is a highly accurate technology for differentiating neoplastic from non-neoplastic lesions in patients with colonic IBD. However, most CLE studies were performed by single expert users within tertiary centres, potentially confounding these results. PMID:29563760

Corneal Structural Changes in Nonneoplastic and Neoplastic Monoclonal Gammopathies.

PubMed

Aragona, Pasquale; Allegra, Alessandro; Postorino, Elisa Imelde; Rania, Laura; Innao, Vanessa; Wylegala, Edward; Nowinska, Anna; Ieni, Antonio; Pisani, Antonina; Musolino, Caterina; Puzzolo, Domenico; Micali, Antonio

2016-05-01

To investigate corneal confocal microscopic changes in nonneoplastic and neoplastic monoclonal gammopathies. Three groups of subjects were considered: group 1, twenty normal subjects; group 2, fifteen patients with monoclonal gammopathy of undetermined significance (MGUS); group 3, eight patients with smoldering multiple myeloma and eight patients with untreated multiple myeloma. After hematologic diagnosis, patients underwent ophthalmologic exam and in vivo confocal microscopic study. The statistical analysis was performed using ANOVA and Student-Newman-Keuls tests and receiver operating characteristic (ROC) curve analysis. Epithelial cells of gammopathic patients showed significantly higher reflectivity than controls, demonstrated by optical density (P < 0.001). Subbasal nerve density, branching, and beading were significantly altered in gammopathic patients (P = 0.01, P = 0.02, P = 0.02, respectively). The number of keratocytes was significantly reduced in neoplastic patients (P < 0.001 versus both normal and MGUS) in the anterior, medium, and posterior stroma. The ROC curve analysis showed good sensitivity and specificity for this parameter. Group 2 and 3 keratocytes showed higher nuclear and cytoplasmatic reflectivity in the medium and posterior stroma. Endothelial cells were not affected. Patients with neoplastic gammopathies showed peculiar alterations of the keratocyte number, which appeared significantly reduced. A follow-up with corneal confocal microscopy of patients with MGUS is suggested as a useful tool to identify peripheral tissue alterations linked to possible neoplastic disease development.

Serum Free Light Chains in Neoplastic Monoclonal Gammopathies: Relative Under-Detection of Lambda Dominant Kappa/Lambda Ratio, and Underproduction of Free Lambda Light Chains, as Compared to Kappa Light Chains, in Patients With Neoplastic Monoclonal Gammopathies.

PubMed

Lee, Won Sok; Singh, Gurmukh

2018-07-01

Quantitative evaluation of serum free light chains is recommended for the work up of monoclonal gammopathies. Immunoglobulin light chains are generally produced in excess of heavy chains. In patients with monoclonal gammopathy, κ/λ ratio is abnormal less frequently with lambda chain lesions. This study was undertaken to ascertain if the levels of overproduction of the two light chain types and their detection rates are different in patients with neoplastic monoclonal gammopathies. Results of serum protein electrophoresis (SPEP), serum protein immunofixation electrophoresis (SIFE), urine protein electrophoresis (UPEP), urine protein immunofixation electrophoresis (UIFE), and serum free light chain assay (SFLCA) in patients with monoclonal gammopathies were examined retrospectively. The κ/λ ratios were appropriately abnormal more often in kappa chain lesions. Ratios of κ/λ were normal in about 25% of patients with lambda chain lesions in whom free homogenous lambda light chains were detectable in urine. An illustrative case suggests underproduction of free lambda light chains, in some instances. The lower prevalence of lambda dominant κ/λ ratio in lesions with lambda light chains is estimated to be due to relative under-detection of lambda dominant κ/λ ratio in about 25% of the patients and because lambda chains are not produced in as much excess of heavy chains as are kappa chains, in about 5% of the patients. The results question the medical necessity and clinical usefulness of the serum free light chain assay. UPEP/UIFE is under-utilized.

Serum Free Light Chains in Neoplastic Monoclonal Gammopathies: Relative Under-Detection of Lambda Dominant Kappa/Lambda Ratio, and Underproduction of Free Lambda Light Chains, as Compared to Kappa Light Chains, in Patients With Neoplastic Monoclonal Gammopathies

PubMed Central

Lee, Won Sok; Singh, Gurmukh

2018-01-01

Background Quantitative evaluation of serum free light chains is recommended for the work up of monoclonal gammopathies. Immunoglobulin light chains are generally produced in excess of heavy chains. In patients with monoclonal gammopathy, κ/λ ratio is abnormal less frequently with lambda chain lesions. This study was undertaken to ascertain if the levels of overproduction of the two light chain types and their detection rates are different in patients with neoplastic monoclonal gammopathies. Methods Results of serum protein electrophoresis (SPEP), serum protein immunofixation electrophoresis (SIFE), urine protein electrophoresis (UPEP), urine protein immunofixation electrophoresis (UIFE), and serum free light chain assay (SFLCA) in patients with monoclonal gammopathies were examined retrospectively. Results The κ/λ ratios were appropriately abnormal more often in kappa chain lesions. Ratios of κ/λ were normal in about 25% of patients with lambda chain lesions in whom free homogenous lambda light chains were detectable in urine. An illustrative case suggests underproduction of free lambda light chains, in some instances. Conclusions The lower prevalence of lambda dominant κ/λ ratio in lesions with lambda light chains is estimated to be due to relative under-detection of lambda dominant κ/λ ratio in about 25% of the patients and because lambda chains are not produced in as much excess of heavy chains as are kappa chains, in about 5% of the patients. The results question the medical necessity and clinical usefulness of the serum free light chain assay. UPEP/UIFE is under-utilized. PMID:29904440

Arrested development: early prefrontal lesions impair the maturation of moral judgement.

PubMed

Taber-Thomas, Bradley C; Asp, Erik W; Koenigs, Michael; Sutterer, Matthew; Anderson, Steven W; Tranel, Daniel

2014-04-01

Learning to make moral judgements based on considerations beyond self-interest is a fundamental aspect of moral development. A deficit in such learning is associated with poor socialization and criminal behaviour. The neural systems required for the acquisition and maturation of moral competency are not well understood. Here we show in a unique sample of neurological patients that focal lesions involving ventromedial prefrontal cortex, acquired during development, result in an abnormally egocentric pattern of moral judgement. In response to simple hypothetical moral scenarios, the patients were more likely than comparison participants to endorse self-interested actions that involved breaking moral rules or physically harming others in order to benefit themselves. This pattern (which we also found in subjects with psychopathy) differs from that of patients with adult-onset ventromedial prefrontal cortex lesions--the latter group showed normal rejection of egocentric rule violations. This novel contrast of patients with ventromedial prefrontal cortex lesions acquired during development versus during adulthood yields new evidence suggesting that the ventromedial prefrontal cortex is a critical neural substrate for the acquisition and maturation of moral competency that goes beyond self-interest to consider the welfare of others. Disruption to this affective neural system early in life interrupts moral development.

Disruption of Smad-dependent signaling for growth of GST-P-positive lesions from the early stage in a rat two-stage hepatocarcinogenesis model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ichimura, Ryohei, E-mail: red0828@hotmail.co.j; Mizukami, Sayaka, E-mail: non_sugar_life@hotmail.co.j; Takahashi, Miwa, E-mail: mtakahashi@nihs.go.j

2010-08-01

To clarify the involvement of signaling of transforming growth factor (TGF)-{beta} during the hepatocarcinogenesis, the immunohistochemical distribution of related molecules was analyzed in relation with liver cell lesions expressing glutathione S-transferase placental form (GST-P) during liver tumor promotion by fenbendazole, phenobarbital, piperonyl butoxide, or thioacetamide, using rats. Our study focused on early-stage promotion (6 weeks after starting promotion) and late-stage promotion (57 weeks after starting promotion). With regard to Smad-dependent signaling, cytoplasmic accumulation of phosphorylated Smad (phospho-Smad)-2/3 - identified as Smad3 by later immunoblot analysis - increased in the subpopulation of GST-P{sup +} foci, while Smad4, a nuclear transporter ofmore » Smad2/3, decreased during early-stage promotion. By late-stage promotion, GST-P{sup +} lesions lacking phospho-Smad2/3 had increased in accordance with lesion development from foci to carcinomas, while Smad4 largely disappeared in most proliferative lesions. With regard to Smad-independent mitogen-activated protein kinases, GST-P{sup +} foci that co-expressed phospho-p38 mitogen-activated protein kinase increased during early-stage promotion; however, p38-downstream phospho-activating transcriptional factor (ATF)-2, ATF3, and phospho-c-Myc, were inversely downregulated without relation to promotion. By late-stage promotion, proliferative lesions downregulated phospho-ATF2 and phospho-c-Myc along with lesion development, as with downregulation of phospho-p38 in all lesions. These results suggest that from the early stages, carcinogenic processes were facilitated by disruption of tumor suppressor functions of Smad-dependent signaling, while Smad-independent activation of p38 was an early-stage phenomenon. GST-P{sup -} foci induced by promotion with agonists of peroxisome proliferator-activated receptor-{alpha} did not change Smad expression, suggesting an aberration in the Smad

iROLL: does 3-D radioguided occult lesion localization improve surgical management in early-stage breast cancer?

PubMed

Bluemel, Christina; Cramer, Andreas; Grossmann, Christoph; Kajdi, Georg W; Malzahn, Uwe; Lamp, Nora; Langen, Heinz-Jakob; Schmid, Jan; Buck, Andreas K; Grimminger, Hanns-Jörg; Herrmann, Ken

2015-10-01

To prospectively evaluate the feasibility of 3-D radioguided occult lesion localization (iROLL) and to compare iROLL with wire-guided localization (WGL) in patients with early-stage breast cancer undergoing breast-conserving surgery and sentinel lymph node biopsy (SLNB). WGL (standard procedure) and iROLL in combination with SLNB were performed in 31 women (mean age 65.1 ± 11.2 years) with early-stage breast cancer and clinically negative axillae. Patient comfort in respect of both methods was assessed using a ten point scale. SLNB and iROLL were guided by freehand SPECT (fhSPECT). The results of the novel 3-D image-based method were compared with those of WGL, ultrasound-based lesion localization, and histopathology. iROLL successfully detected the malignant primary and at least one sentinel lymph node in 97% of patients. In a single patient (3%), only iROLL, and not WGL, enabled lesion localization. The variability between fhSPECT and ultrasound-based depth localization of breast lesions was low (1.2 ± 1.4 mm). Clear margins were achieved in 81% of the patients; however, precise prediction of clear histopathological surgical margins was not feasible using iROLL. Patients rated iROLL as less painful than WGL with a pain score 0.8 ± 1.2 points (p < 0.01) lower than the score for iROLL. iROLL is a well-tolerated and feasible technique for localizing early-stage breast cancer in the course of breast-conserving surgery, and is a suitable replacement for WGL. As a single image-based procedure for localization of breast lesions and sentinel nodes, iROLL may improve the entire surgical procedure. However, no advantages of the image-guided procedure were found with regard to prediction of complete tumour resection.

Xanthogranulomatous hypophysitis: a rare and often mistaken pituitary lesion

PubMed Central

Gopal-Kothandapani, Jaya Sujatha; Bagga, Veejay; Wharton, Stephen B; Connolly, Daniel J; Sinha, Saurabh

2015-01-01

Summary Xanthogranulomatous hypophysitis (XGH) is a very rare form of pituitary hypophysitis that may present both clinically and radiologically as a neoplastic lesion. It may either be primary with an autoimmune aetiology and can occur in isolation or as a part of autoimmune systemic disease or secondary as a reactive degenerative response to an epithelial lesion (e.g. craniopharyngioma (CP), Rathke's cleft cyst, germinoma and pituitary adenomas) or as a part of a multiorgan systemic involvement such as tuberculosis, sarcoidosis or granulomatosis. It may also present with a variation of symptoms in children and adults. Our case series compares the paediatric and adult presentations of XGH and the differential diagnoses considered in one child and two adult patients, highlighting the wide spectrum of this condition. Endocrine investigations suggested panhypopituitarism in all three patients and imaging revealed a suprasellar mass compressing the optic chiasm suggestive of CP or Rathke's cleft cyst in one patient and non-functioning pituitary macroadenoma in two patients. Magnetic resonance imaging (MRI) demonstrated mixed signal intensities on T1- and T2-weighted sequences. Following endoscopic transsphenoidal surgery, histological analysis revealed necrotic material with a xanthogranulomatous reaction confirming XGH in two patients and a necrobiotic granulomatous chronic inflammatory infiltrate with neutrophils in one patient, which is not typical of current descriptions of this disorder. This case series describes the wide spectrum of XGH disease that is yet to be defined. Mixed signal intensities on T1- and T2-weighted MRI sequences may indicate XGH and diagnosis is confirmed by histology. Histological variation may indicate an underlying systemic process. Learning points XGH is a rare form of pituitary hypophysitis with a wide clinical and histological spectrum and can mimic a neoplastic lesion.XGH primarily presents with growth arrest in children and pubertal

Visually evoked responses in extrastriate area MT after lesions of striate cortex in early life.

PubMed

Yu, Hsin-Hao; Chaplin, Tristan A; Egan, Gregory W; Reser, David H; Worthy, Katrina H; Rosa, Marcello G P

2013-07-24

Lesions of striate cortex [primary visual cortex (V1)] in adult primates result in blindness. In contrast, V1 lesions in neonates typically allow much greater preservation of vision, including, in many human patients, conscious perception. It is presently unknown how this marked functional difference is related to physiological changes in cortical areas that are spared by the lesions. Here we report a study of the middle temporal area (MT) of adult marmoset monkeys that received unilateral V1 lesions within 6 weeks of birth. In contrast with observations after similar lesions in adult monkeys, we found that virtually all neurons in the region of MT that was deprived of V1 inputs showed robust responses to visual stimulation. These responses were very similar to those recorded in neurons with receptive fields outside the lesion projection zones in terms of firing rate, signal-to-noise ratio, and latency. In addition, the normal retinotopic organization of MT was maintained. Nonetheless, we found evidence of a very specific functional deficit: direction selectivity, a key physiological characteristic of MT that is known to be preserved in many cells after adult V1 lesions, was absent. These results demonstrate that lesion-induced reorganization of afferent pathways is sufficient to develop robust visual function in primate extrastriate cortex, highlighting a likely mechanism for the sparing of vision after neonatal V1 lesions. However, they also suggest that interactions with V1 in early postnatal life are critical for establishing stimulus selectivity in MT.

Multispectral detection of cutaneous lesions using spectroscopy and microscopy approaches

NASA Astrophysics Data System (ADS)

Borisova, E.; Genova-Hristova, Ts.; Troyanova, P.; Pavlova, E.; Terziev, I.; Semyachkina-Glushkovskaya, O.; Lomova, M.; Genina, E.; Stanciu, G.; Tranca, D.; Avramov, L.

2018-02-01

Autofluorescence, diffuse-reflectance and transmission spectral, and microscopic measurements were made on different cutaneous neoplastic lesions, namely basal cell carcinoma, squamous cell carcinoma, malignant melanoma, and dysplastic and benign lesions related. Spectroscopic measurements were made on ex vivo tissue samples, and confocal microscopy investigations were made on thin tissue slices. Fluorescence spectra obtained reveal statistically significant differences between the different benign, dysplastic and malignant lesions by the level of emission intensity, as well by spectral shape, which are fingerprints applicable for differentiation algorithms. In reflectance mode the most significant differences are related to the influence of skin pigments - melanin and hemoglobin. Transmission spectroscopy mode gave complementary optical properties information about the tissue samples investigated to that one of reflectance and absorption spectroscopy. Using autofluorescence detection of skin lesions we obtain very good diagnostic performance for distinguishing of nonmelanoma lesions. Using diffuse reflectance and transmission spectroscopy we obtain significant tool for pigmented pathologies differentiation, but it is a tool with moderate sensitivity for non-melanoma lesions detection. One could rapidly increase the diagnostic accuracy of the received combined "optical biopsy" method when several spectral detection techniques are applied in common algorithm for lesions' differentiation. Specific spectral features observed in each type of lesion investigated on micro and macro level would be presented and discussed. Correlation between the spectral data received and the microscopic features observed would be discussed in the report.

The potential influence of radiation-induced microenvironments in neoplastic progression

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

1998-01-01

Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

Magnetic resonance imaging differential diagnosis of brainstem lesions in children

PubMed Central

Quattrocchi, Carlo Cosimo; Errante, Yuri; Rossi Espagnet, Maria Camilla; Galassi, Stefania; Della Sala, Sabino Walter; Bernardi, Bruno; Fariello, Giuseppe; Longo, Daniela

2016-01-01

Differential diagnosis of brainstem lesions, either isolated or in association with cerebellar and supra-tentorial lesions, can be challenging. Knowledge of the structural organization is crucial for the differential diagnosis and establishment of prognosis of pathologies with involvement of the brainstem. Familiarity with the location of the lesions in the brainstem is essential, especially in the pediatric population. Magnetic resonance imaging (MRI) is the most sensitive and specific imaging technique for diagnosing disorders of the posterior fossa and, particularly, the brainstem. High magnetic static field MRI allows detailed visualization of the morphology, signal intensity and metabolic content of the brainstem nuclei, together with visualization of the normal development and myelination. In this pictorial essay we review the brainstem pathology in pediatric patients and consider the MR imaging patterns that may help the radiologist to differentiate among vascular, toxico-metabolic, infective-inflammatory, degenerative and neoplastic processes. Helpful MR tips can guide the differential diagnosis: These include the location and morphology of lesions, the brainstem vascularization territories, gray and white matter distribution and tissue selective vulnerability. PMID:26834941

Early invasive vulvar squamous cell carcinoma arising in a woman with vulvar pemphigus vulgaris and systemic lupus erythematosus.

PubMed

Bifulco, Giuseppe; Mandato, Vincenzo D; Piccoli, Roberto; Giampaolino, Pierluigi; Mignogna, Chiara; Mignogna, Michele D; Costagliola, Luigi; Nappi, Carmine

2010-06-23

Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucous membranes. Genital involvement occurs when most other common sites are concurrently affected or are in remission. Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many parts of the body and the skin with occasional bullous lesions. Pemphigus vulgaris and SLE may be associated, albeit rarely. Here, we report the first case of a woman affected with SLE presenting with early invasive squamous cell carcinoma (SCC) arising from Pemphigus Vulgaris of the vulva. A 27-year-old Caucasian woman was admitted to our Gynaecology Unit for bleeding vegetant lesions of the vulva. Her history was characterized by systemic lupus erythematosus and PV. Biopsy showed concomitant PV and vulvar intraepithelial neoplasia (VIN) grade 3. One month later a new biopsy revealed progression from VIN 3 to early SCC. Despite chemotherapy, no remission of disease was observed. She died six months after diagnosis Our case underlines PV as another chronic inflammatory disease of the lower genital tract predisposing to VIN-SCC. It suggests the need for careful follow-up of patients with chronic inflammatory disease, especially when concomitant autoimmune disorders are present. Moreover, a biopsy should be always performed if there are PV lesions because of the possibility of neoplastic disease.

A retrospective analysis of dermatological lesions in kidney transplant patients

PubMed Central

Castello, Michela; Gregorini, Marilena; Rampino, Teresa; Bosio, Francesca; Bedino, Giulia; Piotti, Giovanni; Soccio, Grazia; Esposito, Pasquale; Klersy, Catherine; Abelli, Massimo; Borroni, Giovanni; Canton, Antonio Dal

2013-01-01

Background & objectives: Kidney transplantation is the best option for patients with end-stage renal disease (ESRD) failure. Prolonged use of immunosuppressive drugs often causes opportunistic infections and malignancies of skin and mucosae, but due to lack of a careful dermatological screening in several transplantation centers the diagnosis and the treatment of dermatological lesions in kidney transplant patients are underestimated. In addition after the introduction of interleukin (IL)-2 -receptor antagonists (basiliximab/daclizumab), mTOR inhibitors and mycophenolate mofetil (MMF)/mycophenolic acid (MPA) in new immunosuppressive protocols only a few studies have analyzed the skin and mucosal lesions in kidney transplant patients. This study was undertaken to evaluate the cutaneous and mucosal diseases after kidney transplantation, and to investigate the association between these and different immunosuppressive protocols and/or demographic features. Methods: A retrospective analysis was done using medical records of kidney transplantation between 2000 and 2009 at the Transplant Unit of Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. The study included 183 patients (M 57.3%, F 42.7%) aged 51.5±11.8 yr) with transplant age 52.3±34.9 months. Induction therapy was basiliximab and steroids based; maintenance therapy included combination-regimes from cyclosporine, tacrolimus, steroids, mycophenolate mofetil (MM), mycophenolic acid (MPA), rapamycin, everolimus. Anti-rejection therapy was steroid and/or thymoglobulines based. Diagnosis of cutaneous disease was made through examination of skin, mucous membranes, nails and hair evaluation. Skin biopsies, specific cultures and serological tests were done when required. Results: Skin and mucosal diseases were reported in 173 (95.7%) of patients; 88 (50.81%) showed viral lesions; 92 (53.01%) immunosuppression-related lesions; 28 (16.39%) benign tumours; 26 (15.3%) precancers /neoplastic lesions; 24 (14.21%) mycosis

Lesser-known myelin-related disorders: focal tumour-like demyelinating lesions.

PubMed

Jiménez Arango, J A; Uribe Uribe, C S; Toro González, G

2015-03-01

Focal tumour-like demyelinating lesions are defined as solitary demyelinating lesions with a diameter greater than 2 cm. In imaging studies, these lesions may mimic a neoplasm or brain abscess; as a result, invasive diagnostic and therapeutic measures may be performed that will in some cases increase morbidity. Our aim was to analyse and characterise these lesions according to their clinical, radiological, and pathological characteristics, and this data in addition to our literature review will contribute to a better understanding of these lesions. This descriptive study includes 5 cases with pathological diagnoses. We provide subject characteristics gathered through reviewing their clinical, radiology, and pathology reports. Patients' ages ranged from 12 to 60 years; 3 patients were female. The time delay between symptom onset and hospital admission was 3 to 120 days. Clinical manifestations were diverse and dependent on the location of the lesion, pyramidal signs were found in 80% of patients, there were no clinical or radiological signs of spinal cord involvement, and follow-up times ranged from 1 to 15 years. Brain biopsy is the gold standard for the diagnosis of demyelinating tumour-like lesions; however, their clinical features, along with several magnetic resonance imaging features such as open ring enhancement, venular enhancement, the presence of glutamate in spectroscopy, and others, may be sufficient to differentiate neoplastic lesions from focal tumour-like demyelinating lesions. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Neoplastic causes of abnormal puberty.

PubMed

Wendt, Susanne; Shelso, John; Wright, Karen; Furman, Wayne

2014-04-01

Neoplasm-related precocious puberty (PP) is a rare presenting feature of childhood cancer. Moreover, evaluation of suspected PP in a child is complex, and cancer is often not considered. We characterized the clinicopathologic features of patients presenting with PP at a large pediatric cancer center, reviewed the relevant literature, and developed an algorithm for the diagnostic work-up of these patients. We examined the records of all patients with a neoplasm and concomitant PP treated at St. Jude Children's Research Hospital from January 1975 through October 2011, reviewed the available literature, and analyzed the demographic, clinical, endocrine, and neoplasm-related features. Twenty-four of 13,615 children and adolescents (0.18%) were diagnosed with PP within 60 days of presentation. Primary diagnoses included brain tumor (12), adrenocortical carcinoma (5), hepatoblastoma (4), and others (3). PP was observed 0-48 months before diagnosis of neoplasm; 17 patients had peripheral PP and 7 had central PP. Neoplasm-related PP is rare and takes the form of a paraneoplastic syndrome caused by tumor production of hormones or by alteration of physiologic gonadotropin production. PP can precede diagnosis of malignancy by months or years, and neoplastic causes should be considered early to avoid delayed cancer diagnosis. Treatment of the primary malignancy resolved or diminished PP in surviving patients with an intact hypothalamic-pituitary-gonadal axis. © 2013 Wiley Periodicals, Inc.

Association of malignancy with rapid growth in early lesions induced by irradiation of rat skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGregor, J.F.

1979-04-01

Epithelial lesions induced by irradiation of rat skin were studied to determine (a) the relationship of malignancy to dose, (b) the types of lesions and circumstances leading to overt malignancy, and (c) the growth rates of lesions progressing to malignancy versus those of lesions remaining benign. High doses of radiation were shown to be associated with the production of epidermal cancers, the maximum yield being obtained at 6,400 rads. Conversely, a peak yield of noncancerous lesions was obtained at 1,600 rads. This association between malignancy and high dose was consistent for cancers evolving from warts, cysts, and chronic ulcers. Althoughmore » the proportion of warts among the induced lesions was much higher than that of the cysts or chronic ulcers (76, 14, and 10%, respectively), the likelihood of warts becoming cancerous was substantially lower (14, 23, and 21%). The combined data for all doses showed that the latency period of the epidermal cancers was significantly (P = 0.015) shorter than that of the benign tumors. Rapid growth rates were observed for warts, cysts, and chronic ulcers progressing to overt cancer, and these did not overlap at any point on the growth scale with rates for benign tumors. This finding suggested that the potential for malignant development had been established early in the carcinogenic process, very likely at induction.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jang Choon; Shin, Jimin; Baek, Kwan-Hyuck, E-mail: khbaek@skku.edu

Highlights: •A single extra copy of Dscr1 restrains progression of PanIN-1A to PanIN-1B lesions. •Dscr1 trisomy attenuates calcineurin–NFAT pathway in neoplastic ductal epithelium. •Dscr1 trisomy leads to upregulation of p15{sup INK4b} in neoplastic ductal epithelium. •A single extra copy of Dscr1 reduces epithelial proliferation in early PanIN lesions. •Dscr1 trisomy may protect Down syndrome individuals from pancreatic cancer. -- Abstract: Individuals with Down syndrome exhibit remarkably reduced incidence of most solid tumors including pancreatic cancer. Multiple mechanisms arising from the genetic complexity underlying Down syndrome has been suggested to contribute to such a broad cancer protection. In this study, utilizingmore » a genetically engineered mouse model of pancreatic cancer, we demonstrate that trisomy of the Down syndrome critical region-1 (Dscr1), an endogenous calcineurin inhibitor localized on chromosome 21, suppresses the progression of pancreatic intraepithelial neoplasia-1A (PanIN-1A) to PanIN-1B lesions without affecting the initiation of PanIN lesions mediated by oncogenic Kras{sup G12D}. In addition, we show that Dscr1 trisomy attenuates nuclear localization of nuclear factor of activated T-cells (NFAT) accompanied by upregulation of the p15{sup Ink4b} tumor suppressor and reduction of cell proliferation in early PanIN lesions. Our data suggest that attenuation of calcineurin–NFAT signaling in neoplastic pancreatic ductal epithelium by a single extra copy of Dscr1 is sufficient to inhibit the progression of early PanIN lesions driven by oncogenic Kras, and thus may be a potential mechanism underlying reduced incidence of pancreatic cancer in Down syndrome individuals.« less

Cascade classification of endocytoscopic images of colorectal lesions for automated pathological diagnosis

NASA Astrophysics Data System (ADS)

Itoh, Hayato; Mori, Yuichi; Misawa, Masashi; Oda, Masahiro; Kudo, Shin-ei; Mori, Kensaku

2018-02-01

This paper presents a new classification method for endocytoscopic images. Endocytoscopy is a new endoscope that enables us to perform conventional endoscopic observation and ultramagnified observation of cell level. This ultramagnified views (endocytoscopic images) make possible to perform pathological diagnosis only on endo-scopic views of polyps during colonoscopy. However, endocytoscopic image diagnosis requires higher experiences for physicians. An automated pathological diagnosis system is required to prevent the overlooking of neoplastic lesions in endocytoscopy. For this purpose, we propose a new automated endocytoscopic image classification method that classifies neoplastic and non-neoplastic endocytoscopic images. This method consists of two classification steps. At the first step, we classify an input image by support vector machine. We forward the image to the second step if the confidence of the first classification is low. At the second step, we classify the forwarded image by convolutional neural network. We reject the input image if the confidence of the second classification is also low. We experimentally evaluate the classification performance of the proposed method. In this experiment, we use about 16,000 and 4,000 colorectal endocytoscopic images as training and test data, respectively. The results show that the proposed method achieves high sensitivity 93.4% with small rejection rate 9.3% even for difficult test data.

Long-term follow up of gallbladder polyps.

PubMed

Park, Jeong Youp; Hong, Sung Pil; Kim, Yoon Jae; Kim, Hong Jeoung; Kim, Hee Man; Cho, Jae Hee; Park, Seung Woo; Song, Si Young; Chung, Jae Bock; Bang, Seungmin

2009-02-01

The management of gallbladder polyps (GBP) is directly linked to the early diagnosis of gallbladder cancer (GBC). This study aimed to evaluate the malignant risk of GBP. In total, 1558 patients diagnosed with GBP were followed. Neoplastic polyps were defined as GBC and its premalignant lesions. The risk for malignancy was estimated with the cumulative detection rate of neoplastic polyps. Thirty-three cases (2.1%) were diagnosed with neoplastic polyps. The cumulative detection rates of neoplastic polyps were 1.7% at 1 year, 2.8% at 5 years, and 4% at 8 years after diagnosis. The size of GBP and the presence of gallstones were risk factors for neoplastic polyps. Polyps > or = 10 mm had a 24.2 times greater risk of malignancy than polyps < 10 mm. However, 15 of 33 neoplastic polyps (45.5%) were < 10 mm at the time of diagnosis of GBP. During follow up in 36 (3.5%) of 1027 cases, an increase in size was detected; of these, nine (25%) had neoplastic polyps. Even small polyps have a risk of malignancy, and careful long-term follow up of GBP will help detect and treat early GBC.

Epithelial Membrane Protein-2 Expression is an Early Predictor of Endometrial Cancer Development

PubMed Central

Habeeb, Omar; Goodglick, Lee; Soslow, Robert A.; Rao, Rajiv; Gordon, Lynn K.; Schirripa, Osvaldo; Horvath, Steve; Braun, Jonathan; Seligson, David B.; Wadehra, Madhuri

2010-01-01

BACKGROUND Endometrial cancer (EC) is a common malignancy worldwide. It is often preceded by endometrial hyperplasia, whose management and risk of neoplastic progression vary. Previously, we have shown that the tetraspan protein Epithelial Membrane Protein-2 (EMP2) is a prognostic indicator for EC aggressiveness and survival. Here we validate the expression of EMP2 in EC, and further examine whether EMP2 expression within preneoplastic lesions is an early prognostic biomarker for EC development. METHODS A tissue microarray (TMA) was constructed with a wide representation of benign and malignant endometrial samples. The TMA contains a metachronous cohort of cases from individuals who either developed or did not develop EC. Intensity and frequency of EMP2 expression were assessed using immunohistochemistry. RESULTS There was a stepwise, statistically-significant increase in the average EMP2 expression from benign to hyperplasia to atypia to EC. Furthermore, detailed analysis of EMP2 expression in potentially premalignant cases demonstrated that EMP2 positivity was a strong predictor for EC development. CONCLUSION EMP2 is an early predictor of EC development in preneoplastic lesions. In addition, combined with our previous findings, these results validate that EMP2 as a novel biomarker for EC development. PMID:20578181

Sequence Variants and Haplotype Analysis of Cat ERBB2 Gene: A Survey on Spontaneous Cat Mammary Neoplastic and Non-Neoplastic Lesions

PubMed Central

Santos, Sara; Bastos, Estela; Baptista, Cláudia S.; Sá, Daniela; Caloustian, Christophe; Guedes-Pinto, Henrique; Gärtner, Fátima; Gut, Ivo G.; Chaves, Raquel

2012-01-01

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

Using Fourier transform infrared spectroscopy to evaluate biological effects induced by photodynamic therapy.

PubMed

Lima, Cassio A; Goulart, Viviane P; Correa, Luciana; Zezell, Denise M

2016-07-01

skin was discriminated from healthy tissue with 93.5% accuracy and post-PDT cutaneous lesions was discriminated from healthy tissue with 89.7% accuracy. PC-LDA was able to discriminate ATR-FTIR spectra of non-treated and post-PDT neoplastic lesions, as well as from healthy skin. Thus, the method can be used for early diagnosis of premalignant skin lesions, as well as to evaluate the response to photodynamic treatment. Lasers Surg. Med. 48:538-545, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The value of cyclooxygenase-2 expression in differentiating between early melanomas and histopathologically difficult types of benign human skin lesions.

PubMed

Kuźbicki, Łukasz; Lange, Dariusz; Strączyńska-Niemiec, Anita; Chwirot, Barbara W

2012-02-01

Early cutaneous melanomas may present a substantial diagnostic challenge. We have already reported that expression of cyclooxygenase-2 (COX-2) may be useful for differentiating between cutaneous melanomas and naevi. The purpose of this study was to examine the value of COX-2 in a challenging task of differential diagnosis of early melanomas and melanocytic naevi considered by histopathologists as morphologically difficult to unequivocally diagnose as benign lesions. The material for the study comprised formalin-fixed paraffin-embedded samples of 46 naevi (including 27 cases of dysplastic, Spitz and Reed naevi) and 30 early human cutaneous melanomas. The expression of COX-2 was detected immunohistochemically. Melanomas expressed COX-2 significantly more strongly compared with naevi. The test, on the basis of determination of the percentage fractions of COX-2-positive cells, allows for differentiation of early skin melanomas and naevi with high sensitivity and specificity. Receiver operating characteristic analysis of the test results yielded areas under receiver operating characteristics curves (AUC)=0.946±0.030 for central regions and AUC=0.941±0.031 for the peripheries of the lesions. The performance of the test in differentiating between melanomas and the naevi group comprising dysplastic, Spitz and Reed naevi was also good, with AUC=0.933±0.034 and 0.923±0.037 for the central and the border regions of the lesions, respectively. Using a more complex diagnostic algorithm also accounting for the staining intensity did not result in an improvement in the resolving power of the assay. A diagnostic algorithm using differences in the percentage fractions of cells expressing COX-2 may serve as a useful tool in aiding the differential diagnosis of 'histopathologically difficult' benign melanocytic skin lesions and early melanomas.

In vivo optical characterization of pediatric epileptogenic lesions

NASA Astrophysics Data System (ADS)

Lin, W.-C.; Ragheb, J.; Bhatia, S.; Johnson, Mahlon D.; Sandberg, D.; Fernandez, A.; Morrison, G.; Duchowny, M.; Jayakar, P.

2007-02-01

Epileptogenic lesions and their margins are often difficult to define intraoperatively. We hypothesize that optical spectroscopy can detect unique pathophysiological features of epileptogenic lesions in children and hence differentiate them from normal brain. This hypothesis was tested by comparing the in vivo optical and fluorescence characteristics of epileptogenic brain lesions (non-neoplastic) with those of normal brain. Patients were recruited from those receiving epilepsy surgeries at Miami Children's Hospital. Using a portable spectroscopic system, optical characterization of brain was performed intraoperatively. Fluorescence spectra were measured at 337 nm excitation, and diffuse reflectance spectra were measured between 400 and 850 nm. To date, seven epilepsy patients have been enrolled in the study. A couple interesting trends have been observed in the recorded optical spectra. First, sites within the resection zone, as defined by the intracranial electroencephalogram data, often show higher diffuse reflectance signals than normal sites do. This is especially prominent around 500 nm and between 650 and 850 nm. Secondly, several investigated sites with abnormal electroencephalogram and/or pathology show a unique blue shift in their fluorescence spectra, which is not seen in other cases.

Nonsurgical root canal therapy of large cyst-like inflammatory periapical lesions and inflammatory apical cysts.

PubMed

Lin, Louis M; Ricucci, Domenico; Lin, Jarshen; Rosenberg, Paul A

2009-05-01

It is a general belief that large cyst-like periapical lesions and apical true cysts caused by root canal infection are less likely to heal after nonsurgical root canal therapy. Nevertheless, there is no direct evidence to support this assumption. A large cyst-like periapical lesion or an apical true cyst is formed within an area of apical periodontitis and cannot form by itself. Therefore, both large cyst-like periapical lesions and apical true cysts are of inflammatory and not of neoplastic origin. Apical periodontitis lesions, regardless of whether they are granulomas, abscesses, or cysts, fail to heal after nonsurgical root canal therapy for the same reason, intraradicular and/or extraradicular infection. If the microbial etiology of large cyst-like periapical lesions and inflammatory apical true cysts in the root canal is removed by nonsurgical root canal therapy, the lesions might regress by the mechanism of apoptosis in a manner similar to the resolution of inflammatory apical pocket cysts. To achieve satisfactory periapical wound healing, surgical removal of an apical true cyst must include elimination of root canal infection.

Hypoechoic foci on EUS are simple and strong predictive factors for neoplastic gallbladder polyps.

PubMed

Cho, Jae Hee; Park, Jeong Youp; Kim, Yoon Jae; Kim, Hee Man; Kim, Hong Jeong; Hong, Sung Pil; Park, Seung Woo; Chung, Jae Bock; Song, Si Young; Bang, Seungmin

2009-06-01

EUS is an accurate imaging modality for delineating gallbladder (GB) structures; however, its clinical use in differentiating neoplastic GB polyps from nonneoplastic polyps is limited. Thus, we sought to characterize neoplastic GB polyps by analyzing unique EUS features. Our analysis revealed variably shaped, relatively hypoechoic portions in the core of polyps compared with general background echogenicity. Our purpose was to make a differential diagnosis between neoplastic and nonneoplastic GB polyps of less than 20 mm by use of EUS variables, including hypoechoic foci. Retrospective single-center study. University teaching hospital. Patients (n = 88) underwent preoperative EUS and cholecystectomy for GB polyps smaller than 20 mm. Hypoechoic foci were found in 30 of 33 patients (91%) with neoplastic polyps and 6 of 55 (11%) with nonneoplastic polyps. In a multivariate analysis, hypoechoic foci were the only significant predictive factor for neoplastic polyps (odds ratio [OR] 55.4, 95% CI, 8.26-371, P < .001); the sensitivity and specificity were 90% and 89%, respectively. In addition, polyps >15 mm had an increased risk of malignancy (OR 21.7, 95% CI, 2.35-201, P = .007), as did those with hypoechoic foci (OR 10.9; 95% CI, 1.01-117, P = .049). Retrospective review of selected patients from a tertiary medical center. The presence of hypoechoic foci on EUS is a strong predictive factor for neoplastic polyps. EUS may be useful in developing a treatment strategy for GB polyps.

Predicting Outcome after Pediatric Traumatic Brain Injury by Early Magnetic Resonance Imaging Lesion Location and Volume

PubMed Central

Smitherman, Emily; Hernandez, Ana; Stavinoha, Peter L.; Huang, Rong; Kernie, Steven G.; Diaz-Arrastia, Ramon

2016-01-01

Abstract Brain lesions after traumatic brain injury (TBI) are heterogeneous, rendering outcome prognostication difficult. The aim of this study is to investigate whether early magnetic resonance imaging (MRI) of lesion location and lesion volume within discrete brain anatomical zones can accurately predict long-term neurological outcome in children post-TBI. Fluid-attenuated inversion recovery (FLAIR) MRI hyperintense lesions in 63 children obtained 6.2±5.6 days postinjury were correlated with the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score at 13.5±8.6 months. FLAIR lesion volume was expressed as hyperintensity lesion volume index (HLVI)=(hyperintensity lesion volume / whole brain volume)×100 measured within three brain zones: zone A (cortical structures); zone B (basal ganglia, corpus callosum, internal capsule, and thalamus); and zone C (brainstem). HLVI-total and HLVI-zone C predicted good and poor outcome groups (p<0.05). GOS-E Peds correlated with HLVI-total (r=0.39; p=0.002) and HLVI in all three zones: zone A (r=0.31; p<0.02); zone B (r=0.35; p=0.004); and zone C (r=0.37; p=0.003). In adolescents ages 13–17 years, HLVI-total correlated best with outcome (r=0.5; p=0.007), whereas in younger children under the age of 13, HLVI-zone B correlated best (r=0.52; p=0.001). Compared to patients with lesions in zone A alone or in zones A and B, patients with lesions in all three zones had a significantly higher odds ratio (4.38; 95% confidence interval, 1.19–16.0) for developing an unfavorable outcome. PMID:25808802

2015 update on the diagnosis and management of neoplastic pericardial disease.

PubMed

Lestuzzi, Chiara; Berretta, Massimiliano; Tomkowski, Witold

2015-04-01

The best approach in diagnosis and treatment of neoplastic pericardial disease has not been defined yet. The authors report the most recent literature about the new diagnostic techniques that are useful to improve the diagnosis. The literature about the therapeutic options is critically reviewed, in order to give suggestions of use to the clinical practice. Pericardial effusion may require urgent drainage; the solid component, however, becomes predominant in some cases. Neoplastic pericardial disease should be assessed following oncologic criteria evaluation of the neoplastic burden; outcome classified as complete or partial response, stable or progressive disease and - in cases with progression - event-free survival. Systemic chemotherapy may be effective in lymphomas and possibly in breast carcinomas. Intrapericardial chemotherapy with systemic chemotherapy is the treatment of choice in lung cancer. Pericardial window with systemic chemotherapy is also effective in preventing the accumulation of large amount of fluid.

High milk consumption does not affect prostate tumor progression in two mouse models of benign and neoplastic lesions.

PubMed

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

2015-01-01

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.

Early invasive vulvar squamous cell carcinoma arising in a woman with vulvar pemphigus vulgaris and systemic lupus erythematosus

PubMed Central

2010-01-01

Background Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucous membranes. Genital involvement occurs when most other common sites are concurrently affected or are in remission. Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many parts of the body and the skin with occasional bullous lesions. Pemphigus vulgaris and SLE may be associated, albeit rarely. Here, we report the first case of a woman affected with SLE presenting with early invasive squamous cell carcinoma (SCC) arising from Pemphigus Vulgaris of the vulva. Case presentation A 27-year-old Caucasian woman was admitted to our Gynaecology Unit for bleeding vegetant lesions of the vulva. Her history was characterized by systemic lupus erythematosus and PV. Biopsy showed concomitant PV and vulvar intraepithelial neoplasia (VIN) grade 3. One month later a new biopsy revealed progression from VIN 3 to early SCC. Despite chemotherapy, no remission of disease was observed. She died six months after diagnosis Conclusion Our case underlines PV as another chronic inflammatory disease of the lower genital tract predisposing to VIN-SCC. It suggests the need for careful follow-up of patients with chronic inflammatory disease, especially when concomitant autoimmune disorders are present. Moreover, a biopsy should be always performed if there are PV lesions because of the possibility of neoplastic disease. PMID:20573220

Fine needle aspiration cytology in lesions of the nose, nasal cavity and paranasal sinuses.

PubMed

Gupta, Nalini; Kaur, Jasleen; Srinivasan, Radhika; Das, Ashim; Mohindra, Satyawati; Rajwanshi, Arvind; Nijhawan, Raje

2011-01-01

To assess the spectrum of lesions in the sinonasal region diagnosed on FNAC. This is a retrospective audit of sinonasal lesions diagnosed on FNAC over a period of 12 years (1998-2009). Out of a total of 79,851 FNACs, 158 (0.2%) were from the sinonasal region. FNAC was non-diagnostic in 20 (12.6%) cases. Infective/inflammatory lesions comprised of 30 (19%) cases including non-specific inflammation (19), fungal infection (7), tuberculosis (2), actinomycosis (1) and filariasis (1). Benign cysts (24; 15.2%) included epidermal inclusion cysts, mucocele and aneurysmal bone cyst. Benign bone tumors (4) comprised of giant cell tumor, fibrous dysplasia, chondroma, and osteoblastoma. Other benign tumors included lipoma (6), hemangioma (5), schwannoma (2), meningioma (1), pleomorphic adenoma (1), sebaceous adenoma (1) and other skin adnexal tumors (3). Malignant epithelial tumors (24; 15.2%) included squamous cell carcinoma (10), basal cell carcinoma (5), poorly differentiated carcinoma (4) and metastatic carcinoma (5). Two cases of chordoma and one case each of dermatofibrosarcoma pertuberance and hemangiopericytoma were seen. Sarcomas included sarcoma, not otherwise specified (4), rhabdomyosarcoma (3), osteosarcoma (2), chondrosarcoma (2), leiomyosarcoma (1), malignant fibrous histiocytoma (1), fibrosarcoma (1) and malignant peripheral nerve sheath tumor (1). There were cases of malignant small round cell tumor (11), non-Hodgkin lymphoma (3), plasmacytoma (2) and malignant melanoma (2). A variety of non-neoplastic and neoplastic conditions can involve the sinonasal region. FNAC is a reliable diagnostic procedure in a good number of cases, especially in the light of clinico-radiological data. Copyright © 2011 S. Karger AG, Basel.

Early dynamic imaging in 68Ga- PSMA-11 PET/CT allows discrimination of urinary bladder activity and prostate cancer lesions.

PubMed

Uprimny, Christian; Kroiss, Alexander Stephan; Decristoforo, Clemens; Fritz, Josef; Warwitz, Boris; Scarpa, Lorenza; Roig, Llanos Geraldo; Kendler, Dorota; von Guggenberg, Elisabeth; Bektic, Jasmin; Horninger, Wolfgang; Virgolini, Irene Johanna

2017-05-01

PET/CT with 68 Ga-labelled prostate-specific membrane antigen (PSMA)-ligands has been proven to establish a promising imaging modality in the work-up of prostate cancer (PC) patients with biochemical relapse. Despite a high overall detection rate, the visualisation of local recurrence may be hampered by high physiologic tracer accumulation in the urinary bladder on whole body imaging, usually starting 60 min after injection. This study sought to verify whether early dynamic 68 Ga-PSMA-11 (HBED-CC)PET/CT can differentiate pathologic PC-related tracer uptake from physiologic tracer accumulation in the urinary bladder. Eighty consecutive PC patients referred to 68 Ga -PSMA-11 PET/CT were included in this retrospective analysis (biochemical relapse: n = 64; primary staging: n = 8; evaluation of therapy response/restaging: n = 8). In addition to whole-body PET/CT acquisition 60 min post injection early dynamic imaging of the pelvis in the first 8 min after tracer injection was performed. SUV max of pathologic lesions was calculated and time-activity curves were generated and compared to those of urinary bladder and areas of physiologic tracer uptake. A total of 55 lesions consistent with malignancy on 60 min whole body imaging exhibited also pathologic 68 Ga-PSMA-11 uptake during early dynamic imaging (prostatic bed/prostate gland: n = 27; lymph nodes: n = 12; bone: n = 16). All pathologic lesions showed tracer uptake within the first 3 min, whereas urinary bladder activity was absent within the first 3 min of dynamic imaging in all patients. Suv max was significantly higher in PC lesions in the first 6 min compared to urinary bladder accumulation (p < 0.001). In the subgroup of PC patients with biochemical relapse the detection rate of local recurrence could be increased from 20.3 to 29.7%. Early dynamic imaging in 68 Ga-PSMA-11 PET/CT reliably enables the differentiation of pathologic tracer uptake in PC lesions from physiologic

Liver histopathology in Baltic eelpout (Zoarces viviparus) - A baseline study for use in marine environmental monitoring.

PubMed

Fricke, Nicolai F; Stentiford, Grant D; Feist, Stephen W; Lang, Thomas

2012-12-01

The use of liver histopathology in various fish species as a biomarker in marine monitoring programmes to assess the biological effect of exposure to anthropogenic contaminants is well established. However, although the eelpout (Zoarces viviparus) has repeatedly been recommended as an appropriate bioindicator for monitoring purposes in the Baltic Sea, information on histopathological liver alterations of this species is scarce. In order to obtain an overview, a total of 1070 eelpout, collected in the period between spring 2001 and winter 2010 from 34 sampling sites distributed over large parts of the Baltic Sea, were histologically analyzed. Liver lesions were recorded and classified according to established liver lesion categories. A high prevalence of non-specific and early toxicopathic non-neoplastic hepatic lesions was recorded. In contrast, pre-neoplastic lesions were observed only in rare cases and neoplastic changes were absent. A comparison with published data on other fish species revealed that the observed alterations may indicate effects of environmental stressors including contaminants. The results of the present study, thus, support the application of eelpout liver histopathology in environmental monitoring. Copyright © 2012 Elsevier Ltd. All rights reserved.

Usefulness of Demarcation of Differentiated-Type Early Gastric Cancers after Helicobacter pylori Eradication by Magnifying Endoscopy with Narrow-Band Imaging.

PubMed

Akazawa, Yoichi; Ueyama, Hiroya; Yao, Takashi; Komori, Hiroyuki; Takeda, Tsutomu; Matsumoto, Kohei; Matsumoto, Kenshi; Asaoka, Daisuke; Hojo, Mariko; Watanabe, Sumio; Nagahara, Akihito

2018-06-05

Early gastric cancer after Helicobacter pylori (Hp) eradication is difficult to demarcate. We used the vessel plus surface classification system (VSCS) to determine whether magnifying endoscopy with narrow-band imaging (ME-NBI) could demarcate differentiated-type early gastric cancers after Hp eradication, and to identify causes of an unclear demarcation line (DL). Among 100 lesions of differentiated-type early gastric cancer resected endoscopically, 34 lesions in the Hp-eradicated group and 66 in the Hp-infected group were retrospectively compared. Clinicopathological factors and ME-NBI findings, including the presence or absence of the DL, were examined. Histopathologically, histological gastritis, the surface structure at the tumor border, well-differentiated adenocarcinoma with low-grade atypia (tub1-low), and non-neoplastic epithelium (NE) coverage rate on the tumor surface and at the tumor border were evaluated. DL (-) cases were more frequent in the Hp-eradicated group (11.8%, 4/34) than in the Hp-infected group (1.5%, 1/66; p < 0.05). The Hp-eradicated group had a higher NE coverage rate than the Hp-infected group (p < 0.05). All DL (-) cases had tub1-low or NE at the tumor border. ME-NBI with VSCS can identify the DL in most patients (88.2%) with differentiated-type early gastric cancer after Hp eradication. © 2018 S. Karger AG, Basel.

Characterization of Mouse Models of Early Pancreatic Lesions Induced by Alcohol and Chronic Pancreatitis.

PubMed

Xu, Shiping; Chheda, Chintan; Ouhaddi, Yassine; Benhaddou, Hajar; Bourhim, Mouloud; Grippo, Paul J; Principe, Daniel R; Mascariñas, Emman; DeCant, Brian; Tsukamoto, Hidekazu; Pandol, Stephen J; Edderkaoui, Mouad

2015-08-01

We describe the first mouse model of pancreatic intraepithelial neoplasia (PanIN) lesions induced by alcohol in the presence and absence of chronic pancreatitis. Pdx1-Cre;LSL-K-ras mice were exposed to Lieber-DeCarli alcohol diet for 6 weeks with cerulein injections. The PanIN lesions and markers of fibrosis, inflammation, histone deacetylation, epithelial-to-mesenchymal transition (EMT), and cancer stemness were measured by immunohistochemistry and Western. Exposure of Pdx1-Cre;LSL-K-ras mice to an alcohol diet significantly stimulated fibrosis and slightly but not significantly increased the level of PanIN lesions associated with an increase in tumor-promoting M2 macrophages. Importantly, the alcohol diet did not increase activation of stellate cells. Alcohol diet and cerulein injections resulted in synergistic and additive effects on PanIN lesion and M2 macrophage phenotype induction, respectively. Cerulein pancreatitis caused stellate cell activation, EMT, and cancer stemness in the pancreas. Pancreatitis caused histone deacetylation, which was promoted by the alcohol diet. Pancreatitis increased EMT and cancer stemness markers, which were not further affected by the alcohol diet. The results suggest that alcohol has independent effects on promotion of PDAC associated with fibrosis formed through a stellate cell-independent mechanism and that it further promotes early PDAC and M2 macrophage induction in the context of chronic pancreatitis.

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry.

PubMed

Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

2015-01-01

To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student'st test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

Impact of tissue type and content of neoplastic cells of samples on the quality of epidermal growth factor receptor mutation analysis among patients with lung adenocarcinoma

PubMed Central

PALIOGIANNIS, PANAGIOTIS; ATTENE, FEDERICO; COSSU, ANTONIO; DEFRAIA, EFISIO; PORCU, GIUSEPPE; CARTA, ANNAMARIA; SOTGIU, MARIA IGNAZIA; PAZZOLA, ANTONIO; CORDERO, LORENZO; CAPELLI, FRANCESCA; FADDA, GIOVANNI MARIA; ORTU, SALVATORE; SOTGIU, GIOVANNI; PALOMBA, GRAZIA; SINI, MARIA CRISTINA; PALMIERI, GIUSEPPE; COLOMBINO, MARIA

2015-01-01

Assessment of the epidermal growth factor receptor (EGFR) mutational status has become crucial in recent years in the molecular classification of patients with lung cancer. The impact of the type and quantity of malignant cells of the neoplastic specimen on the quality of mutation analysis remains to be elucidated, and only empirical and sporadic data are available. The aim of the present study was to investigate the impact of tissue type and content of neoplastic cells in the specimen on the quality of EGFR mutation analysis among patients with lung adenocarcinoma. A total of 515 patients with histologically-confirmed disease were included in the present study. Formalin-fixed paraffin embedded tissue samples were used for the mutation analysis and the content of the neoplastic cells was evaluated using light microscopy. Genomic DNA was isolated using a standard protocol. The coding sequences and splice junctions of exons 18, 19 and 21 in the EGFR gene were then screened for mutations by direct automated sequencing. The mean age of the patients examined was 64.9 years and 357 (69.3%) were male. A total of 429 tissue samples (83.3%) were obtained by biopsy and the remaining samples were obtained by surgery. A total of 456 samples (88.5%) were observed from primary lung adenocarcinomas, while 59 (11.5%) were from metastatic lesions. EGFR mutations occurred in 59 cases (11.5%); exon 18 mutations were detected in one case (1.7%), whereas exon 19 and 21 mutations were detected in 30 (51%) and 28 (47.3%) cases, respectively. EGFR mutations were more frequent in females and patients that had never smoked. The distribution of the mutations among primary and metastatic tissues exhibited no significant differences in the proportions of EGFR mutations detected. However, a statistically significant difference in the number of mutations detected was found between samples with at least 50% of neoplastic cells (450 cases-57 mutations; 12.7%) and those with <50% of neoplastic

Relationship between arsenic skin lesions and the age of natural menopause.

PubMed

Yunus, Fakir Md; Rahman, Musarrat Jabeen; Alam, Md Zahidul; Hore, Samar Kumar; Rahman, Mahfuzar

2014-05-02

Chronic exposure to arsenic is associated with neoplastic, cardiovascular, endocrine, neuro-developmental disorders and can have an adverse effect on women's reproductive health outcomes. This study examined the relationship between arsenic skin lesions (a hallmark sign of chronic arsenic poisoning) and age of natural menopause (final menopausal period) in populations with high levels of arsenic exposure in Bangladesh. We compared menopausal age in two groups of women--with and without arsenic skin lesions; and presence of arsenic skin lesions was used as an indicator for chronic arsenic exposure. In a cross-sectional study, a total of 210 participants were randomly identified from two ongoing studies--participants with arsenic skin lesions were identified from an ongoing clinical trial and participants with no arsenic skin lesions were identified from an ongoing cohort study. Mean age of menopause between these two groups were calculated and compared. Multivariable linear regression was used to estimate the relationship between the status of the arsenic skin lesions and age of natural menopause in women. Women with arsenic skin lesions were 1.5 years younger (p <0.001) at the time of menopause compared to those without arsenic skin lesions. After adjusting with contraceptive use, body mass index, urinary arsenic level and family history of premature menopause, the difference between the groups' age at menopause was 2.1 years earlier (p <0.001) for respondents with arsenic skin lesions. The study showed a statistically significant association between chronic exposure to arsenic and age at menopause. Heavily exposed women experienced menopause two years earlier than those with lower or no exposure.

Evaluation of magnetic resonance imaging for the differentiation of inflammatory, neoplastic, and vascular intradural spinal cord diseases in the dog.

PubMed

Masciarelli, Amanda E; Griffin, John F; Fosgate, Geoffrey T; Hecht, Silke; Mankin, Joseph M; Holmes, Shannon P; Platt, Simon R; Kent, Marc; Pancotto, Theresa E; Chen, Annie V; Levine, Jonathan M

2017-07-01

Magnetic resonance imaging (MRI) is a common test for dogs with suspected intradural spinal cord lesions, however studies on diagnostic performance for this test are lacking. Objectives of this multi-institutional, retrospective, case-control study were to estimate sensitivity and specificity of MRI for (1) distinguishing between histopathologically confirmed intradural spinal cord disease versus degenerative myelopathy in dogs, (2) categorizing intradural spinal cord diseases as neoplastic, inflammatory, or vascular; and (3) determining tumor type within the etiologic category of neoplasia. Additional aims were to (1) determine whether knowledge of clinical data affects sensitivity and specificity of MRI diagnoses; and (2) report interrater agreement for MRI classification of intradural spinal lesions. Cases were recruited from participating hospital databases over a 7-year period. Three reviewers independently evaluated each MRI study prior to and after provision of clinical information. A total of 87 cases were sampled (17 degenerative myelopathy, 53 neoplasia, nine inflammatory, and eight vascular). Magnetic resonance imaging had excellent (>97.6%) sensitivity for diagnosis of intradural spinal cord lesions but specificity varied before and after provision of clinical data (68.6% vs. 82.4%, P = 0.023). Magnetic resonance imaging had good sensitivity (86.8%) and moderate specificity (64.7-72.5%) for diagnosing neoplasia. Sensitivity was lower for classifying inflammatory lesions but improved with provision of clinical data (48.1% vs. 81.5%, P = 0.015). Magnetic resonance imaging was insensitive for diagnosing vascular lesions (25.0%). Interrater agreement was very good for correctly diagnosing dogs with intradural lesions (ĸ = 0.882-0.833), and good (ĸ = 0.726-0.671) for diagnosing dogs with neoplasia. © 2017 American College of Veterinary Radiology.

The significance of fluorescein angiography in the early diagnosis of lesions on ocular fundus at pseudoxanthoma elasticum patients.

PubMed

Bogdanowski, T; Gluza, J; Rasiewicz, D

1977-05-27

The role of fluorescein angiography in early diagnosis of lesions on fundus of the eye at pseudoxanthoma elasticum patients has been shown. The authors show angiographic changes on the basis of three cases of pseudoxanthoma elasticum patients.

Cystic lesions of the salivary glands: cytologic features in fine-needle aspiration biopsies.

PubMed

Layfield, Lester J; Gopez, Evelyn V

2002-10-01

A variety of neoplastic and nonneoplastic lesions of the salivary glands have a predominantly cystic architecture. Fine-needle aspirates of these lesions yield watery or mucoid material, frequently of low cellularity. Such aspirates may be obtained from mucus retention cysts, lymphoepithelial cysts, cystadenomas, Warthin's tumors, cystic pleomorphic adenomas, low-grade mucoepidermoid carcinomas, cystadenocarcinomas, and examples of polycystic disease of the parotid gland. The cellular component within the fluid obtained from these lesions may be exceedingly scant or absent, making cytologic diagnosis difficult and, at times, impossible. We studied a series of 56 cystic lesions of the salivary glands, including 38 Warthin's tumors, 6 benign cysts, 2 lymphoepithelial cysts, 5 low-grade mucoepidermoid carcinomas, 1 cystic pleomorphic adenoma, 2 cystadenomas, and 2 cystadenocarcinomas. Careful attention to the cellular elements present often allowed definitive cytologic diagnosis, with an overall accuracy rate of 84%. The presence of atypical squamous metaplasia in oncocytic lesions was a significant cause of false-positive diagnoses of carcinoma (4 cases, 7%). Aspirates of low-grade mucoepidermoid carcinoma may contain no epithelial cells and result in false-negative diagnoses (1 case, 2%). Copyright 2002 Wiley-Liss, Inc.

Short- and long-term efficacy of focused ultrasound therapy for non-neoplastic epithelial disorders of the vulva.

PubMed

Wu, C; Zou, M; Xiong, Y; Wang, L; Chen, H; Fan, Y; Li, C

2017-08-01

To investigate the short- and long-term efficacy and influential factors of focused ultrasound for the treatment of non-neoplastic epithelial disorders of the vulva (NNEDV). A retrospective observational study. A gynaecologic department in a single centre in China. Patients with NNEDV were included in this study: 85 patients were diagnosed with lichen simplex chronicus (LSC), 44 patients with vulva lichen sclerosus (VLS), and seven patients with lichen planus (LP). A total of 136 eligible patients with NNEDV were treated with focused ultrasound. After the treatment, based on changes in the degree of symptom severity and local skin signs (lesion size, skin colour and elasticity) before and after treatment, the treatment effectiveness for each patient was assessed. We further analysed the relations among pathologic type, age, course and curative rate. Statistical analysis was performed using the Chi-square (McNemar) test. Improvement in the symptoms and physical signs and the predictive factors. Symptom relief was observed in all patients. The appearance and colour of the vulva returned to normal after the ultrasound treatment. Complete remission (CR) occurred in 68 of 136 (50%) patients (41 patients with LSC and 12 patients with VLS). The response rate was 93.38% (127/136). Seven patients who had a poor response to the first session of treatment were treated again with ultrasound therapy and a good response was observed. No severe complications were observed. There was no significant difference in treatment results among the different pathological types (P > 0.05). However, the course of the disease and the age of the patients were related to the treatment results (P < 0.05). NNEDV can be treated with focused ultrasound effectively and safely. The course of the disease and the age of the patients may be predictive factors. Patients with non-neoplastic epithelial disorders of the vulva can be safely and effectively treated with focused ultrasound. No significant

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

PubMed Central

Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

2015-01-01

ABSTRACT Objective To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Methods Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. Results The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). Conclusion The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues. PMID:26761548

Aging promotes neoplastic disease through effects on the tissue microenvironment.

PubMed

Marongiu, Fabio; Serra, Maria Paola; Doratiotto, Silvia; Sini, Marcella; Fanti, Maura; Cadoni, Erika; Serra, Monica; Laconi, Ezio

2016-12-06

A better understanding of the complex relationship between aging and cancer will provide important tools for the prevention and treatment of neoplasia. In these studies, the hypothesis was tested that aging may fuel carcinogenesis via alterations imposed in the tissue microenvironment. Preneoplastic hepatocytes isolated from liver nodules were orthotopically injected into either young or old syngeneic rats and their fate was followed over time using the dipeptidyl-peptidase type IV (DPPIV) system to track donor-derived-cells. At 3 months post-Tx, the mean size of donor-derived clusters was 11±3 cells in young vs. 42±8 in old recipients. At 8 months post-Tx, no visible lesion were detected in any of 21 young recipients, while 17/18 animals transplanted at old age displayed hepatic nodules, including 7 large tumors. All tumors expressed the DPPIV marker enzyme, indicating that they originated from transplanted cells. Expression of senescence-associated β-galactosidase was common in liver of 18-month old animals, while it was a rare finding in young controls. Finally, both mRNA and IL6 protein were found to be increased in the liver of aged rats compared to young controls. These results are interpreted to indicate that the microenvironment of the aged liver promotes the growth of pre-neoplastic hepatocytes.

The EGFR family members sustain the neoplastic phenotype of ALK+ lung adenocarcinoma via EGR1

PubMed Central

Voena, C; Di Giacomo, F; Panizza, E; D'Amico, L; Boccalatte, F E; Pellegrino, E; Todaro, M; Recupero, D; Tabbò, F; Ambrogio, C; Martinengo, C; Bonello, L; Pulito, R; Hamm, J; Chiarle, R; Cheng, M; Ruggeri, B; Medico, E; Inghirami, G

2013-01-01

In non-small cell lung cancer (NSCLC), receptor tyrosine kinases (RTKs) stand out among causal dominant oncogenes, and the ablation of RTK signaling has emerged as a novel tailored therapeutic strategy. Nonetheless, long-term RTK inhibition leads invariably to acquired resistance, tumor recurrence and metastatic dissemination. In ALK+ cell lines, inhibition of ALK signaling was associated with coactivation of several RTKs, whose pharmacological suppression reverted the partial resistance to ALK blockade. Remarkably, ERBB2 signaling synergized with ALK and contributed to the neoplastic phenotype. Moreover, the engagement of wild-type epidermal growth factor receptor or MET receptors could sustain cell viability through early growth response 1 (EGR1) and/or Erk1/2; Akt activation and EGR1 overexpression prevented cell death induced by combined ALK/RTK inhibition. Membrane expression of ERBB2 in a subset of primary naive ALK+ NSCLC could be relevant in the clinical arena. Our data demonstrate that the neoplastic phenotype of ALK-driven NSCLC relays ‘ab initio' on the concomitant activation of multiple RTK signals via autocrine/paracrine regulatory loops. These findings suggest that molecular and functional signatures are required in de novo lung cancer patients for the design of efficacious and multi-targeted ‘patient-specific' therapies. PMID:23567620

Systematic review of the relation between smokeless tobacco and non-neoplastic oral diseases in Europe and the United States

PubMed Central

Kallischnigg, Gerd; Weitkunat, Rolf; Lee, Peter N

2008-01-01

Background How smokeless tobacco contributes to non-neoplastic oral diseases is unclear. It certainly increases risk of oral mucosal lesions, but reviewers disagree as to other conditions. In some areas, especially South-East Asia, risk is difficult to quantify due to the many products, compositions (including non-tobacco ingredients), and usage practices involved. This review considers studies from Europe (in practice mainly Scandinavia) and from the USA. Methods Experimental and epidemiological studies published in 1963–2007 were identified that related risk of oral lesions to smokeless tobacco use. Data were assessed separately for oral mucosal lesions, periodontal and gingival diseases, dental caries and tooth loss, and oral pain. Results Oral mucosal lesions: Thirty-three epidemiological studies consistently show a strong dose-related effect of current snuff on oral mucosal lesion prevalence. In Scandinavia, users have a near 100% prevalence of a characteristic "snuff-induced lesion", but prevalence of the varied lesions reported in the USA is lower. Associations with chewing tobacco are weaker. The lack of clear association with former use suggests reversibility following cessation, consistent with experimental studies showing rapid lesion regression on quitting. Periodontal and gingival diseases: Two of four studies report a significant association of snuff with attachment loss and four out of eight with gingival recession. Snuff is not clearly related to gingivitis or periodontal diseases. Limited evidence suggests chewing tobacco is unrelated to periodontal or gingival diseases. Tooth loss: Swedish studies show no association with snuff, but one US study reported an association with snuff, and another with chewing tobacco. Dental caries: Evidence from nine studies suggests a possible relationship with use of smokeless tobacco, particularly chewing tobacco, and the risk of dental caries. Oral pain: Limited evidence precludes any clear conclusion

Enlarging cystic lymphangioma of the mediastinum in an adult: is this a neoplastic lesion related to the recently discovered PIK3CA mutation?

PubMed

Tajima, Shogo; Takanashi, Yusuke; Koda, Kenji

2015-01-01

Cystic lymphangioma, a lymphatic system malformation, is usually observed in infants and children and is rarely found in adults. It most commonly occurs in the cervicofacial region, followed by the axilla. Mediastinal cystic lymphangioma is rare, accounting for 1.8% of all mediastinal cysts. Herein, we present an exceedingly rare adult case of mediastinal cystic lymphangioma that had increased in size over a 5-year period. Although fluid collection might be an alternative explanation for this increase in size, this lymphangioma might harbor a neoplastic nature related to the recently discovered PIK3CA mutation.

Epidemiological study of 534 biopsies of oral mucosal lesions in elderly Brazilian patients.

PubMed

Carvalho, Marianne de Vasconcelos; Iglesias, Déborah Pitta Paraíso; do Nascimento, George João Ferreira; Sobral, Ana Paula Veras

2011-06-01

The number of elderly people in Brazil has increased during the last few decades. Oral lesions are very common in this age group, but few studies have examined the prevalence of these conditions worldwide and, particularly, in Brazil. This study aimed to evaluate the frequency of oral lesions in an elderly Brazilian population. A total of 534 cases of oral lesions retrieved from the files of the Oral Pathology Laboratory of the School of Dentistry, University of Pernambuco, between 1991 and 2008, were descriptively and qualitatively evaluated. In this study, the oral mucosal lesions cases preferentially affected women (n=357; 66.8%), white persons (n=253; 47.3%), in the seventh decade of life (n=361; 67.6%), and with lesions predominantly located on the gingival/alveolar ridge (n=102; 19.1%). The non-neoplastic lesions (n=353; 66.1%) were more prevalent than benign neoplasms (n=85; 15.9%), oral cancers (n=56; 10.4%) and potentially malignant lesions (n=40; 7.4%). The five most predominant diseases were fibrous hyperplasia, non-specific chronic inflammatory processes, oral squamous cell carcinoma, non-specified odontogenic cysts and epithelial dysplasia. Our results may be helpful in understanding the distribution of oral diseases in this very specific age group that requires special attention. © 2010 The Authors. Journal compilation © 2010 The Gerodontology Association and Blackwell Munksgaard Ltd.

Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling.

PubMed

Marques, Adriana; Schwartz, Ira; Wormser, Gary P; Wang, Yanmei; Hornung, Ronald L; Demirkale, Cumhur Y; Munson, Peter J; Turk, Siu-Ping; Williams, Carla; Lee, Chyi-Chia Richard; Yang, Jun; Petzke, Mary M

2017-12-27

The most common clinical manifestation of early Lyme disease is the erythema migrans (EM) skin lesion that develops at the tick bite site typically between 7 and 14 days after infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection. Gene arrays were used to characterize the global transcriptional alterations in skin biopsy samples of EM lesions from untreated adult patients with Lyme disease in comparison to controls. The transcriptional pattern in EM biopsies consisted of 254 differentially regulated genes (180 induced and 74 repressed) characterized by the induction of chemokines, cytokines, Toll-like receptors, antimicrobial peptides, monocytoid cell activation markers, and numerous genes annotated as interferon (IFN)-inducible. The IFN-inducible genes included 3 transcripts involved in tryptophan catabolism (IDO1, KMO, KYNU) that play a pivotal role in immune evasion by certain other microbial pathogens by driving the differentiation of regulatory T cells. This is the first study to globally assess the human skin transcriptional response during early Lyme disease. Borreliella burgdorferi elicits a predominant IFN signature in the EM lesion, suggesting a potential mechanism for spirochetal dissemination via IDO1-mediated localized immunosuppression. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Serum amyloid A protein in amyloidosis, rheumatic, and neoplastic diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, M.D.; Cohen, A.S.

1979-01-01

Serum levels of amyloid protein A (SAA) have been shown to be elevated in different types of amyloidosis and in rheumatic diseases by radioimmunoassay using 125 iodine labeled AA and anti-AA. SAA levels were elevated in both primary and secondary amyloidosis, but there were highly significant differences between these levels. In heredofamilial amyloid, SAA levels were within normal limits. While the mean SAA level was elevated in persons over 70 years, the fact that some persons in this age group had normal levels suggested that marked elevation after age 70 may be due to occult inflammatory or neoplastic disease. Highmore » SAA levels in patients with rheumatoid arthritis correlated, in most cases, with physician evaluation of disease activity and Westergren ESR. SAA levels in patients with systemic lupus erythematosus were lower than those in patients with rheumatoid arthritis, and most patients with degenerative joint disease had normal levels. Very high levels of SAA were found in patients with neoplastic diseases. Patients with carcinoma of the lung and bowel had much higher levels than patients with carcinoma of the breast. Determination of SAA levels may be of value in evaluating different forms of systemic amyloidosis, assessing the activity of rheumatic disease, and screening for occult inflammatory or neoplastic disease.« less

Relationship between arsenic skin lesions and the age of natural menopause

PubMed Central

2014-01-01

Background Chronic exposure to arsenic is associated with neoplastic, cardiovascular, endocrine, neuro-developmental disorders and can have an adverse effect on women’s reproductive health outcomes. This study examined the relationship between arsenic skin lesions (a hallmark sign of chronic arsenic poisoning) and age of natural menopause (final menopausal period) in populations with high levels of arsenic exposure in Bangladesh. Methods We compared menopausal age in two groups of women – with and without arsenic skin lesions; and presence of arsenic skin lesions was used as an indicator for chronic arsenic exposure. In a cross-sectional study, a total of 210 participants were randomly identified from two ongoing studies— participants with arsenic skin lesions were identified from an ongoing clinical trial and participants with no arsenic skin lesions were identified from an ongoing cohort study. Mean age of menopause between these two groups were calculated and compared. Multivariable linear regression was used to estimate the relationship between the status of the arsenic skin lesions and age of natural menopause in women. Results Women with arsenic skin lesions were 1.5 years younger (p <0.001) at the time of menopause compared to those without arsenic skin lesions. After adjusting with contraceptive use, body mass index, urinary arsenic level and family history of premature menopause, the difference between the groups’ age at menopause was 2.1 years earlier (p <0.001) for respondents with arsenic skin lesions. Conclusions The study showed a statistically significant association between chronic exposure to arsenic and age at menopause. Heavily exposed women experienced menopause two years earlier than those with lower or no exposure. PMID:24886424

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

PubMed

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

2016-04-01

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

Review of in situ and invasive penile squamous cell carcinoma and associated non-neoplastic dermatological conditions.

PubMed

Downes, Michelle R

2015-05-01

Penile carcinoma is a rare genitourinary malignancy in North America and Europe with highest rates recorded in South America, Africa and Asia. Recent classifications have refined the terminology used in classifying intraepithelial/in situ lesions and additionally newer entities have been recognised in the invasive category. While increasing recognition of a bimodal pathway of penile carcinogenesis has facilitated understanding and classification of these tumours, handling and subtyping of penile malignancies presents a challenge to the reporting pathologist, in part due to their rarity. This article reviews the terminology and classification of in situ and invasive carcinomas and their relationship to human papilloma virus status. In addition, associated non-neoplastic dermatological conditions of relevance and appropriate ancillary investigations will be addressed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Surveillance for lesions of bovine spongiform encephalopathy in U.S. cattle.

PubMed

Miller, L D; Davis, A J; Jenny, A L; Fekadu, M; Whitfield, S G

1993-01-01

The appearance of bovine spongiform encephalopathy (BSE) as a new disease of cattle in 1985-1987 increased worldwide interest in various aspects of human and animal spongiform encephalopathies. In the United States, a part of the surveillance effort has been directed toward prospective examination of bovine brain specimens for lesions of BSE. One focus area has been to obtain specimens from cattle that (1) are two years of age or older, (2) have documented signs of neurologic disease, and (3) have received protein supplement as a substantial part of the i.v. ration. Another focus area has been to examine rabies-suspect cases that were rabies-negative. A third area has been to obtain the results of bovine neuropathology examinations being conducted at other state and regional laboratories. Specimens have been obtained by direct submission and by referral from other public health and veterinary diagnostic laboratories. Many of the cases have been classified as having (1) inflammatory lesions such as listeriosis, pseudorabies, brain abscesses and inflammation of undetermined cause, (2) degenerative lesions such as polio-encephalomalacia, lead poisoning, Wallerian degeneration, siderocalcinosis, and lipofuscinosis, (3) neoplastic lesions such as meningioma and Schwannoma, and (4) no significant findings. Other case results were reported as inflammation or no significant findings. Of the 459 cases reported here none has contained lesions with the characteristics and distribution typical of BSE.

Development and psychometric testing of the 'Motivation and Self-Efficacy in Early Detection of Skin Lesions' index.

PubMed

Dyson, Judith; Cowdell, Fiona

2014-12-01

To develop and psychometrically test the Motivation and Self-Efficacy in Early Detection of Skin Lesions Index. Skin cancer is the most frequently diagnosed cancer worldwide. The primary strategy used to prevent skin cancer is promotion of sun avoidance and the use of sun protection. However, despite costly and extensive campaigns, cases of skin cancer continue to increase. If found and treated early, skin cancer is curable. Early detection is, therefore, very important. The study was conducted in 2013. Instrument Development. A literature review and a survey identified barriers (factors that hinder) and levers (factors that help) to skin self-examination. These were categorized according to a the Theoretical Domains Framework and this formed the basis of an instrument, which was tested for validity and reliability using confirmatory factor analysis and Cronbach's alpha respectively. A five-factor 20-item instrument was used that tested well for reliability and construct validity. Test-retest reliability was good for all items and domains. The five factors were: (i) Outcome expectancies; (ii) Intention; (iii) Self-efficacy; (iv) Social influences; (v) Memory. The Motivation and Self-Efficacy in Early Detection of Skin Lesions Index provides a reliable and valid method of assessing barriers and levers to skin self-examination. The next step is to design a theory-based intervention that can be tailored according to individual determinants to behaviour change identified by this instrument. © 2014 John Wiley & Sons Ltd.

Comparison of Knoop and Vickers surface microhardness and transverse microradiography for the study of early caries lesion formation in human and bovine enamel.

PubMed

Lippert, F; Lynch, R J M

2014-07-01

The aims of the present laboratory study were twofold: a) to investigate the suitability of Knoop and Vickers surface microhardness (SMH) in comparison to transverse microradiography (TMR) to investigate early enamel caries lesion formation; b) to compare the kinetics of caries lesion initiation and progression between human and bovine enamel. Specimens (90×bovine and 90×human enamel) were divided into six groups (demineralization times of 8/16/24/32/40/48h) of 15 per enamel type and demineralized using a partially saturated lactic acid solution. SMH was measured before and after demineralization and changes in indentation length (ΔIL) calculated. Lesions were characterized using TMR. Data were analyzed (two-way ANOVA) and Pearson correlation coefficients calculated. ΔIL increased with increasing demineralization times but plateaued after 40h, whereas lesion depth (L) and integrated mineral loss (ΔZ) increased almost linearly throughout. No differences between Knoop and Vickers SMH in their ability to measure enamel demineralization were observed as both correlated strongly. Overall, ΔIL correlated strongly with ΔZ and L but only moderately with the degree of surface zone mineralization, whereas ΔZ and L correlated strongly. Bovine demineralized faster than human enamel (all techniques). Lesions in bovine formed faster than in human enamel, although the resulting lesions were almost indistinguishable in their mineral distribution characteristics. Early caries lesion demineralization can be sufficiently studied by SMH, but its limitations on the assessment of the mineral status of more demineralized lesions must be considered. Ideally, complementary techniques to assess changes in both physical and chemical lesion characteristics would be employed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Insights into the Virulence Traits of Streptococcus mutans in Dentine Carious Lesions of Children with Early Childhood Caries.

PubMed

Bezerra, Daniela S; Stipp, Rafael N; Neves, Beatriz G; Guedes, Sarah F F; Nascimento, Marcelle M; Rodrigues, Lidiany K A

2016-01-01

Streptococcus mutans is an oral bacterium considered to play a major role in the development of dental caries. This study aimed to investigate the prevalence of S. mutans in active and arrested dentine carious lesions of children with early childhood caries and to examine the expression profile of selected S. mutans genes associated with survival and virulence, within the same carious lesions. Dentine samples were collected from 29 active and 16 arrested carious lesions that were diagnosed in preschool children aged 2-5 years. Total RNA was extracted from the dentine samples, and reverse transcription quantitative real-time PCR analyses were performed for the quantification of S. mutans and for analyses of the expression of S. mutans genes associated with bacterial survival (atpD, nox, pdhA) and virulence (fabM and aguD). There was no statistically significant difference in the prevalence of S. mutans between active and arrested carious lesions. Expression of the tested genes was detected in both types of carious dentine. The pdhA (p = 0.04) and aguD (p = 0.05) genes were expressed at higher levels in arrested as compared to active lesions. Our findings revealed that S. mutans is part of the viable microbial community in active and arrested dentine carious lesions. The increase in expression of the pdhA and aguD genes in arrested lesions is likely due to the unfavourable environmental conditions for microbial growth, inherent to this type of lesions. © 2016 S. Karger AG, Basel.

Flat epithelial atypia of the breast.

PubMed

Nasser, Selim M

2009-01-01

"Flat epithelial atypia" is the adopted term by the WHO working group on breast tumor referring to an early neoplastic breast lesion affecting the terminal duct-lobular units. Pathologists have described this lesion under a variety of names including columnar cell lesions and low-grade clinging carcinoma in situ. It is usually encountered on breast biopsies performed for mammographically-identified microcalcifications. Because of its relatively frequent association with carcinomas, its recognition in biopsy specimens is important. This review will focus on the histopathologic features, differential diagnosis, biologic potential, clinical significance and management of this lesion.

Morphological, structural, and functional alterations of the prefrontal cortex and the basolateral amygdala after early lesion of the rat mediodorsal thalamus.

PubMed

Ouhaz, Zakaria; Ba-M'hamed, Saadia; Bennis, Mohamed

2017-08-01

Early postnatal damage to the mediodorsal thalamus (MD) produces deficits in cognition and behavior believed to be associated with early prefrontal cortical maldevelopment. We assessed the role of MD afferents during development on the morphological and functional maturation of the prefrontal cortex (PFC) and the basolateral amygdala (BLA). Sprague-Dawley rat pups (n = 56) received a bilateral electrolytic lesion of the MD or a MD Sham lesion on postnatal day 4. 7 weeks later, all rats were tested in anxiety-related and cognitive paradigms using the elevated plus maze and novel object recognition tests. Following behavioral testing (P70), rats were killed and the baseline expression of C-Fos protein and the number of GABAergic neurons were evaluated in the PFC and the BLA. The dendritic morphology and spine density in the PFC using Golgi-Cox staining was also evaluated. Adult rats with early postnatal bilateral MD damage exhibited disrupted recognition memory and increased anxiety-like behaviors. The lesion also caused a significant diminution of C-Fos immunolabeling and an increase of the number of GABAergic neurons in the PFC. In the BLA, the number of GABAergic neurons was significantly reduced, associated with an increase in C-Fos immunolabeling. Furthermore, in the PFC the lesion induced a significant reduction in dendritic branching and spine density. Our data are consistent with the hypothesis that the MD plays a role in the development of the PFC and, therefore, may be a good animal model to investigate cognitive symptoms associated with schizophrenia.

High-resolution sonography for distinguishing neoplastic gallbladder polyps and staging gallbladder cancer.

PubMed

Kim, Jung Hoon; Lee, Jae Young; Baek, Jee Hyun; Eun, Hyo Won; Kim, Young Jae; Han, Joon Koo; Choi, Byung Ihn

2015-02-01

OBJECTIVE. The purposes of this study were to compare staging accuracy of high-resolution sonography (HRUS) with combined low- and high-MHz transducers with that of conventional sonography for gallbladder cancer and to investigate the differences in the imaging findings of neoplastic and nonneoplastic gallbladder polyps. MATERIALS AND METHODS. Our study included 37 surgically proven gallbladder cancer (T1a = 7, T1b = 2, T2 = 22, T3 = 6), including 15 malignant neoplastic polyps and 73 surgically proven polyps (neoplastic = 31, nonneoplastic = 42) that underwent HRUS and conventional transabdominal sonography. Two radiologists assessed T-category and predefined polyp findings on HRUS and conventional transabdominal sonography. Statistical analyses were performed using chi-square and McNemar tests. RESULTS. The diagnostic accuracy for the T category was T1a = 92-95%, T1b = 89-95%, T2 = 78-86%, and T3 = 84-89%, all with good agreement (κ = 0.642) using HRUS. The diagnostic accuracy for differentiating T1 from T2 or greater than T2 was 92% and 89% on HRUS and 65% and 70% with conventional transabdominal sonography. Statistically common findings for neoplastic polyps included size greater than 1 cm, single lobular surface, vascular core, hypoechoic polyp, and hypoechoic foci (p < 0.05). The value of HRUS in the differential diagnosis of a gallbladder polyp was more clearly depicted internal echo foci than conventional transabdominal sonography (39 vs 21). A polyp size greater than 1 cm was independently associated with a neoplastic polyp (odds ratio = 7.5, p = 0.02). The AUC of a polyp size greater than 1 cm was 0.877. The sensitivity and specificity were 66.67% and 89.13%, respectively. CONCLUSION. HRUS is a simple method that enables accurate T categorization of gallbladder carcinoma. It provides high-resolution images of gallbladder polyps and may have a role in stratifying the risk for malignancy.

Nuclear Factor kappa B is central to Marek’s Disease herpesvirus induced neoplastic transformation of CD30 expressing lymphocytes in-vivo

PubMed Central

2012-01-01

Background Marek’s Disease (MD) is a hyperproliferative, lymphomatous, neoplastic disease of chickens caused by the oncogenic Gallid herpesvirus type 2 (GaHV-2; MDV). Like several human lymphomas the neoplastic MD lymphoma cells overexpress the CD30 antigen (CD30hi) and are in minority, while the non-neoplastic cells (CD30lo) form the majority of population. MD is a unique natural in-vivo model of human CD30hi lymphomas with both natural CD30hi lymphomagenesis and spontaneous regression. The exact mechanism of neoplastic transformation from CD30lo expressing phenotype to CD30hi expressing neoplastic phenotype is unknown. Here, using microarray, proteomics and Systems Biology modeling; we compare the global gene expression of CD30lo and CD30hi cells to identify key pathways of neoplastic transformation. We propose and test a specific mechanism of neoplastic transformation, and genetic resistance, involving the MDV oncogene Meq, host gene products of the Nuclear Factor Kappa B (NF-κB) family and CD30; we also identify a novel Meq protein interactome. Results Our results show that a) CD30lo lymphocytes are pre-neoplastic precursors and not merely reactive lymphocytes; b) multiple transformation mechanisms exist and are potentially controlled by Meq; c) Meq can drive a feed-forward cycle that induces CD30 transcription, increases CD30 signaling which activates NF-κB, and, in turn, increases Meq transcription; d) Meq transcriptional repression or activation of the CD30 promoter generally correlates with polymorphisms in the CD30 promoter distinguishing MD-lymphoma resistant and susceptible chicken genotypes e) MDV oncoprotein Meq interacts with proteins involved in physiological processes central to lymphomagenesis. Conclusions In the context of the MD lymphoma microenvironment (and potentially in other CD30hi lymphomas as well), our results show that the neoplastic transformation is a continuum and the non-neoplastic cells are actually pre-neoplastic precursor

[Precancerous lesions of the uterine cervix: morphology and molecular pathology].

PubMed

Horn, L-C; Klostermann, K

2011-11-01

HPV-induced alterations of the uterine cervix are frequently biopsied because of suspicious findings on a Pap smear and/or colposcopy. Precancerous lesions occur at the so called transformation zone. For those representing squamous differentiation, the traditional three-tier grading system in CIN 1 to 3 is used. CIN 1 and CIN 2 represent (spontaneous) regression in 60-90% and 50%, respectively. In CIN 3 lesions progression is seen in 20-50%. For appropriate grading, improvement of inter- and intraobserver correlation as well as the exclusion of non-precancerous lesions, p16 immunohistochemistry might be helpful. The terms endocervical glandular dysplasia and low-grade glandular intraepithelial neoplasia have been suggested for glandular lesions less than adenocarcinoma in situ (AIS). Until now reproducible histological criteria have not been established. Additional studies using HPV analysis, p16 and Ki-67 immunohistochemistry have not been proved for these lesions. In accordance with international consensus meetings, these diagnostic terms are not recommended for use in practice. AIS, characterised by the replacement of glandular epithelium by cytologically malignant cells, has been established as the precancerous lesion of the endocervix. AIS is much less common than CIN 3 with a reported range of 1:50-100. But, AIS is found in association with CIN 3 with 25-75%. The differential diagnosis between AIS and non-neoplastic glandular lesion may be aided by immunohistochemistry (e.g. p16, Ki-67, bcl-2, vimentin). All specimens obtained after the clinical diagnosis of cervical precancerous lesions should be examined using step sectioning to rule out microinvasive growth. Important information for clinicians includes the quality of the specimen (cautery artefacts, transformation zone enclosed within the probe), exact grading of CIN lesions, identification of other lesions responsible for suspicious findings of a Pap smear or at colposcopy, and in the case of conisation

Abrupt skin lesion border cutoff measurement for malignancy detection in dermoscopy images.

PubMed

Kaya, Sertan; Bayraktar, Mustafa; Kockara, Sinan; Mete, Mutlu; Halic, Tansel; Field, Halle E; Wong, Henry K

2016-10-06

Automated skin lesion border examination and analysis techniques have become an important field of research for distinguishing malignant pigmented lesions from benign lesions. An abrupt pigment pattern cutoff at the periphery of a skin lesion is one of the most important dermoscopic features for detection of neoplastic behavior. In current clinical setting, the lesion is divided into a virtual pie with eight sections. Each section is examined by a dermatologist for abrupt cutoff and scored accordingly, which can be tedious and subjective. This study introduces a novel approach to objectively quantify abruptness of pigment patterns along the lesion periphery. In the proposed approach, first, the skin lesion border is detected by the density based lesion border detection method. Second, the detected border is gradually scaled through vector operations. Then, along gradually scaled borders, pigment pattern homogeneities are calculated at different scales. Through this process, statistical texture features are extracted. Moreover, different color spaces are examined for the efficacy of texture analysis. The proposed method has been tested and validated on 100 (31 melanoma, 69 benign) dermoscopy images. Analyzed results indicate that proposed method is efficient on malignancy detection. More specifically, we obtained specificity of 0.96 and sensitivity of 0.86 for malignancy detection in a certain color space. The F-measure, harmonic mean of recall and precision, of the framework is reported as 0.87. The use of texture homogeneity along the periphery of the lesion border is an effective method to detect malignancy of the skin lesion in dermoscopy images. Among different color spaces tested, RGB color space's blue color channel is the most informative color channel to detect malignancy for skin lesions. That is followed by YCbCr color spaces Cr channel, and Cr is closely followed by the green color channel of RGB color space.

Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

PubMed

Enblad, Malin; Birgisson, Helgi; Wanders, Alkwin; Sköldberg, Filip; Ghanipour, Lana; Graf, Wilhelm

2016-04-01

The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.

Visual recognition and visually guided action after early bilateral lesion of occipital cortex: a behavioral study of a 4.6-year-old girl.

PubMed

Amicuzi, Ileana; Stortini, Massimo; Petrarca, Maurizio; Di Giulio, Paola; Di Rosa, Giuseppe; Fariello, Giuseppe; Longo, Daniela; Cannatà, Vittorio; Genovese, Elisabetta; Castelli, Enrico

2006-10-01

We report the case of a 4.6-year-old girl born pre-term with early bilateral occipital damage. It was revealed that the child had non-severely impaired basic visual abilities and ocular motility, a selective perceptual deficit of figure-ground segregation, impaired visual recognition and abnormal navigating through space. Even if the child's visual functioning was not optimal, this was the expression of adaptive anatomic and functional brain modifications that occurred following the early lesion. Anatomic brain structure was studied with anatomic MRI and Diffusor Tensor Imaging (DTI)-MRI. This behavioral study may provide an important contribution to understanding the impact of an early lesion of the visual system on the development of visual functions and on the immature brain's potential for reorganisation related to when the damage occurred.

Oral Lesions in Neonates

PubMed Central

Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

2016-01-01

ABSTRACT Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

Development of a widefield reflectance and fluorescence imaging device for the detection of skin and oral cancer

NASA Astrophysics Data System (ADS)

Pratavieira, S.; Santos, P. L. A.; Bagnato, V. S.; Kurachi, C.

2009-06-01

Oral and skin cancers constitute a major global health problem that cause great impact in patients. The most common screening method for oral cancer is visual inspection and palpation of the mouth. Visual examination relies heavily on the experience and skills of the physician to identify and delineate early premalignant and cancer changes, which is not simple due to the similar characteristics of early stage cancers and benign lesions. Optical imaging has the potential to address these clinical challenges. Contrast between normal and neoplastic areas may be increased, distinct to the conventional white light, when using illumination and detection conditions. Reflectance imaging can detect local changes in tissue scattering and absorption and fluorescence imaging can probe changes in the biochemical composition. These changes have shown to be indicatives of malignant progression. Widefield optical imaging systems are interesting because they may enhance the screening ability in large regions allowing the discrimination and the delineation of neoplastic and potentially of occult lesions. Digital image processing allows the combination of autofluorescence and reflectance images in order to objectively identify and delineate the peripheral extent of neoplastic lesions in the skin and oral cavity. Combining information from different imaging modalities has the potential of increasing diagnostic performance, due to distinct provided information. A simple widefiled imaging device based on fluorescence and reflectance modes together with a digital image processing was assembled and its performance tested in an animal study.

Prevalence of Neoplastic Diseases in Pet Birds Referred for Surgical Procedures

PubMed Central

Castro, Patrícia F.; Fantoni, Denise T.; Miranda, Bruna C.; Matera, Julia M.

2016-01-01

Neoplastic disease is common in pet birds, particularly in psittacines, and treatment should be primarily aimed at tumor eradication. Nineteen cases of pet birds submitted to diagnostic and/or therapeutic surgical procedures due to neoplastic disease characterized by the presence of visible masses were retrospectively analyzed; affected species, types of neoplasms and respective locations, and outcomes of surgical procedures were determined. All birds undergoing surgery belonged to the order Psittaciformes; the Blue-fronted parrot (Amazona aestiva) was the prevalent species. Lipoma was the most frequent neoplasm in the sample studied. Most neoplasms affected the integumentary system, particularly the pericloacal area. Tumor resection was the most common surgical procedure performed, with high resolution and low recurrence rates. PMID:26981315

Advances toward fully automated in vivo assessment of oral epithelial dysplasia by nuclear endomicroscopy-A pilot study.

PubMed

Liese, Jan; Winter, Karsten; Glass, Änne; Bertolini, Julia; Kämmerer, Peer Wolfgang; Frerich, Bernhard; Schiefke, Ingolf; Remmerbach, Torsten W

2017-11-01

Uncertainties in detection of oral epithelial dysplasia (OED) frequently result from sampling error especially in inflammatory oral lesions. Endomicroscopy allows non-invasive, "en face" imaging of upper oral epithelium, but parameters of OED are unknown. Mucosal nuclei were imaged in 34 toluidine blue-stained oral lesions with a commercial endomicroscopy. Histopathological diagnosis showed four biopsies in "dys-/neoplastic," 23 in "inflammatory," and seven in "others" disease groups. Strength of different assessment strategies of nuclear scoring, nuclear count, and automated nuclear analysis were measured by area under ROC curve (AUC) to identify histopathological "dys-/neoplastic" group. Nuclear objects from automated image analysis were visually corrected. Best-performing parameters of nuclear-to-image ratios were the count of large nuclei (AUC=0.986) and 6-nearest neighborhood relation (AUC=0.896), and best parameters of nuclear polymorphism were the count of atypical nuclei (AUC=0.996) and compactness of nuclei (AUC=0.922). Excluding low-grade OED, nuclear scoring and count reached 100% sensitivity and 98% specificity for detection of dys-/neoplastic lesions. In automated analysis, combination of parameters enhanced diagnostic strength. Sensitivity of 100% and specificity of 87% were seen for distances of 6-nearest neighbors and aspect ratios even in uncorrected objects. Correction improved measures of nuclear polymorphism only. The hue of background color was stronger than nuclear density (AUC=0.779 vs 0.687) to detect dys-/neoplastic group indicating that macroscopic aspect is biased. Nuclear-to-image ratios are applicable for automated optical in vivo diagnostics for oral potentially malignant disorders. Nuclear endomicroscopy may promote non-invasive, early detection of dys-/neoplastic lesions by reducing sampling error. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Possible neoplastic effects of acrylamide on rat exocrine pancreas.

PubMed

Yener, Y; Kalipci, E; Öztaş, H; Aydin, A D; Yildiz, H

2013-01-01

We investigated whether the acrylamide formed during cooking carbohydrate-rich foods at high temperatures causes neoplastic changes in rat pancreas. Azaserine, which is an amino acid derivative that has the ability to initiate neoplastic changes in rat pancreas, was injected into 14-day-old male rats once a week for three weeks. Acrylamide was given to both azaserine-injected and non-injected rats at doses of 5 and 10 mg/kg/day in drinking water for 16 weeks after which tissue slides were prepared from the pancreata. Pancreas weights and body weights of rats treated with azaserine and acrylamide together increased significantly compared to the other groups. Moreover, the size, average diameter and volume of atypical acinar cell foci that developed in the pancreata of rats treated with azaserine and acrylamide together increased significantly compared to rats treated with either azaserine or acrylamide alone and control groups. Atypical acinar cell adenoma or adenocarcinoma was not observed in the pancreata of rats in any group.

Apoptosis: its role in pituitary development and neoplastic pituitary tissue.

PubMed

Guzzo, M F; Carvalho, L R S; Bronstein, M D

2014-04-01

Apoptosis, also known as programmed cell death, is a phenomenon in which different stimuli trigger cellular mechanisms that culminate in death, in the absence of inflammatory cell response. Two different activation pathways are known, the intrinsic pathway (or mitochondrial) and extrinsic (or death-receptor pathway), both pathways trigger enzymatic reactions that lead cells to break up and be phagocytized by neighboring cells. This process is a common occurrence in physiological and pathological states, participating in the control of cell proliferation, differentiation and remodeling of organs. In the early steps of pituitary gland formation, numerous apoptotic cells are detected in the separation of Rathke's pouch from the roof of oral ectoderm. In the distal part of the gland, which will form the adenohypophysis, the ratio of apoptosis was significantly lower. However, there is evidence that neoplastic pituitary cells undergo unbalance in genes that control apoptosis leading to uncontrolled cell growth. No direct evidence of apoptosis was found in the drugs used for tumors producing prolactin and growth hormone. In conclusion, an unbalancing in the apoptosis process is the boundary between development and tumor growth.

Pycnogenol reduces talc-induced neoplastic transformation in human ovarian cell cultures.

PubMed

Buz'Zard, Amber R; Lau, Benjamin H S

2007-06-01

Talc and poor diet have been suggested to increase the risk of developing ovarian cancer; which can be reduced by a diet rich in fruit and vegetables. Talc is ubiquitous despite concern about its safety, role as a possible carcinogen and known ability to cause irritation and inflammation. It was recently shown that Pycnogenol (Pyc; a proprietary mixture of water-soluble bioflavonoids extracted from French maritime pine bark) was selectively toxic to established malignant ovarian germ cells. This study investigated talc-induced carcinogenesis and Pyc-induced chemoprevention. Normal human epithelial and granulosa ovarian cell lines and polymorphonuclear neutrophils (PMN) were treated with talc, or pretreated with Pyc then talc. Cell viability, reactive oxygen species (ROS) generation and neoplastic transformation by soft agar assay were measured. Talc increased proliferation, induced neoplastic transformation and increased ROS generation time-dependently in the ovarian cells and dose-dependently in the PMN. Pretreatment with Pyc inhibited the talc-induced increase in proliferation, decreased the number of transformed colonies and decreased the ROS generation in the ovarian cells. The data suggest that talc may contribute to ovarian neoplastic transformation and Pyc reduced the talc-induced transformation. Taken together, Pyc may prove to be a potent chemopreventative agent against ovarian carcinogenesis. (c) 2007 John Wiley & Sons, Ltd.

Immunohistochemical expression of myofibroblasts, TGF-β1 and IFN-γ in oral fibrous lesions.

PubMed

Santos, Pedro Paulo de Andrade; Barroso, Keila Martha Amorim; Nonaka, Cassiano Francisco Weege; Pereira Pinto, Leão; Souza, Lélia Batista de

2018-05-29

Analyze the presence of myofibroblasts (MFBs) in oral fibrous lesions and investigate TGF-β1 and IFN-γ expression by immunohistochemistry during their differentiation. Twenty giant cell fibromas (GCFs), 20 fibromas (FIBs), and 20 fibrous hyperplasias (FHs) were selected. To evaluate the presence of MFBs, anti-α-SMA-immunoreactive cells were quantified in connective tissue. TGF-β1 and IFN-γ expressions were evaluated in epithelial and connective tissue by determining the percentage of immunoreactive cells. Higher MFBs concentrations were observed in GCFs (median of 20.00), followed by FHs (15.00) and FIBs (14.00) (P = 0.072). No significant correlation between TGF-β1 or IFN-γ immunoexpression and the number of MFBs in oral fibrous lesions was observed (P > 0.05). The higher density of MFBs found in GCFs, followed by FHs and FIBs, reaffirms the fibrogenic role of these cells, while the higher concentrations detected in GCFs, including evidence of giant MFBs, also suggest a role in the neoplastic behavior of these lesions. No correlation was observed between TGF-β1 and IFN-γ in the myofibroblastic transdifferentiation process of the analyzed lesions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cytokine Signatures Associated With Early Onset, Active Lesions and Late Cicatricial Events of Retinochoroidal Commitment in Infants With Congenital Toxoplasmosis.

PubMed

Carneiro, Ana Carolina Aguiar Vasconcelos; Machado, Anderson Silva; Béla, Samantha Ribeiro; Costa, Julia Gatti Ladeia; Andrade, Gláucia Manzan Queiroz; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Coelho-Dos-Reis, Jordana Grazziela; Ferro, Eloisa Amália Vieira; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Martins-Filho, Olindo Assis

2016-06-15

Ocular toxoplasmosis is a prominent and severe condition of high incidence in Brazil. The current study provides new insights into the immunological events that can be associated with retinochoroiditis in the setting of congenital toxoplasmosis in human infants. Flow cytometry of intracytoplasmic cytokines in leukocyte subsets following in vitro short-term antigenic recall in infants with congenital T. gondii infection. Our data demonstrates that whereas neutrophils and monocytes from T. gondii-infected infants display a combination of proinflammatory and regulatory cytokine profiles, natural killer cells showed a predominantly proinflammatory profile upon in vitro T. gondii stimulation. The proinflammatory response of CD4(+) and CD8(+) T cells, characterized by the production of interferon γ (IFN-γ) and interleukin 17 in patients with an active retinochoroidal lesion, revealed the presence of IFN-γ and tumor necrosis factor α during early and late immunological events. This specific proinflammatory pattern is associated with early events and active retinochoroidal lesion, whereas a robust monocyte-derived interleukin 10-mediated profile is observed in children with cicatricial ocular lesions. These findings support the existence of a progressive immunological environment concomitant with the initial, apical, and cicatricial phases in the process of retinochoroidal lesion formation in infants with congenital toxoplasmosis that may be relevant in the establishment of stage-specific clinical management. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Proton density fat fraction (PDFF) MRI for differentiation of benign and malignant vertebral lesions.

PubMed

Schmeel, Frederic Carsten; Luetkens, Julian Alexander; Wagenhäuser, Peter Johannes; Meier-Schroers, Michael; Kuetting, Daniel Lloyd; Feißt, Andreas; Gieseke, Jürgen; Schmeel, Leonard Christopher; Träber, Frank; Schild, Hans Heinz; Kukuk, Guido Matthias

2018-06-01

To investigate whether proton density fat fraction (PDFF) measurements using a six-echo modified Dixon sequence can help to differentiate between benign and malignant vertebral bone marrow lesions. Sixty-six patients were prospectively enrolled in our study. In addition to conventional MRI at 3.0-Tesla including at least sagittal T2-weighted/spectral attenuated inversion recovery and T1-weighted sequences, all patients underwent a sagittal six-echo modified Dixon sequence of the spine. The mean PDFF was calculated using regions of interest and compared between vertebral lesions. A cut-off value of 6.40% in PDFF was determined by receiver operating characteristic curves and used to differentiate between malignant (< 6.40%) and benign (≥ 6.40%) vertebral lesions. There were 77 benign and 44 malignant lesions. The PDFF of malignant lesions was statistically significant lower in comparison with benign lesions (p < 0.001) and normal vertebral bone marrow (p < 0.001). The areas under the curves (AUC) were 0.97 for differentiating benign from malignant lesions (p < 0.001) and 0.95 for differentiating acute vertebral fractures from malignant lesions (p < 0.001). This yielded a diagnostic accuracy of 96% in the differentiation of both benign lesions and acute vertebral fractures from malignancy. PDFF derived from six-echo modified Dixon allows for differentiation between benign and malignant vertebral lesions with a high diagnostic accuracy. • Establishing a diagnosis of indeterminate vertebral lesions is a common clinical problem • Benign bone marrow processes may mimic the signal alterations observed in malignancy • PDFF differentiates between benign and malignant lesions with a high diagnostic accuracy • PDFF of non-neoplastic vertebral lesions is significantly higher than that of malignancy • PDFF from six-echo modified Dixon may help avoid potentially harmful bone biopsy.

DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome.

PubMed

Pai, Rish K; Dudley, Beth; Karloski, Eve; Brand, Randall E; O'Callaghan, Neil; Rosty, Christophe; Buchanan, Daniel D; Jenkins, Mark A; Thibodeau, Stephen N; French, Amy J; Lindor, Noralane M; Pai, Reetesh K

2018-06-08

Lynch syndrome is the most common form of hereditary colorectal carcinoma. However, establishing the diagnosis of Lynch syndrome is challenging, and ancillary studies that distinguish between sporadic DNA mismatch repair (MMR) protein deficiency and Lynch syndrome are needed, particularly when germline mutation studies are inconclusive. The aim of this study was to determine if MMR protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. We evaluated the expression of MMR proteins in non-neoplastic intestinal mucosa obtained from colorectal surgical resection specimens from patients with Lynch syndrome-associated colorectal carcinoma (n = 52) and patients with colorectal carcinoma without evidence of Lynch syndrome (n = 70), including sporadic MMR protein-deficient colorectal carcinoma (n = 30), MMR protein proficient colorectal carcinoma (n = 30), and "Lynch-like" syndrome (n = 10). MMR protein-deficient non-neoplastic colonic crypts were identified in 19 of 122 (16%) patients. MMR protein-deficient colonic crypts were identified in 18 of 52 (35%) patients with Lynch syndrome compared to only 1 of 70 (1%) patients without Lynch syndrome (p < 0.001). This one patient had "Lynch-like" syndrome and harbored two MSH2-deficient non-neoplastic colonic crypts. MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma. Our findings suggest that MMR protein-deficient colonic crypts are a novel indicator of Lynch syndrome, and evaluation for MMR protein-deficient crypts may be a helpful addition to Lynch syndrome diagnostics.

SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

PubMed Central

Nowlin, Brian T.; Burdo, Tricia H.; Midkiff, Cecily C.; Salemi, Marco; Alvarez, Xavier; Williams, Kenneth C.

2016-01-01

Macrophage recruitment to the central nervous system (CNS) during AIDS pathogenesis is poorly understood. We measured the accumulation of brain perivascular (CD163+) and inflammatory (MAC387+) macrophages in SIV-infected monkeys. Monocyte progenitors were 5-bromo-2′-deoxyuridine (BrdU) labeled in bone marrow, and CNS macrophages were labeled serially with fluorescent dextrans injected into the cisterna magna. MAC387+ macrophages accumulated in the meninges and choroid plexus in early inflammation and in the perivascular space and SIV encephalitis (SIVE) lesions late. CD163+ macrophages accumulated in the perivascular space and SIVE lesions with late inflammation. Most of the BrdU+ cells were MAC387+; however, CD163+BrdU+ macrophages were present in the meninges and choroid plexus with AIDS. Most (81.6% ± 1.8%) of macrophages in SIVE lesions were present in the CNS before SIVE lesion formation. There was a 2.9-fold increase in SIVp28+ macrophages entering the CNS late compared with those entering early (P < 0.05). The rate of CD163+ macrophage recruitment to the CNS inversely correlated with time to death (P < 0.03) and increased with SIVE. In SIVE animals, soluble CD163 correlated with CD163+ macrophage recruitment (P = 0.02). Most perivascular macrophages that comprise SIVE lesions and multinucleated giant cells are present in the CNS early, before SIVE lesions are formed. Most SIV-infected macrophages traffic to the CNS terminally with AIDS. PMID:25963554

Integrated biophotonics in endoscopic oncology

NASA Astrophysics Data System (ADS)

Muguruma, Naoki; DaCosta, Ralph S.; Wilson, Brian C.; Marcon, Norman E.

2009-02-01

Gastrointestinal endoscopy has made great progress during last decade. Diagnostic accuracy can be enhanced by better training, improved dye-contrast techniques method, and the development of new image processing technologies. However, diagnosis using conventional endoscopy with white-light optical imaging is essentially limited by being based on morphological changes and/or visual attribution: hue, saturation and intensity, interpretation of which depends on the endoscopist's eye and brain. In microlesions in the gastrointestinal tract, we still rely ultimately on the histopathological diagnosis from biopsy specimens. Autofluorescence imaging system has been applied for lesions which have been difficult to morphologically recognize or are indistinct with conventional endoscope, and this approach has potential application for the diagnosis of dysplastic lesions and early cancers in the gastrointestinal tract, supplementing the information from white light endoscopy. This system has an advantage that it needs no administration of a photosensitive agent, making it suitable as a screening method for the early detection of neoplastic tissues. Narrow band imaging (NBI) is a novel endoscopic technique which can distinguish neoplastic and non-neoplastic lesions without chromoendoscopy. Magnifying endoscopy in combination with NBI has an obvious advantage, namely analysis of the epithelial pit pattern and the vascular network. This new technique allows a detailed visualization in early neoplastic lesions of esophagus, stomach and colon. However, problems remain; how to combine these technologies in an optimum diagnostic strategy, how to apply them into the algorithm for therapeutic decision-making, and how to standardize several classifications surrounding them. 'Molecular imaging' is a concept representing the most novel imaging methods in medicine, although the definition of the word is still controversial. In the field of gastrointestinal endoscopy, the future of

Pathology of carcinoma in situ of the urinary bladder and related lesions.

PubMed

Farrow, G M

1992-01-01

In the United States, nearly all cases of bladder cancer are of the transitional cell type, and epidemiological evidence indicates that among these, approximately 80% present initially as more or less well-differentiated, superficial papillary neoplasms with a tendency for multifocal or diffuse involvement of the urothelial surface and/or recurrent tumor episodes, but with limited potential for invasive growth or a lethal outcome. Bladder tumors with lethal potential generally begin as poorly differentiated, sessile growths that are usually invasive at first diagnosis. Carcinoma in situ is a change that must be elicited among intact surface cells before progressive proliferation results in a tumor mass. Evidence for such an association is both temporal and spatial. Since most transitional cell carcinomas begin as well-differentiated tumors, i.e., resembling normal urothelium, recognition of early neoplastic alteration before a papillary structure forms is unlikely and most of the evidence is spatial based upon urothelial changes adjacent to papillary tumors. The morphologic definition of carcinoma in situ is arbitrary and generally defined as a total replacement of the urothelial surface by cells which bear morphologic features of carcinoma, but which lack architectural alteration other than an increase in the number of cell layers, i.e., a flat lesion. The Union Internationále Contra Cancer/American Joint Committee on Cancer (UICC/AJCC) staging scheme for bladder cancer distinguishes non-invasive papillary growths as Ta and carcinoma in situ as Tis. Because detection of carcinoma in situ, either by cytology or biopsy, depends upon recognizable malignant morphologic characteristics, studies of the lesion tend to be limited to the higher grade or more anaplastic examples.(ABSTRACT TRUNCATED AT 250 WORDS)

Automated metastatic brain lesion detection: a computer aided diagnostic and clinical research tool

NASA Astrophysics Data System (ADS)

Devine, Jeremy; Sahgal, Arjun; Karam, Irene; Martel, Anne L.

2016-03-01

The accurate localization of brain metastases in magnetic resonance (MR) images is crucial for patients undergoing stereotactic radiosurgery (SRS) to ensure that all neoplastic foci are targeted. Computer automated tumor localization and analysis can improve both of these tasks by eliminating inter and intra-observer variations during the MR image reading process. Lesion localization is accomplished using adaptive thresholding to extract enhancing objects. Each enhancing object is represented as a vector of features which includes information on object size, symmetry, position, shape, and context. These vectors are then used to train a random forest classifier. We trained and tested the image analysis pipeline on 3D axial contrast-enhanced MR images with the intention of localizing the brain metastases. In our cross validation study and at the most effective algorithm operating point, we were able to identify 90% of the lesions at a precision rate of 60%.

Congenital capillary proliferation of the kidney: a distinctive renal vascular lesion of childhood.

PubMed

Cajaiba, Mariana M; North, Paula E; Gong, Shunyou; Dickman, Paul S; Mroczek-Musulman, Elizabeth; Sauer, David A; Perlman, Elizabeth J

2017-08-01

Renal vascular lesions (RVL) are rare, and their morphological spectrum remains largely unknown, particularly in children. In this study, we characterize the clinicopathological features of RVL in a cohort of 12 children. Seven lesions were classified as previously recognized entities: vascular malformations (4), papillary endothelial hyperplasia (2), and pyogenic granuloma (lobular capillary hemangioma; 1). An eighth lesion showed nonspecific findings, which were interpreted as reactive during our review. The remaining 4 cases presented either prenatally, at birth, or shortly after birth and were morphologically similar. These were characterized by a peculiar pattern of capillary proliferation with entrapment of native renal structures, variable amounts of extramedullary hematopoiesis and reactive lymphocytes, foci of infarction and hemorrhage, and the presence of feeding and draining vessels at their periphery. To our knowledge, this represents a previously undescribed congenital vascular lesion involving the kidney, which we have descriptively and provisionally termed congenital capillary proliferation of the kidney (CCPK). While it is unclear whether CCPK represents a malformation or neoplastic proliferation, it shows overlapping features with congenital hemangioma of the liver (solitary congenital hepatic hemangioma) and congenital nonprogressive hemangioma (CNH) of the skin and soft tissue, suggesting a possible common pathogenesis among these 3 entities. Copyright © 2017 Elsevier Inc. All rights reserved.

The Role of Epilepsy in Early Language Development in a Child with a Congenital Lesion in the Right Hemisphere

ERIC Educational Resources Information Center

Mayor-Dubois, C.; Maeder-Ingvar, M.; Deonna, T.; Roulet-Perez, E.

2008-01-01

Early epilepsy is known to worsen the developmental prognosis of young children with a congenital focal brain lesion, but its direct role is often very difficult to delineate from the other variables. This requires prolonged periods of follow-up with simultaneous serial electrophysiological and developmental assessments which are rarely obtained.…

Analysis of neoplastic lesions in magnetic resonance imaging using self-organizing maps.

PubMed

Mei, Paulo Afonso; de Carvalho Carneiro, Cleyton; Fraser, Stephen J; Min, Li Li; Reis, Fabiano

2015-12-15

To provide an improved method for the identification and analysis of brain tumors in MRI scans using a semi-automated computational approach, that has the potential to provide a more objective, precise and quantitatively rigorous analysis, compared to human visual analysis. Self-Organizing Maps (SOM) is an unsupervised, exploratory data analysis tool, which can automatically domain an image into selfsimilar regions or clusters, based on measures of similarity. It can be used to perform image-domain of brain tissue on MR images, without prior knowledge. We used SOM to analyze T1, T2 and FLAIR acquisitions from two MRI machines in our service from 14 patients with brain tumors confirmed by biopsies--three lymphomas, six glioblastomas, one meningioma, one ganglioglioma, two oligoastrocytomas and one astrocytoma. The SOM software was used to analyze the data from the three image acquisitions from each patient and generated a self-organized map for each containing 25 clusters. Damaged tissue was separated from the normal tissue using the SOM technique. Furthermore, in some cases it allowed to separate different areas from within the tumor--like edema/peritumoral infiltration and necrosis. In lesions with less precise boundaries in FLAIR, the estimated damaged tissue area in the resulting map appears bigger. Our results showed that SOM has the potential to be a powerful MR imaging analysis technique for the assessment of brain tumors. Copyright © 2015. Published by Elsevier B.V.

Thoracic corpectomy for neoplastic vertebral bodies using a navigated lateral extracavitary approach-a single-center consecutive case series: technique and analysis.

PubMed

Hartmann, Sebastian; Wipplinger, Christoph; Tschugg, Anja; Kavakebi, Pujan; Örley, Alexander; Girod, Pierre Pascal; Thomé, Claudius

2018-04-01

Thoracic myelopathy is often caused by vertebral body fractures resulting from neoplastic conditions, traumatic events, or infectious diseases. One of the preferred procedures for treating it is the lateral extracavitary approach (LECA) with single-level or multilevel decompressive corpectomy and reconstruction. The aim of this retrospective study was to analyze the thoracic lateral extracavitary approach with corpectomy using vertebral body replacement systems (VBR-S) and dorsal reconstruction. Twenty-four patients with metastatic or primary lesions of thoracic vertebrae T2-T12 underwent spinal decompression and ventral column reconstruction with correction of spinal deformity via a LECA. One-level to four-level corpectomies were performed with additional navigated dorsal pedicle screw fixation at an average of two levels above and below the corpectomy lesion. None of the patients received preoperative spinal embolization, and the majority of the patients were admitted to radiotherapy postoperatively. Their mean age was 56 years (± 15), with a female-to-male sex ratio of 8 to 16. Patients with a minimum follow-up period of 16 months were included. The Karnofsky index, preoperative and postoperative numeric rating scale (NRS), and Frankel scale were measured. In addition, intraoperative loss of blood (LOB), units of packed red blood cell (PRBC) transfusions, the duration of the operation, and the hospitalization period were evaluated and correlated with preoperative and postoperative values. The majority of the patients were suffering from metastatic lesions and were treated with a 1 level corpectomy (median 1 level, range 1 to 4). The mean duration of surgery was 288 min (± 121) and the mean LOB was 1626 mL (± 1486 mL), with approximately two PRBC units per patient used. All patients were transferred to the intensive care unit (ICU) postoperatively, with a mean ICU stay of 2.0 days (± 1 day). The mean hospitalization period was 13 days (± 7�

Ki-67 expression in early prostate cancer and associated pathological lesions.

PubMed Central

Feneley, M R; Young, M P; Chinyama, C; Kirby, R S; Parkinson, M C

1996-01-01

AIM: To assess cell proliferation in early prostate cancer and associated pathological lesions. METHODS: Using the Ki-67 antibody, the cell proliferation index was measured in early stage prostatic carcinoma in 37 incidental tumours diagnosed at transurethral prostatectomy (TURP) and in 20 low volume cancers treated by radical prostatectomy. Proliferation indexes have also been measured in areas of normal peripheral zone, transition zone hyperplasia, atrophic appearing lobules, and high grade prostatic intraepithelial neoplasia in the radical prostatectomy cases. RESULTS: In the TURP series the proliferation index correlated with grade and stage. Logistic regression analysis, however, showed that Gleason grade was the most reliable predictor of biopsy proven residual disease and clinical progression. In the radical series transition zone carcinoma the proliferation index was half that of peripheral zone carcinoma. The atrophic lobules also showed a high proliferation index of the same order as seen in the peripheral zone carcinoma. Normal peripheral zone showed the lowest proliferation index and in hyperplastic transition zone it was also less than the other areas. CONCLUSIONS: There is only limited support for the correlation of proliferation index with grade in early stage prostatic carcinoma. The findings do not suggest that proliferation index adds to the prognostic information given by grade and stage in pT1 disease. The significant difference in proliferation index in transition zone and peripheral zone carcinomas supports the morphological distinction of these tumour types and is consistent with differences in biological behaviour. The high proliferation index in lobules considered morphologically atrophic is reminiscent of previous observations in which carcinoma was spatially associated with atrophy. Images PMID:9038759

Use of flexible hollow-core CO2 laser in microsurgical resection of CNS lesions: early surgical experience.

PubMed

Killory, Brendan D; Chang, Steve W; Wait, Scott D; Spetzler, Robert F

2010-06-01

The CO2 laser has a long history in both experimental and clinical neurosurgery. However, its use over the past decade has been limited by its cumbersome design and bulky set-up of the micromanipulator. These limitations are amplified when it is used with the operating microscope. These restrictions are addressed by the Omniguide fiber, which delivers the beam through flexible hollow-core photonic bandgap mirror fibers and allows the laser to be wielded like any other surgical instrument. The attending neurosurgeon prospectively assessed the usefulness of the laser in its first 45 consecutive uses at our institution based on a scale of 1 to 5. The series included 11 cavernous malformations, 14 meningiomas, 7 ependymomas, 3 metastases, 3 astrocytomas, and 7 miscellaneous lesions. The laser was set up 91 times and used in 45 cases. The Omniguide fiber failed 5 times. No adverse events involving patients or staff were associated with laser use. The mean utility score was 3.7 +/- 0.8 (range, 2-5). The laser was most helpful in debulking fibrous lesions too tough for ultrasonic aspiration and lesions adherent to delicate neurovascular structures. The laser was not helpful with highly vascular tumors. In our early experience, the Omniguide laser was very helpful in selected cases in resecting specific types of lesions without complications; we have added the device to our neurosurgical armamentarium.

Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus.

PubMed

Kastelein, Florine; Biermann, Katharina; Steyerberg, Ewout W; Verheij, Joanne; Kalisvaart, Marit; Looijenga, Leendert H J; Stoop, Hans A; Walter, Laurens; Kuipers, Ernst J; Spaander, Manon C W; Bruno, Marco J

2013-12-01

The value of surveillance for patients with Barrett's oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of discriminative tests for risk stratification. Histological diagnosis of low-grade dysplasia (LGD) is the only accepted predictor for progression to date, but has a low predictive value. The aim of this study was therefore to evaluate the value of p53 immunohistochemistry for predicting neoplastic progression in patients with BO. We conducted a case-control study within a prospective cohort of 720 patients with BO. Patients who developed high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) were classified as cases and patients without neoplastic progression were classified as controls. P53 protein expression was determined by immunohistochemistry in more than 12 000 biopsies from 635 patients and was scored independently by two expert pathologists who were blinded to long-term outcome. During follow-up, 49 (8%) patients developed HGD or OAC. P53 overexpression was associated with an increased risk of neoplastic progression in patients with BO after adjusting for age, gender, Barrett length and oesophagitis (adjusted relative risks (RR(a)) 5.6; 95% CI 3.1 to 10.3), but the risk was even higher with loss of p53 expression (RR(a) 14.0; 95% CI 5.3 to 37.2). The positive predictive value for neoplastic progression increased from 15% with histological diagnosis of LGD to 33% with LGD and concurrent aberrant p53 expression. Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with BO and appears to be a more powerful predictor of neoplastic progression than histological diagnosis of LGD.

Clinical and histological features of gingival lesions: a 17-year retrospective analysis in a northern Italian population.

PubMed

Carbone, Mario; Broccoletti, Roberto; Gambino, Alessio; Carrozzo, Marco; Tanteri, Carlotta; Calogiuri, Pier-Luigi; Conrotto, Davide; Gandolfo, Sergio; Pentenero, Monica; Arduino, Paolo-Giacomo

2012-07-01

Only few studies on gingival lesions considered large enough populations and contemporary literature does not provide a valid report regarding the epidemiology of gingival lesions within the Italian population. The histopathological and clinical appearance of 538 gingival lesions from northern Italians are described and discussed here. The case records of patients referred for the diagnosis and management of gingival lesions, from October 1993 to October 2009, were reviewed. Data regarding the histological type of lesion were also obtained from the biopsy register for each case, and blindly re-examined. We reported a greater frequency of benign lesions (reactive and/or inflammatory) in non-plaque/non-calculus induced gingival disorders. We confirmed an unambiguous prevalence of oral squamous cell carcinoma above all other malignant neoplasia, and a prevalence of neoplastic malignant lesions in the maxilla, with a slight increase in females and a drift of the incidence peak from the seventh to the eighth decade. There was a prevalence of precancerous gingival lesions in the maxilla, with a higher incidence in females and with a drift from the sixth to the seventh decade. We also reported a prevalence of oral lichen planus and lichenoid lesions as major manifestations of desquamative gingivitis. The high frequency of gingival involvement of such different diseases emphasizes the importance of histological characterization and differential diagnosis for periodontists, but more prospective studies are needed to better describe the true incidence of the non-plaque related gingival diseases.

Methylene Blue as a Diagnostic Aid in the Early Detection of Potentially Malignant and Malignant Lesions of Oral Mucosa.

PubMed

Lejoy, Abraham; Arpita, Rai; Krishna, Burde; Venkatesh, Naikmasur

2016-05-01

In vivo stains are the prompt resources, which have emerged in recent years to aid as clinical diagnostic tools in detecting early potentially malignant and malignant lesions. Toluidine blue, by its property of retaining in the increased DNA and RNA cellular activity areas, aids in delineating the suspicious areas. However, it is hazardous if swallowed, and has been shown to have toxicity to fibroblasts. Methylene blue has a similar chemical structure and exhibits similar physicochemical properties as toluidine blue. It is less toxic to the human body and has recently been proposed for screening some gastrointestinal or prostate tumors. The application of this material in detecting oral lesions has so far not been addressed. The objective of this study was to evaluate the sensitivity and reliability of in vivo staining with methylene blue as a diagnostic adjunct in screening for oral malignant or potentially malignant lesions. The present study involved the examination of 75 patients suspected of having oral malignant or potentially malignant lesions by methylene blue staining. The results of methylene blue uptake were compared with a simultaneous biopsy of these lesions. The overall sensitivity was 95% (100% for malignancy and 92% for potentially malignant lesions) and specificity was 70%. The positive predictive value was 91% and negative predictive value of 80% was observed in the study. We consider that methylene blue staining is a useful diagnostic adjunct in a large, community-based oral cancer screening program for high-risk individuals.

MRI in early prostate cancer detection: how to manage indeterminate or equivocal PI-RADS 3 lesions?

PubMed

Schoots, Ivo G

2018-02-01

This review focuses on indeterminate lesions on prostate magnetic resonance imaging (MRI), assigned as PI-RADS category 3. The prevalence of PI-RADS 3 index lesion in the diagnostic work-up is significant, varying between one in three (32%) to one in five (22%) men, depending on patient cohort of first biopsies, previously negative biopsies, and active surveillance biopsies. A management strategy must be developed for this group of men with an indeterminate suspicion of having clinically significant prostate cancer (csPCa). Currently available data show that the actual prevalence of csPCa after targeted biopsy in PI-RADS 3 lesions vary between patients groups from one in five (21%) to one in six (16%), depending on previous biopsy status. Although this prevalence is lower in comparison to PI-RADS 4 and PI-RADS 5 lesions, still a considerable proportion of men harbor significant disease. Men with such a PI-RADS 3 lesion should therefore be adequately managed. In general, the clinical approach of using a threshold of PI-RADS ≥4 instead of PI-RADS ≥3 to select MRI for targeted biopsies is not supported by data from our explorative literature search using current definitions of csPCa. A possible adaptation to the threshold of PI-RADS ≥4 in combination with other clinical markers could be considered within an active surveillance protocol, where the balance between the individual risk of missing csPCa and the constant process of repeating prostate biopsies is crucial. In the future, improvements in MR imaging and interpretation, combined with molecular biomarkers and multivariate risk models will all be employed in prostate cancer detection and monitoring. These combinations will aid decision-making in challenging circumstances, such as unclear and diagnostic equivocal results for csPCa at early detection.

Clinical and histological features of gingival lesions: A 17-year retrospective analysis in a northern Italian population

PubMed Central

Carbone, Mario; Broccoletti, Roberto; Gambino, Alessio; Carrozzo, Marco; Tanteri, Carlotta; Calogiuri, Pier L.; Conrotto, Davide; Gandolfo, Sergio; Pentenero, Monica

2012-01-01

Objectives: Only few studies on gingival lesions considered large enough populations and contemporary literature does not provide a valid report regarding the epidemiology of gingival lesions within the Italian population. The histopathological and clinical appearance of 538 gingival lesions from northern Italians are described and discussed here. Study Design: The case records of patients referred for the diagnosis and management of gingival lesions, from October 1993 to October 2009, were reviewed. Data regarding the histological type of lesion were also obtained from the biopsy register for each case, and blindly re-examined. Results: We reported a greater frequency of benign lesions (reactive and/or inflammatory) in non-plaque/non-calculus induced gingival disorders. We confirmed an unambiguous prevalence of oral squamous cell carcinoma above all other malignant neoplasia, and a prevalence of neoplastic malignant lesions in the maxilla, with a slight increase in females and a drift of the incidence peak from the seventh to the eighth decade. There was a prevalence of precancerous gingival lesions in the maxilla, with a higher incidence in females and with a drift from the sixth to the seventh decade. We also reported a prevalence of oral lichen planus and lichenoid lesions as major manifestations of desquamative gingivitis. Conclusions: The high frequency of gingival involvement of such different diseases emphasizes the importance of histological characterization and differential diagnosis for periodontists, but more prospective studies are needed to better describe the true incidence of the non-plaque related gingival diseases. Key words:Gingival lesions, clinical appearance, histological analysis. PMID:22322515

Molecular evidence of viral DNA in non-small cell lung cancer and non-neoplastic lung

DOE PAGES

Robinson, Lary A.; Jaing, Crystal J.; Campbell, Christine Pierce; ...

2016-07-14

Although ~20% of human cancers are caused by microorganisms, only suspicion exists for a microbial cause of lung cancer. Potential infectious agents were investigated in non-small cell lung cancer (NSCLC) and non-neoplastic lung. Seventy NSCLC tumours (33 squamous cell carcinomas, 17 adenocarcinomas, 10 adenocarcinomas with lepidic spread, and 10 oligometastases) and 10 non-neoplastic lung specimens were evaluated for molecular evidence of microorganisms. Tissues were subjected to the Lawrence Livermore Microbial Detection Array, an oncovirus panel of the International Agency for Research on Cancer, and human papillomavirus (HPV) genotyping. Associations were examined between microbial prevalence, clinical characteristics, and p16 and EGFRmore » expression. Retroviral DNA was observed in 85% squamous cell carcinomas, 47% adenocarcinomas, and 10% adenocarcinomas with lepidic spread. Human papillomavirus DNA was found in 69% of squamous cell carcinomas with 30% containing high-risk HPV types. No significant viral DNA was detected in non-neoplastic lung. Patients with tumours containing viral DNA experienced improved long-term survival compared with patients with viral DNA-negative tumours. Lastly, most squamous cell carcinomas and adenocarcinomas contained retroviral DNA and one-third of squamous cell carcinomas contained high-risk HPV DNA. Viral DNA was absent in non-neoplastic lung. Trial results encourage further study of the viral contribution to lung carcinogenesis.« less

Molecular evidence of viral DNA in non-small cell lung cancer and non-neoplastic lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, Lary A.; Jaing, Crystal J.; Campbell, Christine Pierce

Although ~20% of human cancers are caused by microorganisms, only suspicion exists for a microbial cause of lung cancer. Potential infectious agents were investigated in non-small cell lung cancer (NSCLC) and non-neoplastic lung. Seventy NSCLC tumours (33 squamous cell carcinomas, 17 adenocarcinomas, 10 adenocarcinomas with lepidic spread, and 10 oligometastases) and 10 non-neoplastic lung specimens were evaluated for molecular evidence of microorganisms. Tissues were subjected to the Lawrence Livermore Microbial Detection Array, an oncovirus panel of the International Agency for Research on Cancer, and human papillomavirus (HPV) genotyping. Associations were examined between microbial prevalence, clinical characteristics, and p16 and EGFRmore » expression. Retroviral DNA was observed in 85% squamous cell carcinomas, 47% adenocarcinomas, and 10% adenocarcinomas with lepidic spread. Human papillomavirus DNA was found in 69% of squamous cell carcinomas with 30% containing high-risk HPV types. No significant viral DNA was detected in non-neoplastic lung. Patients with tumours containing viral DNA experienced improved long-term survival compared with patients with viral DNA-negative tumours. Lastly, most squamous cell carcinomas and adenocarcinomas contained retroviral DNA and one-third of squamous cell carcinomas contained high-risk HPV DNA. Viral DNA was absent in non-neoplastic lung. Trial results encourage further study of the viral contribution to lung carcinogenesis.« less

[Pediatric lung lesions: a clinicopathological study of 215 cases].

PubMed

Niu, Huilin; Wang, Fenghua; Liu, Wei; Wang, Yong; Chen, Zhengrong; Gao, Qiu; Yi, Peng; Li, Liping; Zeng, Rongxin

2015-09-01

To investigate clinical and pathological features of lung lesions in children. Clinical manifestations, radiologic imaging, histopathological features and immunohistochemical results were analyzed in 215 cases of lung lesions in children. A total of 215 cases of lung lesions in children aged 0 day to 13 years (average age of 27.2 months and the median age of 18.0 months) were selected, including 137 male and 78 female patients with a male to female ratio of 1.76:1.00. The incidence of congenital lung disease was higher in patients of less than 1 year old than those of over 1 year old age, and the difference of the two groups was statistically significant (P = 0.004). 142 cases had acquired lung diseases, and 73 cases had congenital bronchopulmonary dysplasia. Lung abscess was the most common lesion seen in 86 cases (40.0%), including 1 case of fungal abscess. Congenital pulmonary airway malformation (CPAM) was the second most common, seen in 44 patients (20.5%), including 20 cases of type 1, 18 cases of type 2 and 6 cases of type 4 CPAM. Pulmonary sequestration was found in 25 cases (11.6%) including 14 cases of intralobar type and 11 cases of extralobar type. Two cases of extralobar pulmonary sequestration showed simultaneous CPAM2 type 2 lesion. Other lesions included tuberculosis (13 cases, 6.0%), emphysema (12 cases, 5.6%), interstitial pneumonia (7 cases, 3.2%), pulmonary hemorrhage (6 cases, 2.8%), bronchogenic cyst (4 cases, 1.9%), bronchiolitis obliterans (2 cases, 0.9%), idiopathic pulmonary hemosiderin deposition disease (2 cases, 0.9%) and 1 cases of lung non-specific changes. 13 cases of neoplastic lesions (6.0%) were found, of which 11 cases were primary tumors (5.1%), including inflammatory myofibroblastic tumor in 5 patients (2.3%), pleuropulmonary blastoma in 5 cases (1 case of type I, 2 type II and 2 type III) and 1 case of mucoepidermoid carcinoma (0.5%) and 2 cases of metastatic tumors (hepatoblastoma and Wilm's tumor, 0.9%). Infectious diseases

Probiotics against neoplastic transformation of gastric mucosa: effects on cell proliferation and polyamine metabolism.

PubMed

Russo, Francesco; Linsalata, Michele; Orlando, Antonella

2014-10-07

Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism.

Expression of a fms-related oncogene in carcinogen-induced neoplastic epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, C.; Nettesheim, P.; Barrett, J.C.

1987-04-01

Following carcinogen exposure in vitro, normal rat tracheal epithelial cells are transformed in a multistage process in which the cultured cells become immortal and ultimately, neoplastic. Five cell lines derived from tumors produced by neoplastically transformed rat tracheal epithelial cells were examined for the expression of 11 cellular oncogenes previously implicated in pulmonary or epithelial carcinogenesis. RNA homologous to fms was expressed at a level 5-19 times higher than normal tracheal epithelial cells in three of five of the tumor-derived lines. All three lines expressing high levels of fms-related RNA gave rise to invasive tumors of epithelial origin when injectedmore » into nude mice. Increased expression of the fms-related mRNA was not due to gene amplification, and no gene rearrangement was detected by Southern analyses. RNA blot analysis using a 3' v-fms probe detected a 9.5-kilobase message in the three tumor-derived lines, whereas both normal rat aveolar macrophages and the human choriocarcinoma line BeWo expressed a fms transcript of approx. = 4 kilobases. The authors conclude from these data that the gene expressed as a 9.5-kilobase transcript in these neoplastic epithelial cells is a member of a fms-related gene family but may be distinct from the gene that encodes the macrophage colony-stimulating factor (CSF-1) receptor.« less

Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats.

PubMed

Heredia, Margarita; Fuente, A; Criado, J; Yajeya, J; Devesa, J; Riolobos, A S

2013-06-15

A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area). Copyright © 2013 Elsevier B.V. All rights

[Practical problems in breast screening. Columnar cell lesions including flat epithelial atypia and lobular neoplasia].

PubMed

Nährig, J

2008-11-01

Columnar cell lesions (CCL) and lobular neoplasia (LN) are encountered with increasing frequency in breast screening biopsies. CCLs are frequently associated with microcalcifications, whereas LN is an incidental finding in most cases. Flat epithelia atypia (FEA) the atypical variant of CLL, LN and atypical ductal hyperplasia (ADH) are frequently associated lesions. Molecular genetic studies of CCL, ductal carcinoma in situ (DCIS) and low grade invasive carcinomas revealed similar chromosomal alterations supporting the assumption that CCLs are neoplastic proliferations. The frequent association of FEA together with well differentiated invasive carcinomas provides further evidence of this concept. There is no internationally accepted classification of CCLs at present. CDH1-gene mutations are the cardinal feature of LN and invasive lobular carcinoma. In immunohistochemically CDH1-positive cases, alternative genetic alterations of the CDH1 pathway can lead to functional loss of CDH1. In our opinion morphologically and immunohistochemically hybrid lesions may represent this group of lobular lesions. Recent follow-up data suggest a higher rate of ipsilateral carcinomas in patients with previously diagnosed LN. It is currently an open question whether FEA and LN are members of a common family of intralobular proliferations, which are non-obligatory precursors of a low nuclear grade breast neoplasia family.

[The effect of neoplastic disease and systemic disease of connective tissue on the occurrence of dehiscence laparotomy].

PubMed

Paunović, Milorad

2013-01-01

Dehiscence after laparotomy is one of the major complications of laparotomy. This is a partial or complete wound with disruption and evisceratio abdominal organs and require urgent reintervention. The aim of this study was to determine the impact of neoplastic disease and systemic disease of connective tissue on the occurrence of dehiscence laparotomy. A prospective study were included 612 patients operated at the Clinic for General Surgery in Nis in the period from January 2009 to December 2010. The effect of neoplastic disease and the presence of systemic disease of connective tissue on the occurrence of dehiscence laparotomy. Results are displayed numerically and in percentages. Of the total 24 patients with dehiscence laparotomy, 15 patients were male or 62.5% and 9 female patients, or 37.5%. There was a statistically significant association between dehiscence laparotomy and neoplastic diseases (c2 = 42,196; p < 0.01). There was no statistically significant association between dehiscence laparo-tomy and systemic disease of connective tissue (c2 = 0,028; p > 0.05). In patients with neoplastic diseases dehis-cence laparotomy is common, and in patients suffering from systemic disease of connective tissue dehiscence laparotomy occurs less frequently.

Depleted uranium induces neoplastic transformation in human lung epithelial cells.

PubMed

Xie, Hong; LaCerte, Carolyne; Thompson, W Douglas; Wise, John Pierce

2010-02-15

Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and noncombatants is frequent and widespread. Previous studies have shown that DU has both chemical and radiological toxicity and that the primary route of exposure of DU to humans is through inhalation and ingestion. However, there is limited research information on the potential carcinogenicity of DU in human bronchial cells. Accordingly, we determined the neoplastic transforming ability of particulate DU to human bronchial epithelial cells (BEP2D). We observed the loss of contact inhibition and anchorage independent growth in cells exposed to DU after 24 h. We also characterized these DU-induced transformed cell lines and found that 40% of the cell lines exhibit alterations in plating efficiency and no significant changes in the cytotoxic response to DU. Cytogenetic analyses showed that 53% of the DU-transformed cell lines possess a hypodiploid phenotype. These data indicate that human bronchial cells are transformed by DU and exhibit significant chromosome instability consistent with a neoplastic phenotype.

All lesions great and small, part 1: diagnostic cytology in veterinary medicine.

PubMed

Sharkey, Leslie C; Seelig, Davis M; Overmann, Jed

2014-06-01

Cytopathology is a minimally invasive, rapid, and cost-effective diagnostic modality with broad utilization in veterinary medicine. Primary care clinicians often screen common cutaneous and subcutaneous aspirates, with other samples most frequently evaluated by board certified veterinary clinical pathologists in reference laboratories. Wright-Giemsa stains are frequently utilized with the application of ancillary diagnostics such as cytochemistry, immunocytochemistry, flow cytometry, and molecular diagnostic techniques complicated by the need to develop and validate species specific reagents and protocols. The interpretation of veterinary cytology samples must be undertaken with extensive knowledge of the breadth of animal species, which includes familiarity with the frequency and biological behavior of inflammatory, infectious, and neoplastic lesions that are influenced by species, breed, and husbandry conditions. This review is the first of two parts that focus on the most common domestic companion animal species (dog, cat, and horse), taking an organ system approach to survey important lesions that may be unique to veterinary species or have interesting correlates in human medicine. The first of the two-part series covers skin and subcutaneous tissue, the musculoskeletal system, and lymphoid organs. The cytologic features and biological behavior of similar lesions are compared, and selected molecular mechanisms of disease and ancillary diagnostics are reviewed when characterized. Supporting figures illustrate a subset of lesions. While not a comprehensive catalog of veterinary cytology, the goal is to give cytopathologists working in human medicine a general impression of correlates in veterinary practice. Copyright © 2014 Wiley Periodicals, Inc.

Expression of Gab1 lacking the pleckstrin homology domain is associated with neoplastic progression.

PubMed

Kameda, H; Risinger, J I; Han, B B; Baek, S J; Barrett, J C; Abe, T; Takeuchi, T; Glasgow, W C; Eling, T E

2001-10-01

An in vitro transformation system of carcinogen-treated Syrian hamster embryo (SHE) cell cultures represents multistep genetic and nongenetic changes that develop during the neoplastic progression of normal cells to tumor cells in vivo. During this neoplastic progression, SHE cells demonstrate an altered response to epidermal growth factor (EGF). In the present report, we examined the role of the adapter protein Gab1 (Grb2-associated binder-1) in the neoplastic progression of SHE cells. We used two asbestos-transformed SHE cell clones in different neoplastic stages: a 10W+8 clone, which is immortal and retains the ability to suppress the tumorigenicity of tumor cells in cell-cell hybrid experiments, and a 10W-1 clone, which has lost this tumor suppressor ability. 10W+8 cells expressed full-length 100-kDa Gab1 and associated 5.2-kb mRNA. Upon repeated cell passaging, 10W-1 cells showed increasing expression of a novel 87-kDa form of Gab1 as well as 4.6-kb mRNA with diminishing expression of the original 100-kDa Gab1. cDNA encoding the 87-kDa Gab1 predicts a form of Gab1 lacking the amino-terminal 103 amino acids (Gab1(Delta1-103)), which corresponds to loss of most of the pleckstrin homology (PH) domain. Gab1(Delta1-103) retains the ability to be phosphorylated in an EGF-dependent manner and to associate with the EGF receptor and SHP-2 upon EGF stimulation. The endogenous expression of Gab1(Delta1-103) in 10W-1 cells appeared closely related to EGF-dependent colony formation in soft agar. Moreover, transfection and expression of Gab1(Delta1-103), but not Gab1, in 10W+8 cells enhanced their EGF-dependent colony formation in soft agar. These results demonstrate that Gab1 is a target of carcinogen-induced transformation of SHE cells and that the expression of a Gab1 variant lacking most of the PH domain plays a specific role in the neoplastic progression of SHE cells.

Probiotics against neoplastic transformation of gastric mucosa: Effects on cell proliferation and polyamine metabolism

PubMed Central

Russo, Francesco; Linsalata, Michele; Orlando, Antonella

2014-01-01

Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism. PMID:25309063

Simultaneous Dual Selective Targeted Delivery of Two Covalent Gemcitabine Immunochemotherapeutics and Complementary Anti-Neoplastic Potency of [Se]-Methylselenocysteine

PubMed Central

Coyne, C. P.; Jones, Toni; Bear, Ryan

2015-01-01

The anti-metabolite chemotherapeutic, gemcitabine is relatively effective for a spectrum of neoplastic conditions that include various forms of leukemia and adenocarcinoma/carcinoma. Rapid systemic deamination of gemcitabine accounts for a brief plasma half-life but its sustained administration is often curtailed by sequelae and chemotherapeutic-resistance. A molecular strategy that diminishes these limitations is the molecular design and synthetic production of covalent gemcitabine immunochemotherapeutics that possess properties of selective “targeted” delivery. The simultaneous dual selective “targeted” delivery of gemcitabine at two separate sites on the external surface membrane of a single cancer cell types represents a therapeutic approach that can increase cytosol chemotherapeutic deposition; prolong chemotherapeutic plasma half-life (reduces administration frequency); minimize innocent exposure of normal tissues and healthy organ systems; and ultimately enhance more rapid and thorough resolution of neoplastic cell populations. Materials and Methods: A light-reactive gemcitabine intermediate synthesized utilizing succinimidyl 4,4-azipentanoate was covalently bound to anti-EGFR or anti-HER2/neu IgG by exposure to UV light (354-nm) resulting in the synthesis of covalent immunochemotherapeutics, gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu]. Cytotoxic anti-neoplastic potency of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] between gemcitabine-equivalent concentrations of 10−12 M and 10−6 M was determined utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKRr-3). The organoselenium compound, [Se]-methylselenocysteine was evaluated to determine if it complemented the anti-neoplastic potency of the covalent gemcitabine immunochemotherapeutics. Results: Gemcitabine-(C4-amide)-[anti-EGFR], gemcitabine-(C4-amide)-[anti-HER2/neu] and the dual simultaneous combination of gemcitabine

Hypothesis: Induction of biomarkers for detection of colonic neoplasms

PubMed Central

Bordonaro, Michael; Lazarova, Darina

2018-01-01

The signing of the National Cancer Act of 1971 by President Nixon marked the beginning of our war on cancer. More than 45 years later, the war is still going steady, with the enemy being almost as strong as in 1971. Furthermore, the increasing rates of obesity not only among adults, but among children and adolescents, are the likely cause for the 30-year trend of colon cancer (CC) becoming a disease of the younger population in the U.S. These trends, however, have not spurred the development of novel screening approaches for CC. Considering the need for a sensitive and non-invasive detection of early stage neoplastic lesions in the colon, we propose the development of a test based on a novel concept - the concept of induced biomarkers. The proposal is based upon our findings that the food additives propolis and gamma-cyclodextrin (gCD) (a) decrease the neoplastic burden in normal weight and obese ApcMin mice, a model of early stage intestinal neoplasia, and (b) elicit significant changes in the serum proteome in ApcMin mice. We posit that gCD and propolis induce the release of neoplasm-associated biomarkers in systemic circulation (e.g., metabolites, neoplastic, apoptotic, and immune response proteins), and these markers could be used to detect early stage intestinal neoplasms. Additional dietary bioactives may also elicit a complement of induced markers. The hypothesis could be ascertained by utilizing a mouse model, the Apc+/1638Nmice, as well as through human subject studies that integrate proteomics and metabolomics analyses. The concept of detecting inducible markers of colonic neoplasms is novel, and is substantiated by the significant physiological effects of gCD and propolis on neoplastic colonic cells in culture and on early neoplastic development in ApcMinmice. The long-term objective is to develop a minimally invasive method that detects early stage neoplastic development in the human colon. PMID:29290782

Sodium hydroxide as a sclerosing agent in patients with neoplastic pleural effusion non-candidates for VATS: results of a minimally invasive protocol.

PubMed

Raices, Micaela; Czerwonko, Matías E; Dietrich, Agustin; Da Lozzo, Alejandro; Beveraggi, Enrique; Smith, David

2017-08-31

Symptomatic neoplastic pleural effusion (SNPE) is a significant cause of morbidity in patients with advanced neoplastic disease. These patients often present a deteriorated general condition which prevents them from undergoing pleurodesis with video-assisted thoracic surgery (VATS). We developed a minimally invasive therapeutic protocol specially designed for this population, achieved by combining chemical pleurodesis with placement of small-bore pleural catheters (PC), which resulted in early hospital discharge, low morbimortality and good therapeutic results. This study reports the safety and efficacy of administration of sodium hydroxide (NaOH) through PC in 60 patients diagnosed with SNPE who were admitted to Hospital Italiano de Buenos Aires between January 2012 and December 2015. Successful pleurodesis was achieved in 96% of procedures. Recurrence occurred in 25% of patients during follow-up, with recurrence occurring earlier than 30 days after pleurodesis in 8% of patients. There were no reports of major morbidity or associated mortality. In total, 44% of patients were discharged within 48 h of pleurodesis. Administration of NaOH through a small-bore PC represents an effective and safe method of pleurodesis in patients who are not candidates for talc pleurodesis by VATS.

Accuracy in clinically evaluating pigmented lesions.

PubMed Central

Curley, R. K.; Cook, M. G.; Fallowfield, M. E.; Marsden, R. A.

1989-01-01

OBJECTIVE--To determine the ability of three doctors experienced in managing melanocytic lesions to diagnose correctly melanoma, dysplastic naevi, and various benign pigmented lesions. DESIGN--Independent clinical evaluation and histopathological assessment. SETTING--Pigmented lesion clinic, which patients attend without an appointment for early diagnosis of melanoma. PATIENTS--86 Patients with lesions that were judged to be benign by at least one of the three doctors. INTERVENTIONS--The lesions were excised under local anaesthesia and sent for histopathological examination in coded bottles without clinical details. MAIN OUTCOME MEASURE--Comparison of clinical with histopathological diagnosis for each lesion. RESULTS--A total of 120 lesions were evaluated by at least two of the three doctors. The histopathological diagnoses were made by the same pathologist. The overall sensitivity (diagnostic accuracy) for the three doctors for all types of lesion was 50%. Of the 39 dysplastic naevi, only 19 were identified correctly by all observers, and a further 24 banal lesions were wrongly diagnosed as dysplastic by at least one doctor. Particular difficulty was experienced with small (less than 5 mm), flat lesions, which can be banal or potentially malignant. CONCLUSIONS--Critical diagnosis and management decisions concerning pigmented lesions should always be based on a combination of clinical and histopathological assessments and the history of the patient. PMID:2503192

Mechanical Properties of Human Cells Change during Neoplastic Processes

NASA Astrophysics Data System (ADS)

Guthold, Martin; Guo, Xinyi; Bonin, Keith; Scarpinato, Karin

2014-03-01

Using an AFM with a spherical probe of 5.3 μm, we determined mechanical properties of individual human mammary epithelial cells that have progressed through four stages of neoplastic transformation: normal, immortal, tumorigenic, and metastatic. Measurements on cells in all four stages were taken over both the nucleus and the cytoplasm. Moreover, the measurements were made for cells outside of a colony (isolated), on the periphery of a colony, and inside a colony. By fitting the AFM force vs. indentation curves to a Hertz model, we determined the Young's modulus, E. We found a distinct contrast in the influence a cell's colony environment has on its stiffness depending on whether the cells are normal or cancer cells. We also found that cells become softer as they advance to the tumorigenic stage and then stiffen somewhat in the final step to metastatic cells. For cells averaged over all locations the stiffness values of the nuclear region for normal, immortal, tumorigenic, and metastatic cells were (mean +/- sem) 880 +/- 50, 940+/-50, 400 +/- 20, and 600 +/-20 Pa respectively. Cytoplasmic regions followed a similar trend. These results point to a complex picture of the mechanical changes that occur as cells undergo neoplastic transformation. This work is supported by NSF Materials and Surface Engineering grant CMMI-1152781.

Differentiation of nonneoplastic and neoplastic gallbladder polyps 1 cm or bigger with multi-detector row computed tomography.

PubMed

Park, Ko Woon; Kim, Seong Hyun; Choi, Seong Ho; Lee, Won Jae

2010-01-01

To evaluate useful computed tomographic features to differentiate nonneoplastic and neoplastic gallbladder polyps 1 cm or bigger. Thirty-one patients with 32 nonneoplastic polyps and 67 patients with 73 neoplastic polyps 1 cm or bigger underwent unenhanced and dual-phase (arterial and portal venous phases) multi-detector row computed tomography. Gallbladder polyps were diagnosed by cholecystectomy. Computed tomographic features including size (1.5 cm), surface (smooth or irregular), shape (pedunculated or sessile), accompanying wall thickening, basal indentation, perception on unenhanced images, and enhancement pattern between 2 groups were compared using univariate and multivariate analyses. On univariate analysis, age 55 years or older (P = 0.0019), size bigger than 1.5 cm (P < 0.0001), irregular surface (P = 0.0033), sessile shape (P = 0.0016), accompanying wall thickening (P = 0.0056), basal indentation (P = 0.0236), and perception on unenhanced images (P < 0.0001) were significantly more frequent in neoplastic polyps as compared with nonneoplastic polyps. On multivariate analysis, size bigger than 1.5 cm (P = 0.0260), sessile shape (P = 0.0397), and perception on unenhanced images (P < 0.0001) were statistically significant. Size bigger than 1.5 cm, sessile shape, and perception on unenhanced images are the main factors that differentiate neoplastic from nonneoplastic gallbladder polyps 1 cm or bigger.

Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using /sup 111/In-DTPA ventriculography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grossman, S.A.; Trump, D.L.; Chen, D.C.

1982-11-01

Cerebrospinal fluid flow dynamics were evaluated by /sup 111/In-diethylenetriamine pentaacetic acid (/sup 111/In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that /sup 111/In-DTPA cerebrospinal fluid flow imaging is useful in characterizingmore » these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.« less

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

DTIC Science & Technology

2016-04-01

prostate, lung, colon and pancreas and have been also reported in the premalignant lesions. This peptide could provide us with an opportunity to...including those of the breast, prostate, lung, colon and pancreas and have been also reported in the premalignant lesions (Erez N, et. al Cancer Cell

Pediatric Awake Craniotomy for Brain Lesions.

PubMed

Akay, Ali; Rükşen, Mete; Çetin, H Yurday; Seval, H Özer; İşlekel, Sertaç

2016-01-01

Awake craniotomy is a special method to prevent motor deficits during the resection of lesions that are located in, or close to, functional areas. Although it is more commonly performed in adult patients, reports of pediatric cases undergoing awake craniotomy are limited in the literature. In our clinic, where we frequently use awake craniotomy in adult patients, we performed this method in 2 selected pediatric cases for lesion surgery. At an early age, these 2 cases diagnosed with epilepsy presented cerebral lesions, but since the lesions enclosed functional areas, surgical resection was not regarded as a treatment option at this time. In these 2 pediatric cases, we successfully completed lesion surgery with awake craniotomy. The method and the techniques employed during surgery are presented concomitant with other reports in the literature. © 2016 S. Karger AG, Basel.

Hexon modification to improve the activity of oncolytic adenovirus vectors against neoplastic and stromal cells in pancreatic cancer.

PubMed

Lucas, Tanja; Benihoud, Karim; Vigant, Frédéric; Schmidt, Christoph Q; Schmidt, Christoph Q Andreas; Wortmann, Andreas; Bachem, Max G; Simmet, Thomas; Kochanek, Stefan

2015-01-01

Primary pancreatic carcinoma has an unfavourable prognosis and standard treatment strategies mostly fail in advanced cases. Virotherapy might overcome this resistance to current treatment modalities. However, data from clinical studies with oncolytic viruses, including replicating adenoviral (Ad) vectors, have shown only limited activity against pancreatic cancer and other carcinomas. Since pancreatic carcinomas have a complex tumor architecture and frequently a strong stromal compartment consisting of non-neoplastic cell types (mainly pancreatic stellate cells = hPSCs) and extracellular matrix, it is not surprising that Ad vectors replicating in neoplastic cells will likely fail to eradicate this aggressive tumor type. Because the TGFβ receptor (TGFBR) is expressed on both neoplastic cells and hPSCs we inserted the TGFBR targeting peptide CKS17 into the hypervariable region 5 (HVR5) of the capsid protein hexon with the aim to generate a replicating Ad vector with improved activity in complex tumors. We demonstrated increased transduction of both pancreatic cancer cell lines and of hPSCs and enhanced cytotoxicity in co-cultures of both cell types. Surface plasmon resonance analysis demonstrated decreased binding of coagulation factor X to CKS17-modified Ad particles and in vivo biodistribution studies performed in mice indicated decreased transduction of hepatocytes. Thus, to increase activity of replicating Ad vectors we propose to relax tumor cell selectivity by genetic hexon-mediated targeting to the TGFBR (or other receptors present on both neoplastic and non-neoplastic cells within the tumor) to enable replication also in the stromal cell compartment of tumors, while abolishing hepatocyte transduction, and thereby increasing safety.

Diagnostic accuracy of transabdominal high-resolution US for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with EUS.

PubMed

Lee, Jeong Sub; Kim, Jung Hoon; Kim, Yong Jae; Ryu, Ji Kon; Kim, Yong-Tae; Lee, Jae Young; Han, Joon Koo

2017-07-01

To compare the diagnostic accuracy of transabdominal high-resolution ultrasound (HRUS) for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with endoscopic ultrasound (EUS) and pathology. Among 125 patients who underwent both HRUS and EUS, we included 29 pathologically proven cancers (T1 = 7, T2 = 19, T3 = 3) including 15 polypoid cancers and 50 surgically proven polyps (neoplastic = 30, non-neoplastic = 20). We reviewed formal reports and assessed the accuracy of HRUS and EUS for diagnosing cancer as well as the differential diagnosis of neoplastic polyps. Statistical analyses were performed using chi-square tests. The sensitivity, specificity, PPV, and NPV for gallbladder cancer were 82.7 %, 44.4 %, 82.7 %, and 44 % using HRUS and 86.2 %, 22.2 %, 78.1 %, and 33.3 % using EUS. HRUS and EUS correctly diagnosed the stage in 13 and 12 patients. The sensitivity, specificity, PPV, and NPV for neoplastic polyps were 80 %, 80 %, 86 %, and 73 % using HRUS and 73 %, 85 %, 88 %, and 69 % using EUS. Single polyps (8/20 vs. 21/30), larger (1.0 ± 0.28 cm vs. 1.9 ± 0.85 cm) polyps, and older age (52.5 ± 13.2 vs. 66.1 ± 10.3 years) were common in neoplastic polyps (p < 0.05). Transabdominal HRUS showed comparable accuracy for diagnosing gallbladder cancer and differentiating neoplastic polyps compared with EUS. HRUS is also easy to use during our routine ultrasound examinations. • HRUS showed comparable diagnostic accuracy for GB cancer compared with EUS. • HRUS and EUS showed similar diagnostic accuracy for differentiating neoplastic polyps. • Single, larger polyps and older age were common in neoplastic polyps. • HRUS is less invasive compared with EUS.

Inflammatory and vascular placental lesions are associated with neonatal amplitude integrated EEG recording in early premature neonates

PubMed Central

Goshen, Sharon; Richardson, Justin; Drunov, VIadimir; Staretz Chacham, Orna; Shany, Eilon

2017-01-01

the first 3 days of life (P = 0.007). Conclusions Depressed neonatal aEEG patterns are associated with placental lesions consistent with maternal under perfusion, and amniotic fluid infection of fetal type, but not with fetal thrombo-oclusive vascular disease of inflammatory type. Our findings highlight the association between the intrauterine mechanisms leading to preterm parturition and subsequent depressed neonatal cerebral function early after birth, which eventually may put premature infants at risk for abnormal neurodevelopmental outcome. PMID:28644831

Neoplastic Fever: All who Shiver are not Infected.

PubMed

Sharma, Yogesh B; More, Aparna Vishal

2017-03-01

We report the case of previously healthy 14 years old male who presented high grade fever and headache. There was a history of convulsion at age of 7 years, so MRI Brain was done. It was suggestive of a central nervous system neoplasm. Our patient had only two days of fever which is an unusual presentation of a neoplasm. The paper should be of interest to the clinicians as neoplastic fever as cause of acute febrile illness is considered as a remote possibility. © Journal of the Association of Physicians of India 2011.

Optical Assessment of Caries Lesion Structure and Activity

NASA Astrophysics Data System (ADS)

Lee, Robert Chulsung

New, more sophisticated diagnostic tools are needed for the detection and characterization of caries lesions in the early stages of development. It is not sufficient to simply detect caries lesions, methods are needed to assess the activity of the lesion and determine if chemical or surgical intervention is needed. Previous studies have demonstrated that polarization sensitive optical coherence tomography (PS-OCT) can be used to nondestructively image the subsurface lesion structure and measure the thickness of the highly mineralized surface zone. Other studies have demonstrated that the rate of dehydration can be correlated with the lesion activity and that the rate can be measured using optical methods. The main objective of this work was to test the hypothesis that optical methods can be used to assess lesion activity on tooth coronal and root surfaces. Simulated caries models were used to develop and validate an algorithm for detecting and measuring the highly mineralized surface layer using PS-OCT. This work confirmed that the algorithm was capable of estimating the thickness of the highly mineralized surface layer with high accuracy. Near-infrared (NIR) reflectance and thermal imaging methods were used to assess activity of caries lesions by measuring the state of lesion hydration. NIR reflectance imaging performed the best for artificial enamel and natural coronal caries lesion samples, particularly at wavelengths coincident with the water absorption band at 1460-nm. However, thermal imaging performed the best for artificial dentin and natural root caries lesion samples. These novel optical methods outperformed the conventional methods (ICDAS II) in accurately assessing lesion activity of natural coronal and root caries lesions. Infrared-based imaging methods have shown potential for in-vivo applications to objectively assess caries lesion activity in a single examination. It is likely that if future clinical trials are a success, this novel imaging

Spectrum of thyroid lesions in hospital Universiti Sains Malaysia over 11years and a review of thyroid cancers in Malaysia.

PubMed

Othman, Nor Hayati; Omar, Effat; Naing, Nyi Nyi

2009-01-01

Endemic goitre is a major concern in many nations including Malaysia. Seven states in the country have been identified by Ministry of Health of Malaysia to have high incidence of goitre and one of these is Kelantan. This is a retrospective study over an 11-year period from 1994 to 2004 on all thyroid specimens submitted to the Pathology Department, Hospital Universiti Sains Malaysia (HUSM), in Kelantan. Epidemiological data were retrieved from the patients' records and pathology findings from the pathology reports. During this period, Department of Pathology HUSM received a total of 1,486 thyroid specimens. The female to male ratio was 6:1 and the median age was 40.0 years. The duration of goitre ranged from one to 15 years. Histopathological examination showed 71.9 percent were non-neoplastic and 28.1 percent neoplastic lesions. The hospital-based incidence of nodular hyperplasia was 9.9 per 100,000 admitted patients per year. The hospital-based incidence of all types of malignant thyroid cancers was 3.5 per 100,000. The most common malignancy was papillary carcinoma 76.6 percent. The majority of the cancers (59.5 percent) occurred in a background of nodular hyperplasia. Thyroid cancers made up 4.9 percent of all cancers seen in HUSM. This study suggests that malignant thyroid lesions arising from multi-nodular goitre are high in a population living in an iodine-deficiency area.

Periapical implant lesion: A systematic review

PubMed Central

Blaya-Tárraga, Juan-Antonio; Cervera-Ballester, Juan; Peñarrocha-Oltra, David; Peñarrocha-Diago, Miguel

2017-01-01

Background The aim of this study was to systematically review the evidence for periapical implant lesion, which makes a patient more susceptible to the periapical lesion, frequency, symptoms, signs (including radiological findings) and possible treatment options. Material and Methods A systematic literature review and analysis of publications included in PubMed, Embase and Cochrane; articles published until March 2016; with a populations, exposures and outcomes (PEO) search strategy was performed, focused on the issue: “In patients with periapical lesion to the implant during the osseointegration, what symptoms, signs, and changes in complementary examination manifested, for according to that stage, be intervened with the appropriate approach?”. The set criteria for inclusion were peer-reviewed articles. Results From a total of 212 papers identified, 36 studies were included in this systematic review, with 15461 implants evaluated and 183 periapical implant lesions. Which 8 papers included more than 5 cases and 28 included equal or less than 5 cases. Analysis of the papers revealed that periapical implant lesion is classified according to evolution stages into acute (non-suppurated and suppurated) and subacute (or suppurated-fistulized). In the acute stage and in the subacute if there is no loss of implant stability, the correct treatment approach is implant periapical surgery. In the subacute stage associated with implant mobility the implant must be removed. Conclusions Evidence on the subject is very limited, there are few studies with small sample, without homogeneity of criteria for diagnosing the disease and without design of scientific evidence. Currently etiology lacks consensus. The early diagnosis of periapical implant periapical lesions during the osseointegration phase and early treatment, will lead to a higher survival rate of implants treated, hence preventing the need for implant extraction. Key words:Apical peri-implantitis, retrograde peri

BRCA1-IRIS overexpression promotes and maintains the tumor initiating phenotype: implications for triple negative breast cancer early lesions

PubMed Central

Sullivan, Lisa M.; Sims, Hillary; Bastawisy, Ahmed El; Yousef, Hend F.; Zekri, Abdel-Rahman N.; Bahnassy, Abeer A.; ElShamy, Wael M.

2017-01-01

Tumor-initiating cells (TICs) are cancer cells endowed with self-renewal, multi-lineage differentiation, increased chemo-resistance, and in breast cancers the CD44+/CD24-/ALDH1+ phenotype. Triple negative breast cancers show lack of BRCA1 expression in addition to enhanced basal, epithelial-to-mesenchymal transition (EMT), and TIC phenotypes. BRCA1-IRIS (hereafter IRIS) is an oncogene produced by the alternative usage of the BRCA1 locus. IRIS is involved in induction of replication, transcription of selected oncogenes, and promoting breast cancer cells aggressiveness. Here, we demonstrate that IRIS overexpression (IRISOE) promotes TNBCs through suppressing BRCA1 expression, enhancing basal-biomarkers, EMT-inducers, and stemness-enforcers expression. IRISOE also activates the TIC phenotype in TNBC cells through elevating CD44 and ALDH1 expression/activity and preventing CD24 surface presentation by activating the internalization pathway EGFR→c-Src→cortactin. We show that the intrinsic sensitivity to an anti-CD24 cross-linking antibody-induced cell death in membranous CD24 expressing/luminal A cells could be acquired in cytoplasmic CD24 expressing IRISOE TNBC/TIC cells through IRIS silencing or inactivation. We show that fewer IRISOE TNBC/TICs cells form large tumors composed of TICs, resembling TNBCs early lesions in patients that contain metastatic precursors capable of disseminating and metastasizing at an early stage of the disease. IRIS-inhibitory peptide killed these IRISOE TNBC/TICs, in vivo and prevented their dissemination and metastasis. We propose IRIS inactivation could be pursued to prevent dissemination and metastasis from early TNBC tumor lesions in patients. PMID:28052035

NON-NEOPLASTIC LESIONS: USE OF DATA FROM PRE- OR NON-NEOPLASTIC LESIONS THAT MAY INDICATE POTENTIAL FOR CARCINOGENESIS

EPA Science Inventory

The Toxicology and Microbiology Division of the US EPA, Health Effects Research Laboratory has initiated a research program to develop a matrix of short-term tests to distinguish carcinogens from non-carcinogens among genotoxic substances and to develop methods for predicting rel...

RAG-induced DNA lesions activate proapoptotic BIM to suppress lymphomagenesis in p53-deficient mice

PubMed Central

Herold, Marco J.

2016-01-01

Neoplastic transformation is driven by oncogenic lesions that facilitate unrestrained cell expansion and resistance to antiproliferative signals. These oncogenic DNA lesions, acquired through errors in DNA replication, gene recombination, or extrinsically imposed damage, are thought to activate multiple tumor suppressive pathways, particularly apoptotic cell death. DNA damage induces apoptosis through well-described p53-mediated induction of PUMA and NOXA. However, loss of both these mediators (even together with defects in p53-mediated induction of cell cycle arrest and cell senescence) does not recapitulate the tumor susceptibility observed in p53−/− mice. Thus, potentially oncogenic DNA lesions are likely to also trigger apoptosis through additional, p53-independent processes. We found that loss of the BH3-only protein BIM accelerated lymphoma development in p53-deficient mice. This process was negated by concomitant loss of RAG1/2-mediated antigen receptor gene rearrangement. This demonstrates that BIM is critical for the induction of apoptosis caused by potentially oncogenic DNA lesions elicited by RAG1/2-induced gene rearrangement. Furthermore, this highlights the role of a BIM-mediated tumor suppressor pathway that acts in parallel to the p53 pathway and remains active even in the absence of wild-type p53 function, suggesting this may be exploited in the treatment of p53-deficient cancers. PMID:27621418

A Case of Suspicious Gangliocytoma with Heterogeneously Distributed Lesions in the Thalamus and Basal Ganglia.

PubMed

Miyake, Yohei; Mishima, Kazuhiko; Suzuki, Tomonari; Adachi, Jun-Ichi; Sasaki, Atsushi; Nishikawa, Ryo

2018-04-01

We report a case of a 24-year-old woman who presented with an uncomfortable feeling in her right foot with a 6-month history of slight weakness in her right hand. Neuroimaging demonstrated irregular shaped lesions in the left thalamus and basal ganglia in addition to spotty lesions in the contralateral thalamus. The MRI showed high-intensity signals on T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted images. The lesions demonstrated low-intensity signaling on T1-weighted images and were slightly enhanced with gadolinium. Other examinations including positron emission tomography, MR spectroscopy, and laboratory tests did not reveal any specific information regarding the lesions. The biopsied specimens, from the left basal ganglia, revealed proliferation of dysplastic neuronal cells without any neoplastic glial elements; thus, gangliocytoma (WHO grade I) was the most likely diagnosis. The patient was further observed based on this diagnosis of suspicious gangliocytoma, and the follow-up MRI, performed a year after the biopsy, revealed that the disease was stable. To our knowledge, gangliocytoma in the thalamus and basal ganglia have not been reported. Additionally, the findings of the magnetic resonance imaging (MRI) in this case were unique and different from those previously reported in cases of gangliocytoma. The authors report this unique case and discuss the radiological, pathological, and genetic findings.

A Case of Suspicious Gangliocytoma with Heterogeneously Distributed Lesions in the Thalamus and Basal Ganglia

PubMed Central

Miyake, Yohei; Mishima, Kazuhiko; Suzuki, Tomonari; Adachi, Jun-ichi; Sasaki, Atsushi; Nishikawa, Ryo

2018-01-01

We report a case of a 24-year-old woman who presented with an uncomfortable feeling in her right foot with a 6-month history of slight weakness in her right hand. Neuroimaging demonstrated irregular shaped lesions in the left thalamus and basal ganglia in addition to spotty lesions in the contralateral thalamus. The MRI showed high-intensity signals on T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted images. The lesions demonstrated low-intensity signaling on T1-weighted images and were slightly enhanced with gadolinium. Other examinations including positron emission tomography, MR spectroscopy, and laboratory tests did not reveal any specific information regarding the lesions. The biopsied specimens, from the left basal ganglia, revealed proliferation of dysplastic neuronal cells without any neoplastic glial elements; thus, gangliocytoma (WHO grade I) was the most likely diagnosis. The patient was further observed based on this diagnosis of suspicious gangliocytoma, and the follow-up MRI, performed a year after the biopsy, revealed that the disease was stable. To our knowledge, gangliocytoma in the thalamus and basal ganglia have not been reported. Additionally, the findings of the magnetic resonance imaging (MRI) in this case were unique and different from those previously reported in cases of gangliocytoma. The authors report this unique case and discuss the radiological, pathological, and genetic findings. PMID:29725570

Screening for high risk human papilloma virus (HR-HPV) subtypes, among Sudanese patients with oral lesions.

PubMed

Babiker, Ali Yousif; Eltom, Faris Margani; Abdalaziz, Mohamed S; Rahmani, Arshad; Abusail, Saadalnour; Ahmed, Hussain Gadelkareem

2013-01-01

HR-HPV subtypes are strongly linked to etiology of many human cancers including oral cancer. The epidemiology of infection with different HPV genotypes greatly varies in different countries. The aim of this study was to identify and genotype the HR-HPV subtypes in oral tissues obtained from Sudanese patients with oral lesions. In this retrospective study 200 patients with oral lesions were screened by molecular methods (PCR) for the presence of HR-HPV subtypes. Of the 200 patients, 100/200 were patients with oral cancer (ascertained as case group) and 100/200 were patients with non-neoplastic oral lesions (ascertained as control group). Out of the 200 patients, 12/200 (6%) were found with HR-HPV infection. Of the 12 positive patients, 8/12 (66.7%) were among cases and the remaining 4/12 (33.3%) were among control group. The distribution of different genotypes was: type HPV 16 6/12 (50%), HPV18 4/12 (34%), HPV 31 1/12 (8%) and HPV 33 1/12 (8%). In view of these findings, HPV particularly subtypes 16 and 18 play a role in the etiology of oral cancer in the Sudan.

Selective amplification of T-cell receptor variable region species is demonstrable but not essential in early lesions of psoriasis vulgaris: analysis by anchored polymerase chain reaction and hypervariable region size spectratyping.

PubMed

Vekony, M A; Holder, J E; Lee, A J; Horrocks, C; Eperon, I C; Camp, R D

1997-07-01

Several groups have investigated the role of T cells in the pathogenesis of psoriasis by determination of T-cell receptor (TCR) B-chain variable (V) region usage, both in chronic plaque (psoriasis vulgaris) and guttate forms, with various results. Because there are no data on TCR expression in early psoriasis vulgaris, when specific cellular immune events may be expected to be most pronounced, we have analyzed early lesions (less than 3 wk old) of ten patients, with highly reproducible results. We have developed a highly controlled anchored polymerase chain reaction (PCR) method in which TCR beta chain species are all amplified with the same primer pair and products are quantified by dot blot hybridization with BV family-specific oligonucleotide probes. Overexpression of certain TCR BV genes was observed in the majority of lesional biopsies, but in samples in which the expanded BV family formed more than 10% of total lesional BV (half of the samples analyzed), BV2 and BV6 predominated. The consistency of overexpression of these BV species between patients was much less than in previous studies of TCRBV usage in established chronic plaque psoriasis lesions. Complementarity-determining region 3 (CDR3) size spectratyping demonstrated evidence for selective clonal T cell accumulation in less than half of the lesional samples showing BV expansion. These results indicate that selective amplification of TCRBV species occurs in early psoriasis vulgaris but is not essential to the pathogenic process and may be more important in the maintenance or expansion of chronic lesions.

The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer

PubMed Central

Antonio, Nicole; Bønnelykke-Behrndtz, Marie Louise; Ward, Laura Chloe; Collin, John; Christensen, Ib Jarle; Steiniche, Torben; Schmidt, Henrik; Feng, Yi; Martin, Paul

2015-01-01

There is a long-standing association between wound healing and cancer, with cancer often described as a “wound that does not heal”. However, little is known about how wounding, such as following surgery, biopsy collection or ulceration, might impact on cancer progression. Here, we use a translucent zebrafish larval model of RasG12V-driven neoplasia to image the interactions between inflammatory cells drawn to a wound, and to adjacent pre-neoplastic cells. We show that neutrophils are rapidly diverted from a wound to pre-neoplastic cells and these interactions lead to increased proliferation of the pre-neoplastic cells. One of the wound-inflammation-induced trophic signals is prostaglandin E2 (PGE2). In an adult model of chronic wounding in zebrafish, we show that repeated wounding with subsequent inflammation leads to a greater incidence of local melanoma formation. Our zebrafish studies led us to investigate the innate immune cell associations in ulcerated melanomas in human patients. We find a strong correlation between neutrophil presence at sites of melanoma ulceration and cell proliferation at these sites, which is associated with poor prognostic outcome. PMID:26136213

Neoplastic sigmoid-uterine fistula. An exceptional complication of large intestine cancer

PubMed Central

ZANGHÌ, G.; LEANZA, V.; VECCHIO, R.; D’AGATI, A.; CORDOVA, S.; RINZIVILLO, N.M.; LODATO, M.; LEANZA, G.

2017-01-01

Neoplastic sigmoid-uterine fistula is an extremely rare condition because the uterus is a thick and muscular organ. A 74-year-old woman was admitted to the First Aid Station suffering from abdominal pain and foul smelling vaginal discharge. Gynaecological examination showed fecal drainage from the cervical orifice, while the uterus was regular in size but very firm and painful. Ovaries and fallopian tubes were not palpable owing to abdominal tenderness. Ultrasounds reveled inhomogeneous thickening of uterine cavity, without detecting fistula. Contrast Medium CT (CMCT) showed Douglas’ recto-uterine pouch occluded. The sigmoid wall was very thin exception a site where a fistula was suspected. At the surgery severe adhesions of the sigma-rectum with the posterior uterine wall were observed. After adhesiolysis, 18 cm colon-sigma-rectum was removed. Total hysterectomy with salpingooophorectomy was performed. Lymphadenectomy ended the procedure. Anatomical specimen confirmed sigmoid-uterine fistula. At histology a mildly differentiated adenocarcinoma of sigma-rectum was shown. Postoperative course was uneventful. Such a case of neoplastic sigmoid-uterine fistula has not been reported so far. PMID:28460202

Hyperspectral imaging of neoplastic progression in a mouse model of oral carcinogenesis

NASA Astrophysics Data System (ADS)

Lu, Guolan; Qin, Xulei; Wang, Dongsheng; Muller, Susan; Zhang, Hongzheng; Chen, Amy; Chen, Zhuo Georgia; Fei, Baowei

2016-03-01

Hyperspectral imaging (HSI) is an emerging modality for medical applications and holds great potential for noninvasive early detection of cancer. It has been reported that early cancer detection can improve the survival and quality of life of head and neck cancer patients. In this paper, we explored the possibility of differentiating between premalignant lesions and healthy tongue tissue using hyperspectral imaging in a chemical induced oral cancer animal model. We proposed a novel classification algorithm for cancer detection using hyperspectral images. The method detected the dysplastic tissue with an average area under the curve (AUC) of 0.89. The hyperspectral imaging and classification technique may provide a new tool for oral cancer detection.

Design and characterization of a handheld multimodal imaging device for the assessment of oral epithelial lesions

NASA Astrophysics Data System (ADS)

Higgins, Laura M.; Pierce, Mark C.

2014-08-01

A compact handpiece combining high resolution fluorescence (HRF) imaging with optical coherence tomography (OCT) was developed to provide real-time assessment of oral lesions. This multimodal imaging device simultaneously captures coregistered en face images with subcellular detail alongside cross-sectional images of tissue microstructure. The HRF imaging acquires a 712×594 μm2 field-of-view at the sample with a spatial resolution of 3.5 μm. The OCT images were acquired to a depth of 1.5 mm with axial and lateral resolutions of 9.3 and 8.0 μm, respectively. HRF and OCT images are simultaneously displayed at 25 fps. The handheld device was used to image a healthy volunteer, demonstrating the potential for in vivo assessment of the epithelial surface for dysplastic and neoplastic changes at the cellular level, while simultaneously evaluating submucosal involvement. We anticipate potential applications in real-time assessment of oral lesions for improved surveillance and surgical guidance.

[Iatrogenic biliary lesions and stenosis].

PubMed

Latteri, S; Vecchio, R; Angilello, A

1997-01-01

Pathogenetic, diagnostic and therapeutic aspects of postoperative bile duct injuries are reviewed. Treatment options are discussed in relation to the time of diagnosis. Lesions detected during the same operation must be immediately repaired through an end-to-end biliary anastomosis or a bilioenteric anastomosis. In limited lesions of the bile duct a T-tube placement should be sufficient. Bile duct lesions recognized postoperatively can be managed through a multimodal surgical, endoscopic, and radiologic approach. In the early postoperative period, surgery is indicated when a complete section of the biliary tract or a severe peritonitis is recognized, or when endoscopic and radiologic treatment has failed. Surgery is also the treatment of choice in the late complete stenosis of the bile duct. Roux-en-Y hepatico-jejunostomy is the most common surgical procedure for the treatment of bile duct lesions and strictures. However, in high bile duct lesions, especially if the risk of anastomotic dehiscence is increased the Authors emphasize the Rodney-Smith technique for the reconstruction of the biliary tract.

Absence of a dose-fractionation effect on neoplastic transformation induced by fission-spectrum neutrons in C3H 10T1/2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saran, A.; Pazzaglia, S.; Coppola, M.

1991-06-01

We have investigated the effect of fission-spectrum neutron dose fractionation on neoplastic transformation of exponentially growing C3H 10T1/2 cells. Total doses of 10.8, 27, 54, and 108 cGy were given in single doses or in five equal fractions delivered at 24-h intervals in the biological channel of the RSV-TAPIRO reactor at CRE-Casaccia. Both cell inactivation and neoplastic transformation were more effectively induced by fission neutrons than by 250-kVp X rays. No significant effect on cell survival or neoplastic transformation was observed with split doses compared to single doses of fission-spectrum neutrons. Neutron RBE values relative to X rays determined frommore » data for survival and neoplastic transformation were comparable.« less

Effectiveness of computer-aided diagnosis of colorectal lesions using novel software for magnifying narrow-band imaging: a pilot study.

PubMed

Tamai, Naoto; Saito, Yutaka; Sakamoto, Taku; Nakajima, Takeshi; Matsuda, Takahisa; Sumiyama, Kazuki; Tajiri, Hisao; Koyama, Ryosuke; Kido, Shoji

2017-08-01

 Magnifying narrow-band imaging (M-NBI) enables detailed observation of microvascular architecture and can be used in endoscopic diagnosis of colorectal lesion. However, in clinical practice, differential diagnosis and estimation of invasion depth of colorectal lesions based on M-NBI findings require experience. Therefore, developing computer-aided diagnosis (CAD) for M-NBI would be beneficial for clinical practice. The aim of this study was to evaluate the effectiveness of software for CAD of colorectal lesions. In collaboration with Yamaguchi University, we developed novel software that enables CAD of colorectal lesions using M-NBI images. This software for CAD further specifically divides original Sano's colorectal M-NBI classification into 3 groups (group A, capillary pattern [CP] type I; group B, CP type II + CP type IIIA; group C, CP type IIIB), which describe hyperplastic polyps (HPs), adenoma/adenocarcinoma (intramucosal [IM] to submucosal [SM]-superficial) lesions, and SM-deep lesions, respectively. We retrospectively reviewed 121 lesions evaluated using M-NBI. The 121 reviewed lesions included 21 HP, 80 adenoma/adenocarcinoma (IM to SM-superficial), and 20 SM-deep lesions. The concordance rate between the CAD and the diagnosis of the experienced endoscopists was 90.9 %. The sensitivity, specificity, positive and negative predictive values, and accuracy of the CAD for neoplastic lesions were 83.9 %, 82.6 %, 53.1 %, 95.6 %, and 82.8 %, respectively. The values for SM-deep lesions were 83.9 %, 82.6 %, 53.1 %, 95.6 %, and 82.8 %, respectively.  Relatively high diagnostic values were obtained using CAD. This software for CAD could possibly lead to a wider use of M-NBI in the endoscopic diagnosis of colorectal lesions.

Impact of Prostate Inflammation on Lesion Development in the POET3+Pten+/− Mouse Model of Prostate Carcinogenesis

PubMed Central

Burcham, Grant N.; Cresswell, Gregory M.; Snyder, Paul W.; Chen, Long; Liu, Xiaoqi; Crist, Scott A.; Henry, Michael D.; Ratliff, Timothy L.

2015-01-01

Evidence linking prostatitis and prostate cancer development is contradictory. To study this link, the POET3 mouse, an inducible model of prostatitis, was crossed with a Pten-loss model of prostate cancer (Pten+/−) containing the ROSA26 luciferase allele to monitor prostate size. Prostatitis was induced, and prostate bioluminescence was tracked over 12 months, with lesion development, inflammation, and cytokine expression analyzed at 4, 8, and 12 months and compared with mice without induction of prostatitis. Acute prostatitis led to more proliferative epithelium and enhanced bioluminescence. However, 4 months after initiation of prostatitis, mice with induced inflammation had lower grade pre-neoplastic lesions. A trend existed toward greater development of carcinoma 12 months after induction of inflammation, including one of two mice with carcinoma developing perineural invasion. Two of 18 mice at the later time points developed lesions with similarities to proliferative inflammatory atrophy, including one mouse with associated carcinoma. Pten+/− mice developed spontaneous inflammation, and prostatitis was similar among groups of mice at 8 and 12 months. Analyzed as one cohort, lesion number and grade were positively correlated with prostatitis. Specifically, amounts of CD11b+Gr1+ cells were correlated with lesion development. These results support the hypothesis that myeloid-based inflammation is associated with lesion development in the murine prostate, and previous bouts of CD8-driven prostatitis may promote invasion in the Pten+/− model of cancer. PMID:25455686

CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer

PubMed Central

Srivastava, Supriya; Samanta, Animesh; Sharma, Neel; Tan, Kar Tong; Yang, Henry; Voon, Dominic C.; Pang, Brendan; Teh, Ming; Murata-Kamiya, Naoko; Hatakeyama, Masanori; Chang, Young-Tae; Yong, Wei Peng; Ito, Yoshiaki; Ho, Khek Yu; Tan, Patrick; Soong, Richie; Koeffler, Phillip H.; Yeoh, Khay Guan; Jeyasekharan, Anand D.

2016-01-01

Early detection of gastric cancers saves lives, but remains a diagnostic challenge. In this study, we aimed to identify cell-surface biomarkers of early gastric cancer. We hypothesized that a subset of plasma membrane proteins induced by the Helicobacter pylori oncoprotein CagA will be retained in early gastric cancers through non-oncogene addiction. An inducible system for expression of CagA was used to identify differentially upregulated membrane protein transcripts in vitro. The top hits were then analyzed in gene expression datasets comparing transcriptome of gastric cancer with normal tissue, to focus on markers retained in cancer. Among the transcripts enriched upon CagA induction in vitro, a significant elevation of CEACAM6 was noted in gene expression datasets of gastric cancer. We used quantitative digital immunohistochemistry to measure CEACAM6 protein levels in tissue microarrays of gastric cancer. We demonstrate an increase in CEACAM6 in early gastric cancers, when compared to matched normal tissue, with an AUC of 0.83 for diagnostic validity. Finally, we show that a fluorescently conjugated CEACAM6 antibody binds avidly to freshly resected gastric cancer xenograft samples and can be detected by endoscopy in real time. Together, these results suggest that CEACAM6 upregulation is a cell surface response to H. pylori CagA, and is retained in early gastric cancers. They highlight a novel link between CEACAM6 expression and CagA in gastric cancer, and suggest CEACAM6 to be a promising biomarker to aid with the fluorescent endoscopic diagnosis of early neoplastic lesions in the stomach. PMID:27421133

Selective binding of lectins to normal and neoplastic urothelium in rat and mouse bladder carcinogenesis models.

PubMed

Zupančič, Daša; Kreft, Mateja Erdani; Romih, Rok

2014-01-01

Bladder cancer adjuvant intravesical therapy could be optimized by more selective targeting of neoplastic tissue via specific binding of lectins to plasma membrane carbohydrates. Our aim was to establish rat and mouse models of bladder carcinogenesis to investigate in vivo and ex vivo binding of selected lectins to the luminal surface of normal and neoplastic urothelium. Male rats and mice were treated with 0.05 % N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water and used for ex vivo and in vivo lectin binding experiments. Urinary bladder samples were also used for paraffin embedding, scanning electron microscopy and immunofluorescence labelling of uroplakins. During carcinogenesis, the structure of the urinary bladder luminal surface changed from microridges to microvilli and ropy ridges and the expression of urothelial-specific glycoproteins uroplakins was decreased. Ex vivo and in vivo lectin binding experiments gave comparable results. Jacalin (lectin from Artocarpus integrifolia) exhibited the highest selectivity for neoplastic compared to normal urothelium of rats and mice. The binding of lectin from Amaranthus caudatus decreased in rat model and increased in mouse carcinogenesis model, indicating interspecies variations of plasma membrane glycosylation. Lectin from Datura stramonium showed higher affinity for neoplastic urothelium compared to the normal in rat and mouse model. The BBN-induced animal models of bladder carcinogenesis offer a promising approach for lectin binding experiments and further lectin-mediated targeted drug delivery research. Moreover, in vivo lectin binding experiments are comparable to ex vivo experiments, which should be considered when planning and optimizing future research.

[Bile duct lesions in laparoscopic cholecystectomy].

PubMed

Siewert, J R; Ungeheuer, A; Feussner, H

1994-09-01

Laparoscopic cholecystectomy is both resulting in a slightly higher incidence of biliary lesions and a change of prevalence of the type of lesions. Damage to the biliary system occurs in 4 different types: The most severe case is the lesion with a structural defect of the hepatic or common bile duct with (IVa) or without (IVb) vascular injury. Tangential lesions without structural loss of the duct should be denominated as type III (IIIa with additional lesion to the vessels, type IIIb without). Type II comprehends late strictures without obvious intraoperative trauma to the duct. Type I includes immediate biliary fistulae of usually good prognosis. The increasing prevalence of structural defects of the bile ducts appears to be a peculiarity of laparoscopic cholecystectomy necessitating highly demanding operative repair. In the majority of cases, hepatico-jejunostomy or even intraparenchymatous anastomoses are required. Adaptation of well proven principles of open surgery is the best prevention of biliary lesions in laparoscopic cholecystectomy as well as the readiness to convert early to the open procedure.

Analysis of gingival biopsies in the Gujarati population: a retrospective study.

PubMed

Manjunatha, Bhari Sharanesha; Sutariya, Rakesh; Nagamahita, V; Dholia, Bhavik; Shah, Vandana

2014-01-01

Biopsy is an important diagnostic tool used in the diagnosis of lesions ranging from simple non-neoplastic, tumor-like lesions to malignancies, and is often the only way to diagnose oral lesions and diseases. The gingiva is the most common site for some kind of irritation or low-grade injury, resulting in localized overgrowths that are considered to be reactive and non-neoplastic lesions. This aim of this study is to analyze the frequency and distribution of gingival lesions in the Gujarati population. In this retrospective study, gingival biopsies submitted for a period of five years were included. Microscopic slides of all the cases were reviewed by two observers for confirmation of the diagnosis. Among the 106 cases of gingival biopsies, the most frequent category of lesions encountered was the non-neoplastic category, which accounted for 73.58% of the cases. Both benign and malignant neoplasms constituted 26.42% of the cases. Among the non-neoplastic lesions, Pyogenic granuloma was the most frequent lesion (38.46%), followed by fibrous hyperplasia (20.51%), inflammatory hyperplasia (19.23%), and Epulis (8.97%). Neoplasms accounted for 26.42% of the gingival biopsies (92.85% benign and 7.15% malignant). Among the benign neoplastic lesions, Fibroma (30.76%) and Fibrolipoma (26.92%) were the most frequent, followed by peripheral ossifying fibroma (23.08%) and peripheral giant cell granuloma (11%). It is difficult to compare studies carried out in various countries due to differences in people's attitudes toward oral health and the accessibility of various population groups to biopsy services. Nevertheless, this study has provided some information about the frequency and distribution of biopsied gingival lesions in the Gujarati population over a period of five years.

Imaging inflammatory acne: lesion detection and tracking

NASA Astrophysics Data System (ADS)

Cula, Gabriela O.; Bargo, Paulo R.; Kollias, Nikiforos

2010-02-01

It is known that effectiveness of acne treatment increases when the lesions are detected earlier, before they could progress into mature wound-like lesions, which lead to scarring and discoloration. However, little is known about the evolution of acne from early signs until after the lesion heals. In this work we computationally characterize the evolution of inflammatory acne lesions, based on analyzing cross-polarized images that document acne-prone facial skin over time. Taking skin images over time, and being able to follow skin features in these images present serious challenges, due to change in the appearance of skin, difficulty in repositioning the subject, involuntary movement such as breathing. A computational technique for automatic detection of lesions by separating the background normal skin from the acne lesions, based on fitting Gaussian distributions to the intensity histograms, is presented. In order to track and quantify the evolution of lesions, in terms of the degree of progress or regress, we designed a study to capture facial skin images from an acne-prone young individual, followed over the course of 3 different time points. Based on the behavior of the lesions between two consecutive time points, the automatically detected lesions are classified in four categories: new lesions, resolved lesions (i.e. lesions that disappear completely), lesions that are progressing, and lesions that are regressing (i.e. lesions in the process of healing). The classification our methods achieve correlates well with visual inspection of a trained human grader.

Polypoid lesions of the gallbladder: report of 160 cases with special reference to diagnosis and treatment in China

PubMed Central

Guo, Jingjing; Wu, Gang; Zhou, Zhongwen

2015-01-01

Background: The preoperative diagnosis of gallbladder polypoid lesions is difficult, justifying the lack of consensus on the appropriate treatment. Objective: The aim of this study was to identify the characteristics of each type of polypoid lesion of the gallbladder and the indications for surgery. Methods: Between January 1999 and December 2012, clinical data were retrospectively correlated with the histopathologic characteristics of polypoid lesions in 160 patients who underwent cholecystectomy. Results: A total of 160 patients with benign polypoid lesions (including 49 tumor-like lesions and 75 adenomas) and 14 patients with malignant polypoid lesions (including 2 adenocarcinomas and 12 adenomas with malignant changes) were included in this study. One hundred and five (65.6%) of the patients had associated symptoms, and 70 (43.8%) had gallstones. Of the 49 patients with tumor-like lesions, 49 (100%) were correlated with chronic cholecystitis. A total of 72 (83.8%) patients with neoplasms had a single polyp compared with 25 (59.5%) of those with non-neoplastic polyps. The mean age of the patients with malignancy was 59.07±13.465 years, and 12 (85.7%) of these patients were over 50 years of age. The mean diameters of the benign and malignant polyps were 1.0±0.77 cm and 2.15±1.16 cm, respectively. Ten (100%) of the patients with malignancy had polyps of over 1 cm in size, as shown by ultrasound. Conclusion: Our findings indicate that tumor-like lesions, adenomas, and adenocarcinomas are the most common polypoid lesions of the gallbladder. Cholecystecomy should be done in patients with symptoms. The risk of malignancy is high in patients over 50 years of age; those with polyps with diameters of greater than 10 mm; and those with single polypoid lesions. The remainder of PLG patients without cholecystectomy should be followed up at regular intervals. PMID:26617893

Polypoid lesions of the gallbladder: report of 160 cases with special reference to diagnosis and treatment in China.

PubMed

Guo, Jingjing; Wu, Gang; Zhou, Zhongwen

2015-01-01

The preoperative diagnosis of gallbladder polypoid lesions is difficult, justifying the lack of consensus on the appropriate treatment. The aim of this study was to identify the characteristics of each type of polypoid lesion of the gallbladder and the indications for surgery. Between January 1999 and December 2012, clinical data were retrospectively correlated with the histopathologic characteristics of polypoid lesions in 160 patients who underwent cholecystectomy. A total of 160 patients with benign polypoid lesions (including 49 tumor-like lesions and 75 adenomas) and 14 patients with malignant polypoid lesions (including 2 adenocarcinomas and 12 adenomas with malignant changes) were included in this study. One hundred and five (65.6%) of the patients had associated symptoms, and 70 (43.8%) had gallstones. Of the 49 patients with tumor-like lesions, 49 (100%) were correlated with chronic cholecystitis. A total of 72 (83.8%) patients with neoplasms had a single polyp compared with 25 (59.5%) of those with non-neoplastic polyps. The mean age of the patients with malignancy was 59.07 ± 13.465 years, and 12 (85.7%) of these patients were over 50 years of age. The mean diameters of the benign and malignant polyps were 1.0 ± 0.77 cm and 2.15 ± 1.16 cm, respectively. Ten (100%) of the patients with malignancy had polyps of over 1 cm in size, as shown by ultrasound. Our findings indicate that tumor-like lesions, adenomas, and adenocarcinomas are the most common polypoid lesions of the gallbladder. Cholecystecomy should be done in patients with symptoms. The risk of malignancy is high in patients over 50 years of age; those with polyps with diameters of greater than 10 mm; and those with single polypoid lesions. The remainder of PLG patients without cholecystectomy should be followed up at regular intervals.

Associations of dietary fat with risk of early neoplasia in the proximal colon in a population-based case-control study.

PubMed

Mo, Allen; Wu, Rong; Grady, James P; Hanley, Matthew P; Toro, Margaret; Swede, Helen; Devers, Thomas J; Hartman, Terryl J; Rosenberg, Daniel W

2018-07-01

Excess dietary fat consumption is strongly associated with the risk of colorectal cancer, but less is known about its role in the earliest stages of carcinogenesis, particularly within the proximal colon. In the following case-control study, we evaluated the relationship between the intake of dietary fats and the frequency of early proximal neoplasia [aberrant crypt foci (ACF) or polyps], detectable by high-definition colonoscopy with contrast dye-spray. Average-risk screening individuals underwent a high-definition colonoscopy procedure as part of larger ongoing clinical study of precancerous lesions in the proximal colon. Dietary fat intake was assessed using the Block Brief Food Frequency Questionnaire, which estimates average dietary intake based on 70 food items. The diets of individuals with no endoscopically identifiable lesions (n = 36) were compared to those with either ACF or polyps detected in the proximal colon. In multivariate analysis, high dietary intake of total polyunsaturated fatty acids (PUFAs) and intake of omega-6 and omega-3 fatty acids were positively associated with neoplastic lesions in the proximal colon. When comparing ACF and polyp groups separately, a positive association was observed for both proximal polyps (OR 2.28; CI 1.16-7.09) and ACF (OR 2.86; CI 1.16-7.09) for total PUFA intake. Furthermore, the prevalence of proximal ACF was increased with higher intake of omega-6 (OR 3.54; CI 1.32-9.47) and omega-3 fatty acids (OR 2.29; CI 1.02-5.13), although there was no discernible difference in the omega-6/omega-3 ratio. These results suggest that dietary PUFAs may be positively associated with risk of early neoplasia in the proximal colon. This study provides further evidence that dietary PUFA composition may play an important role in altering the microenvironment within the human colon.

Serum big endothelin-1 as a clinical marker for cardiopulmonary and neoplastic diseases in dogs.

PubMed

Fukumoto, Shinya; Hanazono, Kiwamu; Miyasho, Taku; Endo, Yoshifumi; Kadosawa, Tsuyoshi; Iwano, Hidetomo; Uchide, Tsuyoshi

2014-11-24

Many studies of human subjects have demonstrated the utility of assessing serum levels of endothelin-1 (ET-1) and big ET-1 as clinical biomarkers in cardiopulmonary and neoplastic diseases. In this study we explored the feasibility of using serum big ET-1 as a reliable veterinary marker in dogs with various cardiopulmonary and neoplastic diseases. Serum big ET-1 levels were measured by ELISA in dogs with cardiopulmonary (n=21) and neoplastic diseases (n=57). Dogs exhibiting cardiopulmonary disease were divided into two groups based on the velocity of tricuspid valve regurgitation (3.0>m/s) measured by ultrasound: without and with pulmonary hypertension. Big ET-1 levels for the dogs with the diseases were compared with levels in normal healthy dogs (n=17). Dogs with cardiopulmonary disease (4.6±4.6 pmol/l) showed a significantly (P<0.01) higher level of big ET-1 than healthy control dogs (1.1±0.53 pmol/l). Serum levels in the dogs with pulmonary hypertension (6.2±5.3 pmol/l) were significantly (P<0.01) higher than those without pulmonary hypertension (2.0±0.6 pmol/l). Dogs with hemangiosarcoma (5.6±2.2 pmol/l), adenocarcinoma (2.0±1.8 pmol/l), histiocytic sarcoma (3.3±1.9 pmol/l), chondrosarcoma or osteosarcoma (3.0±1.6 pmol/l) and hepatocellular carcinoma (2.7±1.8 pmol/l) showed significantly (P<0.05) higher levels than healthy control dogs. These findings point to the potential of serum big ET-1 as a clinical marker for cardiopulmonary and neoplastic diseases in dogs. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues.

PubMed

Morimoto, Ryo; Satoh, Fumitoshi; Murakami, Osamu; Hirose, Takuo; Totsune, Kazuhito; Imai, Yutaka; Arai, Yoichi; Suzuki, Takashi; Sasano, Hironobu; Ito, Sadayoshi; Takahashi, Kazuhiro

2008-07-01

Adrenomedullin 2/intermedin (AM2/IMD) is a new member of calcitonin/calcitonin gene-related peptide family. AM is expressed in various tumors including adrenocortical tumors and modulates tumor growth. The AM2/IMD expression has not been studied, however, in adrenal tumors. The expression of AM2/IMD and AM was therefore studied in human adrenal tumors and attached non-neoplastic adrenal tissues by immunocytochemistry (ICC). Immunoreactive (IR)-AM2/IMD was measured by RIA. Furthermore, the expression of AM2/IMD and its receptor components, calcitonin receptor-like receptor (CRLR), and receptor activity-modifying proteins (RAMPs) 1, 2, and 3 mRNA in these tissues was studied by reverse transcription PCR (RT-PCR). ICC showed that AM2/IMD and AM immunoreactivities were localized in adrenocortical tumors and pheochromocytomas. AM2/IMD and AM immunoreactivities were detected in medulla of attached non-neoplastic tissues, while the degree of immunoreactivity for AM2/IMD and AM in cortices of attached adrenals was relatively weak or undetectable. RIA detected IR-AM2/IMD in adrenal tumors (0.414+/-0.12 to 0.786+/-0.27 pmol/g wet weight, mean+/-S.E.M.) and attached adrenal tissues (0.397+/-0.052 pmol/g wet weight). Reverse-phase high-performance liquid chromatography showed one broad peak eluted in the similar position to synthetic AM2/IMD with several minor peaks. RT-PCR showed expression of AM2/IMD, CRLR, and RAMP1, RAMP2, and RAMP3 mRNA in tissues of adrenal tumors and attached adrenal glands. In conclusion, AM2/IMD is expressed in human adrenal tumors and attached non-neoplastic adrenal tissues and may play (patho-)physiological roles in normal and neoplastic adrenals as an autocrine/paracrine regulator.

Border preserving skin lesion segmentation

NASA Astrophysics Data System (ADS)

Kamali, Mostafa; Samei, Golnoosh

2008-03-01

Melanoma is a fatal cancer with a growing incident rate. However it could be cured if diagnosed in early stages. The first step in detecting melanoma is the separation of skin lesion from healthy skin. There are particular features associated with a malignant lesion whose successful detection relies upon accurately extracted borders. We propose a two step approach. First, we apply K-means clustering method (to 3D RGB space) that extracts relatively accurate borders. In the second step we perform an extra refining step for detecting the fading area around some lesions as accurately as possible. Our method has a number of novelties. Firstly as the clustering method is directly applied to the 3D color space, we do not overlook the dependencies between different color channels. In addition, it is capable of extracting fine lesion borders up to pixel level in spite of the difficulties associated with fading areas around the lesion. Performing clustering in different color spaces reveals that 3D RGB color space is preferred. The application of the proposed algorithm to an extensive data-base of skin lesions shows that its performance is superior to that of existing methods both in terms of accuracy and computational complexity.

M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells.

PubMed

Hara, Yasushi; Obata, Yuuki; Horikawa, Keita; Tasaki, Yasutaka; Suzuki, Kyohei; Murata, Takatsugu; Shiina, Isamu; Abe, Ryo

2017-01-01

Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib. Recently, we showed that in neoplastic mast cells that endogenously express an imatinib-resistant Kit mutant, Kit causes oncogenic activation of the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway and the signal transducer and activator of transcription 5 (STAT5) but only on endolysosomes and on the endoplasmic reticulum (ER), respectively. Here, we show a strategy for inhibition of the Kit-PI3K-Akt pathway in neoplastic mast cells by M-COPA (2-methylcoprophilinamide), an inhibitor of this secretory pathway. In M-COPA-treated cells, Kit localization in the ER is significantly increased, whereas endolysosomal Kit disappears, indicating that M-COPA blocks the biosynthetic transport of Kit from the ER. The drug greatly inhibits oncogenic Akt activation without affecting the association of Kit with PI3K, indicating that ER-localized Kit-PI3K complex is unable to activate Akt. Importantly, M-COPA but not imatinib suppresses neoplastic mast cell proliferation through inhibiting anti-apoptotic Akt activation. Results of our M-COPA treatment assay show that Kit can activate Erk not only on the ER but also on other compartments. Furthermore, Tyr568/570, Tyr703, Tyr721, and Tyr936 in Kit are phosphorylated on the ER, indicating that these five tyrosine residues are all phosphorylated before mutant Kit reaches the plasma membrane (PM). Our study provides evidence that Kit is tyrosine-phosphorylated soon after synthesis on the ER but is unable to

M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells

PubMed Central

Hara, Yasushi; Obata, Yuuki; Horikawa, Keita; Tasaki, Yasutaka; Suzuki, Kyohei; Murata, Takatsugu; Shiina, Isamu; Abe, Ryo

2017-01-01

Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib. Recently, we showed that in neoplastic mast cells that endogenously express an imatinib-resistant Kit mutant, Kit causes oncogenic activation of the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway and the signal transducer and activator of transcription 5 (STAT5) but only on endolysosomes and on the endoplasmic reticulum (ER), respectively. Here, we show a strategy for inhibition of the Kit-PI3K-Akt pathway in neoplastic mast cells by M-COPA (2-methylcoprophilinamide), an inhibitor of this secretory pathway. In M-COPA-treated cells, Kit localization in the ER is significantly increased, whereas endolysosomal Kit disappears, indicating that M-COPA blocks the biosynthetic transport of Kit from the ER. The drug greatly inhibits oncogenic Akt activation without affecting the association of Kit with PI3K, indicating that ER-localized Kit-PI3K complex is unable to activate Akt. Importantly, M-COPA but not imatinib suppresses neoplastic mast cell proliferation through inhibiting anti-apoptotic Akt activation. Results of our M-COPA treatment assay show that Kit can activate Erk not only on the ER but also on other compartments. Furthermore, Tyr568/570, Tyr703, Tyr721, and Tyr936 in Kit are phosphorylated on the ER, indicating that these five tyrosine residues are all phosphorylated before mutant Kit reaches the plasma membrane (PM). Our study provides evidence that Kit is tyrosine-phosphorylated soon after synthesis on the ER but is unable to

[Vascular lesions of vocal folds--part 1: horizontal vascular lesions].

PubMed

Voigt-Zimmermann, S; Arens, C

2014-12-01

In recent decades, the endoscopic methods and technologies for laryngeal examination have improved so much that not only epithelial changes, but also vascular changes are recognizable at earlier stages. When comparing newer and older literature, the associated increasingly differentiated descriptions of such visible vascular changes of the vocal folds lead to terminological blurring and shifts of meaning. This complicates the technical-scientific discourse. The aim of the present work is a theoretical and conceptual clarification of early vascular changes of vocal folds. Horizontal changes of benigne vascular diseases, e. g. vessel ectasia, meander, increasing number and branching of vessels, change of direction may develop in to manifest vascular lesions, like varicosis, polyps and in case of ruptures to haemorrhages of vocal folds. These beginning and reversible vascular changes, when early detected and discussed basing on etiological knowledge, may lead to more differentiated prognostic statements and adequate therapeutic decisions, e. g. phonosurgery, functional voice therapy, voice hygiene and voice rest. Vertical vascular changes, like vessel loops, occur primarily in laryngeal papilloma, pre-cancerous and cancerous changes of the vocal folds. Already in small cancerous lesions of the vocal folds the vascular architecture is completely destroyed. © Georg Thieme Verlag KG Stuttgart · New York.

Crohn’s disease and extra intestinal granulomatous lesions.

PubMed

Tomasello, G; Scaglione, M; Mazzola, M; Gerges Geaga, A; Jurjus, A; Gagliardo, C; Sinagra, E; Damiani, P; Carini, F; Leone, A

2018-01-01

Crohn’s disease (CD) is an inflammatory bowel disease with a multifactorial etiology. Clinical features include mucosal erosion, diarrhea, weight loss and other complications such as formation of granuloma. In CD, granuloma is a non-neoplastic epithelioid lesion, formed by a compact aggregate of histiocytes with the absence of a central necrosis, however, the correlation among CD and the formation of granulomas is unknown. Many cases of granulomas in the extracellular site, related to CD, have been reported in the literature. These granulomas, at times, represented the only visible manifestation of the pathology. Extra intestinal granulomas have been found on ovaries, lungs, male genitalia, female genitalia, orofacial regions and skin. From the data in the literature it could be hypothesized that there is a cross-reaction of the immune system with similar antigenic epitopes belonging to different sites. This hypothesis, if checked, can place CD not only among inflammatory bowel disease but also among inflammatory diseases with systemic involvement.

Quantitative bone scan lesion area as an early surrogate outcome measure indicative of overall survival in metastatic prostate cancer.

PubMed

Brown, Matthew S; Kim, Grace Hyun J; Chu, Gregory H; Ramakrishna, Bharath; Allen-Auerbach, Martin; Fischer, Cheryce P; Levine, Benjamin; Gupta, Pawan K; Schiepers, Christiaan W; Goldin, Jonathan G

2018-01-01

A clinical validation of the bone scan lesion area (BSLA) as a quantitative imaging biomarker was performed in metastatic castration-resistant prostate cancer (mCRPC). BSLA was computed from whole-body bone scintigraphy at baseline and week 12 posttreatment in a cohort of 198 mCRPC subjects (127 treated and 71 placebo) from a clinical trial involving a different drug from the initial biomarker development. BSLA computation involved automated image normalization, lesion segmentation, and summation of the total area of segmented lesions on bone scan AP and PA views as a measure of tumor burden. As a predictive biomarker, treated subjects with baseline BSLA [Formula: see text] had longer survival than those with higher BSLA ([Formula: see text] and [Formula: see text]). As a surrogate outcome biomarker, subjects were categorized as progressive disease (PD) if the BSLA increased by a prespecified 30% or more from baseline to week 12 and non-PD otherwise. Overall survival rates between PD and non-PD groups were statistically different ([Formula: see text] and [Formula: see text]). Subjects without PD at week 12 had longer survival than subjects with PD: median 398 days versus 280 days. BSLA has now been demonstrated to be an early surrogate outcome for overall survival in different prostate cancer drug treatments.

Chronic toxic and carcinogenic effects of oral cadmium in the Noble (NBL/Cr) rat: induction of neoplastic and proliferative lesions of the adrenal, kidney, prostate, and testes.

PubMed

Waalkes, M P; Anver, M R; Diwan, B A

1999-10-29

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

Penile intraepithelial neoplasia and other premalignant lesions of the penis.

PubMed

Crispen, Paul L; Mydlo, Jack H

2010-08-01

Invasive penile cancer is an aggressive malignancy that often requires partial or complete penile amputation. Premalignant penile lesions, such as penile intraepithelial neoplasia, will have been present prior to the development of invasive disease in a substantial percentage of patients. Early detection and treatment of premalignant penile lesions may prevent malignant progression while avoiding penile amputation. This review focuses on premalignant penile lesions and the associations of these lesions with the development of invasive penile cancer. Copyright 2010 Elsevier Inc. All rights reserved.

PROPOSED DIAGNOSTIC CRITERIA FOR PROLIFERATIVE THYROID LESIONS IN BONY FISHES

EPA Science Inventory

Distinguishing hyperplastic lesions from neoplasia in the thyroid of bony fishes has been debated by scientists for about one hundred years. As early as the first decade of the last century, the histological interpretation of some of the striking proliferative lesions observed in...

Identification of the G protein-coupled estrogen receptor (GPER) in human prostate: expression site of the estrogen receptor in the benign and neoplastic gland.

PubMed

Rago, V; Romeo, F; Giordano, F; Ferraro, A; Carpino, A

2016-01-01

Estrogens are involved in growth, differentiation and pathogenesis of human prostate through the mediation of the classical estrogen receptors ERα and ERβ. The G protein-coupled estrogen receptor (GPER) is a 'novel' mediator of estrogen signaling which has been recently recognized in some human reproductive tissues, but its expression in the prostate gland is still unknown. Here, we investigated GPER in benign (from 5 patients) and neoplastic prostatic tissues (from 50 patients) by immunohistochemical analysis and Western blotting. Normal areas of benign prostates revealed a strong GPER immunoreactivity in the basal epithelial cells while luminal epithelial cells were unreactive and stromal cells were weakly immunostained. GPER was also immunolocalized in adenocarcinoma samples but the immunoreactivity of tumoral areas decreased from Gleason pattern 2 to Gleason pattern 4. Furthermore, a strong GPER immunostaining was also revealed in cells of pre-neoplastic lesions (high-grade prostatic intra-epithelial neoplasia). Western blot analysis of benign and tumor protein extracts showed the presence of a ~42 kDa band, consistent with the GPER molecular weight. An increase in both pAkt and p cAMP-response-binding protein (pCREB) levels was also observed in poorly differentiated PCa samples. Finally, this work identified GPER in the epithelial basal cells of benign human prostate, with a different localization with respect to the classical estrogen receptors. Furthermore, the expression of GPER in prostatic adenocarcinoma cells was also observed but with a modulation of the immunoreactivity according to tumor cell arrangements. © 2015 American Society of Andrology and European Academy of Andrology.

[High-risk HPV genotyping PCR testing as a means of cervical cancer and precancerous lesions early screening].

PubMed

Ma, Li; Cong, Xiao; Bian, Meilu; Shi, Mai; Wang, Xiuhong; Liu, Jun; Liu, Haiyan

2015-04-01

To explored high-risk HPV genotyping PCR testing whether as a feasible means for the early screening of cervical cancer and precancerous lesions. From January 2013 to June 2014, 15,192 outpatients in China-Japan Friendship Hospital voluntary were tested by high-risk type HPV genotyping PCR. The average age of them were (33±8) years old. High-risk HPV types genotyping PCR tested by fluorescence PCR technology, in which 13 kinds of high-risk HPV subtypes were detected, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68. A total of 4,315 cases of them were tested by the liquid-based cytology (LCT), among them with positive of high-risk HPV genotyping tested by PCR (n=2,366) were biopsy under colposcope (648 cases) in those LCT results were positive or LCT negative but HPV16 positive or LCT negative but had the clear clinical symptoms or and non-HPV16 positive but with clear clinical symptoms. (1) Analysis high-risk HPV infection status of 15 192 women. (2) As the pathological diagnosis was the gold standard in the diagnosis of cervical lesions, analysis of the relationship among high-risk HPV infection, virus loads and cervical lesions. (3) To evaluated the value of high-risk HPV genotyping PCR tested method in screening of cervical cancer and precancerous lesions. ⑴ Of 15,192 cases tested by high-risk HPV genotyping PCR, 2,366 cases were HPV positive (HPV infection), the overall infection rate was 15.57% (2,366/15,192), in which a single subtype of HPV infection in 1,767 cases, infection rate was 11.63% (1,767/15,192), and multiple subtypes of HPV infection (two and more subtypes HPV infection) in 599 cases, infection rate was 3.94% (599/15,192). The HPV16, 52 and 58 infections were the most common HPV subtypes in 13 subtypes, the infection rate was 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively. (2) The most relevant subtypes with cervical intraepithelial neoplasia (CIN) II and even higher lesion were HPV16, 52 and 58

PD-L1 overexpression in ampulla of Vater carcinoma and its pre-invasive lesions.

PubMed

Saraggi, Deborah; Galuppini, Francesca; Remo, Andrea; Urso, Emanuele D L; Bacchin, Deborah; Salmaso, Roberta; Lanza, Cristiano; Bao, Riccardo Q; Fanelli, Giuseppe N; Guzzardo, Vincenza; Luchini, Claudio; Scarpa, Marco; Farinati, Fabio; Fassan, Matteo; Rugge, Massimo

2017-09-01

PD-1/PD-L1 checkpoint immunotherapy has been proposed recently as a promising treatment in relapsed/refractory disease, used eventually in combination with traditional chemotherapy in different cancer settings. To date, no data are available concerning PD-L1 expression in ampulla of Vater carcinoma and its pre-invasive lesions. We assessed the immunohistochemical expression of PD-L1 in a series of 26 ampullary adenocarcinomas, 50 ampullary dysplastic lesions and 10 normal duodenal mucosa samples. Moreover, in all cases DNA mismatch repair proteins status was investigated. PD-L1 was expressed in seven of 26 (26.9%) invasive carcinomas and three of 50 (6.0%) dysplastic samples. Most of the PD-L1-positive tumours (seven of 10) were intestinal-type and poorly differentiated (G3). The number of PD-L1-positive stromal lymphoid cells was significantly higher in dysplastic and invasive lesions than in the normal samples (P = 0.011). Nineteen dysplastic lesions and eight invasive carcinomas did not show any evident epithelial or stromal PD-L1 expression. Four of the carcinomas were mismatch repair-deficient and two of these were PD-L1-positive. Furthermore, mismatch repair-deficient lesions showed a significantly higher average of PD-L1-positive stromal lymphoid cells than those of neoplastic PD-L1-negative samples (62.8 versus 21.6; P < 0.001). The present results suggest a role of the PD-1/PD-L1 axis in ampullary adenocarcinomas, and therefore this may also prompt consideration of checkpoint immunotherapy as a novel promising treatment for these tumours. © 2017 John Wiley & Sons Ltd.

Percutaneous Image-Guided Cryoablation of Challenging Mediastinal Lesions Using Large-Volume Hydrodissection: Technical Considerations and Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garnon, Julien, E-mail: juliengarnon@gmail.com; Koch, Guillaume, E-mail: Guillaume.koch@gmail.com; Caudrelier, Jean, E-mail: caudjean@yahoo.fr

ObjectiveThis study was designed to describe the technique of percutaneous image-guided cryoablation with large-volume hydrodissection for the treatment of challenging mediastinal lesions.MethodsBetween March 2014 and June 2015, three patients (mean age 62.7 years) with four neoplastic anterior mediastinal lesions underwent five cryoablation procedures using large-volume hydrodissection. Procedures were performed under general anaesthesia using CT guidance. Lesion characteristics, hydrodissection and cryoablation data, technical success, complications, and clinical outcomes were assessed using retrospective chart review.ResultsLesions (mean size 2.7 cm; range 2–4.3 cm) were in contact with great vessels (n = 13), trachea (n = 3), and mediastinal nerves (n = 6). Hydrodissection was performed intercostally (n = 4), suprasternally (n = 2), transsternally (n = 1), ormore » via the sternoclavicular joint (n = 1) using 1–3 spinal needles over 13.4 (range 7–26) minutes; 450 ml of dilute contrast was injected (range 300–600 ml) and increased mean lesion-collateral structure distance from 1.9 to 7.7 mm. Vulnerable mediastinal nerves were identified in four of five procedures. Technical success was 100 %, with one immediate complication (recurrent laryngeal nerve injury). Mean follow-up period was 15 months. One lesion demonstrated residual disease on restaging PET-CT and was retreated to achieve complete ablation. At last follow-up, two patients remained disease-free, and one patient developed distant disease after 1 year without local recurrence.ConclusionsCryoablation using large-volume hydrodissection is a feasible technique, enabling safe and effective treatment of challenging mediastinal lesions.« less

Lymphangioma circumscriptum of the penis mimicking venereal lesions.

PubMed

Gupta, S; Radotra, B D; Javaheri, S M; Kumar, B

2003-09-01

Lymphangioma circumscriptum (LC) involving the penis is rare. We report two patients with penile LC. The lesions developed in early infancy in one patient, and during puberty in the other. The lesions resembled molluscum contagiosum in one and genital warts in the other. The first patient was previously treated with a diagnosis of venereal disease. A literature search found only 4 LC patients with penile lesions reported in the English literature. These cases are presented for their rarity, and to increase diagnostic vigilance and desirability of non-intervention.

Early dynamic 18F-FDG PET to detect hyperperfusion in hepatocellular carcinoma liver lesions.

PubMed

Schierz, Jan-Henning; Opfermann, Thomas; Steenbeck, Jörg; Lopatta, Eric; Settmacher, Utz; Stallmach, Andreas; Marlowe, Robert J; Freesmeyer, Martin

2013-06-01

In addition to angiographic data on vascularity and vascular access, demonstration of hepatocellular carcinoma (HCC) liver nodule hypervascularization is a prerequisite for certain intrahepatic antitumor therapies. Early dynamic (ED) (18)F-FDG PET/CT could serve this purpose when the current standard method, contrast-enhanced (CE) CT, or other CE morphologic imaging modalities are unsuitable. A recent study showed ED (18)F-FDG PET/CT efficacy in this setting but applied a larger-than-standard (18)F-FDG activity and an elaborate protocol likely to hinder routine use. We developed a simplified protocol using standard activities and easily generated visual and descriptive or quantitative endpoints. This pilot study assessed the ability of these endpoints to detect HCC hyperperfusion and, thereby, evaluated the suitability in of the protocol everyday practice. Twenty-seven patients with 34 HCCs (diameter ≥ 1.5 cm) with hypervascularization on 3-phase CE CT underwent liver ED (18)F-FDG PET for 240 s, starting with (18)F-FDG (250-MBq bolus injection). Four frames at 15-s intervals, followed by 3 frames at 60-s intervals were reconstructed. Endpoints included focal tracer accumulation in the first 4 frames (60 s), subsequent focal washout, and visual and quantitative differences between tumor and liver regions of interest in maximum and mean ED standardized uptake value (ED SUVmax and ED SUVmean, respectively) 240-s time-activity curves. All 34 lesions were identified by early focal (18)F-FDG accumulation and faster time-to-peak ED SUVmax or ED SUVmean than in nontumor tissue. Tumor peak ED SUVmax and ED SUVmean exceeded liver levels in 85% and 53%, respectively, of lesions. Nadir tumor signal showed no consistent pattern relative to nontumor signal. HCC had a significantly shorter time to peak and significantly faster rate to peak for both ED SUVmax and ED SUVmean curves and a significantly higher peak ED SUVmax but not peak ED SUVmean than the liver. This pilot study

Multiple angiomatous nodules: a novel skin tumor in Birt-Hogg-Dubé syndrome.

PubMed

Nikolaidou, C; Moscarella, E; Longo, C; Rosato, S; Cavazza, A; Piana, S

2016-12-01

Birt-Hogg-Dubé syndrome (BHDS), first described in 1977, is a rare autosomal dominant disorder, linked to germline mutations in the FLCN (folliculin) gene. Patients may present with different skin tumors, pulmonary cysts with recurrent spontaneous pneumothorax, and renal cancers, but it has also been estimated that about 25% of carriers older than 20 years do not show skin involvement. So far, besides the triad of skin lesions of the original description (fibrofolliculomas, trichodischomas and acrochordons), a wide range of neoplastic and non-neoplastic skin conditions have been reported, i.e. melanomas, trichoblastoma, neural- and connective tissue tumors, lipomas, angiolipomas and focal cutaneous mucinosis. We describe a patient with BHDS developing multiple skin angiomatous lesions with prominent signet-ring features, an association never reported so far. As renal carcinomas represent the most threatening complication in BHDS and the identification of the patients with BHDS is mainly based on the clinical and histopathologic identification of the diagnostic skin lesions, the role of the dermatologist can be crucial in the prevention and early detection of a potentially aggressive renal cancer. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

CCR4 is expressed on infiltrating cells in lesional skin of early mycosis fungoides and atopic dermatitis.

PubMed

Sugaya, Makoto; Morimura, Sohshi; Suga, Hiraku; Kawaguchi, Makiko; Miyagaki, Tomomitsu; Ohmatsu, Hanako; Fujita, Hideki; Sato, Shinichi

2015-06-01

CCR4 is expressed on tumor cells of mycosis fungoides (MF) and Sézary syndrome (SS). In MF, most infiltrating cells in patches and plaques express CXCR3, while tumor cells express CCR4 in advanced stages. Poteligeo Test IHC (CCR4 staining kit) is a newly developed staining kit that can examine the presence of CCR4 expressed on tumor cells of adult T-cell leukemia/lymphoma, peripheral T-cell lymphoma and cutaneous T-cell lymphoma before treatment of anti-CCR4 antibody using paraffin-embedded samples. In this study, we analyzed CCR4 expression in lesional skin of MF, SS, atopic dermatitis (AD) and psoriasis with this new kit. CCR4 was expressed on infiltrating cells in lesional skin of patch, plaque, tumor MF and SS, and the number of positive cells increased as the disease progressed. Immunohistochemistry with frozen sections also showed some positive cells scattered in the dermis, although the quality was not high enough to quantify positive cells. There were significant positive correlations between CCR4(+) cells and serum lactate dehydrogenase levels. Interestingly, CCR4(+) cells were also detected in AD skin, whose number was larger than that in psoriatic skin. Previous studies showed only scattered CCR4(+) cells in skin samples by standard immunohistochemical staining. The new, sensitive CCR4 staining kit has revealed that CCR4 is expressed on infiltrating cells in lesional skin of early MF and AD as well as advanced MF and SS. These cells can be therapeutic targets for patients who are resistant to standard treatments. © 2015 Japanese Dermatological Association.

Quantitative susceptibility mapping of multiple sclerosis lesions at various ages.

PubMed

Chen, Weiwei; Gauthier, Susan A; Gupta, Ajay; Comunale, Joseph; Liu, Tian; Wang, Shuai; Pei, Mengchao; Pitt, David; Wang, Yi

2014-04-01

To assess multiple sclerosis (MS) lesions at various ages by using quantitative susceptibility mapping (QSM) and conventional magnetic resonance (MR) imaging. Retrospectively selected were 32 clinically confirmed MS patients (nine men and 23 women; 39.3 years ± 10.9) who underwent two MR examinations (interval, 0.43 years ± 0.16) with three-dimensional gradient-echo sequence from August 2011 to August 2012. To estimate the ages of MS lesions, MR examinations performed 0.3-10.6 years before study examinations were studied. Hyperintensity on T2-weighted images was used to define MS lesions. QSM images were reconstructed from gradient-echo data. Susceptibility of MS lesions and temporal rates of change were obtained from QSM images. Lesion susceptibilities were analyzed by t test with intracluster correlation adjustment and Bonferroni correction in multiple comparisons. MR imaging of 32 patients depicted 598 MS lesions, of which 162 lesions (27.1%) in 23 patients were age measurable and six (1.0%) were only visible at QSM. The susceptibilities relative to normal-appearing white matter (NAWM) were 0.53 ppb ± 3.34 for acute enhanced lesions, 38.43 ppb ± 13.0 (positive; P < .01) for early to intermediately aged nonenhanced lesions, and 4.67 ppb ± 3.18 for chronic nonenhanced lesions. Temporal rates of susceptibility changes relative to cerebrospinal fluid were 12.49 ppb/month ± 3.15 for acute enhanced lesions, 1.27 ppb/month ± 2.31 for early to intermediately aged nonenhanced lesions, and -0.004 ppb/month ± 0 for chronic nonenhanced lesions. Magnetic susceptibility of MS lesions increased rapidly as it changed from enhanced to nonenhanced, it attained a high susceptibility value relative to NAWM during its initial few years (approximately 4 years), and it gradually dissipated back to susceptibility similar to that of NAWM as it aged, which may provide new insight into pathophysiologic features of MS lesions. Online supplemental material is available for this

[Precancerous conditions and lesions of the stomach].

PubMed

Falt, P; Hanousek, M; Kundrátová, E; Urban, O

2013-01-01

Gastric carcinoma is a common malignant disease associated with an unfavorable prognosis in the case of late dia-gnosis. The most significant precancerous condition is chronic atrophic gastritis and intestinal metaplasia caused by Helicobacter pylori infection. These longlasting changes may lead to formation of dysplastic precancerous lesions. Upper endoscopy and histologic examination of forceps bio-psy specimens play a key role in the dia-gnosis of gastric precancerous conditions and lesions. Helicobacter pylori eradication therapy and endoscopic surveillance are main therapeutic modalities of gastric precancerous conditions. Localized precancerous lesions and early gastric neoplasia without the risk of lymphatic spread could be cured by means of endoscopic resection techniques.

Comfrey (Symphytum Officinale. l.) and Experimental Hepatic Carcinogenesis: A Short-term Carcinogenesis Model Study

PubMed Central

Gomes, Maria Fernanda Pereira Lavieri; de Oliveira Massoco, Cristina; Xavier, José Guilherme

2010-01-01

Comfrey or Symphytum officinale (L.) (Boraginaceae) is a very popular plant used for therapeutic purposes. Since the 1980s, its effects have been studied in long-term carcinogenesis studies, in which Comfrey extract is administered at high doses during several months and the neoplastic hepatic lesions are evaluated. However, the literature on this topic is very poor considering the studies performed under short-term carcinogenesis protocols, such as the ‘resistant hepatocyte model’ (RHM). In these studies, it is possible to observe easily the phenomena related to the early phases of tumor development, since pre-neoplastic lesions (PNLs) rise in about 1–2 months of chemical induction. Herein, the effects of chronic oral treatment of rats with 10% Comfrey ethanolic extract were evaluated in a RHM. Wistar rats were sequentially treated with N-nitrosodiethylamine (ip) and 2-acetilaminofluorene (po), and submitted to hepatectomy to induce carcinogenesis promotion. Macroscopic/microscopic quantitative analysis of PNL was performed. Non-parametric statistical tests (Mann–Whitney and χ2) were used, and the level of significance was set at P ≤ 0.05. Comfrey treatment reduced the number of pre-neoplastic macroscopic lesions up to 1 mm (P ≤ 0.05), the percentage of oval cells (P = 0.0001) and mitotic figures (P = 0.007), as well as the number of Proliferating Cell Nuclear Antigen (PCNA) positive cells (P = 0.0001) and acidophilic pre-neoplastic nodules (P = 0.05). On the other hand, the percentage of cells presenting megalocytosis (P = 0.0001) and vacuolar degeneration (P = 0.0001) was increased. Scores of fibrosis, glycogen stores and the number of nucleolus organizing regions were not altered. The study indicated that oral treatment of rats with 10% Comfrey alcoholic extract reduced cell proliferation in this model. PMID:18955295

Spectroscopic analysis of normal and neoplastic (WI-FTC) thyroid tissue.

PubMed

Depciuch, Joanna; Stanek-Widera, Agata; Lange, Dariusz; Biskup-Frużyńska, Magdalena; Stanek-Tarkowska, Jadwiga; Czarny, Wojciech; Cebulski, Jozef

2018-06-07

Thyroid cancer holds the first place of the malignant tumors of the endocrine system. One of the less common thyroid cancers is follicular thyroid carcinoma (FTC), which is very difficult to diagnose because it gives the same image as adenoma, which is benign. Certainty of the diagnosis is gained only when FTC gives metastases. Therefore, it was decided to compare normal and neoplastic (FTC) thyroid tissues with Fourier Transform Infrared (FTIR) spectroscopy. The obtained FTIR spectra and Principal Component Analysis (PCA) allowed us to conclude that there are differences in the FTIR spectrum between normal tissues and those affected by cancer. In addition, the results indicate that there is a decrease in the number of functional groups that build cellular and tissue structures in tumoral tissues. The shifts of wave numbers corresponding to the protein and lipid function group vibrations, as well as the calculated second derivative of the FTIR spectra showed the structural changes in neoplastic tissues. Moreover, the deconvolution of the amide I massif indicates that in cancerous tissues the prevailing secondary structure is β-sheet structure, while in normal tissues it is α-helix. The obtained results allow us to conclude that infrared spectroscopy, in addition to providing information on the composition of tested samples, can be an excellent diagnostic tool contributing to understanding the FTC substrate. Copyright © 2018. Published by Elsevier B.V.

Circulating microRNA-22-3p Predicts the Malignant Progression of Precancerous Gastric Lesions from Intestinal Metaplasia to Early Adenocarcinoma.

PubMed

Chen, Tsung-Hsing; Chiu, Cheng-Tang; Lee, Chieh; Chu, Yin-Yi; Cheng, Hao-Tsai; Hsu, Jun-Te; Wu, Ren-Chin; Yeh, Ta-Sen; Lin, Kwang-Huei

2018-05-07

Gastric cancer has a poor outcome and identifying useful biomarkers from peripheral blood or tissue could allow its early detection, or potentially precancerous changes, thus improving the curative rates. MicroRNAs (miRNAs) have been shown to offer great potential in cancer diagnosis and prediction. Here, we investigated the role of plasma miRNAs in the natural course of gastric cancer, from intestinal metaplasia to early cancer. The findings were used to understand whether patients at a high risk of malignancy could be given appropriate interventions in the early disease process, such as using endoscopic submucosal dissection to treat gastric dysplasia or early gastric cancer. Participants were divided into healthy control, intestinal metaplasia (IM), and dysplasia/early cancer (pT1a/b) groups. Microarray was used to select potential markers in tissue. Quantitative real-time polymerase chain reaction data showed circulating miRNA-22-3p had significantly different expression in patients with precancerous lesions or gastric adenocarcinoma. The areas under the curve of incomplete IM versus healthy control, low-grade/high-grade dysplasia, early gastric cancer, and GED were 0.8080, 0.8040, 0.8494, and 0.8095, respectively (all P values < 0.05). Circulating miRNA-22-3p could be a potential biomarker for gastric precancerous dysplasia and early cancer detection.

Matrix Metalloproteinases in Non-Neoplastic Disorders

PubMed Central

Tokito, Akinori; Jougasaki, Michihisa

2016-01-01

The matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases belonging to the metzincin superfamily. There are at least 23 members of MMPs ever reported in human, and they and their substrates are widely expressed in many tissues. Recent growing evidence has established that MMP not only can degrade a variety of components of extracellular matrix, but also can cleave and activate various non-matrix proteins, including cytokines, chemokines and growth factors, contributing to both physiological and pathological processes. In normal conditions, MMP expression and activity are tightly regulated via interactions between their activators and inhibitors. Imbalance among these factors, however, results in dysregulated MMP activity, which causes tissue destruction and functional alteration or local inflammation, leading to the development of diverse diseases, such as cardiovascular disease, arthritis, neurodegenerative disease, as well as cancer. This article focuses on the accumulated evidence supporting a wide range of roles of MMPs in various non-neoplastic diseases and provides an outlook on the therapeutic potential of inhibiting MMP action. PMID:27455234

Lymphatic vessel density in the neoplastic progression of Barrett's oesophagus to adenocarcinoma

PubMed Central

Brundler, M‐A; Harrison, J A; de Saussure, B; de Perrot, M; Pepper, M S

2006-01-01

Background Oesophageal adenocarcinoma is an aggressive neoplasm with poor prognosis as a result of early lymph node metastasis. Aims To measure lymphatic vessel density (LVD) in the neoplastic progression from Barrett's metaplasia to adenocarcinoma and determine whether LVD can predict the risk of cancer. In addition, to correlate LVD with lymph node metastasis and assess whether LVD could be used as a prognostic indicator for outcome or survival. Methods LVD and microvascular density (MVD) were assessed after immunohistochemical staining of vessels in Barrett's metaplasia, dysplasia, and adenocarcinoma tissues and were correlated with clinicopathological features. Results LVD was significantly reduced in adenocarcinoma, being half that seen in normal stomach/oesophagus or metaplasia/dysplasia. LVD did not correlate with tumour grade, stage, or clinical outcome; however, patients who had either lymph node metastasis or invasion of tumour cells into peritumorous lymphatic vessels had a significantly worse overall survival. MVD was also assessed as a prognostic marker; its increase appeared to be linked more with the development of Barrett's metaplasia than adenocarcinoma. Conclusions The reduction in lymphatic vessel numbers was not useful for determining disease outcome in the patient group studied. It is the entry of tumour cells into pre‐existing peritumorous lymphatic vessels that confers a significantly worse overall survival. PMID:16443737

Diagnostic value of apparent diffusion coefficients to differentiate benign from malignant vertebral bone marrow lesions.

PubMed

Balliu, E; Vilanova, J C; Peláez, I; Puig, J; Remollo, S; Barceló, C; Barceló, J; Pedraza, S

2009-03-01

The aim of this study is to evaluate the value of the apparent diffusion coefficient (ADC) obtained in diffusion-weighted (DW) MR sequences for the differentiation between malignant and benign bone marrow lesions. Forty-five patients with altered signal intensity vertebral bodies on conventional MR sequences were included. The cause of altered signal intensity was benign osteoporotic collapse in 16, acute neoplastic infiltration in 15, and infectious processes in 14; based on plain-film, CT, bone scintigraphy, conventional MR studies, biopsy or follow-up. All patients underwent isotropic DW MR images (multi-shot EPI, b values of 0 and 500 s/mm(2)). Signal intensity at DW MR images was evaluated and ADC values were calculated and compared between malignancy, benign edema and infectious spondylitis. Acute malignant fractures were hyperintense compared to normal vertebral bodies on the diffusion-weighted sequence, except in one patient with sclerotic metastases. Mean ADC value from benign edema (1.9+/-0.39 x 10(-3) mm(2)/s) was significantly (p<0.0001) higher than untreated metastasic lesions (0.9+/-1.3 x 10(-3)mm (2)/s). Mean ADC value of infectious spondilytis (0.96+/-0.49 x 10(-3) mm(2)/s) was not statistically (p>0.05) different from untreated metastasic lesions. ADC value was low (0.75 x 10(-3) mm(2)/s) in one case of subacute benign fracture. ADC values are a useful complementary tool to characterize bone marrow lesions, in order to distinguish acute benign fractures from malignant or infectious bone lesions. However, ADC values are not valuable in order to differentiate malignancy from infection.

Intraductal papillary-mucinous neoplasia of the pancreas: Histopathology and molecular biology.

PubMed

Verbeke, Caroline S

2010-10-27

Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a clinically and morphologically distinctive precursor lesion of pancreatic cancer, characterized by gradual progression through a sequence of neoplastic changes. Based on the nature of the constituting neoplastic epithelium, degree of dysplasia and location within the pancreatic duct system, IPMNs are divided in several types which differ in their biological properties and clinical outcome. Molecular analysis and recent animal studies suggest that IPMNs develop in the context of a field-defect and reveal their possible relationship with other neoplastic precursor lesions of pancreatic cancer.

Pathology of spontaneous tumour lesions in pullets and adult chickens in commercial farms - Short communication.

PubMed

Ikezawa, Mitsutaka; Sasaki, Jun; Goryo, Masanobu

2012-09-01

Twenty pullets and adult chickens, aged 100 to 403 days, from several commercial chicken farms were examined by gross and histopathology. Grossly, all chickens had white-greyish masses in the visceral organs with or without enlargement of the peripheral nerves. Histopathological examination revealed Marek's disease (MD) lymphoma, lymphoid leukosis (LL) and myeloid leukosis (ML) in 14/20, 5/20 and 1/20 of the chickens, respectively. Lesions of the sciatic nerves in chickens diagnosed as having MD lymphoma were various. No neoplastic and/or inflammatory cells were noted in the peripheral nerves of chickens diagnosed as having LL and ML. These results indicated that MD lymphoma could also develop in older chickens; thus, microscopic examination is needed to identify MD in older chickens showing lymphocyte-derived tumours.

Diode laser treatment and clinical management of multiple oral lesions in patients with hereditary haemorrhagic telangiectasia.

PubMed

Favia, G; Tempesta, A; Limongelli, L; Suppressa, P; Sabbà, C; Maiorano, E

2016-05-01

Hereditary haemorrhagic telangiectasia (HHT) is rare, and characterised by vascular dysplasia that leads to various symptoms including visceral arteriovenous malformations and mucocutaneous telangiectatic lesions. Our aim was to describe the clinical features and options for the treatment of multiple oral lesions, and to illustrate the efficacy of the diode laser in the treatment of early (<2mm) and advanced lesions (2mm or more). We report 24 patients with 1200 oral telangiectatic lesions, which were often associated with regular bleeding (from monthly to daily), superinfection, pain, and swelling, and treated with multiple sessions of laser according to the number and size of the lesions. Early lesions were treated with a single laser impulse in ultrapulsed mode, and advanced lesions with repeated laser impulses in pulsed mode (t-on 200ms/t-off 500ms), at a power of 8W. Early lesions healed completely after laser photocoagulation with no operative or postoperative complications, while advanced lesions improved with a remarkable reduction in size but more discomfort. Protective occlusal plates were sometimes used to reduce the incidence of new lesions caused by dental trauma. The treatment of oral telangiectatic lesions is still being debated, and it is important to improve quality of life for patients. Diode laser surgery could be an effective treatment for oral lesions in those with hereditary haemorrhagic telangiectasia. Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Remineralization of early enamel caries lesions using different bioactive elements containing toothpastes: An in vitro study.

PubMed

Wang, Yu; Mei, Li; Gong, Lin; Li, Jialing; He, Shaowei; Ji, Yan; Sun, Weibin

2016-09-14

found in surface hardness and roughness between Colgate Sensitive Pro-Relief and NovaMin® during the pH-cycling test and acid resistance test (P= 0.45 and P= 0.83, respectively). Colgate Sensitive Pro-Relief and NovaMin® present an advantage in enhancing remineralization and inhibiting demineralization for early enamel carious lesions in comparison with GC Tooth Mousse.

Small incision guarded hydroaspiration of iris lesions.

PubMed

Singh, Arun D

2017-11-01

To describe the technique and results of a minimally invasive surgical technique for resection of small iris lesions. Consecutive case series of 22 patients with localised, small iris lesions that were resected using the described surgical technique that composed of multiple, small corneal incisions created to allow for internal iris resection with 23-gauge horizontal vitrectomy scissors, followed by guarded tumour aspiration through a clear plastic tubing (diameter 3.5 mm) primed with viscoelastic agent. The mean largest basal diameter was 3.0 mm (range 1.5-5.0 mm; median 3.0 mm) and mean thickness was 1.3 mm (range 0.5-2.5 mm; median 1.0 mm). Use of multiple (2-4) small corneal incisions (range 2.0-3.0 mm; mean 2.8 mm) allowed reduced postoperative morbidity (significant hyphema (0%), hypotony (0%), wound leak (0%), >2 line change in best corrected visual acuity at postoperative 1 week (4.5%) and mean corneal astigmatism of 1.0 D (range 0.14-2.99 D; median 0.8 D) at postoperative 4-12 weeks. The tumour could be resected with clear surgical margins in all neoplastic cases (benign (2), borderline (1) and malignant (16)). Local recurrence or metastases were not observed in any melanoma case over a mean follow-up of 33.0 months (range 1.0-90.0 months; median 33.5 months). Small incision guarded hydroaspiration is a minimally invasive surgical technique for resection of select small iris lesions. Use of multiple small corneal incisions avoids morbidity associated with a single large corneoscleral incision, and use of guarded aspiration may eliminate the risk of wound contamination by the malignant tumour. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.

PubMed

Haycock, Philip C; Burgess, Stephen; Nounu, Aayah; Zheng, Jie; Okoli, George N; Bowden, Jack; Wade, Kaitlin Hazel; Timpson, Nicholas J; Evans, David M; Willeit, Peter; Aviv, Abraham; Gaunt, Tom R; Hemani, Gibran; Mangino, Massimo; Ellis, Hayley Patricia; Kurian, Kathreena M; Pooley, Karen A; Eeles, Rosalind A; Lee, Jeffrey E; Fang, Shenying; Chen, Wei V; Law, Matthew H; Bowdler, Lisa M; Iles, Mark M; Yang, Qiong; Worrall, Bradford B; Markus, Hugh Stephen; Hung, Rayjean J; Amos, Chris I; Spurdle, Amanda B; Thompson, Deborah J; O'Mara, Tracy A; Wolpin, Brian; Amundadottir, Laufey; Stolzenberg-Solomon, Rachael; Trichopoulou, Antonia; Onland-Moret, N Charlotte; Lund, Eiliv; Duell, Eric J; Canzian, Federico; Severi, Gianluca; Overvad, Kim; Gunter, Marc J; Tumino, Rosario; Svenson, Ulrika; van Rij, Andre; Baas, Annette F; Bown, Matthew J; Samani, Nilesh J; van t'Hof, Femke N G; Tromp, Gerard; Jones, Gregory T; Kuivaniemi, Helena; Elmore, James R; Johansson, Mattias; Mckay, James; Scelo, Ghislaine; Carreras-Torres, Robert; Gaborieau, Valerie; Brennan, Paul; Bracci, Paige M; Neale, Rachel E; Olson, Sara H; Gallinger, Steven; Li, Donghui; Petersen, Gloria M; Risch, Harvey A; Klein, Alison P; Han, Jiali; Abnet, Christian C; Freedman, Neal D; Taylor, Philip R; Maris, John M; Aben, Katja K; Kiemeney, Lambertus A; Vermeulen, Sita H; Wiencke, John K; Walsh, Kyle M; Wrensch, Margaret; Rice, Terri; Turnbull, Clare; Litchfield, Kevin; Paternoster, Lavinia; Standl, Marie; Abecasis, Gonçalo R; SanGiovanni, John Paul; Li, Yong; Mijatovic, Vladan; Sapkota, Yadav; Low, Siew-Kee; Zondervan, Krina T; Montgomery, Grant W; Nyholt, Dale R; van Heel, David A; Hunt, Karen; Arking, Dan E; Ashar, Foram N; Sotoodehnia, Nona; Woo, Daniel; Rosand, Jonathan; Comeau, Mary E; Brown, W Mark; Silverman, Edwin K; Hokanson, John E; Cho, Michael H; Hui, Jennie; Ferreira, Manuel A; Thompson, Philip J; Morrison, Alanna C; Felix, Janine F; Smith, Nicholas L; Christiano, Angela M; Petukhova, Lynn; Betz, Regina C; Fan, Xing; Zhang, Xuejun; Zhu, Caihong; Langefeld, Carl D; Thompson, Susan D; Wang, Feijie; Lin, Xu; Schwartz, David A; Fingerlin, Tasha; Rotter, Jerome I; Cotch, Mary Frances; Jensen, Richard A; Munz, Matthias; Dommisch, Henrik; Schaefer, Arne S; Han, Fang; Ollila, Hanna M; Hillary, Ryan P; Albagha, Omar; Ralston, Stuart H; Zeng, Chenjie; Zheng, Wei; Shu, Xiao-Ou; Reis, Andre; Uebe, Steffen; Hüffmeier, Ulrike; Kawamura, Yoshiya; Otowa, Takeshi; Sasaki, Tsukasa; Hibberd, Martin Lloyd; Davila, Sonia; Xie, Gang; Siminovitch, Katherine; Bei, Jin-Xin; Zeng, Yi-Xin; Försti, Asta; Chen, Bowang; Landi, Stefano; Franke, Andre; Fischer, Annegret; Ellinghaus, David; Flores, Carlos; Noth, Imre; Ma, Shwu-Fan; Foo, Jia Nee; Liu, Jianjun; Kim, Jong-Won; Cox, David G; Delattre, Olivier; Mirabeau, Olivier; Skibola, Christine F; Tang, Clara S; Garcia-Barcelo, Merce; Chang, Kai-Ping; Su, Wen-Hui; Chang, Yu-Sun; Martin, Nicholas G; Gordon, Scott; Wade, Tracey D; Lee, Chaeyoung; Kubo, Michiaki; Cha, Pei-Chieng; Nakamura, Yusuke; Levy, Daniel; Kimura, Masayuki; Hwang, Shih-Jen; Hunt, Steven; Spector, Tim; Soranzo, Nicole; Manichaikul, Ani W; Barr, R Graham; Kahali, Bratati; Speliotes, Elizabeth; Yerges-Armstrong, Laura M; Cheng, Ching-Yu; Jonas, Jost B; Wong, Tien Yin; Fogh, Isabella; Lin, Kuang; Powell, John F; Rice, Kenneth; Relton, Caroline L; Martin, Richard M; Davey Smith, George

2017-05-01

The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Genomewide association studies (GWAS) published up to January 15, 2015. GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of

Oral mucosal lesions during orthodontic treatment.

PubMed

Baricevic, Marinka; Mravak-Stipetic, Marinka; Majstorovic, Martina; Baranovic, Marijan; Baricevic, Denis; Loncar, Bozana

2011-03-01

Oral mucosal lesions can result from irritation caused by orthodontic appliances or malocclusion, but their frequency is not known. To examine the frequency of oral mucosal lesions in wearers of orthodontic appliances in comparison to children with malocclusion. This study comprised 111 subjects: 60 wearers of orthodontic appliances and 51 controls (aged between 6 and 18 years). Type and severity of mucosal lesions, their topography, gingival inflammation, and oral hygiene status were determined by using clinical indices. Mucosal lesions were more present in wearers of orthodontic appliances than in children with malocclusion. Gingival inflammation, erosion, ulceration, and contusion were the most common findings in orthodontic patients. The severity of gingival inflammation was in correlation with oral hygiene status; the poorer oral hygiene, the more severe gingival inflammation was. Better oral hygiene status was found in children during orthodontic treatment than in children with malocclusion. Orthodontic treatment carries a higher risk of mucosal lesions and implies greater awareness of better oral hygiene as shown by the results of this study. Oral hygiene instructions and early treatment of oral lesions are important considerations in better patient's motivation, treatment planning, and successful outcome. © 2010 The Authors. International Journal of Paediatric Dentistry © 2010 BSPD, IAPD and Blackwell Publishing Ltd.

The CGL1 (HeLa × Normal Skin Fibroblast) Human Hybrid Cell Line: A History of Ionizing Radiation Induced Effects on Neoplastic Transformation and Novel Future Directions in SNOLAB.

PubMed

Pirkkanen, Jake S; Boreham, Douglas R; Mendonca, Marc S

2017-10-01

Cellular transformation assays have been utilized for many years as powerful in vitro methods for examining neoplastic transformation potential/frequency and mechanisms of carcinogenesis for both chemical and radiological carcinogens. These mouse and human cell based assays are labor intensive but do provide quantitative information on the numbers of neoplastically transformed foci produced after carcinogenic exposure and potential molecular mechanisms involved. Several mouse and human cell systems have been generated to undertake these studies, and they vary in experimental length and endpoint assessment. The CGL1 human cell hybrid neoplastic model is a non-tumorigenic pre-neoplastic cell that was derived from the fusion of HeLa cervical cancer cells and a normal human skin fibroblast. It has been utilized for the several decades to study the carcinogenic/neoplastic transformation potential of a variety of ionizing radiation doses, dose rates and radiation types, including UV, X ray, gamma ray, neutrons, protons and alpha particles. It is unique in that the CGL1 assay has a relatively short assay time of 18-21 days, and rather than relying on morphological endpoints to detect neoplastic transformation utilizes a simple staining method that detects the tumorigenic marker alkaline phosphatase on the neoplastically transformed cells cell surface. In addition to being of human origin, the CGL1 assay is able to detect and quantify the carcinogenic potential of very low doses of ionizing radiation (in the mGy range), and utilizes a neoplastic endpoint (re-expression of alkaline phosphatase) that can be detected on both viable and paraformaldehyde fixed cells. In this article, we review the history of the CGL1 neoplastic transformation model system from its initial development through the wide variety of studies examining the effects of all types of ionizing radiation on neoplastic transformation. In addition, we discuss the potential of the CGL1 model system to

Animal models of neoplastic development.

PubMed

Pitot, H C

2001-01-01

The basic animal model for neoplastic development used by regulatory agencies is the two-year chronic bioassay developed more than 30 years ago and based on the presumed mechanism of action of a few potential chemical carcinogens. Since that time, a variety of other model carcinogenic systems have been developed, usually involving shorter duration, single organ endpoints, multistage models, and those in genetically-engineered mice. The chronic bioassay is still the "gold standard" of regulatory agencies despite a number of deficiencies, while in this country the use of shorter term assays based on single organ endpoints has not been popular. The multistage model of carcinogenesis in mouse epidermis actually preceded the development of the chronic two-year bioassay, but it was not until multistage models in other organ systems were developed that the usefulness of such systems became apparent. Recently, several genetically-engineered mouse lines involving mutations in proto-oncogenes and tumour suppressor genes have been proposed as additional model systems for use in regulatory decisions. It is likely that a combination of several of these model systems may be most useful in both practical and basic applications of cancer prevention and therapy.

[Vascular Lesions of Vocal Folds - Part 2: Perpendicular Vascular Lesions].

PubMed

Arens, C; Glanz, H; Voigt-Zimmermann, S

2015-11-01

The present work aims at a systematic pathogenetic description of perpendicular vascular changes in the vocal folds. Unlike longitudinal vascular changes, like ectasia and meander, perpendicular vascular changes can be observed in bening lesions. They predominantly occur as typical vascular loops in exophytic lesions, especially in recurrent respiratory papillomatosis (RRP), pre-cancerous and cancerous diseases of the larynx and vocal folds. Neoangiogenesis is caused by an epithelial growth stimulus in the early phase of cancerous genesis. In RRP the VVC impress by a single, long vessel loop with a narrow angle turning point in the each single papilla of the papilloma. In pre- and cancerous lesions the vascular loop is located directly underneath the epithelium. During progressive tumor growth, vascular loops develop an increasingly irregular, convoluted, spirally shape. The arrangement of the vascular loops is primarily still symmetrical. In the preliminary stage of tumor development occurs by neoangiogenesis to a microvascular compression. In advanced vocal fold carcinoma the regular vascular vocal fold structure is destroyed. The various stages of tumor growth are also characterized by typical primary epithelial and secondary connective tissue changes. The characteristic triad of vascular, epithelial and connective tissue changes therefore plays an important role in differential diagnosis. © Georg Thieme Verlag KG Stuttgart · New York.

Postirradiation malignant fibrous histiocytoma of the lung. Demonstration of alpha 1-antitrypsin-like material in neoplastic cells.

PubMed

Chowdhury, L N; Swerdlow, M A; Jao, W; Kathpalia, S; Desser, R K

1980-12-01

A metastasizing fibrous histiocytoma arising in the lung of a patient who received radiation therapy and long-term chemotherapy for malignant lymphoma is presented. Ultrastructural studies revealed fibroblast-like and histiocyte-like cells, cells of intermediate type showing ultrastructural features of both fibroblast-like and histiocyte-like cells, primitive mesenchymal cells, multinucleate tumor cells, and xanthomatous cells. The neoplastic cells showed dilated rough endoplasmic reticula with intracisternal accumulation of electron-dense material forming lattice-like structures. Direct immunofluorescence staining of the neoplastic cells using antihuman alpha 1-antitrypsin showed specific activity, with fluorescent deposits exhibiting interlacing globular formations. These findings and their implications are discussed.

Red lesion detection using background estimation and lesions characteristics in diabetic retinal image

NASA Astrophysics Data System (ADS)

Zhang, Dongbo; Peng, Yinghui; Yi, Yao; Shang, Xingyu

2013-10-01

Detection of red lesions [hemorrhages (HRs) and microaneurysms (MAs)] is crucial for the diagnosis of early diabetic retinopathy. A method based on background estimation and adapted to specific characteristics of HRs and MAs is proposed. Candidate red lesions are located by background estimation and Mahalanobis distance measure and then some adaptive postprocessing techniques, which include vessel detection, nonvessel exclusion based on shape analysis, and noise points exclusion by double-ring filter (only used for MAs detection), are conducted to remove nonlesion pixels. The method is evaluated on our collected image dataset, and experimental results show that it is better than or approximate to other previous approaches. It is effective to reduce the false-positive and false-negative results that arise from incomplete and inaccurate vessel structure.

Automated detection of red lesions from digital colour fundus photographs.

PubMed

Jaafar, Hussain F; Nandi, Asoke K; Al-Nuaimy, Waleed

2011-01-01

Earliest signs of diabetic retinopathy, the major cause of vision loss, are damage to the blood vessels and the formation of lesions in the retina. Early detection of diabetic retinopathy is essential for the prevention of blindness. In this paper we present a computer-aided system to automatically identify red lesions from retinal fundus photographs. After pre-processing, a morphological technique was used to segment red lesion candidates from the background and other retinal structures. Then a rule-based classifier was used to discriminate actual red lesions from artifacts. A novel method for blood vessel detection is also proposed to refine the detection of red lesions. For a standarised test set of 219 images, the proposed method can detect red lesions with a sensitivity of 89.7% and a specificity of 98.6% (at lesion level). The performance of the proposed method shows considerable promise for detection of red lesions as well as other types of lesions.

The most common mistakes on dermatoscopy of melanocytic lesions

PubMed Central

Kamińska-Winciorek, Grażyna

2015-01-01

Dermatoscopy is a method of in vivo evaluation of the structures within the epidermis and dermis. Currently, it may be the most precise pre-surgical method of diagnosing melanocytic lesions. Diagnostic errors may result in unnecessary removal of benign lesions or what is even worse, they can cause early and very early melanomas to be overlooked. Errors in assessment of dermatoscopy can be divided into those arising from failure to maintain proper test procedures (procedural and technical errors) and knowledge based mistakes related to the lack of sufficient familiarity and experience in dermatoscopy. The article discusses the most common mistakes made by beginner or inexperienced dermatoscopists. PMID:25821425

Hyperplastic polyps of the colon and rectum - reclassification, BRAF and KRAS status in index polyps and subsequent colorectal carcinoma.

PubMed

Janjua, Huma Gul Rehana; Høgdall, Estrid; Linnemann, Dorte

2015-04-01

Hyperplastic polyps (HP) of the colon and rectum were previously considered benign. Newer studies have suggested that colorectal HP are different entities. The aim of this study was to reclassify lesions from a 5-year period previously classified as colorectal HP into traditional hyperplastic polyp (THP), sessile serrated lesions (SSL), and other lesions. All patients were confirmed in the Danish National Pathology Database for the occurrence of metachronous polyps/adenomas, colorectal cancer (CRC), and other gastrointestinal malignancies. Molecular pathology of the CRC were characterized and correlated with the index lesion. In total, 591 HP biopsy specimens were obtained from 480 patients. The lesions were reclassified as: 358 THP, 109 SSL, 35 TA, 81 unspecified non-neoplastic lesions, four traditional serrated adenoma, and 4 SSL with cytological dysplasia. Seven patients developed CRC in the follow-up period (1 patient had SSL, 4 had THP, and 2 had unspecified non-neoplastic lesions). Ten patients developed other gastrointestinal malignancies. The patient with SSL as index lesions who developed CRC harbored V600E BRAF mutation in both index lesion and the carcinoma. Sixteen percent of patients with SSL subsequently developed a neoplastic lesion. Further studies are needed to clarify the cancer risk of SSL. © 2015 APMIS. Published by John Wiley & Sons Ltd.

Hormone Receptor Expression Analyses in Neoplastic and Non-Neoplastic Canine Mammary Tissue by a Bead Based Multiplex Branched DNA Assay: A Gene Expression Study in Fresh Frozen and Formalin-Fixed, Paraffin-Embedded Samples.

PubMed

Mohr, Annika; Lüder Ripoli, Florenza; Hammer, Susanne Conradine; Willenbrock, Saskia; Hewicker-Trautwein, Marion; Kiełbowicz, Zdzisław; Murua Escobar, Hugo; Nolte, Ingo

2016-01-01

Immunohistochemistry (IHC) is currently considered the method of choice for steroid hormone receptor status evaluation in human breast cancer and, therefore, it is commonly utilized for assessing canine mammary tumors. In case of low hormone receptor expression, IHC is limited and thus is complemented by molecular analyses. In the present study, a multiplex bDNA assay was evaluated as a method for hormone receptor gene expression detection in canine mammary tissues. Estrogen receptor (ESR1), progesterone receptor (PGR), prolactin receptor (PRLR) and growth hormone receptor (GHR) gene expressions were evaluated in neoplastic and non-neoplastic canine mammary tissues. A set of 119 fresh frozen and 180 formalin-fixed, paraffin-embedded (FFPE) was comparatively analyzed and used for assay evaluation. Furthermore, a possible association between the hormone receptor expression in different histological subtypes of canine malignant mammary tumors and the castration status, breed and invasive growth of the tumor were analyzed. The multiplex bDNA assay proved to be more sensitive for fresh frozen specimens. Hormone receptor expression found was significantly decreased in malignant mammary tumors in comparison to non-neoplastic tissue and benign mammary tumors. Among the histological subtypes the lowest gene expression levels of ESR1, PGR and PRLR were found in solid, anaplastic and ductal carcinomas. In summary, the evaluation showed that the measurement of hormone receptors with the multiplex bDNA assay represents a practicable method for obtaining detailed quantitative information about gene expression in canine mammary tissue for future studies. Still, comparison with IHC or quantitative real-time PCR is needed for further validation of the present method.

Casein phosphopeptide-amorphous calcium phosphate remineralization of primary teeth early enamel lesions.

PubMed

Zhou, Chunhua; Zhang, Dongliang; Bai, Yuxing; Li, Song

2014-01-01

Early childhood caries (ECC) is a serious problem that progresses rapidly and often goes untreated. Current traumatic treatments may be replaced by safe and effective remineralization at very early stages. The aim of this in vitro study was to evaluate the remineralization effects of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste on enamel lesions by assessing ultrastructure, nanomechanical properties, and compound and elemental analysis. Enamel specimens from 6-year-old children were divided into groups: (1) native enamel; (2) water as negative control; (3) 500ppm NaF as positive control; and (4-7) CPP-ACP paste for 4, 8, 12, and 24h, as test groups. Ultrastructure and roughness were observed by atomic force microscopy (AFM); nanohardness and elastic modulus were measured by nanoindentation; compound and crystal size of enamel surface patterns were investigated by X-ray diffractometer (XRD). An electron microprobe (EPMA) was used for element analysis. Data were analyzed using one-way ANOVA. The CPP-ACP paste repaired the microstructure of enamel, including prism and interprism, through significantly increased hydroxyapatite crystal size (12.06±0.21nm) and Ca/P molar ratios (1.637±0.096) as compared with NaF (8.56±0.13nm crystal size and 1.397±0.086 Ca/P, p<0.01). Both CPP-ACP and NaF decrease roughness, and increase the nanohardness and elastic modulus, with no significant differences between the materials. The CPP-ACP paste is more suitable for children than NaF, due to advantages for remineralization. The AFM, nanoindentation, EPMA, and XRD are very helpful methods for further understanding of microscale and nanoscale remineralization mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Efficacy of the ViziLite system in the identification of oral lesions.

PubMed

Oh, Esther S; Laskin, Daniel M

2007-03-01

Early detection of oral cancer is crucial in improving survival rate. To improve early detection, the use of a dilute acetic acid rinse and observation under a chemiluminescent light (ViziLite; Zila Pharmaceuticals, Phoenix, AZ) has been recommended. However, to date, the contributions of the individual components of the system have not been studied. The present study was done to investigate the efficacy of the individual components of the ViziLite system in providing improved visualization of early oral mucosal lesions. A total of 100 patients, 39 males and 61 females, age 18 to 93 years (mean age, 44 years), who presented to the Virginia Commonwealth University School of Dentistry for dental screening were examined. There were 58 Caucasians, 29 African-Americans, 5 Hispanics, 6 Asians, and 2 of mixed ethnicity. Thirty-five patients smoked, 53 used alcohol, and 25 both smoked and drank. After written consent, the oral cavity was examined under incandescent light for soft tissue abnormalities. After 1-minute rinse with 1% acetic acid, the mouth was re-examined for additional mucosal abnormalities. Then, the mouth was examined once again using the ViziLite system's chemiluminescent light. Any lesions detected by these 3 examinations that were clinically undiagnosable were brush biopsied (Oral CDx) for determination of cellular representation. In the original examination of the 100 patients, 57 clinically diagnosable benign lesions (eg, linea alba, leukoedema) and 29 clinically undiagnosable lesions were detected. After the rinse, 6 additional diagnosable lesions (linea alba) and 3 undiagnosable lesions were found. No additional lesions were detected with the chemiluminescent light. Of the 32 undiagnosable lesions that were brush biopsied, 2 were positive for atypical cellular characterization and warranted further investigation with a scalpel biopsy. Neither of these lesions was found to be premalignant or malignant. Although the acid rinse accentuated some lesions

Surgical treatment of temporal lobe epilepsy: clinical, radiological, and histopathological findings in 178 patients.

PubMed Central

Zentner, J; Hufnagel, A; Wolf, H K; Ostertun, B; Behrens, E; Campos, M G; Solymosi, L; Elger, C E; Wiestler, O D; Schramm, J

1995-01-01

The surgical treatment of pharmacoresistant temporal lobe epilepsy is increasing rapidly. The correlation of preoperative MRI, histopathological findings, and postoperative seizure control is reported for 178 patients with chronic medically intractable temporal lobe epilepsy who were operated on between November 1987 and January 1993. Histopathologically there were distinct structural abnormalities in 97.2% of the surgical specimens. Signal abnormalities on MRI were present in 98.7% of patients with neoplastic lesions (n = 79), 76.6% of patients with non-neoplastic focal lesions (n = 55), and 69.2% of patients with Ammon's horn sclerosis (n = 39). Overall, structural abnormalities were detected by MRI in 82.7% of all patients. The mean postoperative follow up period was three years. Some 92% of the patients benefited from surgery: 103 patients (61.7%) were seizure free, 26 (15.5%) had no more than two seizures a year, and 24 (14.4%) showed a reduction of seizure frequency of at least 75%. Fourteen patients (8.4%) had a < 75% reduction of seizure frequency. The percentage of patients who were completely free of seizures after operation was 68.5% for patients with neoplastic lesions, 66.7% for Ammon's horn sclerosis, and 54.0% for patients with non-neoplastic focal lesions. By contrast, none of the patients in whom histopathological findings were normal became seizure free postoperatively. The data show that the presence of focal lesions or Ammon's horn sclerosis as determined by histopathological examination is associated with improved postoperative seizure control compared with patients without specific pathological findings. Brain MRI was very sensitive in detecting neoplasms; however, its sensitivity and specificity were limited with respect to non-neoplastic focal lesions and Ammon's horn sclerosis. Improvement of imaging techniques may provide a more precise definition of structural lesions in these cases and facilitate limited surgical resections of the

Radiofrequency Ablation Versus Endoscopic Submucosal Dissection in Treating Large Early Esophageal Squamous Cell Neoplasia

PubMed Central

Wang, Wen-Lun; Chang, I-Wei; Chen, Chien-Chuan; Chang, Chi-Yang; Mo, Lein-Ray; Lin, Jaw-Town; Wang, Hsiu-Po; Lee, Ching-Tai

2015-01-01

Abstract Radiofrequency ablation (RFA) and endoscopic submucosal dissection (ESD) can potentially be applied for early esophageal squamous cell neoplasia (ESCN); however, no study has directly compared these 2 modalities. We retrospectively enrolled the patients with flat-type “large” (length ≥3 cm extending ≥1/2 of the circumference of esophagus) early ESCNs treated endoscopically. The main outcome measurements were complete response at 12 months, and adverse events. Of a total of 65 patients, 18 were treated with RFA and 47 with ESD. The procedure time of RFA was significantly shorter than that of ESD (126.6 vs 34.8 min; P < 0.001). The complete resection rate of ESD and complete response rate after primary RFA were 89.3% and 77.8%, respectively. Based on the histological evaluation of the post-ESD specimens showed 14 of 47 (29.8%) had histological upstaging compared with the pre-ESD biopsies, and 4 of them had lymphovascular invasion requiring chemoradiation or surgery. After additional therapy for residual lesions, 46 (97.9%) patients in the ESD group and 17 (94.4%) patients in the RFA group achieved a complete response at 12 months. Four patients (8.5%) developed major procedure-related adverse events in the ESD group, but none in the RFA group. In patients with lesions occupying more than 3/4 of the circumference, a significantly higher risk of esophageal stenosis was noted in the ESD group compared with RFA group (83% vs 27%, P = 0.01), which required more sessions of dilatation to resolve the symptoms (median, 13 vs 3, P = 0.04). There were no procedure-related mortality or neoplastic progression in either group; however, 1 patient who received ESD and 1 who received RFA developed local recurrence during a median follow-up period of 32.4 (range, 13–68) and 18.0 (range, 13–41) months, respectively. RFA and ESD are equally effective in the short-term treatment of early flat large ESCNs; however, more adverse events occur with ESD

The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Yu; Wong, Nicholas; Guan, Yinghui

2008-04-25

Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is a transcriptional repressor, enhanced expression of eEF1A2. In this study, array comparative genomic hybridization, single nucleotide polymorphism and Affymetrix analysis of ZNF217-overexpressing cell lines confirmed consistently increased expression of eEF1A2 but not of other oncogenes, and revealed early changes in EEF1A2 gene copy numbers and increased expression at crisis during immortalization. We definedmore » the influence of eEF1A2 overexpression on immortalized ovarian surface epithelial cells, and investigated interrelationships between effects of ZNF217 and eEF1A2 on cellular phenotypes. Lentivirally induced eEF1A2 overexpression caused delayed crisis, apoptosis resistance and increases in serum-independence, saturation densities, and anchorage independence. siRNA to eEF1A2 reversed apoptosis resistance and reduced anchorage independence in eEF1A2-overexpressing lines. Remarkably, siRNA to eEF1A2 was equally efficient in inhibiting both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression. Our data define neoplastic properties that are caused by eEF1A2 in nontumorigenic ovarian cancer precursor cells, and suggest that eEF1A2 plays a role in mediating ZNF217-induced neoplastic progression.« less

Frequency and characteristics of dual pathology in patients with lesional epilepsy.

PubMed

Cendes, F; Cook, M J; Watson, C; Andermann, F; Fish, D R; Shorvon, S D; Bergin, P; Free, S; Dubeau, F; Arnold, D L

1995-11-01

We studied 167 patients who had identifiable lesions and temporal or extratemporal partial epilepsy. Pathology included neuronal migration disorders (NMDs) (48), low-grade tumors (52), vascular malformations (34), porencephalic cysts (16), and gliotic lesions as a result of cerebral insults early in life (17). MRI volumetric studies using thin (1.5- or 3-mm) coronal images were performed in all patients and in 44 age-matched normal controls. An atrophic hippocampal formation (HF), indicating dual pathology, was present in 25 patients (15%). Abnormal HF volumes were present in those with lesions involving temporal (17%) but also extratemporal (14%) areas. Age at onset and duration of epilepsy did not influence the presence of HF atrophy. However, febrile seizures in early childhood were more frequently, although not exclusively, found in patients with hippocampal atrophy. The frequency of hippocampal atrophy in our patients with low-grade tumors (2%) and vascular lesions (9%) was low. Dual pathology was far more common in patients with NMDs (25%), porencephalic cysts (31%), and reactive gliosis (23.5%). Some structural lesions, such as NMDs, are more likely to be associated with hippocampal atrophy, independent of the distance of the lesion from the HF. In other types of lesions, such as vascular malformations, dual pathology was found when the lesion was close to the HF. A common pathogenic mechanism during pre- or perinatal development may explain the occurrence of concomitant mesial temporal sclerosis and other structural lesions because of either (1) associated developmental abnormalities or (2) predisposition to prolonged febrile convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

Photodynamic therapy and the treatment of neoplastic diseases of the larynx

NASA Astrophysics Data System (ADS)

Biel, Merrill A.

1995-05-01

Photodynamic therapy (PDT) is an innovative treatment involving the use of light-sensitive drugs to selectively identify and destroy diseased cells. Therefore, photodynamic therapy has the potential to treat and cure precancerous and early cancerous lesions (carcinoma in situ (CIS), T1 and T2) of the larynx while preserving normal tissue. Twenty-four patients with recurrent leukoplakia and carcinomas of the larynx were treated with PDT with follow-up to 60 months. Fourteen patients with T1 squamous cell carcinomas of the vocal cord, 2 patients with a T2 squamous cell carcinoma of the vocal cord failing radiotherapy, and 6 patients with CIS and sever atypia were treated with PDT and obtained a complete response and are disease free. One patient with a T3 carcinoma of the larynx was treated with PDT but died 5 weeks post-treatment of unrelated causes and could not be assessed. Photodynamic therapy is a promising therapy for treatment of precancerous and cancerous lesions of the larynx. This therapy may be particularly beneficial for the treatment of recurrent carcinomas of the larynx that have failed conventional radiotherapy, thereby preserving voice and eliminating the need for destructive laryngeal surgery.

Assessment of ultrasonography and computed tomography for the evaluation of unilateral orbital disease in dogs.

PubMed

Boroffka, Susanne A E B; Verbruggen, Anne-Marie; Grinwis, Guy C M; Voorhout, George; Barthez, Paul Y

2007-03-01

To describe clinical, ultrasonographic, and computed tomographic (CT) features of confirmed neoplastic and nonneoplastic disease in dogs with unilateral orbital diseases, determine criteria to differentiate between the 2 conditions, and assess the relative value of ultrasonography and CT for the differential diagnosis of these 2 conditions. Prospective study. 29 dogs with unilateral neoplastic orbital disease and 16 dogs with unilateral nonneoplastic orbital disease. Clinical history and results of physical and ophthalmologic examinations were recorded. Ultrasonographic and CT images were evaluated, and discriminating factors were identified to differentiate neoplastic from nonneoplastic diseases. Diagnostic value of ultrasonography and CT was assessed. Dogs with neoplastic disease were significantly older; had clinical signs for a longer time before initial examination; had more progressive onset of clinical signs; and more frequently had protrusion of the nictitating membrane, fever, and anorexia. The most discriminating factor for both imaging modalities was delineation of the margins (odds ratio was 41.7 for ultrasonography and 45 for CT), with neoplastic lesions clearly delineated more often. Ultrasonographically, neoplastic lesions were more frequently hypoechoic and homogeneous, with indentation of the globe and bone involvement evident more frequently than for nonneoplastic lesions. Mineralization was detected only with neoplasia. Fluctuant fluid was seen more frequently in dogs with nonneoplastic disease. Computed tomography more frequently revealed extraorbital involvement. Diagnostic value was similar for both imaging modalities. Ultrasonography and CT are valuable imaging modalities to assist in differentiating neoplastic from nonneoplastic unilateral orbital disease in dogs.

Histogenesis of splenic lesions in Hodgkin's disease.

PubMed

Yam, L T; Li, C Y

1976-12-01

Histochemical markers were used to identify the various cellular and structural components of the human spleen, and to investigate the histogenesis of the splenic lesions of Hodgkin's disease. The early lesions appear in areas near the central artery (periarterial lymphatic sheath) in the white pulp. The white pulp becomes hypertrophic. The lesions enlarge, extend into the red pulp, and compress the sinuses and the cords of Billroth. The derivations of various "histiocytes" contained with the lesions are differentiated by using cytochemical stains for lysosomal enzymes and for granulocytes. The epithelioid cells in the granulomas are rich in those lysosomal enzymes typically seen in phagocytic histiocytes, suggesting that they are indeed true histiocytes. The malignant "histiocytes," including the mononuclear Hodgkin cells, the binucleated Sternberg-Reed cells, and the multinucleated giant cells, do not contain significant amounts of lysosomal enzymes and more closely resemble stimulated lymphocytes. The splenic lesions in Hodkin's disease may be the result of a lymphocytic and histiocytic cellular response to an unknown agent, which reaches the spleen through the central artery in the white pulp.

Traumatic lesions of the posterior urethra.

PubMed

Velarde-Ramos, L; Gómez-Illanes, R; Campos-Juanatey, F; Portillo-Martín, J A

2016-11-01

The posterior urethral lesions are associated with pelvis fractures in 5-10% of cases. The posterior urethra is attached to the pelvis bone by puboprostatic ligaments and the perineal membrane, which explains why disruption of the pelvic ring can injure the urethra at this level. To identify suspected cases of posterior urethral trauma and to perform the diagnosis and its immediate or deferred management. Search in PubMed of articles related to traumatic posterior urethral lesions, written in English or Spanish. We reviewed the relevant publications including literature reviews and chapters from books related to the topic. With patients with pelvis fractures, we must always rule out posterior urethral lesions. The diagnostic examination of choice is retrograde urethrography, which, along with the severity of the condition, will determine the management in the acute phase and whether the treatment will be performed immediately or deferred. Early diagnosis and proper acute management decrease the associated complications, such as strictures, urinary incontinence and erectile dysfunction. Despite the classical association between posterior urethral lesions and pelvic fractures, the management of those lesions (whether immediate or deferred) remains controversial. Thanks to the growing interest in urethral disease, there are an increasing number of studies that help us achieve better management of these lesions. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Anaplastic ganglioglioma arising from a Lhermitte-Duclos-like lesion. Case report.

PubMed

Takei, Hidehiro; Dauser, Robert; Su, Jack; Chintagumpala, Murali; Bhattacharjee, Meenakshi B; Jones, Jeremy; Adesina, Adekunle M

2007-08-01

The authors report the case of a 7-year-old boy with a history of developmental delay who presented with aggressive behavior. A magnetic resonance (MR) image showed a mass lesion originating from the cerebellar vermis with an atypical folial pattern and contrast enhancement. Histologically, the subtotally resected specimen consisted mostly of neuropil with nodular foci of ganglion cells. Lhermitte-Duclos disease (LDD) was diagnosed in the patient. A retrospective review of the tissue sections showed a nidus of associated astrocytic proliferation, suggesting a diagnosis of ganglioglioma. Five years later, the patient experienced an altered mental state and a facial droop. An MR image revealed a cerebellar mass with cystic areas and an enhancing nodule. The resected tissue specimen consisted primarily of a mixed proliferation of glial and ganglion cells consistent with a ganglioglioma. Two years later, a third craniectomy was performed in the patient for worsening headache and ataxia. Histologically, the tumor showed progressive anaplasia and was most accurately classified as an anaplastic ganglioglioma. Immunohistochemically, most of the tumor cells were immunoreactive for anti-phospho-mammalian target of rapamycin (mTOR) and phospho-S6 ribosomal protein antibodies. In contrast, the subpopulation of neoplastic ganglion cells in the tissue, particularly from the first surgery, did not express phosphatase and tensin homolog deleted from chromosome 10 (PTEN). This immunohistochemical pattern suggests that the large dysplastic ganglion cells (the gangliocytomatous component) forming the greater part of the lesion were associated with activation of the phosphatidylinositol 3-kinase-PTEN/Akt/mTOR signaling pathway, a feature previously reported in LDD. This case represents the first report of an anaplastic ganglioglioma arising in an LDD-like lesion.

pH imaging reveals worsened tissue acidification in diffusion kurtosis lesion than the kurtosis/diffusion lesion mismatch in an animal model of acute stroke.

PubMed

Wang, Enfeng; Wu, Yin; Cheung, Jerry S; Zhou, Iris Yuwen; Igarashi, Takahiro; Zhang, XiaoAn; Sun, Phillip Zhe

2017-10-01

Diffusion weighted imaging (DWI) has been commonly used in acute stroke examination, yet a portion of DWI lesion may be salvageable. Recently, it has been shown that diffusion kurtosis imaging (DKI) defines the most severely damaged DWI lesion that does not renormalize following early reperfusion. We postulated that the diffusion and kurtosis lesion mismatch experience heterogeneous hemodynamic and/or metabolic injury. We investigated tissue perfusion, pH, diffusion, kurtosis and relaxation from regions of the contralateral normal area, diffusion lesion, kurtosis lesion and their mismatch in an animal model of acute stroke. Our study revealed significant kurtosis and diffusion lesion volume mismatch (19.7 ± 10.7%, P < 0.01). Although there was no significant difference in perfusion and diffusion between the kurtosis lesion and kurtosis/diffusion lesion mismatch, we showed lower pH in the kurtosis lesion (pH = 6.64 ± 0.12) from that of the kurtosis/diffusion lesion mismatch (6.84 ± 0.11, P < 0.05). Moreover, pH in the kurtosis lesion and kurtosis/diffusion mismatch agreed well with literature values for regions of ischemic core and penumbra, respectively. Our work documented initial evidence that DKI may reveal the heterogeneous metabolic derangement within the commonly used DWI lesion.

CDX1 protein expression in normal, metaplastic, and neoplastic human alimentary tract epithelium.

PubMed

Silberg, D G; Furth, E E; Taylor, J K; Schuck, T; Chiou, T; Traber, P G

1997-08-01

CDX1 is an intestine-specific transcription factor expressed early in intestinal development that may be involved in regulation of proliferation and differentiation of intestinal epithelial cells. We examined the pattern of CDX1 protein expression in metaplastic and neoplastic tissue to provide insight into its possible role in abnormal differentiation. Tissue samples were stained by immunohistochemistry using an affinity-purified, polyclonal antibody against a peptide epitope of CDX1. Specific nuclear staining was found in epithelial cells of the small intestine and colon. Esophagus and stomach did not express CDX1 protein; however, adjacent areas of intestinal metaplastic tissue intensely stained for CDX1. Adenocarcinomas of the stomach and esophagus had both positive and negative nuclear staining for CDX1. Colonic epithelial cells in adenomatous polyps and adenocarcinomas had a decreased intensity of staining compared with normal colonic crypts in the same specimen. CDX1 may be important in the transition from normal gastric and esophageal epithelium to intestinal-type metaplasia. The variability in expression of CDX1 in gastric and esophageal adenocarcinomas suggests more than one pathway in the development of these carcinomas. The decrease of CDX1 in colonic adenocarcinomas may indicate a role for CDX1 in growth regulation and in the maintenance of the differentiated phenotype.

Systematic alphanumeric-coded endoscopy versus chromoendoscopy for the detection of precancerous gastric lesions and early gastric cancer in subjects at average risk for gastric cancer.

PubMed

Pérez-Mendoza, A; Zárate-Guzmán, Á M; Galvis García, E S; Sobrino Cossío, S; Djamus Birch, J

Gastric cancer is one of the main causes of cancer worldwide, but there is currently no global screening strategy for the disease. Endoscopy is the screening method of choice in some Asian countries, but no standardized technique has been recognized. Systematic alphanumeric-coded endoscopy can increase gastric lesion detection. The aim of the present article was to compare the usefulness of systematic alphanumeric-coded endoscopy with conventional endoscopy for the detection of premalignant lesions and early gastric cancer in subjects at average risk for gastric cancer. A cross-sectional, comparative, prospective, randomized study was conducted on patients at average risk for gastric cancer (40-50 years of age, no history of H. pylori infection, intestinal metaplasia, gastric atrophy, or gastrointestinal surgery). Before undergoing endoscopy, the patients had gastric preparation (200mg of oral acetylcysteine or 50mg of oral dimethicone). Conventional chromoendoscopy was performed with indigo carmine dye for contrast enhancement. Fifty consecutive cases (mean age 44.4 ± 3.34 years, 60% women, BMI 27.6 ± 5.82 kg/m 2 ) were evaluated. Endoscopic imaging quality was satisfactory in all the cases, with no differences between methods (p = 0.817). The detection rate of premalignant lesions and early gastric cancer was 14% (6 cases of intestinal metaplasia and one case of gastric adenocarcinoma). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 100, 95, 80, 100 and 96%, respectively, for systematic alphanumeric-coded endoscopy, and 100, 45, 20, 100, and 52%, respectively, for conventional endoscopy. Lesion detection through systematic alphanumeric-coded endoscopy was superior to that of conventional endoscopy (p = 0.003; OR = 12). Both techniques were effective, but systematic alphanumeric-coded endoscopy significantly reduced the false positive rate. Copyright © 2018 Asociación Mexicana de

Stokes shift spectroscopy for the early diagnosis of epithelial precancers in DMBA treated mouse skin carcinogenesis

NASA Astrophysics Data System (ADS)

Jeyasingh, Ebenezar; Singaravelu, Ganesan; Prakasarao, Aruna

2018-02-01

In this study, we aim to characterize the tissue transformation in dimethylbenz(a)anthracene (DMBA) treated mouse skin tumor model using stokes shift spectroscopy (SSS) technique for early detection of the neoplastic changes. Stokes shift (SS) spectra measured by scanning both excitation and emission wavelength simultaneously with a fixed wavelength of interval (Δλ=20 nm) in vivo from 33 DMBA treated animals and 6 control animals. The SS spectra of normal (n=6), hyperplasia (n=10), dysplasia (n=10), and WDSCC (n=13) of mice skin shows the distinct peaks around 300, 350, and 386 nm may be attributed to tryptophan, collagen, and NADH respectively. From the observed spectral differences and the ratio variables that resulted in better classification between groups, it is concluded that tryptophan, collagen, and NADH are the key fluorophores that undergo changes during tissue transformation process and hence they can be targeted as tumor markers for early neoplastic changes.

Pathologic observations of the duodenum in 615 consecutive duodenal specimens: I. benign lesions

PubMed Central

Terada, Tadashi

2012-01-01

The author investigated histopathology of 615 consecutive duodenal specimens in our pathology laboratory. Computer search of the duodenal lesions was performed. Review of histological slides was done, when appropriate. The duodenal specimens were composed of 567 benign lesions and 48 malignant lesions. The 567 benign lesions were composed of chronic non-specific duodenitis in 334 cases (60.0%), duodenal ulcer in 101 cases (17,8%), heterotopic gastric mucosa in 81 cases (14.3%), hyperplastic polyp in 16 cases (2.8%), Brunner's gland hyperplasia in 14 cases (2.5%), Brunner's gland adenoma in 8 cases (1.4%), lymphoid polyp in 5 cases (0.8%), tubular adenoma in 4 cases (0.7%), lymphangioma in 2 cases (0.4%), endocrine nests in 1 case (0.2%), and amyloidosis in 1 case (0.2%). The chronic non-specific duodenitis was characterized by edema and lymphocytic infiltration. The duodenal ulcer was characterized by exudate, necrosis, granulation tissue and regenerative epithelium. The heterotopic gastric mucosa consisted of two types: one was composed of only foveolar epithelium (n=21) and another foveolar epithelium and fundic glands (n=60). Hyperplastic polyp was characterized by proliferation of gastric foveolar-like epithelium. The Brunner's gland hyperplasia was characterized by hyperplastic proliferation of the gland. The Brunner gland adenoma was characterized by neoplastic proliferation of the gland. The lymphoid polyp was characterized by large lymph follicles with large germinal centers. The tubular adenoma was characterized by adenomatous proliferation of intestinal epithelium, similar to colon adenoma. The lymphangioma was characterized by submucosal cavernous proliferation of lymphatics. The endocrine cell nests were characterized by non-neoplasmic proliferation of neuroendocrine cells. The amyloidosis was characterized by deposition of amorphous materials positive with Congo-red stain. PMID:22295146

Pathologic observations of the duodenum in 615 consecutive duodenal specimens: I. benign lesions.

PubMed

Terada, Tadashi

2012-01-01

The author investigated histopathology of 615 consecutive duodenal specimens in our pathology laboratory. Computer search of the duodenal lesions was performed. Review of histological slides was done, when appropriate. The duodenal specimens were composed of 567 benign lesions and 48 malignant lesions. The 567 benign lesions were composed of chronic non-specific duodenitis in 334 cases (60.0%), duodenal ulcer in 101 cases (17,8%), heterotopic gastric mucosa in 81 cases (14.3%), hyperplastic polyp in 16 cases (2.8%), Brunner's gland hyperplasia in 14 cases (2.5%), Brunner's gland adenoma in 8 cases (1.4%), lymphoid polyp in 5 cases (0.8%), tubular adenoma in 4 cases (0.7%), lymphangioma in 2 cases (0.4%), endocrine nests in 1 case (0.2%), and amyloidosis in 1 case (0.2%). The chronic non-specific duodenitis was characterized by edema and lymphocytic infiltration. The duodenal ulcer was characterized by exudate, necrosis, granulation tissue and regenerative epithelium. The heterotopic gastric mucosa consisted of two types: one was composed of only foveolar epithelium (n=21) and another foveolar epithelium and fundic glands (n=60). Hyperplastic polyp was characterized by proliferation of gastric foveolar-like epithelium. The Brunner's gland hyperplasia was characterized by hyperplastic proliferation of the gland. The Brunner gland adenoma was characterized by neoplastic proliferation of the gland. The lymphoid polyp was characterized by large lymph follicles with large germinal centers. The tubular adenoma was characterized by adenomatous proliferation of intestinal epithelium, similar to colon adenoma. The lymphangioma was characterized by submucosal cavernous proliferation of lymphatics. The endocrine cell nests were characterized by non-neoplasmic proliferation of neuroendocrine cells. The amyloidosis was characterized by deposition of amorphous materials positive with Congo-red stain.

Laser speckle imaging for lesion detection on tooth

NASA Astrophysics Data System (ADS)

Gavinho, Luciano G.; Silva, João. V. P.; Damazio, João. H.; Sfalcin, Ravana A.; Araujo, Sidnei A.; Pinto, Marcelo M.; Olivan, Silvia R. G.; Prates, Renato A.; Bussadori, Sandra K.; Deana, Alessandro M.

2018-02-01

Computer vision technologies for diagnostic imaging applied to oral lesions, specifically, carious lesions of the teeth, are in their early years of development. The relevance of this public problem, dental caries, worries countries around the world, as it affects almost the entire population, at least once in the life of each individual. The present work demonstrates current techniques for obtaining information about lesions on teeth by segmentation laser speckle imagens (LSI). Laser speckle image results from laser light reflection on a rough surface, and it was considered a noise but has important features that carry information about the illuminated surface. Even though these are basic images, only a few works have analyzed it by application of computer vision methods. In this article, we present the latest results of our group, in which Computer vision techniques were adapted to segment laser speckle images for diagnostic purposes. These methods are applied to the segmentation of images between healthy and lesioned regions of the tooth. These methods have proven to be effective in the diagnosis of early-stage lesions, often imperceptible in traditional diagnostic methods in the clinical practice. The first method uses first-order statistical models, segmenting the image by comparing the mean and standard deviation of the intensity of the pixels. The second method is based on the distance of the chi-square (χ2 ) between the histograms of the image, bringing a significant improvement in the precision of the diagnosis, while a third method introduces the use of fractal geometry, exposing, through of the fractal dimension, more precisely the difference between lesioned areas and healthy areas of a tooth compared to other methods of segmentation. So far, we can observe efficiency in the segmentation of the carious regions. A software was developed for the execution and demonstration of the applicability of the models

Low plasma selenium concentration is associated with elevated risk to neoplastic polyps of the colon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, L.C.; Hixson, L.G.; Sampliner, R.E.

1991-03-11

A cross-sectional study was conducted to examine the relationship of selenium (Se) status and polyps incidence in a sequential series of 100 patients undergoing outpatient colonoscopies at the Tucson VA Hospital. Se was measured in plasma samples by electrothermal atomic absorption spectrophotometry with Zeeman background correction using a reduced palladium matrix modified. The activities of the Se-dependent enzyme glutathione peroxidase (SeGSHpx) were measured using H{sub 2}O{sub 2} as substrate in all plasma samples and in colonic mucosal biopsies obtained from some patients. The mean plasma Se concentration of patients without polyps was 134 ng/ml. Mean plasma Se levels of patientsmore » with only diminutive or large polyps were 127 ng/ml and 125 ng/ml; while patients with polyps of both sizes had a mean plasma Se level of 121 ng/ml. Patients with no reported history of cancer, neoplastic polyps or prior colonoscopy, showed an inverse association of plasma Se level and risk of benign colonic neoplasms. The age-adjusted odds ratio for neoplastic polyps was 3.8 for patients with plasma Se levels below vs. above the median value. This association was stronger for patients under 68 yrs of age than for older patients. Activities of SeGSHpx in plasma or colonic mucosa were not related to plasma Se level; however, smokers showed greater SeGSHpx activities than non-smokers. This study is the first to detect an association of Se status and risk to neoplastic polyps of the colon.« less

Early malignant syphilis*

PubMed Central

Ortigosa, Yara Martins; Bendazzoli, Paulo Salomão; Barbosa, Angela Marques; Ortigosa, Luciena Cegatto Martins

2016-01-01

Early malignant syphilis is a rare and severe variant of secondary syphilis. It is clinically characterized by lesions, which can suppurate and be accompanied by systemic symptoms such as high fever, asthenia, myalgia, and torpor state. We report a diabetic patient with characteristic features of the disease showing favorable evolution of the lesions after appropriate treatment. PMID:28300925

Skin signs of systemic infections and neoplastic diseases.

PubMed

Manuelyan, Karen L; Bogdanov, Ivan A; Darlenski, Razvigor B

2017-10-01

In recent years, emphasis on the physical examination has made way for a plethora of laboratory tests and sophisticated imaging diagnostic techniques. In addition, we are witnessing an underestimation of dermatology as a specialty around the world, which is accepted as an ambulatory specialty on the border of cosmetology and beautification. However, recognizing specific cutaneous clinical signs can facilitate timely diagnosis of various systemic infections and neoplastic diseases. Thus, a skilled dermatologist can play an essential role in the multidisciplinary team, involved in the care for systemically ill patients. In this article, we will focus on some life threatening systemic infections in which the skin changes can be a major clue for the diagnosis. Recent deadly epidemics will also be focused. Classic examples of paraneoplastic skin conditions will also be provided.

Surgical induction, histological evaluation, and MRI identification of cartilage necrosis in the distal femur in goats to model early lesions of osteochondrosis.

PubMed

Tóth, F; Nissi, M J; Wang, L; Ellermann, J M; Carlson, C S

2015-02-01

Identify and interrupt the vascular supply to portions of the distal femoral articular-epiphyseal cartilage complex (AECC) in goat kids to induce cartilage necrosis, characteristic of early lesions of osteochondrosis (OC); then utilize magnetic resonance imaging (MRI) to identify necrotic areas of cartilage. Distal femora were perfused and cleared in goat kids of various ages to visualize the vascular supply to the distal femoral AECC. Vessels located on the axial aspect of the medial femoral condyle (MFC) and on the abaxial side of the lateral trochlear ridge were transected in eight 4- to 5-day-old goats to induce cartilage necrosis. Goats were euthanized 1, 2, 3, 4, 5, 6, 9, and 10 weeks post operatively and operated stifles were harvested. Adiabatic T1ρ relaxation time maps of the harvested distal femora were generated using a 9.4 T MR scanner, after which samples were evaluated histologically. Interruption of the vascular supply to the MFC caused lesions of cartilage necrosis in 6/8 goat kids that were demonstrated histologically. Adiabatic T1ρ relaxation time mapping identified these areas of cartilage necrosis in 5/6 cases. No significant findings were detected after transection of perichondrial vessels supplying the lateral trochlear ridge. Cartilage necrosis, characteristic of early OC, can be induced by interrupting the vascular supply to the distal femoral AECC in goat kids. The ability of high field MRI to identify these areas of cartilage necrosis in the AECC using the adiabatic T1ρ sequence suggests that this technique may be useful in the future for the early diagnosis of OC. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia

PubMed Central

Foster, K. Wade; Liu, Zhaoli; Nail, Clinton D.; Li, Xingnan; Fitzgerald, Thomas J.; Bailey, Sarah K.; Frost, Andra R.; Louro, Iuri D.; Townes, Tim M.; Paterson, Andrew J.; Kudlow, Jeffrey E.; Lobo-Ruppert, Susan M.; Ruppert, J. Michael

2006-01-01

KLF4/GKLF normally functions in differentiating epithelial cells, but also acts as a transforming oncogene in vitro. To examine the role of this zinc finger protein in skin, we expressed the wild-type human allele from inducible and constitutive promoters. When induced in basal keratinocytes KLF4 rapidly abolished the distinctive properties of basal and parabasal epithelial cells. KLF4 caused a transitory apoptotic response and the skin progressed through phases of hyperplasia and dysplasia. By 6 weeks, lesions exhibited nuclear KLF4 and other morphologic and molecular similarities to squamous cell carcinoma in situ. p53 determined the patch size sufficient to establish lesions, as induction in a mosaic pattern produced skin lesions only when p53 was deficient. Compared with p53 wild-type animals, p53 hemizygous animals had early onset of lesions and a pronounced fibrovascular response that included outgrowth of subcutaneous sarcoma. A KLF4-estrogen receptor fusion protein showed tamoxifen-dependent nuclear localization and conditional transformation in vitro. The results suggest that KLF4 can function in the nucleus to induce squamous epithelial dysplasia, and indicate roles for p53 and epithelial-mesenchymal signaling in these early neoplastic lesions. PMID:15674344

Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia.

PubMed

Foster, K Wade; Liu, Zhaoli; Nail, Clinton D; Li, Xingnan; Fitzgerald, Thomas J; Bailey, Sarah K; Frost, Andra R; Louro, Iuri D; Townes, Tim M; Paterson, Andrew J; Kudlow, Jeffrey E; Lobo-Ruppert, Susan M; Ruppert, J Michael

2005-02-24

KLF4/GKLF normally functions in differentiating epithelial cells, but also acts as a transforming oncogene in vitro. To examine the role of this zinc finger protein in skin, we expressed the wild-type human allele from inducible and constitutive promoters. When induced in basal keratinocytes, KLF4 rapidly abolished the distinctive properties of basal and parabasal epithelial cells. KLF4 caused a transitory apoptotic response and the skin progressed through phases of hyperplasia and dysplasia. By 6 weeks, lesions exhibited nuclear KLF4 and other morphologic and molecular similarities to squamous cell carcinoma in situ. p53 determined the patch size sufficient to establish lesions, as induction in a mosaic pattern produced skin lesions only when p53 was deficient. Compared with p53 wild-type animals, p53 hemizygous animals had early onset of lesions and a pronounced fibrovascular response that included outgrowth of subcutaneous sarcoma. A KLF4-estrogen receptor fusion protein showed tamoxifen-dependent nuclear localization and conditional transformation in vitro. The results suggest that KLF4 can function in the nucleus to induce squamous epithelial dysplasia, and indicate roles for p53 and epithelial-mesenchymal signaling in these early neoplastic lesions.

Prevalence and features of colorectal lesions among Hispanics: A hospital-based study.

PubMed

Ashktorab, Hassan; Laiyemo, Adeyinka O; Lee, Edward; Cruz-Correa, Marcia; Ghuman, Amita; Nouraie, Mehdi; Brim, Hassan

2015-12-14

To evaluate the prevalence and characteristics of colorectal adenoma and carcinoma in an inner city Hispanic population. We reviewed the reports of 1628 Hispanic patients who underwent colonoscopy at Howard University from 2000 to 2010. Advanced adenoma was defined as adenoma ≥ 1 cm in size, adenomas with villous histology, high grade dysplasia and/or invasive cancer. Statistical analysis was performed using χ(2) statistics and t-test. The median age of the patients was 54 years, 64.2% were females. Polyps were observed in 489 (30.0%) of patients. Adenoma prevalence was 16.8% (n = 273), advanced adenoma 2.4% (n = 39), and colorectal cancer 0.4% (n = 7). Hyperplastic polyps were seen in 6.6% of the cohort (n = 107). Adenomas predominantly exhibited a proximal colonic distribution (53.7%, n = 144); while hyperplastic polyps were mostly located in the distal colon (70%, n = 75). Among 11.7% (n = 191) patients who underwent screening colonoscopy, the prevalence of colorectal lesions was 21.4% adenoma, 2.6% advanced adenoma; and 8.3% hyperplastic polyps. Our data showed low colorectal cancer prevalence among Hispanics in the Washington DC area. However, the pre-neoplastic pattern of colonic lesions in Hispanics likely points toward a shift in this population that needs to be monitored closely through large epidemiological studies.

Prevalence and features of colorectal lesions among Hispanics: A hospital-based study

PubMed Central

Ashktorab, Hassan; Laiyemo, Adeyinka O; Lee, Edward; Cruz-Correa, Marcia; Ghuman, Amita; Nouraie, Mehdi; Brim, Hassan

2015-01-01

AIM: To evaluate the prevalence and characteristics of colorectal adenoma and carcinoma in an inner city Hispanic population. METHODS: We reviewed the reports of 1628 Hispanic patients who underwent colonoscopy at Howard University from 2000 to 2010. Advanced adenoma was defined as adenoma ≥ 1 cm in size, adenomas with villous histology, high grade dysplasia and/or invasive cancer. Statistical analysis was performed using χ2 statistics and t-test. RESULTS: The median age of the patients was 54 years, 64.2% were females. Polyps were observed in 489 (30.0%) of patients. Adenoma prevalence was 16.8% (n = 273), advanced adenoma 2.4% (n = 39), and colorectal cancer 0.4% (n = 7). Hyperplastic polyps were seen in 6.6% of the cohort (n = 107). Adenomas predominantly exhibited a proximal colonic distribution (53.7%, n = 144); while hyperplastic polyps were mostly located in the distal colon (70%, n = 75). Among 11.7% (n = 191) patients who underwent screening colonoscopy, the prevalence of colorectal lesions was 21.4% adenoma, 2.6% advanced adenoma; and 8.3% hyperplastic polyps. CONCLUSION: Our data showed low colorectal cancer prevalence among Hispanics in the Washington DC area. However, the pre-neoplastic pattern of colonic lesions in Hispanics likely points toward a shift in this population that needs to be monitored closely through large epidemiological studies. PMID:26673447

Measuring effectiveness of the cervical cancer vaccine in an Australian setting (the VACCINE study).

PubMed

Young, Elisa J; Tabrizi, Sepehr N; Brotherton, Julia Ml; Wark, John D; Pyman, Jan; Saville, Marion; Wrede, C David; Jayasinghe, Yasmin; Tan, Jeffrey; Gertig, Dorota M; Pitts, Marian; Garland, Suzanne M

2013-06-19

The quadrivalent human papillomavirus vaccine has been provided in Australia through the National Human Papillomavirus Vaccination Program since April 2007. National registry data demonstrates good coverage of the vaccine, with 73% of school-aged girls having received all three doses. To evaluate the effectiveness of the program, we propose a two-pronged approach. In one (sub study A), the prevalence of the vaccine-targeted human papillomavirus genotypes in a population cohort is being estimated, and will be analysed in relation to vaccination status, cervical cytology screening status, demographic, social, behavioural, medical and clinical factors. In sub study B, the distribution of human papillomavirus genotypes detected in high grade cervical intraepithelial neoplastic lesions from vaccine eligible women is being assessed. Sub Study A involves the recruitment of 1569 women aged 18-25, residing in Victoria, Australia, through Facebook advertising. Women who are sexually active are being asked to provide a self-collected vaginal swab, collected at home and posted into the study centre, where human papillomavirus DNA detection and genotyping is performed. Participants also complete an online questionnaire regarding sexual history, experience with, knowledge of, and attitudes towards human papillomavirus, the human papillomavirus vaccine, and cervical screening.Sub Study B will involve the collection of 500 cervical biopsies, positively identified as containing high grade cervical intraepithelial neoplastic lesions and/or adenocarcinoma in situ. Five serial sections are being taken from each case: sections 1 and 5 are being assessed to confirm the presence of the high grade cervical intraepithelial neoplastic lesions or adenocarcinoma in situ; human papillomavirus genotyping is performed on sections 2 and 3; single lesions are excised from section 4 using laser capture microdissection to specifically define causality of a human papillomavirus genotyping of each

Althaea rosea Cavanil and Plantago major L. suppress neoplastic cell transformation through the inhibition of epidermal growth factor receptor kinase.

PubMed

Choi, Eun-Sun; Cho, Sung-Dae; Shin, Ji-Ae; Kwon, Ki Han; Cho, Nam-Pyo; Shim, Jung-Hyun

2012-10-01

For thousands of years in Asia, Althaea rosea Cavanil (ARC) and Plantago major L. (PML) have been used as powerful non-toxic therapeutic agents that inhibit inflammation. However, the anticancer mechanisms and molecular targets of ARC and PML are poorly understood, particularly in epidermal growth factor (EGF)-induced neoplastic cell transformation. The aim of this study was to evaluate the chemopreventive effects and mechanisms of the methanol extracts from ARC (MARC) and PML (MPML) in EGF-induced neoplastic cell transformation of JB6 P+ mouse epidermal cells using an MTS assay, anchorage-independent cell transformation assay and western blotting. Our results showed that MARC and MPML significantly suppressed neoplastic cell transformation by inhibiting the kinase activity of the EGF receptor (EGFR). The activation of EGFR by EGF was suppressed by MARC and MPML treatment in EGFR(+/+) cells, but not in EGFR(-/-) cells. In addition, MARC and MPML inhibited EGF-induced cell proliferation in EGFR-expressing murine embryonic fibroblasts (EGFR(+/+)). These results strongly indicate that EGFR targeting by MARC and MPML may be a good strategy for chemopreventive or chemotherapeutic applications.

Reactive oral lesions associated with dental implants. A systematic review.

PubMed

Atarbashi-Moghadam, Fazele; Atarbashi-Moghadam, Saede; Namdari, Mahshid; Shahrabi-Farahani, Shokoufeh

2018-05-11

Reactive lesion formation around dental implants a complication that has been given much consideration. These lesions can lead to marginal bone loss, and consequently, implant failure. In the present systematic review, all reported reactive lesions associated with dental implants in the literature were assessed. An electronic search was performed using PubMed Central, Scopus, Google Scholar, and Science Direct. The search strategy was limited to human studies (case reports and case series), full-text English language articles, published until May 2017. A total of 19 articles reporting 27 lesions in 25 cases were included. Peripheral giant cell granuloma and pyogenic granuloma were the most reactive lesions found around dental implants. The mean age of the patients was 51.28 ± 14.48 years, with a slight female predilection. Posterior mandibular gingiva was the most common location for these lesions. The recurrence rate of lesions was 33.33%, and the chance of implant removal was 29.62%. Due to the clinical significance of these lesions, early histopathologic examination is recommended to exclude the presence of such pathological lesions. © 2018 John Wiley & Sons Australia, Ltd.

Thermographic diagnostics to discriminate skin lesions: a clinical study

NASA Astrophysics Data System (ADS)

Stringasci, Mirian Denise; Moriyama, Lilian Tan; Salvio, Ana Gabriela; Bagnato, Vanderlei Salvador; Kurachi, Cristina

2015-06-01

Cancer is responsible for about 13% of all causes of death in the world. Over 7 million people die annually of this disease. In most cases, the survival rates are greater when diagnosed in early stages. It is known that tumor lesions present a different temperature compared with the normal tissues. Some studies have been performed in an attempt to establish new diagnosis methods, targeting this temperature difference. In this study, we aim to investigate the use of a handheld thermographic camera to discriminate skin lesions. The patients presenting Basal Cell Carcinoma, Squamous Cell Carcinoma, Actinic Keratosis, Pigmented Seborrheic Keratosis, Melanoma or Intradermal Nevus lesions have been investigated at the Skin Departament of Amaral Carvalho Hospital. Patients are selected by a dermatologist, and the lesion images are recorded using an infrared camera. The images are evaluated taken into account the temperature level, and differences into lesion areas, borders, and between altered and normal skin. The present results show that thermography may be an important tool for aiding in the clinical diagnostics of superficial skin lesions.

Automatic Classification of Specific Melanocytic Lesions Using Artificial Intelligence.

PubMed

Jaworek-Korjakowska, Joanna; Kłeczek, Paweł

2016-01-01

Given its propensity to metastasize, and lack of effective therapies for most patients with advanced disease, early detection of melanoma is a clinical imperative. Different computer-aided diagnosis (CAD) systems have been proposed to increase the specificity and sensitivity of melanoma detection. Although such computer programs are developed for different diagnostic algorithms, to the best of our knowledge, a system to classify different melanocytic lesions has not been proposed yet. In this research we present a new approach to the classification of melanocytic lesions. This work is focused not only on categorization of skin lesions as benign or malignant but also on specifying the exact type of a skin lesion including melanoma, Clark nevus, Spitz/Reed nevus, and blue nevus. The proposed automatic algorithm contains the following steps: image enhancement, lesion segmentation, feature extraction, and selection as well as classification. The algorithm has been tested on 300 dermoscopic images and achieved accuracy of 92% indicating that the proposed approach classified most of the melanocytic lesions correctly. A proposed system can not only help to precisely diagnose the type of the skin mole but also decrease the amount of biopsies and reduce the morbidity related to skin lesion excision.

All-optical photoacoustic imaging and detection of early-stage dental caries

NASA Astrophysics Data System (ADS)

Sampathkumar, Ashwin; Hughes, David A.; Longbottom, Chris; Kirk, Katherine J.

2015-02-01

Dental caries remain one of the most common oral diseases in the world. Current detection methods, such as dental explorer and X-ray radiography, suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease because of the small size (< 100 microns) of early-stage lesions. We have developed a fine-resolution (480 nm), ultra-broadband (1 GHz), all-optical photoacoustic imaging (AOPAI) system to image and detect early stages of tooth decay. This AOPAI system provides a non-contact, non-invasive and non-ionizing means of detecting early-stage dental caries. Ex-vivo teeth exhibiting early-stage, white-spot lesions were imaged using AOPAI. Experimental scans targeted each early-stage lesion and a reference healthy enamel region. Photoacoustic (PA) signals were generated in the tooth using a 532-nm pulsed laser and the light-induced broadband ultrasound signal was detected at the surface of the tooth with an optical path-stabilized Michelson interferometer operating at 532 nm. The measured time-domain signal was spatially resolved and back-projected to form 2D and 3D maps of the lesion using k-wave reconstruction methods. Experimental data collected from areas of healthy and diseased enamel indicate that the lesion generated a larger PA response compared to healthy enamel. The PA-signal amplitude alone was able to detect a lesion on the surface of the tooth. However, time- reversal reconstructions of the PA scans also quantitatively depicted the depth of the lesion. 3D PA reconstruction of the diseased tooth indicated a sub-surface lesion at a depth of 0.6 mm, in addition to the surface lesion. These results suggest that our AOPAI system is well suited for rapid clinical assessment of early-stage dental caries. An overview of the AOPAI system, fine-resolution PA and histology results of diseased and healthy teeth will be presented.

Automatic colonic lesion detection and tracking in endoscopic videos

NASA Astrophysics Data System (ADS)

Li, Wenjing; Gustafsson, Ulf; A-Rahim, Yoursif

2011-03-01

The biology of colorectal cancer offers an opportunity for both early detection and prevention. Compared with other imaging modalities, optical colonoscopy is the procedure of choice for simultaneous detection and removal of colonic polyps. Computer assisted screening makes it possible to assist physicians and potentially improve the accuracy of the diagnostic decision during the exam. This paper presents an unsupervised method to detect and track colonic lesions in endoscopic videos. The aim of the lesion screening and tracking is to facilitate detection of polyps and abnormal mucosa in real time as the physician is performing the procedure. For colonic lesion detection, the conventional marker controlled watershed based segmentation is used to segment the colonic lesions, followed by an adaptive ellipse fitting strategy to further validate the shape. For colonic lesion tracking, a mean shift tracker with background modeling is used to track the target region from the detection phase. The approach has been tested on colonoscopy videos acquired during regular colonoscopic procedures and demonstrated promising results.

THE SIGNIFICANCE OF LESIONS IN PERIPHERAL GANGLIA IN CHIMPANZEE AND IN HUMAN POLIOMYELITIS

PubMed Central

Bodian, David; Howe, Howard A.

1947-01-01

1. The peripheral ganglia of eighteen inoculated chimpanzees and thirteen uninoculated controls, and of eighteen fatal human poliomyelitis cases, were studied for histopathological evidence of the route of transmission of virus from the alimentary tract to the CNS. 2. Lesions thought to be characteristic of poliomyelitis in inoculated chimpanzees could not be sharply differentiated from lesions of unknown origin in uninoculated control animals. Moreover, although the inoculated animals as a group, in comparison with the control animals, had a greater number of infiltrative lesions in sympathetic as well as in sensory ganglia, it was not possible to make satisfactory correlations between the distribution of these lesions and the routes of inoculation. 3. In sharp contrast with chimpanzees, the celiac and stellate ganglia of the human poliomyelitis cases were free of any but insignificant infiltrative lesions. Lesions in human trigeminal and spinal sensory ganglia included neuronal damage as well as focal and perivascular inflitrative lesions, as is well known. In most ganglia, as in monkey and chimpanzee sensory ganglia, these were correlated in intensify with the degree of severity of lesions in the region of the CNS receiving their axons. This suggested that lesions in sensory ganglia probably resulted from spread of virus centrifugally from the CNS, in accord with considerable experimental evidence. 4. Two principal difficulties in the interpretation of histopathological findings in peripheral ganglia were revealed by this study. The first is that the specificity of lesions in sympathetic ganglia has not been established beyond doubt as being due to poliomyelitis. The second is that the presence of characteristic lesions in sensory ganglia does not, and cannot, reveal whether the virus reached the ganglia from the periphery or from the central nervous system, except in very early preparalytic stages or in exceptional cases of early arrest of virus spread and of

Differentiation of early from advanced coronary atherosclerotic lesions: systematic comparison of CT, intravascular US, and optical frequency domain imaging with histopathologic examination in ex vivo human hearts.

PubMed

Maurovich-Horvat, Pál; Schlett, Christopher L; Alkadhi, Hatem; Nakano, Masataka; Stolzmann, Paul; Vorpahl, Marc; Scheffel, Hans; Tanaka, Atsushi; Warger, William C; Maehara, Akiko; Ma, Shixin; Kriegel, Matthias F; Kaple, Ryan K; Seifarth, Harald; Bamberg, Fabian; Mintz, Gary S; Tearney, Guillermo J; Virmani, Renu; Hoffmann, Udo

2012-11-01

To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques. All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen κ statistic. Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both P<.0001), while mixed plaque at coronary CT angiography, calcified plaque at intravascular US, and lipid-rich plaque at OFDI were associated with advanced lesions (OR: 2.49, P=.0003; OR: 2.60, P=.002; and OR: 31.2, P<.0001, respectively). OFDI had higher accuracy for discriminating early from advanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, P<.0001). Interobserver agreement was excellent for OFDI and coronary CT angiography (κ=0.87 and 0.85, respectively) and was good for intravascular US (κ=0.66). Systematic and standardized comparison between invasive and noninvasive modalities for coronary plaque characterization in ex vivo specimens demonstrated that coronary CT angiography and intravascular US are

Suppression of Medulloblastoma Lesions by Forced Migration of Preneoplastic Precursor Cells with Intracerebellar Administration of the Chemokine Cxcl3.

PubMed

Ceccarelli, Manuela; Micheli, Laura; Tirone, Felice

2016-01-01

Medulloblastoma (MB), tumor of the cerebellum, remains a leading cause of cancer-related mortality in childhood. We previously showed, in a mouse model of spontaneous MB ( Ptch1 +/- / Tis21 -/- ), that a defect of the migration of cerebellar granule neuron precursor cells (GCPs) correlates with an increased frequency of MB. This occurs because GCPs, rather than migrating internally and differentiating, remain longer in the proliferative area at the cerebellar surface, becoming targets of transforming insults. Furthermore, we identified the chemokine Cxcl3 as responsible for the inward migration of GCPs. As it is known that preneoplastic GCPs (pGCPs) can still migrate and differentiate like normal GCPs, thus exiting the neoplastic program, in this study we tested the hypothesis that pGCPs within a MB lesion could be induced by Cxcl3 to migrate and differentiate. We observed that the administration of Cxcl3 for 28 days within the cerebellum of 1-month-old Ptch1 +/- / Tis21 -/- mice, i.e., when MB lesions are already formed, leads to complete disappearance of the lesions. However, a shorter treatment with Cxcl3 (2 weeks) was ineffective, suggesting that the suppression of MB lesions is dependent on the duration of Cxcl3 application. We verified that the treatment with Cxcl3 causes a massive migration of pGCPs from the lesion to the internal granular layer, where they differentiate. Thus, the induction of migration of pGCPs in MB lesions may open new ways to treat MB that exploit the plasticity of the pGCPs, forcing their differentiation. It remains to be tested whether this plasticity continues at advanced stages of MB. If so, these findings would set a potential use of the chemokine Cxcl3 as therapeutic agent against MB development in human preclinical studies.

Lesion progression in post-treatment persistent endodontic lesions.

PubMed

Yu, Victoria Soo Hoon; Messer, Harold Henry; Shen, Liang; Yee, Robert; Hsu, Chin-ying Stephen

2012-10-01

Radiographic lesions related to root-filled teeth may persist for long periods after treatment and are considered to indicate failure of initial treatment. Persistent lesions are found in a proportion of cases, but information on lesion progression is lacking. This study examined the incidence of lesion improvement, remaining unchanged, and deterioration among persistent lesions in a group of patients recruited from a university-based clinic and identified potential predictors for lesion progression. Patients of a university clinic with persistent endodontic lesions at least 4 years since treatment and with original treatment radiographs available were recruited with informed consent. Data were obtained by interview and from dental records and clinical and radiographic examinations. Univariate and multivariate statistical analyses were carried out by using SPSS (version 19). One hundred fifty-one persistent lesions were identified in 114 patients. A majority of the lesions (107, 70.9%) received treatment between 4 and 5 years prior. Eighty-six lesions (57.0%) improved, 18 (11.9%) remained unchanged, and 47 (31.1%) deteriorated since treatment. Potential predictors for lesions that did not improve included recall lesion size, pain on biting at recall examination, history of a postobturation flare-up, and a non-ideal root-filling length (P < .05). Lesions that had persisted for a longer period appeared less likely to be improving (relative risk, 1.038; 95% confidence interval, 1.000-1.077). A specific time interval alone should not be used to conclude that a lesion will not resolve without intervention. This study identified several clinical factors that are associated with deteriorating persistent lesions, which should aid in identifying lesions that require further intervention. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Computer-Aided Diagnosis of Micro-Malignant Melanoma Lesions Applying Support Vector Machines.

PubMed

Jaworek-Korjakowska, Joanna

2016-01-01

Background. One of the fatal disorders causing death is malignant melanoma, the deadliest form of skin cancer. The aim of the modern dermatology is the early detection of skin cancer, which usually results in reducing the mortality rate and less extensive treatment. This paper presents a study on classification of melanoma in the early stage of development using SVMs as a useful technique for data classification. Method. In this paper an automatic algorithm for the classification of melanomas in their early stage, with a diameter under 5 mm, has been presented. The system contains the following steps: image enhancement, lesion segmentation, feature calculation and selection, and classification stage using SVMs. Results. The algorithm has been tested on 200 images including 70 melanomas and 130 benign lesions. The SVM classifier achieved sensitivity of 90% and specificity of 96%. The results indicate that the proposed approach captured most of the malignant cases and could provide reliable information for effective skin mole examination. Conclusions. Micro-melanomas due to the small size and low advancement of development create enormous difficulties during the diagnosis even for experts. The use of advanced equipment and sophisticated computer systems can help in the early diagnosis of skin lesions.

Global aphasia without hemiparesis: language profiles and lesion distribution

PubMed Central

Hanlon, R.; Lux, W.; Dromerick, A.

1999-01-01

OBJECTIVES—Global aphasia without hemiparesis (GAWH) is an uncommon stroke syndrome involving receptive and expressive language impairment, without the hemiparesis typically manifested by patients with global aphasia after large left perisylvian lesions. A few cases of GAWH have been reported with conflicting conclusions regarding pathogenesis, lesion localisation, and recovery. The current study was conducted to attempt to clarify these issues.
METHODS—Ten cases of GAWH were prospectively studied with language profiles and lesion analysis; five patients had multiple lesions, four patients had a single lesion, and one had a subarachnoid haemorrhage. Eight patients met criteria for cardioembolic ischaemic stroke.
RESULTS—Cluster analysis based on acute language profiles disclosed three subtypes of patients with GAWH; these clusters persisted on follow up language assessment. Each cluster evolved into a different aphasia subtype: persistent GAWH, Wernicke's aphasia, or transcortical motor aphasia (TCM). Composite lesion analysis showed that persistent GAWH was related to lesioning of the left superior temporal gyrus. Patients with acute GAWH who evolved into TCM type aphasia had common lesioning of the left inferior frontal gyrus and adjacent subcortical white matter. Patients with acute GAWH who evolved into Wernicke's type aphasia were characterised by lesioning of the left precentral and postcentral gyri. Recovery of language was poor in all but one patient.
CONCLUSIONS—Although patients with acute GAWH are similar on neurological examination, they are heterogeneous with respect to early aphasia profile, language recovery, and lesion profile.

 PMID:10084536

Early storage lesions in apheresis platelets are induced by the activation of the integrin αIIbβ₃ and focal adhesion signaling pathways.

PubMed

Thiele, Thomas; Iuga, Cristina; Janetzky, Susann; Schwertz, Hansjorg; Gesell Salazar, Manuela; Fürll, Birgit; Völker, Uwe; Greinacher, Andreas; Steil, Leif

2012-12-05

Production and storage of platelet concentrates (PC) induce protein changes in platelets leading to impaired platelet function. This study aimed to identify signaling pathways involved in the development of early platelet storage lesions in apheresis-PCs stored in plasma or additive solution (PAS). Apheresis-PCs from four donors were stored in plasma or in PAS at 22°C (n=4 each). Platelets were analyzed at day 0 (production day) and after 1, 6 and 9 days of storage. Platelet response to agonists (TRAP, collagen, ADP) and to hypotonic shock decreased, CD62P expression increased in both storage media over time. Using DIGE 1550 protein spots were monitored and compared to baseline values at day 0. Platelets in plasma displayed changes in 352 spots (166/day 1, 263/day 6 and 201/day 9); in PAS 325 spots changed (202/day 1, 221/day 6, 200/day 9). LC-ESI-MS/MS analysis of 405 platelet proteins revealed 32 proteins changed during storage in plasma (9/day 1, 15/day 6 and 26/day 9) and 28 in PAS (5/day 1, 20/day 6, 26/day 9). Ingenuity pathway analysis found integrin-αII(b)β(3) and focal adhesion signaling pathways involved in early alterations, being confirmed by Western blotting. Corresponding mRNAs in platelets were identified by next generation sequencing for 84 changed proteins. Integrin-αII(b)β(3) and focal adhesion signaling cause irreversible early storage lesions in apheresis platelets. This article is part of a Special Issue entitled: Integrated omics. Copyright © 2012 Elsevier B.V. All rights reserved.

Human herpesvirus-8 (HHV-8) sero-detection and HIV association in Kaposi's sarcoma (KS), non-KS tumors and non-neoplastic conditions

PubMed Central

Mwakigonja, Amos R; Pyakurel, Pawan; Kokhaei, Parviz; Pak, Fatemeh; Lema, Leonard K; Kaaya, Ephata E; Biberfeld, Peter

2008-01-01

Background The association of the human herpesvirus-8/Kaposi's sarcoma (KS)-associated herpesvirus (HHV-8/KSHV) serology with various malignancies in Tanzania is not currently well established while previous studies were based on either PCR or immunofluorescence assays [IFA] but not with a sensitive enzyme-linked immunosorbent assay (ELISA). Selected archival diagnostic biopsies (n = 184) and sera from indigenous patients with KS (n = 120), non-KS tumors (n = 24) and non-neoplastic lesions (n = 40) at Muhimbili National Hospital (MNH), Tanzania, were evaluated by diagnostic histopathology, immunohistology [anti-HHV-8 latency-associated nuclear antigen (LANA)] and serology for HIV (ELISA) and HHV-8 (IFA and ELISA). Results About 66.3% (n = 122) cases including AIDS-associated Kaposi's sarcoma (AKS) (n = 93), reactive conditions (n = 28) and only one non-KS tumour were HIV positive. Endemic KS (EKS) patients were mostly males (96.3%, 26/27) who were less (69.9%, 65/93) predominant in AIDS-associated (AKS). A high (89%) percentage of patients with anti-HHV-8 antibodies was found in the cohort including the HIV positive (92%) cases, males (81.2%), KS patients (93%), non-KS tumors (92%), and reactive conditions (75%). All HHV-8 seronegative KS cases were nodular stage whereas both sera and corresponding biopsies from early stage KS were HHV-8+. Assay sensitivity, positive predictive value (PPV) and specificity were 98.6%, 93.5% and 16.7% for IFA and 93.5%, 98.6% and 50.0% for ELISA respectively. Conclusion HHV-8 seroprevalence at MNH appears high as expected among AKS cases and males but also in non-KS patients. ELISA showed a combination of high HHV-8 sensitivity as well as higher PPV and specificity than IFA which however, showed higher sensitivity. The apparent stage-dependent, inverted serum HHV-8 immunoreactivity supports a notion of viral immune-segregation during KS development. Routine HHV-8 screening should be considered particularly in patients at risk of KS

Oral mucosal lesions in Anorexia Nervosa, Bulimia Nervosa and EDNOS.

PubMed

Panico, Rene; Piemonte, Eduardo; Lazos, Jerónimo; Gilligan, Gerardo; Zampini, Anibal; Lanfranchi, Héctor

2018-01-01

The aim of this study is to describe oral lesions in patients with eating disorders (ED), including Anorexia Nervosa (AN), Bulimia Nervosa (BN) and eating disorders not otherwise specified (EDNOS). A prospective case-control study was carried out from April 2003 to May 2004. Inclusion criteria for the study group were individuals with a diagnosis of ED; age and sex-matched individuals without ED were included as controls. Clinical data regarding ED, medical complications and oral examination were performed by previously calibrated professionals. Study group (n = 65) presented 46 cases of BN (71%), 13 of EDNOS (20%) and 6 of AN (9%); also, 94% (n = 61) showed oral lesions. The most common were: labial erythema, exfoliative cheilitis, orange-yellow palate, hemorrhagic lesions, lip-cheek biting and non-specific oral atrophies. Only two patients of the study group had dental erosions, and no case of major salivary gland swelling was found. ED display a wide array of oral mucosal lesions that can be regarded as their early manifestations. The dentist could be the first professional to detect symptoms of eating disorders, potentially improving early detection and treatment of ED. Copyright © 2017 Elsevier Ltd. All rights reserved.

Local Immune Responsiveness of Mice Bearing Premalignant Oral Lesions to PD-1 Antibody Treatment.

PubMed

Levingston, Corinne A; Young, M Rita I

2017-06-02

A carcinogen-induced premalignant oral lesion model that progresses to oral cancer was used to examine the immunological impact of a 5-week treatment regimen to block programmed cell death protein 1 (PD-1). PD-1 antibody treatment resulted in concurrent, but transient, increases in interleukin (IL)-2, IFN-γ and IL-17, and delayed increases in IL-6 and IL-10 within the lesion-bearing tongue epithelium. In contrast, cytokine secretion by lymph node cells of PD-1 antibody-treated mice was lower than for mice treated with control antibodies, with the exception of interferon (IFN)-γ, whose secretion increased late in the treatment period. This delayed secretion of IFN-γ coincided with an increase in CD4⁺ lymph node cells expressing IFN-γ. Lymph node cells of PD-1 antibody-treated mice reacted to a challenge with lysates of lesions or cancer by early production of IFN-γ, but this rapidly subsided. There also was increased production IL-17 and tumor necrosis factor (TNF)-α in response to the challenge, but the response was greatest by cells of control lesion-bearing mice. Clinical assessment showed an early but transient, stabilization of disease in mice treated with PD-1 antibody. These results show an early beneficial, but time-limited, response to PD-1 antibody treatment, which then fails with continued lesion progression.

A clinicopathologic and epidemiologic study of chronic white lesions in the oral mucosa.

PubMed

Ghosh, Sampurna; Pal, Sudipta; Ghatak, Soumya; Saha, Somnath; Biswas, Surajit; Srivastava, Prabha

2017-08-01

Invasive oral squamous cell carcinoma is often preceded by the presence of clinically identifiable premalignant changes of the oral mucosa, including white lesions. We conducted a cross-sectional, observational study to assess the clinicopathologic and epidemiologic aspects of chronic oral mucosal white lesions to determine the necessity of early biopsy in these cases. Our study population was made up of 77 patients-50 males and 27 females, aged 15 to 70 years (mean: 42.9)-who presented with white lesions persisting for at least 4 weeks. All but 3 patients underwent a biopsy; the 3 exceptions were diagnosed with smear-proven candidiasis. Patients with moderate or severe dysplasia underwent an excision biopsy. The buccal mucosa was the single most common site of white lesions, occurring in 15 patients (19.5%), although 21 patients (27.3%) exhibited a diffuse involvement of the oral mucosa. Of the 77 patients, 59 (76.6%) had concerning findings: premalignant lesions in 45 patients (58.4%) and malignant lesions in 14 (18.2%). Also, dysplasia was seen in 8 patients (10.4%), all of whom had premalignant lesions. Tobacco chewing (p = 0.008) and betel quid chewing (p = 0.029) were significantly associated with the development of premalignant and malignant lesions; a longer duration of tobacco chewing (≥10 yr) was significantly associated with a higher risk of malignant but not premalignant lesions (p = 0.031). Finally, illiteracy was a significant risk factor for premalignant and malignant lesions (p = 0.03). Our findings support the necessity of biopsy in every case. Early detection of oral carcinoma by biopsy of all oral white lesions would not only prevent patients from undergoing disfiguring surgery and chemoradiation, but it also would increase the 5-year survival rate.

[Penile fracture with associated urethra lesion: case report and bibliographic review].

PubMed

García Marchiñena, Patricio; Capiel, Leandro; Juarez, Diego; Liyo, Juan; Giudice, Carlos; Gueglio, Guillermo; Damia, Oscar

2008-10-01

Penile fracture is a rare lesion that occurs almost exclusively during erection. This lesion may be associated with rupture of the urethra in 20-30% of the cases. We describe a case that has been treated at our institution and review the literature. A-42-year-old patient suffered fracture of penis, with urethral section, during sexual intercourse. The patient underwent surgical exploration, the lesions of the corporal bodies and urethra were identified. Both lesions were repaired. patient's recovery was satisfactory without complications or esthetical or functional sequelae. Penile fracture with urethral section is an exceptional disease, the most frequent cause of which in occident is violent sexual activity. For diagnosis it is necessary in most cases a correct anamnesis and physical examination. Early surgical approach and closure of the albuginea's lesion and repair of the urethral lesion is the best way of treatment.

Comparison of the diagnostic ability of blue laser imaging magnification versus pit pattern analysis for colorectal polyps.

PubMed

Nakano, Arihiro; Hirooka, Yoshiki; Yamamura, Takeshi; Watanabe, Osamu; Nakamura, Masanao; Funasaka, Kohei; Ohno, Eizaburo; Kawashima, Hiroki; Miyahara, Ryoji; Goto, Hidemi

2017-04-01

Background and study aims  There have been few evaluations of the diagnostic ability of new narrow band light observation blue laser imaging (BLI). The present prospective study compared the diagnostic ability of BLI magnification and pit pattern analysis for colorectal polyps. Patients and methods  We collected lesions prospectively, and the analysis of images was made by two endoscopists, retrospectively. A total of 799 colorectal polyps were examined by BLI magnification and pit pattern analysis at Nagoya University Hospital. The Hiroshima narrow-band imaging classification was used for BLI. Differentiation of neoplastic from non-neoplastic lesions and diagnosis of deeply invasive submucosal cancer (dSM) were compared between BLI magnification and pit pattern analysis. Type C2 in the Hiroshima classification was evaluated separately, because application of this category as an index of the depth of cancer invasion was considered difficult. Results  We analyzed 748 colorectal polyps, excluding 51 polyps that were inflammatory polyps, sessile serrated adenoma/polyps, serrated adenomas, advanced colorectal cancers, or other lesions. The accuracy of differential diagnosis between neoplastic and non-neoplastic lesions was 98.4 % using BLI magnification and 98.7 % with pit pattern analysis. In addition, the diagnostic accuracy of BLI magnification and pit pattern analysis for dSM for cancer was 89.5 % and 92.1 %, respectively. When type C2 lesions were excluded, the diagnostic accuracy of BLI for dSM was 95.9 %. The 18 type C2 lesions comprised 1 adenoma, 9 intramucosal or slightly invasive submucosal cancers, and 8 dSM. Pit pattern analysis allowed accurate diagnosis of the depth of invasion in 13 lesions (72.2 %). Conclusions  Most colorectal polyps could be diagnosed accurately by BLI magnification without pit pattern analysis, but we should add pit pattern analysis for type C2 lesions in the Hiroshima classification.

Neoplastic transformation of human thyroid epithelial cells by ionizing radiation

NASA Astrophysics Data System (ADS)

Herceg, Zdenko

Neoplastic transformation of human thyroid epithelial cells has been investigated following exposure to ionizing radiation in vitro. The effects of radiation type, irradiation regime, and postirradiation passaging were examined using a human thyroid epithelial cell line, designated HToriS, which was previously immortalized with SV40 genome. Exponentially growing HToriS cells were irradiated with graded doses of 137 Cs gamma- and 238pu alpha-irradiation. Cells were irradiated with either a single or multiple doses of 0.5, 1, 2, 3, or 4 Gy gamma-radiation, or single doses of 0.125, 0.25, 0.5, 1, or 1.5 Gy gamma-radiation. Following passaging, the cells were transplanted into the athymic nude mice, and the animals were screened for tumour formation. Statistically significant increases in tumour incidence were obtained with both gamma- and alpha-irradiation and with both single and multiple irradiation regimes as compared with the un-irradiated group. Regardless of radiation type and or radiation regime there appears to be a trend, with increasing doses of radiation, in which tumour incidence increases and reaches a maximum, after which the tumour incidence decreases. Tumours were characterized by histopathological examination as undifferentiated carcinomas. Investigation of expression time following irradiation demonstrated that post-irradiation passaging, generally regarded as a critical step for expression of radiation-induced DNA damage, was not a prerequisite for the neoplastic conversion of irradiated cells with this system. Cell lines were established from the tumours and their identification and characterization carried out. All cell lines established were determined to be derived from the parent HTori3 cells by DNA fingerprinting, karyotype analysis, cytokeratin staining, and SV40 large T-antigen staining. Tumorigenicity of the cell lines was confirmed by retransplantation. Comparison of the morphology in vitro showed that the tumour cell lines retained the

Morel-Lavallée lesion: A closed degloving injury that requires real attention.

PubMed

Nair, Anirudh V; Nazar, Pk; Sekhar, Resmi; Ramachandran, Pv; Moorthy, Srikanth

2014-07-01

Morel-Lavallée lesions are post-traumatic, closed degloving injuries occurring deep to subcutaneous plane due to disruption of capillaries resulting in an effusion containing hemolymph and necrotic fat. Magnetic resonance imaging (MRI) is the modality of choice in the evaluation of Morel-Lavallée lesion. Early diagnosis and management is essential as any delay in diagnosis or missed lesion will lead to the effusion becoming infected or leading to extensive skin necrosis.

Relationship between somatosensory deficit and brain somatosensory system after early brain lesion: A morphometric study.

PubMed

Perivier, Maximilien; Delion, Matthieu; Chinier, Eva; Loustau, Sebastien; Nguyen, Sylvie; Ter Minassian, Aram; Richard, Isabelle; Dinomais, Mickael

2016-05-01

Cerebral Palsy (CP) is a group of permanent motor disorders due to non-progressive damage to the developing brain. Poor tactile discrimination is common in children with unilateral CP. Previous findings suggest the crucial role of structural integrity of the primary (S1) and secondary (S2) somatosensory areas located in the ipsilesional hemisphere for somatosensory function processing. However, no focus on the relationship between structural characteristics of ipsilesional S1 and S2 and tactile discrimination function in paretic hands has been proposed. Using structural MRI and a two-point discrimination assessment (2 PD), we explore this potential link in a group of 21 children (mean age 13 years and 7 months) with unilateral CP secondary to a periventricular white matter injury (PWMI) or middle cerebral artery infarct (MCA). For our whole sample there was a significant negative correlation between the 2 PD and the gray matter volume in the ipsilesional S2 (rho = -0.50 95% confidence interval [-0.76, -0.08], one-tailed p-value = 0.0109) and in the ipsilesional S1 (rho = -0.57, 95% confidence interval [-0.81, -0.19], one-tailed p-value = 0.0032). When studying these relationships with regard to the lesion types, we found these correlations were non-significant in the patients with PWMI but stronger in patients with MCA. According to our results, the degree of sensory impairment is related to the spared gray matter volume in ipsilesional S1 and S2 and is marked after an MCA stroke. Our work contributes to a better understanding of why some patients with CP have variable somatosensory deficit following an early brain lesion. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The formation of inflammatory demyelinated lesions in cerebral white matter

PubMed Central

Maggi, Pietro; Cummings Macri, Sheila M.; Gaitán, María I.; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L.; Ellis, Mary; Wu, Tianxia; Silva, Afonso C.; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S.

2016-01-01

Objective Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. Methods At 7 tesla MRI, T1 maps, proton density and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain-barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. Results On average, BBB permeability increased 3.5 fold (p<0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, though permeability within the foci, but not outside, increased in the weeks before the animals died (p<0.0001). Interpretation This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. PMID:25088017

The formation of inflammatory demyelinated lesions in cerebral white matter.

PubMed

Maggi, Pietro; Macri, Sheila M Cummings; Gaitán, María I; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L; Ellis, Mary; Wu, Tianxia; Silva, Afonso C; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S

2014-10-01

Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. By 7T magnetic resonance imaging (MRI), T1 maps, proton density, and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. On average, BBB permeability increased 3.5-fold (p < 0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, although permeability within the foci, but not outside, increased in the weeks before the animals died (p < 0.0001). This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. © 2014 American Neurological Association.

Postoperative MRI Evaluation of a Radiofrequency Cordotomy Lesion for Intractable Cancer Pain

PubMed Central

Vedantam, A.; Hou, P.; Chi, T.L.; Hess, K.R; Dougherty, P.M.; Bruera, E.; Viswanathan, A.

2017-01-01

BACKGROUND AND PURPOSE There are limited data on the use of postoperative imaging to evaluate the cordotomy lesion. We aimed to describe the cordotomy lesion by using postoperative MR imaging in patients after percutaneous cordotomy for intractable cancer pain. MATERIALS AND METHODS Postoperative MR imaging and clinical outcomes were prospectively obtained for 10 patients after percutaneous cordotomy for intractable cancer pain. Area, signal intensity, and location of the lesion were recorded. Clinical outcomes were measured by using the Visual Analog Scale and the Brief Pain Inventory–Short Form, and correlations with MR imaging metrics were evaluated. RESULTS Ten patients (5 men, 5 women; mean age, 58.5 ± 9.6 years) were included in this study. The cordotomy lesion was hyperintense with central hypointense foci on T2-weighted MR imaging, and it was centered in the anterolateral quadrant at the C1–C2 level. The mean percentage of total cord area lesioned was 24.9% ± 7.9%, and most lesions were centered in the dorsolateral region of the anterolateral quadrant (66% of the anterolateral quadrant). The number of pial penetrations correlated with the percentage of total cord area that was lesioned (r = 0.78; 95% CI, 0.44–0.89; P = .008) and the length of T2-weighted hyperintensity (r = 0.85; 95% CI, 0.54–0.89; P = .002). No significant correlations were found between early clinical outcomes and quantitative MR imaging metrics. CONCLUSIONS We describe qualitative and quantitative characteristics of a cordotomy lesion on early postoperative MR imaging. The size and length of the lesion on MR imaging correlate with the number of pial penetrations. Larger studies are needed to further investigate the clinical correlates of MR imaging metrics after percutaneous cordotomy. PMID:28209581

Visual navigation in adolescents with early periventricular lesions: knowing where, but not getting there.

PubMed

Pavlova, Marina; Sokolov, Alexander; Krägeloh-Mann, Ingeborg

2007-02-01

Visual navigation in familiar and unfamiliar surroundings is an essential ingredient of adaptive daily life behavior. Recent brain imaging work helps to recognize that establishing connectivity between brain regions is of importance for successful navigation. Here, we ask whether the ability to navigate is impaired in adolescents who were born premature and suffer congenital bilateral periventricular brain damage that might affect the pathways interconnecting subcortical structures with cortex. Performance on a set of visual labyrinth tasks was significantly worse in patients with periventricular leukomalacia (PVL) as compared with premature-born controls without lesions and term-born adolescents. The ability for visual navigation inversely relates to the severity of motor disability, leg-dominated bilateral spastic cerebral palsy. This agrees with the view that navigation ability substantially improves with practice and might be compromised in individuals with restrictions in active spatial exploration. Visual navigation is negatively linked to the volumetric extent of lesions over the right parietal and frontal periventricular regions. Whereas impairments of visual processing of point-light biological motion are associated in patients with PVL with bilateral parietal periventricular lesions, navigation ability is specifically linked to the frontal lesions in the right hemisphere. We suggest that more anterior periventricular lesions impair the interrelations between the right hippocampus and cortical areas leading to disintegration of neural networks engaged in visual navigation. For the first time, we show that the severity of right frontal periventricular damage and leg-dominated motor disorders can serve as independent predictors of the visual navigation disability.

Automatic Classification of Specific Melanocytic Lesions Using Artificial Intelligence

PubMed Central

Jaworek-Korjakowska, Joanna; Kłeczek, Paweł

2016-01-01

Background. Given its propensity to metastasize, and lack of effective therapies for most patients with advanced disease, early detection of melanoma is a clinical imperative. Different computer-aided diagnosis (CAD) systems have been proposed to increase the specificity and sensitivity of melanoma detection. Although such computer programs are developed for different diagnostic algorithms, to the best of our knowledge, a system to classify different melanocytic lesions has not been proposed yet. Method. In this research we present a new approach to the classification of melanocytic lesions. This work is focused not only on categorization of skin lesions as benign or malignant but also on specifying the exact type of a skin lesion including melanoma, Clark nevus, Spitz/Reed nevus, and blue nevus. The proposed automatic algorithm contains the following steps: image enhancement, lesion segmentation, feature extraction, and selection as well as classification. Results. The algorithm has been tested on 300 dermoscopic images and achieved accuracy of 92% indicating that the proposed approach classified most of the melanocytic lesions correctly. Conclusions. A proposed system can not only help to precisely diagnose the type of the skin mole but also decrease the amount of biopsies and reduce the morbidity related to skin lesion excision. PMID:26885520

Vesiculobullous lesions in lipoid proteinosis: a case report.

PubMed

Rao, Raghavendra; Prabhu, Smitha Smitha; Sripathi, H; Gupta, Sachi

2008-07-15

Vesiculobullous disorders in a child can be a diagnostic challenge. Common causes of blisters in early childhood include genodermatoses like epidermolysis bullosa and infections like herpes simplex. Lipoid proteinosis may rarely present with vesiculobullous lesions in childhood. We report a child, who presented in early childhood with blistering dermatosis. On long term follow-up, typical features of lipoid proteinosis developed. A high index of suspicion is required when one deals with blistering dermatosis in a child.

[Early flat colorectal cancer].

PubMed

Castelletto, R H; Chiarenza, C; Ottino, A; Garay, M L

1991-01-01

We report three cases of flat early colorectal carcinoma which were detected during the examination of 51 surgical specimens of colorectal resection. Two of them were endoscopically diagnosed, but the smallest one was not seen in the luminal instrumental examination. From the bibliographic analysis and our own experience we deduce the importance of flat lesions in the development of early colorectal carcinoma, either originated from pre-existent adenoma or de novo. Flat variants of adenoma, and presumably flush or depressed ones, must be considered as important factors in the early sequence adenoma-cancer. An appropriate endoscopic equipment with employment of additional staining techniques (such as carmine indigo and methylene blue) and the correct investigation during inflation-deflation procedures facilitates the identification of small lesions, their eradication and prevention from advanced forms of colorectal carcinoma.

Predictive cytogenetic biomarkers for colorectal neoplasia in medium risk patients.

PubMed

Ionescu, E M; Nicolaie, T; Ionescu, M A; Becheanu, G; Andrei, F; Diculescu, M; Ciocirlan, M

2015-01-01

DNA damage and chromosomal alterations in peripheral lymphocytes parallels DNA mutations in tumor tissues. The aim of our study was to predict the presence of neoplastic colorectal lesions by specific biomarkers in "medium risk" individuals (age 50 to 75, with no personal or family of any colorectal neoplasia). We designed a prospective cohort observational study including patients undergoing diagnostic or opportunistic screening colonoscopy. Specific biomarkers were analyzed for each patient in peripheral lymphocytes - presence of micronuclei (MN), nucleoplasmic bridges (NPB) and the Nuclear Division Index (NDI) by the cytokinesis-blocked micronucleus assay (CBMN). Of 98 patients included, 57 were "medium risk" individuals. MN frequency and NPB presence were not significantly different in patients with neoplastic lesions compared to controls. In "medium risk" individuals, mean NDI was significantly lower for patients with any neoplastic lesions (adenomas and adenocarcinomas, AUROC 0.668, p 00.5), for patients with advanced neoplasia (advanced adenoma and adenocarcinoma, AUROC 0.636 p 0.029) as well as for patients with adenocarcinoma (AUROC 0.650, p 0.048), for each comparison with the rest of the population. For a cut-off of 1.8, in "medium risk" individuals, an NDI inferior to that value may predict any neoplastic lesion with a sensitivity of 97.7%, an advanced neoplastic lesion with a sensitivity of 97% and adenocarcinoma with a sensitivity of 94.4%. NDI score may have a role as a colorectal cancer-screening test in "medium risk" individuals. DNA = deoxyribonucleic acid; CRC = colorectal cancer; EU = European Union; WHO = World Health Organization; FOBT = fecal occult blood test; CBMN = cytokinesis-blocked micronucleus assay; MN = micronuclei; NPB = nucleoplasmic bridges; NDI = Nuclear Division Index; FAP = familial adenomatous polyposis; HNPCC = hereditary non-polypoid colorectal cancer; IBD = inflammatory bowel diseases; ROC = receiver operating

Skin Lesion Analysis towards Melanoma Detection Using Deep Learning Network

PubMed Central

2018-01-01

Skin lesions are a severe disease globally. Early detection of melanoma in dermoscopy images significantly increases the survival rate. However, the accurate recognition of melanoma is extremely challenging due to the following reasons: low contrast between lesions and skin, visual similarity between melanoma and non-melanoma lesions, etc. Hence, reliable automatic detection of skin tumors is very useful to increase the accuracy and efficiency of pathologists. In this paper, we proposed two deep learning methods to address three main tasks emerging in the area of skin lesion image processing, i.e., lesion segmentation (task 1), lesion dermoscopic feature extraction (task 2) and lesion classification (task 3). A deep learning framework consisting of two fully convolutional residual networks (FCRN) is proposed to simultaneously produce the segmentation result and the coarse classification result. A lesion index calculation unit (LICU) is developed to refine the coarse classification results by calculating the distance heat-map. A straight-forward CNN is proposed for the dermoscopic feature extraction task. The proposed deep learning frameworks were evaluated on the ISIC 2017 dataset. Experimental results show the promising accuracies of our frameworks, i.e., 0.753 for task 1, 0.848 for task 2 and 0.912 for task 3 were achieved. PMID:29439500

Skin Lesion Analysis towards Melanoma Detection Using Deep Learning Network.

PubMed

Li, Yuexiang; Shen, Linlin

2018-02-11

Skin lesions are a severe disease globally. Early detection of melanoma in dermoscopy images significantly increases the survival rate. However, the accurate recognition of melanoma is extremely challenging due to the following reasons: low contrast between lesions and skin, visual similarity between melanoma and non-melanoma lesions, etc. Hence, reliable automatic detection of skin tumors is very useful to increase the accuracy and efficiency of pathologists. In this paper, we proposed two deep learning methods to address three main tasks emerging in the area of skin lesion image processing, i.e., lesion segmentation (task 1), lesion dermoscopic feature extraction (task 2) and lesion classification (task 3). A deep learning framework consisting of two fully convolutional residual networks (FCRN) is proposed to simultaneously produce the segmentation result and the coarse classification result. A lesion index calculation unit (LICU) is developed to refine the coarse classification results by calculating the distance heat-map. A straight-forward CNN is proposed for the dermoscopic feature extraction task. The proposed deep learning frameworks were evaluated on the ISIC 2017 dataset. Experimental results show the promising accuracies of our frameworks, i.e., 0.753 for task 1, 0.848 for task 2 and 0.912 for task 3 were achieved.

Endoscopy and polyps-diagnostic and therapeutic advances in management

PubMed Central

Steele, Scott R; Johnson, Eric K; Champagne, Bradley; Davis, Brad; Lee, Sang; Rivadeneira, David; Ross, Howard; Hayden, Dana A; Maykel, Justin A

2013-01-01

Despite multiple efforts aimed at early detection through screening, colon cancer remains the third leading cause of cancer-related deaths in the United States, with an estimated 51000 deaths during 2013 alone. The goal remains to identify and remove benign neoplastic polyps prior to becoming invasive cancers. Polypoid lesions of the colon vary widely from hyperplastic, hamartomatous and inflammatory to neoplastic adenomatous growths. Although these lesions are all benign, they are common, with up to one-quarter of patients over 60 years old will develop pre-malignant adenomatous polyps. Colonoscopy is the most effective screening tool to detect polyps and colon cancer, although several studies have demonstrated missed polyp rates from 6%-29%, largely due to variations in polyp size. This number can be as high as 40%, even with advanced (> 1 cm) adenomas. Other factors including sub-optimal bowel preparation, experience of the endoscopist, and patient anatomical variations all affect the detection rate. Additional challenges in decision-making exist when dealing with more advanced, and typically larger, polyps that have traditionally required formal resection. In this brief review, we will explore the recent advances in polyp detection and therapeutic options. PMID:23885138

Early Diagnosis and Early Intervention in Cerebral Palsy

PubMed Central

Hadders-Algra, Mijna

2014-01-01

This paper reviews the opportunities and challenges for early diagnosis and early intervention in cerebral palsy (CP). CP describes a group of disorders of the development of movement and posture, causing activity limitation that is attributed to disturbances that occurred in the fetal or infant brain. Therefore, the paper starts with a summary of relevant information from developmental neuroscience. Most lesions underlying CP occur in the second half of gestation, when developmental activity in the brain reaches its summit. Variations in timing of the damage not only result in different lesions but also in different neuroplastic reactions and different associated neuropathologies. This turns CP into a heterogeneous entity. This may mean that the best early diagnostics and the best intervention methods may differ for various subgroups of children with CP. Next, the paper addresses possibilities for early diagnosis. It discusses the predictive value of neuromotor and neurological exams, neuroimaging techniques, and neurophysiological assessments. Prediction is best when complementary techniques are used in longitudinal series. Possibilities for early prediction of CP differ for infants admitted to neonatal intensive care and other infants. In the former group, best prediction is achieved with the combination of neuroimaging and the assessment of general movements, in the latter group, best prediction is based on carefully documented milestones and neurological assessment. The last part reviews early intervention in infants developing CP. Most knowledge on early intervention is based on studies in high-risk infants without CP. In these infants, early intervention programs promote cognitive development until preschool age; motor development profits less. The few studies on early intervention in infants developing CP suggest that programs that stimulate all aspects of infant development by means of family coaching are most promising. More research is urgently needed

When are circular lesions square? A national clinical education skin lesion audit and study.

PubMed

Miranda, Benjamin H; Herman, Katie A; Malahias, Marco; Juma, Ali

2014-09-01

Skin cancer is the most prevalent cancer by organ type and referral accuracy is vital for diagnosis and management. The British Association of Dermatologists (BAD) and literature highlight the importance of accurate skin lesion examination, diagnosis and educationally-relevant studies. We undertook a review of the relevant literature, a national audit of skin lesion description standards and a study of speciality training influences on these descriptions. Questionnaires (n=200), with pictures of a circular and an oval lesion, were distributed to UK dermatology/plastic surgery consultants and speciality trainees (ST), general practitioners (GP), and medical students (MS). The following variables were analysed against a pre-defined 95% inclusion accuracy standard: site, shape, size, skin/colour, and presence of associated scars. There were 250 lesion descriptions provided by 125 consultants, STs, GPs, and MSs. Inclusion accuracy was greatest for consultants over STs (80% vs. 68%; P<0.001), GPs (57%) and MSs (46%) (P<0.0001), for STs over GPs (P<0.010) and MSs (P<0.0001) and for GPs over MSs (P<0.010), all falling below audit standard. Size description accuracy sub-analysis according to circular/oval dimensions was as follows: consultants (94%), GPs (80%), STs (73%), MSs (37%), with the most common error implying a quadrilateral shape (66%). Addressing BAD guidelines and published requirements for more empirical performance data to improve teaching methods, we performed a national audit and studied skin lesion descriptions. To improve diagnostic and referral accuracy for patients, healthcare professionals must strive towards accuracy (a circle is not a square). We provide supportive evidence that increased speciality training improves this process and propose that greater focus is placed on such training early on during medical training, and maintained throughout clinical practice.

Reduced Pms2 expression in non-neoplastic flat mucosa from patients with colon cancer correlates with reduced apoptosis competence.

PubMed

Bernstein, Harris; Prasad, Anil; Holubec, Hana; Bernstein, Carol; Payne, Claire M; Ramsey, Lois; Dvorakova, Katerina; Wilson, Megan; Warneke, James A; Garewal, Harinder

2006-06-01

Pms2 protein is a component of the DNA mismatch repair complex responsible both for post-replication correction of DNA nucleotide mispairs and for early steps in apoptosis. Germline mutations in DNA mismatch repair genes give rise to hereditary non-polyposis colon cancer, which accounts for about 4% of colon cancers. However, little is known about the expression of mismatch repair proteins in relation to sporadic colon cancer, which accounts for the great majority of colon cancers. Multiple samples were taken from the non-neoplastic flat mucosa of colon resections from patients with no colonic neoplasia, a tubulovillous adenoma, or an adenocarcinoma. Expression of Pms2 was assessed using semiquantitative immunohistochemistry. Apoptosis was assessed in polychrome-stained epoxy sections using morphologic criteria. Samples from patients without colonic neoplasia had moderate to strong staining for Pms2 in cell nuclei at the base of crypts, while samples from 2 of the 3 colons with a tubulovillous adenoma, and from 6 of the 10 colons with adenocarcinomas, showed reduced Pms2 expression. Samples from patients with an adenocarcinoma that had reduced Pms2 expression also exhibited reduced apoptosis capability in nearby tissue samples, evidenced when this paired tissue was stressed ex vivo with bile acid. Reduced Pms2 expression in the colonic mucosa may be an early step in progression to colon cancer. This reduction may cause decreased mismatch repair, increased genetic instability, and/or reduced apoptotic capability. Immunohistochemical determination of reduced Pms2 expression, upon further testing, may prove to be a promising early biomarker of risk of progression to malignancy.

Clinical impact of confocal laser endomicroscopy in the management of gastrointestinal lesions with an uncertain diagnosis.

PubMed

Robles-Medranda, Carlos; Vargas, Maria; Ospina, Jesenia; Puga-Tejada, Miguel; Valero, Manuel; Soria, Miguel; Bravo, Gladys; Robles-Jara, Carlos; Lukashok, Hannah Pitanga

2017-08-16

To evaluate the clinical impact of confocal laser endomicroscopy (CLE) in the diagnosis and management of patients with an uncertain diagnosis. A retrospective chart review was performed. Patients who underwent CLE between November 2013 and October 2015 and exhibited a poor correlation between endoscopic and histological findings were included. Baseline characteristics, indications, previous diagnostic studies, findings at the time of CLE, clinical management and histological results were analyzed. Interventions based on CLE findings were also analyzed. We compared the diagnostic accuracy of CLE and target biopsies of surgical specimens. A total of 144 patients were included. Of these, 51% (74/144) were female. The mean age was 51 years old. In all, 41/144 (28.4%) lesions were neoplastic (13 bile duct, 10 gastric, 8 esophageal, 6 colonic, 1 duodenal, 1 rectal, 1 ampulloma and 1 pancreatic). The sensitivity, specificity, positive predictive value, negative predictive value, and observed agreement when CLE was used to detect N-lesions were 85.37%, 87.38%, 72.92%, 93.75% and 86.81%, respectively. Cohen's Kappa was 69.20%, thus indicating good agreement. Changes in management were observed in 54% of the cases. CLE is a new diagnostic tool that has a significant clinical impact on the diagnosis and treatment of patients with uncertain diagnosis.

Discrimination of benign and neoplastic mucosa with a high-resolution microendoscope (HRME) in head and neck cancer.

PubMed

Vila, Peter M; Park, Chan W; Pierce, Mark C; Goldstein, Gregg H; Levy, Lauren; Gurudutt, Vivek V; Polydorides, Alexandros D; Godbold, James H; Teng, Marita S; Genden, Eric M; Miles, Brett A; Anandasabapathy, Sharmila; Gillenwater, Ann M; Richards-Kortum, Rebecca; Sikora, Andrew G

2012-10-01

The efficacy of ablative surgery for head and neck squamous cell carcinoma (HNSCC) depends critically on obtaining negative margins. Although intraoperative "frozen section" analysis of margins is a valuable adjunct, it is expensive, time-consuming, and highly dependent on pathologist expertise. Optical imaging has potential to improve the accuracy of margins by identifying cancerous tissue in real time. Our goal was to determine the accuracy and inter-rater reliability of head and neck cancer specialists using high-resolution microendoscopic (HRME) images to discriminate between cancerous and benign mucosa. Thirty-eight patients diagnosed with head and neck squamous cell carcinoma (HNSCC) were enrolled in this single-center study. HRME was used to image each specimen after application of proflavine, with concurrent standard histopathologic analysis. Images were evaluated for quality control, and a training set containing representative images of benign and neoplastic tissue was assembled. After viewing training images, seven head and neck cancer specialists with no previous HRME experience reviewed 36 test images and were asked to classify each. The mean accuracy of all reviewers in correctly diagnosing neoplastic mucosa was 97% (95% confidence interval (CI), 94-99%). The mean sensitivity and specificity were 98% (97-100%) and 92% (87-98%), respectively. The Fleiss kappa statistic for inter-rater reliability was 0.84 (0.77-0.91). Medical professionals can be quickly trained to use HRME to discriminate between benign and neoplastic mucosa in the head and neck. With further development, the HRME shows promise as a method of real-time margin determination at the point of care.

Discrimination of Benign and Neoplastic Mucosa with a High-Resolution Microendoscope (HRME) in Head and Neck Cancer

PubMed Central

Vila, Peter M.; Park, Chan W.; Pierce, Mark C.; Goldstein, Gregg H.; Levy, Lauren; Gurudutt, Vivek V.; Polydorides, Alexandras D.; Godbold, James H.; Teng, Marita S.; Genden, Eric M.; Miles, Brett A.; Anandasabapathy, Sharmila; Gillenwater, Ann M.; Richards-Kortum, Rebecca; Sikora, Andrew G.

2012-01-01

Background The efficacy of ablative surgery for head and neck squamous cell carcinoma (HNSCC) depends critically on obtaining negative margins. While intraoperative "frozen section" analysis of margins is a valuable adjunct, it is expensive, time-consuming, and highly dependent on pathologist expertise. Optical imaging has potential to improve the accuracy of margins by identifying cancerous tissue in real time. Our aim was to determine the accuracy and inter-rater reliability of head and neck cancer specialists using high-resolution microendoscopic (HRME) images to discriminate between cancerous and benign mucosa. Methods Thirty-eight patients diagnosed with HNSCC were enrolled in this single-center study. HRME was used to image each specimen after application of proflavine, with concurrent standard histopathologic analysis. Images were evaluated for quality control, and a training set containing representative images of benign and neoplastic tissue was assembled. After viewing training images, seven head and neck cancer specialists with no prior HRME experience reviewed 37 test images and were asked to classify each. Results The mean accuracy of all reviewers in correctly diagnosing neoplastic mucosa was 97 percent (95% Cl = 94–99%). The mean sensitivity and specificity were 98 percent (97–100%) and 92 percent (87–98%), respectively. The Fleiss kappa statistic for inter-rater reliability was 0.84 (0.77–0.91). Conclusions Medical professionals can be quickly trained to use HRME to discriminate between benign and neoplastic mucosa in the head and neck. With further development, the HRME shows promise as a method of real-time margin determination at the point of care. PMID:22492225

The Impact of Quantitative Data Provided by a Multi-spectral Digital Skin Lesion Analysis Device on Dermatologists'Decisions to Biopsy Pigmented Lesions.

PubMed

Farberg, Aaron S; Winkelmann, Richard R; Tucker, Natalie; White, Richard; Rigel, Darrell S

2017-09-01

BACKGROUND: Early diagnosis of melanoma is critical to survival. New technologies, such as a multi-spectral digital skin lesion analysis (MSDSLA) device [MelaFind, STRATA Skin Sciences, Horsham, Pennsylvania] may be useful to enhance clinician evaluation of concerning pigmented skin lesions. Previous studies evaluated the effect of only the binary output. OBJECTIVE: The objective of this study was to determine how decisions dermatologists make regarding pigmented lesion biopsies are impacted by providing both the underlying classifier score (CS) and associated probability risk provided by multi-spectral digital skin lesion analysis. This outcome was also compared against the improvement reported with the provision of only the binary output. METHODS: Dermatologists attending an educational conference evaluated 50 pigmented lesions (25 melanomas and 25 benign lesions). Participants were asked if they would biopsy the lesion based on clinical images, and were asked this question again after being shown multi-spectral digital skin lesion analysis data that included the probability graphs and classifier score. RESULTS: Data were analyzed from a total of 160 United States board-certified dermatologists. Biopsy sensitivity for melanoma improved from 76 percent following clinical evaluation to 92 percent after quantitative multi-spectral digital skin lesion analysis information was provided ( p <0.0001). Specificity improved from 52 percent to 79 percent ( p <0.0001). The positive predictive value increased from 61 percent to 81 percent ( p <0.01) when the quantitative data were provided. Negative predictive value also increased (68% vs. 91%, p<0.01), and overall biopsy accuracy was greater with multi-spectral digital skin lesion analysis (64% vs. 86%, p <0.001). Interrater reliability improved (intraclass correlation 0.466 before, 0.559 after). CONCLUSION: Incorporating the classifier score and probability data into physician evaluation of pigmented lesions led to both

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, I.T.; Vanderlaan, M.; Kromhout, L.

Improved early detection of neoplasia by screening of urothelial cells requires an understanding of the features distinguishing normal and neoplastic cell populations. The authors have begun a program of study based upon a rate model system for the controlled observation of early-stage lesions produced by the carcinogen N-butyl-N-(4-hydroxybutyl)- nitrosamine. Cells dissociated directly from normal and malignant urothelium were characterized by conventional cytopathology techniques and by quantitative microscopy (for nuclear texture and nuclear and cytoplasmic size, shape, and stain content) to derive a comprehensive picture of bladder tumor development. By following the changes that occur in the dissociated urothelial cells themore » authors have found that the nuclear area, total nuclear stain, nuclear shape, and the nuclear chromatin change significantly over a 48-wk interval as the lesions progress toward malignancy. 24 references, 10 figures, 1 table.« less

Factors affecting the palpability of breast lesion by self-examination.

PubMed

Lam, W W M; Chan, C P; Chan, C F; Mak, C C C; Chan, C F; Chong, K W H; Leung, M H J; Tang, M H

2008-03-01

This study aims to assess the accuracy of detection of breast lesion by breast self-examination and to assess different factors affecting the accuracy. All consecutive Chinese female patients, who attended our breast imaging unit in 2001, completed our questionnaire, had retrievable hard copy films, and had more than three years clinical follow-up, were recruited for this study. Different factors, such as age, menopausal status, previous experience of breastfeeding, family history of breast cancer, previous history of mastectomy or lumpectomy, hormonal therapy, oral contraceptive pills and previous history of mammography, were correlated with accuracy in self-detection of breast lesions retrospectively. The nature, size and location of the lesion, and breast size based on imaging, were also correlated with the accuracy in self-detection of breast lesions. A total of 163 questionnaires were analysed. 111 patients detected a breast lesion themselves and 24 of these lesions were false-positives. A total of 173 lesions (27 cancerous, 146 benign lesions) were documented by either ultrasonography and/or mammography, and confirmed by either histology or three-year clinical follow-up. The overall sensitivity in detecting both benign and malignant breast lesions was 71% when number of breast lesions was used as the denominator, and up to 78% sensitivity was achieved when number of patients was used as the denominator. History of mastectomy, and size and nature of the lesions were found to affect the accuracy of self-detection of breast lesions. Overall, breast self-examinations were effective in the detection of breast lesions and factors such as size of lesion, nature of the lesion and history of mastectomy affect the accuracy of the detections. Breast self-examination should be promoted for early detection of breast cancer.

Transforming Growth Factor-Beta Inhibition Reduces Progression of Early Choroidal Neovascularization Lesions in Rats: P17 and P144 Peptides

PubMed Central

Zarranz-Ventura, Javier; Fernández-Robredo, Patricia; Recalde, Sergio; Salinas-Alamán, Angel; Borrás-Cuesta, Francisco; Dotor, Javier; García-Layana, Alfredo

2013-01-01

The purpose of this study was to assess the effects of transforming growth factor beta (TGF-β) inhibitor peptides (P17 & P144) on early laser-induced choroidal neovascularization (LI-CNV) lesions in rats, two weeks after laser CNV induction. Seventy-one Long Evans rats underwent diode laser application in an established LI-CNV model. Baseline fluorescein angiography (FA) was performed 14 days following laser procedure, and treatments were administered 16 days post-laser application via different administration routes. Intravenous groups included control (IV-Control), P17 (IV-17), and P144 (IV-144) groups, whereas intravitreal groups included P17 (IVT-17), P144 (IVT-144), and a mixture of both peptides (IVT-17+144) (with fellow eyes receiving vehicle alone). CNV evolution was assessed using FA performed weekly for four weeks after treatment. Following sacrifice, VEGF, TGF-β, COX-2, IGF-1, PAI-1, IL-6, MMP-2, MMP-9, and TNF-α gene expression was assessed using RT-PCR. VEGF and p-SMAD2 protein levels were also assessed by western-blot, while MMP-2 activity was assessed with gelatin zymography. Regarding the FA analysis, the mean CNV area was lower from the 3rd week in IVT-17 and IVT-144 groups, and also from the 2nd week in IVT-17+144. Biochemical analysis revealed that gene expression was lower for VEGF and COX-2 genes in IV-17 and IV-144 groups, VEGF gene in IVT-17+144 group and MMP-2 gene in IVT-17 and IVT-144 groups. VEGF protein expression was also decreased in IV-17, IV-144, IVT-17 and IVT-144, whereas pSMAD-2 levels were lower in IV-17, IV-144 and IVT-17+144 groups. Zymogram analysis revealed decreased MMP-2 activity in IV-17, IV-144, IVT-17 and IVT-144 groups. These data suggest that the use of TGF-β inhibitor peptides (P17 & P144) decrease the development of early CNV lesions by targeting different mediators than those typically affected using current anti-angiogenic therapies. Its potential role in the treatment of early CNV appears promising as a single

Molecular pathogenesis of precursor lesions of pancreatic ductal adenocarcinoma.

PubMed

Biankin, Andrew V; Kench, James G; Dijkman, Floriaan P; Biankin, Sandra A; Henshall, Susan M

2003-02-01

Precursor lesions are assuming greater importance in the study of pancreatic ductal adenocarcinoma. As pancreatic cancer is almost universally fatal due to late clinical presentation and biological aggressiveness, characterisation of its precursor lesions may create scope for early diagnosis and improved outcome with conventional therapies as well as the development of novel therapeutic and preventative strategies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous tumours (IPMTs) are thought to be precursor lesions of ductal adenocarcinoma of the pancreas. Recent work has focused on the molecular aberrations associated with these lesions leading to the formulation of a progression model for pancreatic cancer. Progressive histopathological changes along the progression model are associated with aberrations of cell cycle regulatory and growth factor signalling molecules that occur in pancreatic cancer at high frequency and are common to many cancers. Characterisation of these molecular aberrations provides scope for the development of novel diagnostic and treatment strategies that will ultimately impact on the outcome for people who develop pancreatic cancer.

Textural analysis of early-phase spatiotemporal changes in contrast enhancement of breast lesions imaged with an ultrafast DCE-MRI protocol.

PubMed

Milenković, Jana; Dalmış, Mehmet Ufuk; Žgajnar, Janez; Platel, Bram

2017-09-01

New ultrafast view-sharing sequences have enabled breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to be performed at high spatial and temporal resolution. The aim of this study is to evaluate the diagnostic potential of textural features that quantify the spatiotemporal changes of the contrast-agent uptake in computer-aided diagnosis of malignant and benign breast lesions imaged with high spatial and temporal resolution DCE-MRI. The proposed approach is based on the textural analysis quantifying the spatial variation of six dynamic features of the early-phase contrast-agent uptake of a lesion's largest cross-sectional area. The textural analysis is performed by means of the second-order gray-level co-occurrence matrix, gray-level run-length matrix and gray-level difference matrix. This yields 35 textural features to quantify the spatial variation of each of the six dynamic features, providing a feature set of 210 features in total. The proposed feature set is evaluated based on receiver operating characteristic (ROC) curve analysis in a cross-validation scheme for random forests (RF) and two support vector machine classifiers, with linear and radial basis function (RBF) kernel. Evaluation is done on a dataset with 154 breast lesions (83 malignant and 71 benign) and compared to a previous approach based on 3D morphological features and the average and standard deviation of the same dynamic features over the entire lesion volume as well as their average for the smaller region of the strongest uptake rate. The area under the ROC curve (AUC) obtained by the proposed approach with the RF classifier was 0.8997, which was significantly higher (P = 0.0198) than the performance achieved by the previous approach (AUC = 0.8704) on the same dataset. Similarly, the proposed approach obtained a significantly higher result for both SVM classifiers with RBF (P = 0.0096) and linear kernel (P = 0.0417) obtaining AUC of 0.8876 and 0.8548, respectively

Transoral Laser Microsurgery in Early Glottic Lesions.

PubMed

Sjögren, E V

2017-01-01

To give an overview of the evolvement of transoral laser microsurgery (TLM) in the treatment of early glottic carcinoma and highlight the contribution of recent literature. The indications and limits of TLM have been well specified. Effects on swallowing have been well documented. Introduction of narrow-band imaging (NBI) and diffusion-weighted magnetic resonance has been shown of additional value for outcome. The first reports on transoral robotic surgery show that it may be of added value in the future. TLM for early glottic carcinoma (Tis-T2) has very good oncological outcomes with indications of higher larynx preservation in TLM than that in radiotherapy. The anterior commissure is a risk factor if involved in the cranio-caudal plane, and reduced vocal fold mobility is a risk factor when this is due to arytenoid involvement. The best voice results are achieved when the anterior commissure can be left intact along with part of the vocal fold muscle although even in larger resections, patient self-reported voice handicap is still limited.

On the stability of lung parenchymal lesions with applications to early pneumothorax diagnosis.

PubMed

Bhandarkar, Archis R; Banerjee, Rohan; Seshaiyer, Padmanabhan

2013-01-01

Spontaneous pneumothorax, a prevalent medical challenge in most trauma cases, is a form of sudden lung collapse closely associated with risk factors such as lung cancer and emphysema. Our work seeks to explore and quantify the currently unknown pathological factors underlying lesion rupture in pneumothorax through biomechanical modeling. We hypothesized that lesion instability is closely associated with elastodynamic strain of the pleural membrane from pulsatile air flow and collagen-elastin dynamics. Based on the principles of continuum mechanics and fluid-structure interaction, our proposed model coupled isotropic tissue deformation with pressure from pulsatile air motion and the pleural fluid. Next, we derived mathematical instability criteria for our ordinary differential equation system and then translated these mathematical instabilities to physically relevant structural instabilities via the incorporation of a finite energy limiter. The introduction of novel biomechanical descriptions for collagen-elastin dynamics allowed us to demonstrate that changes in the protein structure can lead to a transition from stable to unstable domains in the material parameter space for a general lesion. This result allowed us to create a novel streamlined algorithm for detecting material instabilities in transient lung CT scan data via analyzing deformations in a local tissue boundary.

Clinical scoring system to detect malignant and premalignant vulval lesions.

PubMed

Tyagi, Shakun; Tripathi, Reva; Batra, Swaraj

2014-02-01

To construct a simple clinical scoring system for evaluation of vulval lesions that will be helpful in clinically detecting the premalignant or malignant lesions of vulva. Seventy women referred for vulval examination at a tertiary care centre in north India were examined over a period of 2 years. Biopsy was performed in 66 consenting women. Association of high-grade vulval lesion with various clinical parameters such as age, duration of symptoms, presenting complaints, the presence of depigmentation, ulceration, hyperkeratosis, acetowhite changes on acetic acid application, asymmetrical distribution of the lesion, surface elevation on naked eye or colposcopy, induration on palpation and toluidine blue stain retention was studied. The significantly associated factors were assigned a value of 0 or 1 depending on whether they were present or absent. Score was then formulated for detection of high-grade lesion defined as moderate to severe dysplasia and early malignancy. Histopathology. Out of the various parameters that were studied, duration of symptoms more than 6 months, hyperkeratosis, asymmetrical distribution of the lesion, surface elevation on naked eye or colposcopy, induration on palpation and positive toluidine blue stain retention of the lesion were found to be significantly associated with a malignant or premalignant lesion. It was found that a score of equal to or greater than 3/6 was significantly associated with a malignant or premalignant lesion. This simple scoring system has a potential to identify the high-grade lesions and can be used to identify the vulval lesion requiring a biopsy or further referral to higher centre.

MiR-137: an important player in neural development and neoplastic transformation

PubMed Central

Mahmoudi, E; Cairns, M J

2017-01-01

MicroRNAs (miRNAs) represent an important class of small regulatory RNAs that control gene expression posttranscriptionally by targeting mRNAs for degradation or translation inhibition. Early studies have revealed a complex role for miRNAs in major biological processes such as development, differentiation, growth and metabolism. MiR-137 in particular, has been of great interest due to its critical role in brain function and putative involvement in the etiology of both neuropsychiatric disorders and cancer. Several lines of evidence suggest that development, differentiation and maturation of the nervous system is strongly linked to the expression of miR-137 and its regulation of a large number of downstream target genes in various pathways. Dysregulation of this molecule has also been implicated in major mental illnesses through its position in a variant allele highly associated with schizophrenia in the largest mega genome-wide association studies. Interestingly, miR-137 has also been shown to act as a tumor suppressor, with numerous studies finding reduced expression in neoplasia including brain tumor. Restoration of miR-137 expression has also been shown to inhibit cell proliferation, migration and metastasis, and induce cell cycle arrest, differentiation and apoptosis. These properties of miR-137 propose its potential for prognosis, diagnosis and as a therapeutic target for treatment of several human neurological and neoplastic disorders. In this review, we provide details on the discovery, targets, function, regulation and disease involvement of miR-137 with a broad look at recent discovery in this area. PMID:27620842

An S100P-positive biliary epithelial field is a preinvasive intraepithelial neoplasm in nodular-sclerosing cholangiocarcinoma.

PubMed

Nakanuma, Yasuni; Uchida, Tsuneyuki; Sato, Yasunori; Uesaka, Katsuhiko

2017-02-01

Nodular-sclerosing cholangiocarcinoma (NS-CCA) is a common CCA of the intrahepatic large, perihilar, and distal bile ducts. Intraepithelial biliary neoplasms, such as the mucosal extension of carcinoma and preinvasive neoplastic lesions (ie, biliary intraepithelial neoplasia) reportedly occur in the bile ducts around CCA. In the present study, we collectively refer to these intraepithelial lesions as "intraepithelial neoplasms of the bile duct (IENBs)". We examined the IENBs in 57 surgically resected cases of NS-CCA. S100P immunostaining was used to help detect IENBs. The IENBs formed field(s) of continuous neoplastic biliary epithelial cells and showed a flat, micropapillary, or papillotubular configuration. IENBs could be classified into 3 categories based on their atypia: group A (neoplastic but not enough for malignancy), B (neoplastic and sufficiently well differentiated for high-grade dysplasia), and C (overtly malignant and variably differentiated). IENB was found in 31 of 57 cases, with group C the most common (26 cases) followed by group B (22 cases) and group A (16 cases). The expression of cancer-related molecules and MIB-1 index of groups A and B differed from those of invasive CCA, whereas these features of group C were relatively similar to those of invasive CCA. In conclusion, IENB was not infrequently found in NS-CCA and could be classified into 3 grades. Preinvasive lesions (biliary intraepithelial neoplasias) are likely to be found in groups A and B, whereas cancerization would be included in group C. The classification of IENB may be useful for future studies of the preinvasive intraepithelial neoplastic lesions of NS-CCAs. Copyright © 2016. Published by Elsevier Inc.

IL-4 downregulates expression of the target receptor CD30 in neoplastic canine mast cells

PubMed Central

Bauer, K.; Hadzijusufovic, E.; Cerny-Reiterer, S.; Hoermann, G.; Reifinger, M.; Pirker, A.; Valent, P.; Willmann, M.

2018-01-01

CD30 is a novel therapeutic target in human mast cell (MC) neoplasms. In this ‘comparative oncology’ study, we examined CD30 expression and regulation in neoplastic canine MC using a panel of immunomodulatory cytokines [interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-13 and stem cell factor (SCF)] and the canine mastocytoma cell lines NI-1 and C2. Of all cytokines tested IL-4 was found to downregulate expression of CD30 in NI-1 and C2 cells. We also found that the CD30-targeting antibody-conjugate brentuximab vedotin induces growth inhibition and apoptosis in both MC lines. Next, we asked whether IL-4-induced downregulation of CD30 interferes with brentuximab vedotin-effects. Indeed, pre-incubation of NI-1 cells with IL-4 decreased responsiveness towards brentuximab vedotin. To overcome IL-4-mediated resistance, we applied drug combinations and found that brentuximab vedotin synergizes with the Kit-targeting drugs masitinib and PKC412 in inhibiting growth of NI-1 and C2 cells. In summary, CD30 is a new marker and IL-4-regulated target in neoplastic canine MC. PMID:27507155

Developmental outcomes after early prefrontal cortex damage.

PubMed

Eslinger, Paul J; Flaherty-Craig, Claire V; Benton, Arthur L

2004-06-01

The neuropsychological bases of cognitive, social, and moral development are minimally understood, with a seemingly wide chasm between developmental theories and brain maturation models. As one approach to bridging ideas in these areas, we review 10 cases of early prefrontal cortex damage from the clinical literature, highlighting overall clinical profiles and real life developmental outcomes. Based on these cases, there is preliminary evidence to support distinctive developmental differences after: (1) dorsolateral, (2) mesial, and (3) orbital-polar prefrontal lesions, for more profound impairments after bilateral damage, and possibly for recovery differences after very early vs. later childhood lesion onset. Further case and group studies are needed to confirm reliable effects of specific lesion locations, the influence of age of lesion onset, and related experiential and treatment variables in determining adult outcomes. Rather than a single underlying deficit associated with early prefrontal cortex damage, we interpret the findings to suggest that it is the altered integration and interplay of cognitive, emotional, self-regulatory, and executive/metacognitive deficits that contribute to diverse developmental frontal lobe syndromes. The findings support the fundamental importance of prefrontal cortex maturation in protracted cognitive, social-emotional, and moral development.