Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.

PubMed

Deevi, Ravi Kiran; Javadi, Arman; McClements, Jane; Vohhodina, Jekaterina; Savage, Kienan; Loughrey, Maurice Bernard; Evergren, Emma; Campbell, Frederick Charles

2018-04-01

Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring. PKCz regulates interdependent processes that control centrosome positioning. Among these, interaction between the cytoskeletal linker protein ezrin and its binding partner NHERF1 promotes the formation of a localized cue for anchoring interphase centrosomes to the cell cortex. Perturbation of these phenomena induced different outcomes in cells with single or extra centrosomes. Defective anchoring of a single centrosome promoted bipolar spindle misorientation, multi-lumen formation, and aberrant epithelial stratification. Collectively, these disturbances induce cribriform multicellular morphology that is typical of some categories of low-grade CRC. By contrast, defective anchoring of extra centrosomes promoted multipolar spindle formation, chromosomal instability (CIN), disruption of glandular morphology, and cell outgrowth across the extracellular matrix interface characteristic of aggressive, high-grade CRC. Because PKCz enhances apical NHERF1 intensity in 3D epithelial cultures, we used an immunohistochemical (IHC) assay of apical NHERF1 intensity as an indirect readout of PKCz activity in translational studies. We show that apical NHERF1 IHC intensity is inversely associated with multipolar spindle frequency and high-grade morphology in formalin-fixed human CRC samples. To conclude, defective PKCz control of interphase centrosome anchoring may underlie distinct categories of mitotic slippage that shape the development of low- or high-grade CRC phenotypes. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Susceptibility Imaging in Glial Tumor Grading; Using 3 Tesla Magnetic Resonance (MR) System and 32 Channel Head Coil.

PubMed

Aydin, Omer; Buyukkaya, Ramazan; Hakyemez, Bahattin

2017-01-01

Susceptibility weighted imaging (SWI) is a velocity compensated, high-resolution three-dimensional (3D) spoiled gradient-echo sequence that uses magnitude and filtered-phase data. SWI seems to be a valuable tool for non-invasive evaluation of central nervous system gliomas. Relative cerebral blood volume (rCBV) ratio is one of the best noninvasive methods for glioma grading. Degree of intratumoral susceptibility signal (ITSS) on SWI correlates with rCBV ratio and histopathological grade. This study investigated the effectiveness of ITSS grading and rCBV ratio in preoperative assessment. Thirty-one patients (17 males and 14 females) with histopathogical diagnosis of glial tumor undergoing routine cranial MRI, SWI, and perfusion MRI examinations between October 2011 and July 2013 were retrospectively enrolled. All examinations were performed using 3T apparatus with 32-channel head coil. We used ITSS number for SWI grading. Correlations between SWI grade, rCBV ratio, and pathological grading were evaluated. ROC analysis was performed to determine the optimal rCBV ratio to distinguish between high-grade and low-grade glial tumors. There was a strong positive correlation between both pathological and SWI grading. We determined the optimal rCBV ratio to discriminate between high-grade and low-grade tumors to be 2.21. In conclusion, perfusion MRI and SWI using 3T MR and 32-channel head coil may provide useful information for preoperative glial tumor grading. SWI can be used as an accessory to perfusion MR technique in preoperative tumor grading.

Automated Grading of Gliomas using Deep Learning in Digital Pathology Images: A modular approach with ensemble of convolutional neural networks.

PubMed

Ertosun, Mehmet Günhan; Rubin, Daniel L

2015-01-01

Brain glioma is the most common primary malignant brain tumors in adults with different pathologic subtypes: Lower Grade Glioma (LGG) Grade II, Lower Grade Glioma (LGG) Grade III, and Glioblastoma Multiforme (GBM) Grade IV. The survival and treatment options are highly dependent of this glioma grade. We propose a deep learning-based, modular classification pipeline for automated grading of gliomas using digital pathology images. Whole tissue digitized images of pathology slides obtained from The Cancer Genome Atlas (TCGA) were used to train our deep learning modules. Our modular pipeline provides diagnostic quality statistics, such as precision, sensitivity and specificity, of the individual deep learning modules, and (1) facilitates training given the limited data in this domain, (2) enables exploration of different deep learning structures for each module, (3) leads to developing less complex modules that are simpler to analyze, and (4) provides flexibility, permitting use of single modules within the framework or use of other modeling or machine learning applications, such as probabilistic graphical models or support vector machines. Our modular approach helps us meet the requirements of minimum accuracy levels that are demanded by the context of different decision points within a multi-class classification scheme. Convolutional Neural Networks are trained for each module for each sub-task with more than 90% classification accuracies on validation data set, and achieved classification accuracy of 96% for the task of GBM vs LGG classification, 71% for further identifying the grade of LGG into Grade II or Grade III on independent data set coming from new patients from the multi-institutional repository.

Automated Grading of Gliomas using Deep Learning in Digital Pathology Images: A modular approach with ensemble of convolutional neural networks

PubMed Central

Ertosun, Mehmet Günhan; Rubin, Daniel L.

2015-01-01

Brain glioma is the most common primary malignant brain tumors in adults with different pathologic subtypes: Lower Grade Glioma (LGG) Grade II, Lower Grade Glioma (LGG) Grade III, and Glioblastoma Multiforme (GBM) Grade IV. The survival and treatment options are highly dependent of this glioma grade. We propose a deep learning-based, modular classification pipeline for automated grading of gliomas using digital pathology images. Whole tissue digitized images of pathology slides obtained from The Cancer Genome Atlas (TCGA) were used to train our deep learning modules. Our modular pipeline provides diagnostic quality statistics, such as precision, sensitivity and specificity, of the individual deep learning modules, and (1) facilitates training given the limited data in this domain, (2) enables exploration of different deep learning structures for each module, (3) leads to developing less complex modules that are simpler to analyze, and (4) provides flexibility, permitting use of single modules within the framework or use of other modeling or machine learning applications, such as probabilistic graphical models or support vector machines. Our modular approach helps us meet the requirements of minimum accuracy levels that are demanded by the context of different decision points within a multi-class classification scheme. Convolutional Neural Networks are trained for each module for each sub-task with more than 90% classification accuracies on validation data set, and achieved classification accuracy of 96% for the task of GBM vs LGG classification, 71% for further identifying the grade of LGG into Grade II or Grade III on independent data set coming from new patients from the multi-institutional repository. PMID:26958289

Concomitant glenohumeral pathologies associated with acute and chronic grade III and grade V acromioclavicular joint injuries.

PubMed

Jensen, Gunnar; Millett, Peter J; Tahal, Dimitri S; Al Ibadi, Mireille; Lill, Helmut; Katthagen, Jan Christoph

2017-08-01

The purpose of this study was to identify the risk of concomitant glenohumeral pathologies with acromioclavicular joint injuries grade III and V. Patients who underwent arthroscopically-assisted stabilization of acromioclavicular joint injuries grade III or grade V between 01/2007 and 12/2015 were identified in the patient databases of two surgical centres. Gender, age at index surgery, grade of acromioclavicular joint injury (Rockwood III or Rockwood V), and duration between injury and index surgery (classified as acute or chronic) were of interest. Concomitant glenohumeral pathologies were noted and their treatment was classified as debridement or reconstructive procedure. A total of 376 patients (336 male, 40 female) were included. Mean age at time of arthroscopic acromioclavicular joint reconstruction surgery was 42.1 ± 14.0 years. Overall, 201 patients (53%) had one or more concomitant glenohumeral pathologies. Lesions of the biceps tendon complex and rotator cuff were the most common. Forty-five patients (12.0%) had concomitant glenohumeral pathologies that required an additional repair. The remaining 156 patients (41.5%) received a debridement of their concomitant pathologies. Rockwood grade V compared to Rockwood grade III (p = 0.013; odds ratio 1.7), and chronic compared to acute injury were significantly associated with having a concomitant glenohumeral pathology (p = 0.019; odds ratio 1.7). The probability of having a concomitant glenohumeral pathology was also significantly associated with increasing age (p < 0.0001). Concomitant glenohumeral pathologies were observed in 53% of surgically treated patients with an acute or chronic acromioclavicular joint injury of either grade III or V. Twenty-two percent of these patients with concomitant glenohumeral pathologies received an additional dedicated repair procedure. Although a significant difference in occurrence of concomitant glenohumeral pathologies was seen between Rockwood grades III and V, and between acute and chronic lesions, increasing age was identified as the most dominant predictor. Level IV, case series.

Prevalence and pattern of glenohumeral injuries among acute high-grade acromioclavicular joint instabilities.

PubMed

Pauly, Stephan; Kraus, Natascha; Greiner, Stefan; Scheibel, Markus

2013-06-01

With increasing numbers of arthroscopically assisted acromioclavicular (AC) joint stabilization procedures has come an increase in reports of concomitant glenohumeral injuries among AC joint separations. The aim of the present study was to evaluate the prevalence, pattern, and cause of glenohumeral pathologies among a large patient population with acute high-grade AC joint instability. A total of 125 patients (13 women, 112 men) with high-grade AC joint dislocation (6 Rockwood II; 119 Rockwood V) underwent diagnostic glenohumeral arthroscopy before AC joint repair. Pathologic lesions were evaluated for acute or degenerative origin and, if considered relevant, treated all-arthroscopically. Concomitant glenohumeral pathologies were found in 38 of 125 patients (30.4%). Analysis of pathogenesis distinguished different patterns of accompanying injuries: acute intra-articular lesions, related to the recent shoulder trauma, were found in 9 patients (7.2%), degenerative lesions, considered to be unrelated to the recent trauma, were found in 18 (14.4%), and 11 (8.8%) had an unclear traumatic correlation (intermediate group). Within the acute and the degenerative group, affected structures were predominantly partial, articular-sided tears of the anterosuperior rotator cuff, including instabilities of the pulley complex, followed by pathologies of the long head of the biceps and superior labrum anteroposterior lesions. The intermediate group presented mainly with articular-sided partial tears of the subscapularis tendon. This prospective study showed a high prevalence (30%) of concomitant glenohumeral pathologies, of which some indicate additional surgical therapy and could be missed by an isolated open AC repair. Hence, the arthroscopic approach for AC joint stabilization allows for the diagnosis and treatment of associated intra-articular pathologies. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia.

PubMed

Montironi, Rodolfo; Thompson, Deborah; Scarpelli, Marina; Mazzucchelli, Roberta; Peketi, Prasanthi; Hamilton, Peter W; Bostwick, David G; Bartels, Peter H

2004-08-01

This digital texture analysis-based study evaluates the chromatin organization state in flat and cribriform high-grade prostatic intraepithelial neoplasia (PIN), in the adjacent normal looking secretory epithelium and in the co-occurring adenocarcinoma. Digital texture analysis (karyometry) was carried out on hematoxylin and eosin-stained sections from 24 radical prostatectomy specimens with high-grade PIN (12 with flat and 12 with cribriform architectural pattern, respectively) and cancer. Quantification was also conducted on the normal looking secretory epithelium. Discriminant analysis and the nonsupervised learning algorithm P-index were used to identify suitable subsets of features useful for the discrimination and classification of pathological groups and to explore multivariate data structure in the pathological subgroups. The average nuclear abnormality increases monotonically from the histologically normal appearing secretory epithelium to high-grade PIN and to adenocarcinoma. The nuclei from the so-called perimeter compartment of the flat high-grade PIN lesions show a higher nuclear abnormality compared to the nuclei of the cribriform high-grade PINs. Discriminant analysis shows that flat and cribriform high-grade PINs fall into two populations. Processing by the nonsupervised learning algorithm P-index revealed the existence of three well-defined, distinct subpopulations of nuclei of different chromatin phenotype. In the flat high-grade PIN lesions the proportions of nuclei in the three subpopulations are 16.5% (low abnormality), 25.0% (mid abnormality) and 58.5% (high abnormality), respectively. In the cribriform high-grade PIN lesions, 100% of the nuclei are in the mid-abnormality subpopulation. These differences are also discernible in the co-occurring adenocarcinoma and the histologically normal appearing secretory epithelium. To conclude, karyometry and statistical analysis detect the existence of distinct cell subpopulations of different chromatin packaging and phenotype, with the nuclei from the flat high-grade PIN lesions, adjacent normal looking epithelium and co-occurring adenocarcinoma expressing a greater nuclear abnormality than in the specimens with cribriform high-grade PIN.

Prevention of Ovarian High Grade Serous Carcinoma by Elucidating Its Early Changes

DTIC Science & Technology

2015-10-01

journals including J Pathol (PMID: 23378270), Am J Surg Pathol (PMID: 22892598) and Mod Pathology (PMID: 25216223). Task 2d. Telomere FISH on STICs...STICs have shorter telomere length and lower degree of centrosome amplification than the adjacent high- grade serous carcinomas (HGSC). Therefore, our

Evaluation of anatomic and morphologic nomogram to predict malignant and high-grade disease in a cohort of patients with small renal masses.

PubMed

Bagrodia, Aditya; Harrow, Brian; Liu, Zhuo-Wei; Olweny, Ephrem O; Faddegon, Stephen; Yin, Gang; Tan, Yung Khan; Han, Woong Kyu; Lotan, Yair; Margulis, Vitaly; Cadeddu, Jeffrey A

2014-01-01

To evaluate a nomogram using the RENAL Nephrometry Score (RENAL-NS) that was developed to characterize masses as benign vs. malignant and high vs. low grade in our patients with small renal masses treated with partial nephrectomy (PN). The nomogram was previously developed and validated in patients with widely variable tumor sizes. Retrospective review of PN performed between 1/2003 and 7/2011. Imaging was reviewed by a urologic surgeon for RENAL-NS. Final pathology was used to classify tumors as benign or malignant and low (I/II) or high (III/IV) Fuhrman grade. Patient age, gender, and RENAL score were entered into the nomogram described by Kutikov et al. to determine probabilities of cancer and high-grade disease. Area under the curve was determined to assess agreement between observed and expected outcomes for prediction of benign vs. malignant disease and for prediction of high- vs. low-grade or benign disease. A total of 250 patients with 252 masses underwent PN during the study period; 179/250 (71.6%) had preoperative imaging available. RENAL-NS was assigned to 181 masses. Twenty-two percent of tumors were benign. Eighteen percent of tumors were high grade. Area under the curve was 0.648 for predicting benign vs. malignant disease and 0.955 for predicting low-grade or benign vs. high-grade disease. The RENAL-NS score nomogram by Kutikov does not discriminate well between benign and malignant disease for small renal masses. The nomogram may potentially be useful in identifying high-grade tumors. Further validation is required where the nomogram probability and final pathologic specimen are available. Copyright © 2014 Elsevier Inc. All rights reserved.

A High-Grade Chondrosarcoma of Calcaneum Mimicking as a Benign Pathology: Delayed Diagnosis and Management.

PubMed

Baba, Muzamil Ahmad; Nazir, Naila; Shabeer, Maajid; Mir, Bashir Ahmed; Kawoosa, Altaf Ahmad

2016-10-01

This case is presented to highlight a rare case of chondrosarcoma of calcaneum in a young adult mimicking as a benign pathology and to highlight the diagnosis and early management of such cases to prevent complications and even death. Chondrosarcoma constitutes less than 10% of all primary malignancies of bone and occurs mostly in proximal locations such as pelvis, proximal femur, and proximal humerus. We present a case of high-grade chondrosarcoma at a very rare site, calcaneum of a 40-year-old male that was mimicking as a benign pathology. This case report highlights the importance of proper clinical examination, evaluation, and suspicion for benign occurring lesions to prevent complications related to a delay in diagnosis. Therapeutic, Level IV: Case study. © 2016 The Author(s).

The Role of Lifestyle Factors in Ovarian Cancer Prognosis

DTIC Science & Technology

2016-10-01

cancer (while the rest would be low grade or borderline ). We have now reviewed the pathology reports of all the participants in the case-control study...and, in fact, ~50% are high-grade ovarian cancers (25% are low-grade and 25% are borderline ), which is much lower than expected based on the

Pathological Gambling and Related Problems among Adolescents.

ERIC Educational Resources Information Center

Ladouceur, Robert; Boudreault, Normand; Jacques, Christian; Vitaro, Frank

1999-01-01

Evaluates the prevalence of pathological gambling and related problems among 3,426 students in junior and senior high schools in Quebec City. Results indicate that 77% have gambled in the last twelve months and 13% gamble at least once a week. Results also reveal that pathological gambling is associated with drug and alcohol use, poor grades, and…

Stratification of HPV-Induced Cervical Pathology using the Virally-Encoded Molecular Marker E4 in Combination with p16 or MCM

PubMed Central

Griffin, Heather; Soneji, Yasmina; Van Baars, Romy; Arora, Rupali; Jenkins, David; van de Sandt, Miekel; Wu, Zhonglin; Quint, Wim; Jach, Robert; Okon, Krzysztof; Huras, Hubert; Singer, Albert; Doorbar, John

2015-01-01

High-risk HPV types cause cervical lesions of varying severity, ranging from transient productive infections to high-grade neoplasia. Disease stratification requires the examination of lesional pathology, and possibly also the detection of biomarkers. P16INK4a and MCM are established surrogates of high-risk HPV E6/E7 activity, and can be extensively expressed in high-grade lesions. Here we have combined these two cellular biomarkers with detection of the abundant HPV-encoded E4 protein in order to identify both productive and transforming lesions. This approach has allowed us to distinguish true papillomavirus infections from similar pathologies, and has allowed us to divide the heterogeneous CIN2 category into those that are CIN1-like and express E4, and those that more closely resemble non-productive CIN3. To achieve this, 530 lesional areas were evaluated according to standard pathology criteria and by using a multiple staining approach that allows us to superimpose biomarker patterns either singly or in combination onto an annotated haematoxylin & eosin image. Conventional grading of neoplasia was established by review panel, and compared directly to the composite molecular pathology visualised on the same tissue section. The detection of E4 coincided with the onset of vacuolation, becoming abundant in koilocytes as the MCM marker declined and cells lost their defined nuclear margins as visualised by standard H&E staining. Of the dual marker approaches, p16INK4a and E4 appeared most promising, with E4 generally identifying areas of low-grade disease even when p16INK4a was present. Extensive p16INK4a expression usually coincided with an absence of E4 expression or its focal retention in sporadic cells within the lesion. Our results suggest that a straightforward molecular evaluation of HPV life-cycle deregulation in cervical neoplasia may help improve disease stratification, and that this can be achieved using complementary molecular biomarker pairs such as MCM/E4 or more promisingly, p16INK4a/E4 as an adjunct to conventional pathology. PMID:25953390

Vascularity as assessed by Doppler intraoral ultrasound around the invasion front of tongue cancer is a predictor of pathological grade of malignancy and cervical lymph node metastasis.

PubMed

Yamamoto, Chika; Yuasa, Kenji; Okamura, Kazuhiko; Shiraishi, Tomoko; Miwa, Kunihiro

2016-01-01

To quantitatively evaluate the relationship of vascularity of tongue cancer as demonstrated on intraoral ultrasonography images and tumour thickness with pathological grade of malignancy and the presence of cervical lymph node metastases. 18 patients with tongue cancer were enrolled in this retrospective study. Using Doppler ultrasonography images of the invasion front of the cancers along the length of their tumour boundaries, three vascular indexes were analysed quantitatively, namely ratio of blood flow signal area within the cancer to whole tumour area (BAR), blood flow signal number ratio (BNR) and blood flow signal width ratio (BWR). The associations between these three indexes and occurrence of cervical lymph node metastasis and pathological grade of malignancy [Yamamoto-Kohama (YK) classification] were assessed. Furthermore, the relationship between tumour thickness and occurrence of cervical lymph node metastasis was evaluated on B-mode intraoral ultrasonography images. There was no significant association between BAR and tumour thickness or occurrence of cervical lymph node metastasis. The BNRs and BWRs of patients with cervical lymph node metastasis were significantly higher than those of patients without nodal involvement. The BWRs of patients with high-grade malignancy (YK-4C) were significantly higher than those of patients with low-grade malignancy (YK-2 or 3). BNR and BWR on the invasion front of the tongue cancer are predictors of pathological grade of malignancy and cervical lymph node metastasis.

The influence of different classification standards of age groups on prognosis in high-grade hemispheric glioma patients.

PubMed

Chen, Jian-Wu; Zhou, Chang-Fu; Lin, Zhi-Xiong

2015-09-15

Although age is thought to correlate with the prognosis of glioma patients, the most appropriate age-group classification standard to evaluate prognosis had not been fully studied. This study aimed to investigate the influence of age-group classification standards on the prognosis of patients with high-grade hemispheric glioma (HGG). This retrospective study of 125 HGG patients used three different classification standards of age-groups (≤ 50 and >50 years old, ≤ 60 and >60 years old, ≤ 45 and 45-65 and ≥ 65 years old) to evaluate the impact of age on prognosis. The primary end-point was overall survival (OS). The Kaplan-Meier method was applied for univariate analysis and Cox proportional hazards model for multivariate analysis. Univariate analysis showed a significant correlation between OS and all three classification standards of age-groups as well as between OS and pathological grade, gender, location of glioma, and regular chemotherapy and radiotherapy treatment. Multivariate analysis showed that the only independent predictors of OS were classification standard of age-groups ≤ 50 and > 50 years old, pathological grade and regular chemotherapy. In summary, the most appropriate classification standard of age-groups as an independent prognostic factor was ≤ 50 and > 50 years old. Pathological grade and chemotherapy were also independent predictors of OS in post-operative HGG patients. Copyright © 2015. Published by Elsevier B.V.

Concomitant glenohumeral pathologies in high-grade acromioclavicular separation (type III - V).

PubMed

Markel, Jochen; Schwarting, Tim; Malcherczyk, Dominik; Peterlein, Christian-Dominik; Ruchholtz, Steffen; El-Zayat, Bilal Farouk

2017-11-10

Acromioclavicular joint (ACJ) dislocations are common injuries of the shoulder associated with physical activity. The diagnosis of concomitant injuries proves complicated due to the prominent clinical symptoms of acute ACJ dislocation. Because of increasing use of minimally invasive surgery techniques concomitant pathologies are diagnosed more often than with previous procedures. The aim of this study was to identify the incidence of concomitant intraarticular injuries in patients with high-grade acromioclavicular separation (Rockwood type III - V) as well as to reveal potential risk constellations. The concomitant pathologies were compiled during routine arthroscopically assisted treatment in altogether 163 patients (147 male; 16 female; mean age 36.8 years) with high-grade acromioclavicular separation (Rockwood type III: n = 60; Rockwood type IV: n = 6; Rockwood type V: n = 97). Acromioclavicular separation occurred less often in women than men (1:9). In patients under 35, the most common cause for ACJ dislocation was sporting activity (37.4%). Rockwood type V was observed significantly more often than the other types with 57.5% (Rockwood type III = 36.8%, Rockwood type IV 3.7%). Concomitant pathologies were diagnosed in 39.3% of the patients with that number rising to as much as 57.3% in patients above 35 years. Most common associated injuries were rotator cuff injuries (32.3%), chondral defects (30.6%) and SLAP-lesions (22.6%). Of all patients, 8.6% needed additional reconstructive surgery. Glenohumeral injuries are a much more common epiphenomenon during acromioclavicular separation than previously ascertained. High risk group for accompanying injuries are patients above 35 years with preexisting degenerative disease. The increasing use of minimally invasive techniques allows for an easier diagnosis and simultaneous treatment of the additional pathologies.

Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration.

PubMed

Margulis, Vitaly; Shariat, Shahrokh F; Matin, Surena F; Kamat, Ashish M; Zigeuner, Richard; Kikuchi, Eiji; Lotan, Yair; Weizer, Alon; Raman, Jay D; Wood, Christopher G

2009-03-15

The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified. Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected. All pathologic slides were re-reviewed by genitourinary pathologists according to strict criteria. Pathologic review revealed renal pelvis location (64%), necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in situ (28.7%), and high-grade disease (63.7%). A total of 590 patients (43.3%) underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) -positive. Over a mean follow-up of 51 months, 379 (28%) patients experienced disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5-year recurrence-free and cancer-specific survival probabilities (+/-SD) were 69%+/-1% and 73%+/-1%, respectively. On multivariate analysis, high tumor grade (hazards ratio [HR]: 2.0, P<.001), advancing pathologic T stage (P-for-trend<.001), LN metastases (HR: 1.8, P<.001), infiltrative growth pattern (HR: 1.5, P<.001), and LVI (HR: 1.2, P=.041) were associated with disease recurrence. Similarly, patient age (HR: 1.1, P=.001), high tumor grade (HR: 1.7, P=.001), increasing pathologic T stage (P-for-trend<.001), LN metastases (HR: 1.7, P<.001), sessile architecture (HR: 1.5, P=.002), and LVI (HR: 1.4, P=.02) were independently associated with cancer-specific survival. Radical nephroureterectomy provided durable local control and cancer-specific survival in patients with localized UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI were important prognostic variables associated with oncologic outcomes, which could potentially be used to select patients for adjuvant systemic therapy. Copyright (c) 2009 American Cancer Society.

Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study.

PubMed

Bodurka, Diane C; Deavers, Michael T; Tian, Chunqiao; Sun, Charlotte C; Malpica, Anais; Coleman, Robert L; Lu, Karen H; Sood, Anil K; Birrer, Michael J; Ozols, Robert; Baergen, Rebecca; Emerson, Robert E; Steinhoff, Margaret; Behmaram, Behnaz; Rasty, Golnar; Gershenson, David M

2012-06-15

A study was undertaken to use the 2-tier system to reclassify the grade of serous ovarian tumors previously classified using the International Federation of Gynecology and Obstetrics (FIGO) 3-tier system and determine the progression-free survival (PFS) and overall survival (OS) of patients treated on Gynecologic Oncology Group (GOG) Protocol 158. The authors retrospectively reviewed demographic, pathologic, and survival data of 290 patients with stage III serous ovarian carcinoma treated with surgery and chemotherapy on GOG Protocol 158, a cooperative multicenter group trial. A blinded pathology review was performed by a panel of 6 gynecologic pathologists to verify histology and regrade tumors using the 2-tier system. The association of tumor grade with PFS and OS was assessed. Of 241 cases, both systems demonstrated substantial agreement when combining FIGO grades 2 and 3 (overall agreement, 95%; kappa statistic, 0.68). By using the 2-tier system, patients with low-grade versus high-grade tumors had significantly longer PFS (45.0 vs 19.8 months, respectively; P = .01). By using FIGO criteria, median PFS for patients with grade 1, 2, and 3 tumors was 37.5, 19.8, and 20.1 months, respectively (P = .07). There was no difference in clinical outcome in patients with grade 2 or 3 tumors in multivariate analysis. Woman with high-grade versus low-grade tumors demonstrated significantly higher risk of death (hazard ratio, 2.43; 95% confidence interval, 1.17-5.04; P = .02). Women with high-grade versus low-grade serous carcinoma of the ovary are 2 distinct patient populations. Adoption of the 2-tier grading system provides a simple yet precise framework for predicting clinical outcomes. Copyright © 2011 American Cancer Society.

A Novel Candidate Molecule in Pathological Grading Of Gliomas: ELABELA.

PubMed

Artas, Gokhan; Ozturk, Sait; Kuloglu, Tuncay; Dagli, Adile Ferda; Gonen, Murat; Artas, Hakan; Aydin, Suleyman; Erol, Fatih Serhat

2018-04-06

This study aimed to investigate the possible role of ELABELA (ELA) in the histopathological grading of gliomas. We retrospectively assessed pathological specimens of patients who underwent surgery for intracranial space-occupying lesions. Only primary glioma specimens were included in this study. We enrolled 11 patients histologically diagnosed with low-grade glioma and 22 patients with high-grade glioma. The ELA antibody was applied to 4-6-µm-thick sections obtained from paraffin blocks. Histoscores were calculated using the distribution and intensity of staining immunoreactivity. An independent sample t-test was used for two-point inter-group assessments, whereas one-way analysis of variance was used for the other assessments. P 0.05 was considered statistically significant. The histoscores of the control brain, low-grade glioma, and high-grade glioma tissues were found to be 0.08, 0.37, and 0.92, respectively. The difference in ELA immunoreactivity between the control brain tissue and glioma tissue was statistically significant (p 0.05). In addition, a statistically significant increase was observed in ELA immunoreactivity in high-grade glioma tissues compared with that in low-grade glioma tissues (p 0.05). ELA has an angiogenetic role in the progression of glial tumors. ELA, which is an endogenous ligand of the apelin receptor, activates the apelinergic system and causes the progression of glial tumors. Further studies with a large number of patients are necessary to investigate the angiogenetic role of ELA in glial tumors.

Comparison study of five different display modalities for whole slide images in surgical pathology and cytopathology in Europe

NASA Astrophysics Data System (ADS)

D'Haene, Nicky; Maris, Calliope; Rorive, Sandrine; Moles Lopez, Xavier; Rostang, Johan; Marchessoux, Cédric; Pantanowitz, Liron; Parwani, Anil V.; Salmon, Isabelle

2013-03-01

User experience with viewing images in pathology is crucial for accurate interpretation and diagnosis. With digital pathology, images are being read on a display system, and this poses new types of questions: such as what is the difference in terms of pixelation, refresh lag or obscured features compared to an optical microscope. Is there a resultant change in user performance in terms of speed of slide review, perception of adequacy and quality or in diagnostic confidence? A prior psychophysical study was carried out comparing various display modalities on whole slide imaging (WSI) in pathology at the University of Pittsburgh Medical Center (UPMC) in the USA. This prior study compared professional and non-professional grade display modalities and highlighted the importance of using a medical grade display to view pathological digital images. This study was duplicated in Europe at the Department of Pathology in Erasme Hospital (Université Libre de Bruxelles (ULB)) in an attempt to corroborate these findings. Digital WSI with corresponding glass slides of 58 cases including surgical pathology and cytopathology slides of varying difficulty were employed. Similar non-professional and professional grade display modalities were compared to an optical microscope (Olympus BX51). Displays ranged from a laptop (DELL Latitude D620), to a consumer grade display (DELL E248WFPb), to two professional grade monitors (Eizo CG245W and Barco MDCC-6130). Three pathologists were selected from the Department of Pathology in Erasme Hospital (ULB) in Belgium to view and interpret the pathological images on these different displays. The results show that non-professional grade displays (laptop and consumer) have inferior user experience compared to professional grade monitors and the optical microscope.

High-grade tumor differentiation is an indicator of poor prognosis in African Americans with colonic adenocarcinomas.

PubMed

Alexander, Dominik; Jhala, Nirag; Chatla, Chakrapani; Steinhauer, Jon; Funkhouser, Ellen; Coffey, Christopher S; Grizzle, William E; Manne, Upender

2005-05-15

To identify the factors that contribute to poorer colon carcinoma survival rates for African Americans compared with Caucasians, the authors evaluated survival differences based on the histologic grade (differentiation) of the tumor. All 169 African Americans and 229 randomly selected non-Hispanic Caucasians who underwent surgery during 1981-1993 for first primary sporadic colon carcinoma at the University of Alabama at Birmingham or its affiliated Veterans Affairs hospital were included in the current study. None of these patients received presurgery or postsurgery therapies. Recently, the authors reported an increased risk of colon carcinoma death for African Americans in this patient population, after adjustment for stage and other clinicodemographic features. The authors generated Kaplan-Meier survival probabilities according to race and tumor differentiation and multivariate Cox proportional hazards models to estimate hazard ratios (HR) with 95% confidence intervals (95% CI). There were no differences in the distribution of pathologic tumor stage between racial groups after stratifying by histologic tumor grade. Among patients with high-grade tumors, 54% of African Americans and 21% of Caucasians died within the first year after surgery (P = 0.007). African Americans with high-grade tumors were 3 times (HR = 3.05; 95% CI, 1.32-7.05) more likely to die of colon carcinoma within 5 years postsurgery, compared with Caucasians with high-grade tumors. There were no survival differences by race among patients with low-grade tumors. These findings suggested that poorer survival among African-American patients with adenocarcinomas of the colon may not be attributable to an advanced pathologic stage of disease at diagnosis, but instead may be due to aggressive biologic features like high tumor grades.

Convolutional neural networks for an automatic classification of prostate tissue slides with high-grade Gleason score

NASA Astrophysics Data System (ADS)

Jiménez del Toro, Oscar; Atzori, Manfredo; Otálora, Sebastian; Andersson, Mats; Eurén, Kristian; Hedlund, Martin; Rönnquist, Peter; Müller, Henning

2017-03-01

The Gleason grading system was developed for assessing prostate histopathology slides. It is correlated to the outcome and incidence of relapse in prostate cancer. Although this grading is part of a standard protocol performed by pathologists, visual inspection of whole slide images (WSIs) has an inherent subjectivity when evaluated by different pathologists. Computer aided pathology has been proposed to generate an objective and reproducible assessment that can help pathologists in their evaluation of new tissue samples. Deep convolutional neural networks are a promising approach for the automatic classification of histopathology images and can hierarchically learn subtle visual features from the data. However, a large number of manual annotations from pathologists are commonly required to obtain sufficient statistical generalization when training new models that can evaluate the daily generated large amounts of pathology data. A fully automatic approach that detects prostatectomy WSIs with high-grade Gleason score is proposed. We evaluate the performance of various deep learning architectures training them with patches extracted from automatically generated regions-of-interest rather than from manually segmented ones. Relevant parameters for training the deep learning model such as size and number of patches as well as the inclusion or not of data augmentation are compared between the tested deep learning architectures. 235 prostate tissue WSIs with their pathology report from the publicly available TCGA data set were used. An accuracy of 78% was obtained in a balanced set of 46 unseen test images with different Gleason grades in a 2-class decision: high vs. low Gleason grade. Grades 7-8, which represent the boundary decision of the proposed task, were particularly well classified. The method is scalable to larger data sets with straightforward re-training of the model to include data from multiple sources, scanners and acquisition techniques. Automatically generated heatmaps for theWSIs could be useful for improving the selection of patches when training networks for big data sets and to guide the visual inspection of these images.

Factors influencing histologic confirmation of high-grade squamous intraepithelial lesion cytology.

PubMed

Castle, Philip E; Cox, J Thomas; Schiffman, Mark; Wheeler, Cosette M; Solomon, Diane

2008-09-01

To examine the predictors of histologic confirmation of high-grade squamous intraepithelial lesion (HSIL) cytology occurring in follow-up of young women originally referred into a trial because of less severe cytology. We used enrollment HSIL cytology (N=411) as read by clinical center pathologists for women participating in the ASCUS-LSIL Triage Study (ALTS). The primary outcome was histologic cervical intraepithelial neoplasia (CIN) grade 3 and early cancer (n=195; 191 CIN 3 and four cancers) as diagnosed by the Pathology Quality Control Group during the 2-year duration of ALTS. The 2-year absolute risk of CIN 3 or worse after an HSIL cytology was 47.4% (95% confidence interval 42.5-52.4%). The 2-year absolute risk of CIN 3 or worse was lowest (14.3%) for women who were human papillomavirus (HPV)-16-negative, had colposcopic impression of less than low-grade, and whose HSIL cytology as called by the clinical center was not also called HSIL or equivocal HSIL cytology by the Pathology Quality Control Group. The 2-year absolute risk of CIN 3 or worse was highest (82.4%) for women who were HPV16-positive, had colposcopic impression of low-grade or worse, and whose HSIL cytology also was called HSIL or equivocal HSIL cytology by the Pathology Quality Control Group. Histologic confirmation of precancer among young women with HSIL cytology was more likely when other risk factors (eg, HPV16) for cervical precancer were present.

Histopathologic grading of anaplasia in retinoblastoma.

PubMed

Mendoza, Pia R; Specht, Charles S; Hubbard, G Baker; Wells, Jill R; Lynn, Michael J; Zhang, Qing; Kong, Jun; Grossniklaus, Hans E

2015-04-01

To determine whether the degree of tumor anaplasia has prognostic value by evaluating its correlation with high-risk histopathologic features and clinical outcomes in a series of retinoblastoma patients. Retrospective clinicopathologic study. The clinical and pathologic findings in 266 patients who underwent primary enucleation for retinoblastoma were reviewed. The histologic degree of anaplasia was graded as retinocytoma, mild, moderate, or severe as defined by increasing cellular pleomorphism, number of mitoses, nuclear size, and nuclear hyperchromatism. Nuclear morphometric characteristics were measured. The clinical and pathologic data of 125 patients were compared using Kaplan-Meier estimates of survival. Fisher exact test and multivariate regression were used to analyze the association between anaplasia grade and high-risk histologic features. Increasing grade of anaplasia was associated with decreased overall survival (P = .003) and increased risk of metastasis (P = .0007). Histopathologic features that were associated with anaplasia included optic nerve invasion (P < .0001), choroidal invasion (P < .0001), and anterior segment invasion (P = .04). Multivariate analysis considering high-risk histopathology and anaplasia grading as predictors of distant metastasis and death showed that high-risk histopathology was statistically significant as an independent predictor (P = .01 for metastasis, P = .03 for death) but anaplasia was not (P = .63 for metastasis, P = .30 for death). In the absence of high-risk features, however, severe anaplasia identified an additional risk for metastasis (P = .0004) and death (P = .01). Grading of anaplasia may be a useful adjunct to standard histopathologic criteria in identifying retinoblastoma patients who do not have high-risk histologic features but still have an increased risk of metastasis and may need adjuvant therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Computed tomography of the anterior mediastinum in myasthemia gravis: a radiologic-pathologic correlative study

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

Fon, G.T.; Bein, M.E.; Mancuso, A.A.

1982-01-01

Chest radiographs and computed tomographic (CT) scans of the mediastinum were correlated with pathologic findings of the thymus following thymectomy in 57 patients with myasthenia gravis. Based on the patient's age and the overall morphology of the anterior mediastinum, CT scans were assigned one of four grades in an attempt to predict thymus pathologic findings. Using this grading, 14 of 16 cases of thymoma were suspected or definitely diagnosed. One of the two cases not diagnosed on CT was a microscopic tumor. There were no false-positive diagnoses in 11 cases graded as definitely thymoma. We conclude that thymoma can bemore » sensitively diagnosed in patients older than 40 years of age. However, thymoma cannot be predicted with a high level of confidence in patients younger than 40 because of the difficulty in differentiating normal thymus or hyperplasia from thymoma. Recommendations for the use of CT in the preoperative evaluation of myasthenic patients are presented.« less

Pathology of Neuroendocrine Tumours of the Female Genital Tract.

PubMed

Howitt, Brooke E; Kelly, Paul; McCluggage, W Glenn

2017-09-01

Neuroendocrine tumours are uncommon or rare at all sites in the female genital tract. The 2014 World Health Organisation (WHO) Classification of neuroendocrine tumours of the endometrium, cervix, vagina and vulva has been updated with adoption of the terms low-grade neuroendocrine tumour and high-grade neuroendocrine carcinoma. In the endometrium and cervix, high-grade neoplasms are much more prevalent than low-grade and are more common in the cervix than the corpus. In the ovary, low-grade tumours are more common than high-grade carcinomas and the term carcinoid tumour is still used in WHO 2014. The term ovarian small-cell carcinoma of pulmonary type is included in WHO 2014 for a tumour which in other organs is termed high small-cell neuroendocrine carcinoma. Neuroendocrine tumours at various sites within the female genital tract often occur in association with other neoplasms and more uncommonly in pure form.

Determination of hepatocellular carcinoma grade by needle biopsy is unreliable for liver transplant candidate selection.

PubMed

Court, Colin M; Harlander-Locke, Michael P; Markovic, Daniela; French, Samuel W; Naini, Bita V; Lu, David S; Raman, Steven S; Kaldas, Fady M; Zarrinpar, Ali; Farmer, Douglas G; Finn, Richard S; Sadeghi, Saeed; Tomlinson, James S; Busuttil, Ronald W; Agopian, Vatche G

2017-09-01

The objective of this article is to evaluate the utility of preoperative needle biopsy (PNB) grading of hepatocellular carcinoma (HCC) as a biomarker for liver transplantation (LT) candidate selection. Given the prognostic significance of HCC tumor grade, PNB grading has been proposed as a biomarker for LT candidate selection. Clinicopathologic characteristics of HCC LT recipients (1989-2014) with a PNB were analyzed, and the concordance of PNB grade to explant grade and vascular invasion was assessed to determine whether incorporation of PNB grade to accepted transplant criteria improved candidate selection. Of 965 patients undergoing LT for HCC, 234 (24%) underwent PNB at a median of 280 days prior to transplant. Grade by PNB had poor concordance to final explant pathology (κ = 0.22; P = 0.003), and low sensitivity (29%) and positive predictive value (35%) in identifying poorly differentiated tumors. Vascular invasion was predicted by explant pathologic grade (r s = 0.24; P < 0.001) but not PNB grade (r s = -0.05; P = 0.50). Increasing explant pathology grade (P = 0.02), but not PNB grade (P = 0.65), discriminated post-LT HCC recurrence risk. The incorporation of PNB grade to the established radiologic Milan criteria (MC) did not result in improved prognostication of post-LT recurrence (net reclassification index [NRI] = 0%), whereas grade by explant pathology resulted in significantly improved reclassification of risk (NRI = 19%). Preoperative determination of HCC grade by PNB has low concordance with explant pathologic grade and low sensitivity and positive predictive value in identifying poorly differentiated tumors. PNB grade did not accurately discriminate post-LT HCC recurrence and had no utility in improving prognostication compared with the MC alone. Incorporation of PNB to guide transplant candidate selection appears unjustified. Liver Transplantation 23 1123-1132 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

A Tissue Systems Pathology Test Detects Abnormalities Associated with Prevalent High-Grade Dysplasia and Esophageal Cancer in Barrett's Esophagus.

PubMed

Critchley-Thorne, Rebecca J; Davison, Jon M; Prichard, Jeffrey W; Reese, Lia M; Zhang, Yi; Repa, Kathleen; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory G; DeMarshall, Maureen; Foxwell, Tyler; Jobe, Blair A; Zaidi, Ali H; Duits, Lucas C; Bergman, Jacques J G H M; Rustgi, Anil; Falk, Gary W

2017-02-01

There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC. We performed a multi-institutional case-control study to evaluate a previously developed risk classifier that is based upon quantitative image features derived from 9 biomarkers and morphology, and predicts risk for HGD/EAC in Barrett's esophagus patients. The risk classifier was evaluated in ND, IND, and LGD biopsies from Barrett's esophagus patients diagnosed with HGD/EAC on repeat endoscopy (prevalent cases, n = 30, median time to HGD/EAC diagnosis 140.5 days) and nonprogressors (controls, n = 145, median HGD/EAC-free surveillance time 2,015 days). The risk classifier stratified prevalent cases and non-progressor patients into low-, intermediate-, and high-risk classes [OR, 46.0; 95% confidence interval, 14.86-169 (high-risk vs. low-risk); P < 0.0001]. The classifier also provided independent prognostic information that outperformed the subspecialist and generalist diagnosis. A tissue systems pathology test better predicts prevalent HGD/EAC in Barrett's esophagus patients than pathologic variables. The results indicate that molecular and cellular changes associated with malignant transformation in Barrett's esophagus may be detectable as a field effect using the test. A tissue systems pathology test may provide an objective method to facilitate earlier identification of Barrett's esophagus patients requiring therapeutic intervention. Cancer Epidemiol Biomarkers Prev; 26(2); 240-8. ©2016 AACR. ©2016 American Association for Cancer Research.

Histopathologic Grading of Anaplasia in Retinoblastoma

PubMed Central

Mendoza, Pia R.; Specht, Charles S.; Hubbard, G. Baker; Wells, Jill R.; Lynn, Michael J.; Zhang, Qing; Kong, Jun; Grossniklaus, Hans E.

2014-01-01

Purpose To determine whether the degree of tumor anaplasia has prognostic value by evaluating its correlation with high-risk histopathologic features and clinical outcomes in a series of retinoblastoma patients. Design Retrospective clinicopathologic study. Methods The clinical and pathologic findings in 266 patients who underwent primary enucleation for retinoblastoma were reviewed. The histologic degree of anaplasia was graded as retinocytoma, mild, moderate, or severe as defined by increasing cellular pleomorphism, number of mitoses, nuclear size, and nuclear hyperchromatism. Nuclear morphometric characteristics were measured. The clinical and pathologic data of 125 patients were compared using Kaplan-Meier estimates of survival. Fisher's exact test and multivariate regression were used to analyze the association between anaplasia grade and high-risk histologic features. Results Increasing grade of anaplasia was associated with decreased overall survival (p=0.003) and increased risk of metastasis (p=0.0007). Histopathologic features that were associated with anaplasia included optic nerve invasion (p<0.0001), choroidal invasion (p=<0.0001), and anterior segment invasion (p=0.04). Multivariate analysis considering high-risk histopathology and anaplasia grading as predictors of distant metastasis and death showed that high-risk histopathology was statistically significant as an independent predictor (p=0.01 for metastasis, p=0.03 for death) but anaplasia was not (p=0.63 for metastasis, p=0.30 for death). In the absence of high-risk features, however, severe anaplasia identified an additional risk for metastasis (p=0.0004) and death (p=0.01). Conclusion Grading of anaplasia may be a useful adjunct to standard histopathologic criteria in identifying retinoblastoma patients who do not have high-risk histologic features but still have an increased risk of metastasis and may need adjuvant therapy. PMID:25528954

Use of Severity Grades to Characterize Histopathologic Changes.

PubMed

Schafer, Kenneth A; Eighmy, John; Fikes, James D; Halpern, Wendy G; Hukkanen, Renee R; Long, Gerald G; Meseck, Emily K; Patrick, Daniel J; Thibodeau, Michael S; Wood, Charles E; Francke, Sabine

2018-04-01

The severity grade is an important component of a histopathologic diagnosis in a nonclinical toxicity study that helps distinguish treatment-related effects from background findings and aids in determining adverse dose levels during hazard characterization. Severity grades should be assigned based only on the extent (i.e., amount and complexity) of the morphologic change in the examined tissue section(s) and be clearly defined in the pathology report for critical lesions impacting study interpretation. However, the level of detail provided and criteria by which severity grades are assigned can vary, which can lead to inappropriate comparisons and confusion when evaluating pathology results. To help address this issue, a Working Group of the Society of Toxicologic Pathology's Scientific and Regulatory Policy Committee was formed to provide a "points to consider" article on the assignment and application of pathology severity grades. Overall, the Working Group supports greater transparency and consistency in the reporting of grading scales and provides recommendations to improve selection of diagnoses requiring more detailed severity criteria. This information should enhance the overall understanding by toxicologic pathologists, toxicologists, and regulatory reviewers of pathology findings and thereby improve effective communication in regulatory submissions.

Molecular approaches for classifying endometrial carcinoma.

PubMed

Piulats, Josep M; Guerra, Esther; Gil-Martín, Marta; Roman-Canal, Berta; Gatius, Sonia; Sanz-Pamplona, Rebeca; Velasco, Ana; Vidal, August; Matias-Guiu, Xavier

2017-04-01

Endometrial carcinoma is the most common cancer of the female genital tract. This review article discusses the usefulness of molecular techniques to classify endometrial carcinoma. Any proposal for molecular classification of neoplasms should integrate morphological features of the tumors. For that reason, we start with the current histological classification of endometrial carcinoma, by discussing the correlation between genotype and phenotype, and the most significant recent improvements. Then, we comment on some of the possible flaws of this classification, by discussing also the value of molecular pathology in improving them, including interobserver variation in pathologic interpretation of high grade tumors. Third, we discuss the importance of applying TCGA molecular approach to clinical practice. We also comment on the impact of intratumor heterogeneity in classification, and finally, we will discuss briefly, the usefulness of TCGA classification in tailoring immunotherapy in endometrial cancer patients. We suggest combining pathologic classification and the surrogate TCGA molecular classification for high-grade endometrial carcinomas, as an option to improve assessment of prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative CT analysis for the preoperative prediction of pathologic grade in pancreatic neuroendocrine tumors

NASA Astrophysics Data System (ADS)

Chakraborty, Jayasree; Pulvirenti, Alessandra; Yamashita, Rikiya; Midya, Abhishek; Gönen, Mithat; Klimstra, David S.; Reidy, Diane L.; Allen, Peter J.; Do, Richard K. G.; Simpson, Amber L.

2018-02-01

Pancreatic neuroendocrine tumors (PanNETs) account for approximately 5% of all pancreatic tumors, affecting one individual per million each year.1 PanNETs are difficult to treat due to biological variability from benign to highly malignant, indolent to very aggressive. The World Health Organization classifies PanNETs into three categories based on cell proliferative rate, usually detected using the Ki67 index and cell morphology: low-grade (G1), intermediate-grade (G2) and high-grade (G3) tumors. Knowledge of grade prior to treatment would select patients for optimal therapy: G1/G2 tumors respond well to somatostatin analogs and targeted or cytotoxic drugs whereas G3 tumors would be targeted with platinum or alkylating agents.2, 3 Grade assessment is based on the pathologic examination of the surgical specimen, biopsy or ne-needle aspiration; however, heterogeneity in the proliferative index can lead to sampling errors.4 Based on studies relating qualitatively assessed shape and enhancement characteristics on CT imaging to tumor grade in PanNET,5 we propose objective classification of PanNET grade with quantitative analysis of CT images. Fifty-five patients were included in our retrospective analysis. A pathologist graded the tumors. Texture and shape-based features were extracted from CT. Random forest and naive Bayes classifiers were compared for the classification of G1/G2 and G3 PanNETs. The best area under the receiver operating characteristic curve (AUC) of 0:74 and accuracy of 71:64% was achieved with texture features. The shape-based features achieved an AUC of 0:70 and accuracy of 78:73%.

What does it take to have a high-grade pivot shift?

PubMed

Tanaka, M; Vyas, D; Moloney, G; Bedi, A; Pearle, A D; Musahl, V

2012-04-01

The pivot shift is the most specific clinical test to assess pathological knee joint rotatory laxity following ACL injury. This article attempts to describe the anatomic structures responsible for creating a high-grade pivot shift and their potential role in customizing ACL reconstruction. A review of the literature demonstrates that disruption of the secondary stabilizers of anterior translation of the lateral compartment including the lateral meniscus, anterolateral capsule, and IT band contributes to a high-grade pivot shift in the ACL-deficient knee. The morphology of the lateral tibial plateau, including increased posteroinferior tibial slope and small size, can also contribute to high-grade pivot shift. Factors that may decrease the grade of the pivot shift include medial compartment injury, MCL injury, patient guarding, and osteoarthritis. In conclusion, a high-grade pivot shift in the ACL-deficient knee is often associated with incompetence of the lateral soft tissue envelope. Rotatory laxity as assessed by the pivot shift may also be falsely underestimated by concomitant injuries. IV.

The histogram analysis of diffusion-weighted intravoxel incoherent motion (IVIM) imaging for differentiating the gleason grade of prostate cancer.

PubMed

Zhang, Yu-Dong; Wang, Qing; Wu, Chen-Jiang; Wang, Xiao-Ning; Zhang, Jing; Liu, Hui; Liu, Xi-Sheng; Shi, Hai-Bin

2015-04-01

To evaluate histogram analysis of intravoxel incoherent motion (IVIM) for discriminating the Gleason grade of prostate cancer (PCa). A total of 48 patients pathologically confirmed as having clinically significant PCa (size > 0.5 cm) underwent preoperative DW-MRI (b of 0-900 s/mm(2)). Data was post-processed by monoexponential and IVIM model for quantitation of apparent diffusion coefficients (ADCs), perfusion fraction f, diffusivity D and pseudo-diffusivity D*. Histogram analysis was performed by outlining entire-tumour regions of interest (ROIs) from histological-radiological correlation. The ability of imaging indices to differentiate low-grade (LG, Gleason score (GS) ≤6) from intermediate/high-grade (HG, GS > 6) PCa was analysed by ROC regression. Eleven patients had LG tumours (18 foci) and 37 patients had HG tumours (42 foci) on pathology examination. HG tumours had significantly lower ADCs and D in terms of mean, median, 10th and 75th percentiles, combined with higher histogram kurtosis and skewness for ADCs, D and f, than LG PCa (p < 0.05). Histogram D showed relatively higher correlations (ñ = 0.641-0.668 vs. ADCs: 0.544-0.574) with ordinal GS of PCa; and its mean, median and 10th percentile performed better than ADCs did in distinguishing LG from HG PCa. It is feasible to stratify the pathological grade of PCa by IVIM with histogram metrics. D performed better in distinguishing LG from HG tumour than conventional ADCs. • GS had relatively higher correlation with tumour D than ADCs. • Difference of histogram D among two-grade tumours was statistically significant. • D yielded better individual features in demonstrating tumour grade than ADC. • D* and f failed to determine tumour grade of PCa.

Expert Review of Cervical Cytology: Does it Affect Patient Care?

PubMed

Mark, Jaron; Morrell, Kayla; Eng, Kevin; Alfiero, Alexandra; Frederick, Peter J

2018-04-01

The aim of the study was to evaluate whether expert review of outside cervical cytology affects patient care. A retrospective study was conducted of 424 new patient referrals for cervical dysplasia between 2004 and 2016 at Roswell Park Cancer Institute. Records were analyzed for outside cervical cytology reports and compared with expert cervical cytology review. Differences between expert review and outside reports were documented. Charts with a difference were then assessed for additional evaluation and procedures performed. We specifically analyzed the data for cytology being upgraded or downgraded after expert review. Two hundred forty-six patient charts were eligible for this study. We identified 165 patients with congruent pathology reports. Of the 81 different reports, 41 led to significant pathologic differences. Twenty-four reports with different pathology were low-grade squamous intraepithelial lesions (LSIL) upgraded to high-grade squamous intraepithelial lesions (HSIL). Six were HSIL downgraded to LSIL, 4 LSIL downgraded to negative, 3 AGC upgraded to HSIL, 2 AGC upgraded to cancer, 1 each for HSIL downgraded to negative, and AGC downgraded to negative. Of the 24 patients whose cytology changed from low grade to high grade, 17 underwent an excisional procedure and 1 had a laser ablative procedure. Cervical intraepithelial neoplasia 2 or 3 was found in 11 specimens. Cervical intraepithelial neoplasia 1 was found in 4 of excisional specimens and no dysplasia found in 2. Expert review of cervical cytology significantly impacts patient management at a tertiary referral center, resulting in both upgrading and downgrading of community cytology reports.

Predictors of Nodal Upstaging in Clinical Node Negative Patients With Penile Carcinoma: A National Cancer Database Analysis.

PubMed

Winters, Brian R; Mossanen, Matthew; Holt, Sarah K; Lin, Daniel W; Wright, Jonathan L

2016-10-01

To examine the risk factors associated with upstaging at inguinal lymph node dissection (ILND) in men with penile cancer and clinically negative lymph nodes (cN0) using a large US cancer database. The National Cancer Data Base was queried from 1998 to 2012 to identify men with penile cancer who underwent ILND and had complete clinical or pathologic node status available. Lymphovascular invasion (LVI) was available after 2010. Multivariate logistic regression evaluated factors (cT stage, grade, LVI) associated with pathologic nodal upstaging in those with cN0 disease. Correlations between clinical and pathologic node status were also calculated with weighted kappa statistics. Complete clinical and pathologic LN status was available for 875 patients. Of these, 461 (53%) were cN0. Upstaging occurred in 111 (24%). When stratified by low, intermediate, and high-risk groups, the proportion with pathologically positive LNs was 16%, 20%, and 27%, respectively (P = .12). On multivariate analysis, limited to men with LVI data available (N = 206), LVI (odds ratio 3.10, 95% confidence interval 1.39-6.92), but not increasing stage (univariate only) or grade (univariate only), was significantly associated with upstaging at ILND. In this analysis, of 461 patients with node-negative penile cancer undergoing ILND, upstaging was observed in 24%. LVI was the strongest independent predictor of occult lymph node disease. These findings corroborate the presence of LVI as the significant risk factor for occult micrometastases and suggest a possible improvement in existing risk stratification groupings, with the presence of LVI, regardless of stage or grade, to be considered high-risk disease. Copyright © 2016 Elsevier Inc. All rights reserved.

High-grade poorly differentiated neuroendocrine carcinoma of the breast with low oncotype Dx recurrence score: A case report.

PubMed

Munoz-Zuluaga, Carlos A; Kotiah, Sandy; Studeman, Kimberley D

2017-01-01

Primary neuroendocrine carcinoma of the breast (NECB) is a rare malignant tumor with controversial biological behavior and a lack of data guiding treatment decisions due to its scarcity. Cancer gene-expression profiling tests provide a better indication of clinical prognosis and help determine the best clinical management versus the traditional clinical and pathological parameters. This is a report of a NECB with a genetic assay that showed a low-risk tumor despite high-grade and poorly differentiated histopathological features. Patient outcomes correlate with the low risk classification without the need for adjuvant chemotherapy despite the standard clinical-pathologic approach. Analysis of cancer related genes expression and outcomes in historical NECB may elucidate new insight of this rare disease.

The prognostic significance of the 2014 International Society of Urological Pathology (ISUP) grading system for prostate cancer.

PubMed

Samaratunga, Hemamali; Delahunt, Brett; Gianduzzo, Troy; Coughlin, Geoff; Duffy, David; LeFevre, Ian; Johannsen, Shulammite; Egevad, Lars; Yaxley, John

2015-10-01

The 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system was further amended in 2014 with the establishment of grade groupings (ISUP grading). This study examined the predictive value of ISUP grading, comparing results with recognised prognostic parameters.Of 3700 men undergoing radical prostatectomy (RP) reported at Aquesta Pathology between 2008 and 2013, 2079 also had a positive needle biopsy available for review. We examined the association between needle biopsy 2014 ISUP grade and 2005 modified Gleason score, tumour volume, pathological stage of the subsequent RP tumour, as well as biochemical recurrence-free survival (BRFS). The median age was 62 (range 32-79 years). Median serum prostate specific antigen was 5.9 (range 0.4-69 ng/mL). For needle biopsies, 280 (13.5%), 1031 (49.6%), 366 (17.6%), 77 (3.7%) and 325 (15.6%) were 2014 ISUP grades 1-5, respectively. Needle biopsy 2014 ISUP grade showed a significant association with RP tumour volume (p < 0.001), TNM pT and N stage (p < 0.001) and BRFS (p < 0.001). Multivariate analysis using Cox proportional hazards regression model showed serum prostate specific antigen (PSA) at the time of diagnosis and ISUP grade >2 to be significantly associated with BRFS.This study provides evidence of the prognostic significance of ISUP grading for thin core needle biopsy of prostate.

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2.

PubMed

Silvestri, Valentina; Barrowdale, Daniel; Mulligan, Anna Marie; Neuhausen, Susan L; Fox, Stephen; Karlan, Beth Y; Mitchell, Gillian; James, Paul; Thull, Darcy L; Zorn, Kristin K; Carter, Natalie J; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Ramus, Susan J; Nussbaum, Robert L; Olopade, Olufunmilayo I; Rantala, Johanna; Yoon, Sook-Yee; Caligo, Maria A; Spugnesi, Laura; Bojesen, Anders; Pedersen, Inge Sokilde; Thomassen, Mads; Jensen, Uffe Birk; Toland, Amanda Ewart; Senter, Leigha; Andrulis, Irene L; Glendon, Gord; Hulick, Peter J; Imyanitov, Evgeny N; Greene, Mark H; Mai, Phuong L; Singer, Christian F; Rappaport-Fuerhauser, Christine; Kramer, Gero; Vijai, Joseph; Offit, Kenneth; Robson, Mark; Lincoln, Anne; Jacobs, Lauren; Machackova, Eva; Foretova, Lenka; Navratilova, Marie; Vasickova, Petra; Couch, Fergus J; Hallberg, Emily; Ruddy, Kathryn J; Sharma, Priyanka; Kim, Sung-Won; Teixeira, Manuel R; Pinto, Pedro; Montagna, Marco; Matricardi, Laura; Arason, Adalgeir; Johannsson, Oskar Th; Barkardottir, Rosa B; Jakubowska, Anna; Lubinski, Jan; Izquierdo, Angel; Pujana, Miguel Angel; Balmaña, Judith; Diez, Orland; Ivady, Gabriella; Papp, Janos; Olah, Edith; Kwong, Ava; Nevanlinna, Heli; Aittomäki, Kristiina; Perez Segura, Pedro; Caldes, Trinidad; Van Maerken, Tom; Poppe, Bruce; Claes, Kathleen B M; Isaacs, Claudine; Elan, Camille; Lasset, Christine; Stoppa-Lyonnet, Dominique; Barjhoux, Laure; Belotti, Muriel; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Hahnen, Eric; Kast, Karin; Arnold, Norbert; Varon-Mateeva, Raymonda; Wand, Dorothea; Godwin, Andrew K; Evans, D Gareth; Frost, Debra; Perkins, Jo; Adlard, Julian; Izatt, Louise; Platte, Radka; Eeles, Ros; Ellis, Steve; Hamann, Ute; Garber, Judy; Fostira, Florentia; Fountzilas, George; Pasini, Barbara; Giannini, Giuseppe; Rizzolo, Piera; Russo, Antonio; Cortesi, Laura; Papi, Laura; Varesco, Liliana; Palli, Domenico; Zanna, Ines; Savarese, Antonella; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Barile, Monica; Bonanni, Bernardo; Viel, Alessandra; Pensotti, Valeria; Tommasi, Stefania; Peterlongo, Paolo; Weitzel, Jeffrey N; Osorio, Ana; Benitez, Javier; McGuffog, Lesley; Healey, Sue; Gerdes, Anne-Marie; Ejlertsen, Bent; Hansen, Thomas V O; Steele, Linda; Ding, Yuan Chun; Tung, Nadine; Janavicius, Ramunas; Goldgar, David E; Buys, Saundra S; Daly, Mary B; Bane, Anita; Terry, Mary Beth; John, Esther M; Southey, Melissa; Easton, Douglas F; Chenevix-Trench, Georgia; Antoniou, Antonis C; Ottini, Laura

2016-02-09

BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)). On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

High-grade dysplasia and adenocarcinoma are frequent in side-branch intraductal papillary mucinous neoplasm measuring less than 3 cm on endoscopic ultrasound.

PubMed

Wong, Joyce; Weber, Jill; Centeno, Barbara A; Vignesh, Shivakumar; Harris, Cynthia L; Klapman, Jason B; Hodul, Pamela

2013-01-01

Surgical resection for intraductal papillary mucinous neoplasm (IPMN) of the pancreas has increased over the last decade. While IPMN with main duct communication are generally recommended for resection, indications for resection of side-branch IPMN (SDIPMN) have been less clear. We reviewed our single institutional experience with SDIPMN and indications for resection. Patients who underwent resection for IPMN were identified from a prospectively maintained IRB-approved database. Patients with main pancreatic duct communication were excluded. Outcome, clinical and pathologic characteristics were correlated with endoscopic ultrasound (EUS) findings. From 2000 to 2010, 105 patients who underwent preoperative EUS evaluation and resection for SDIPMN were identified. The mean age was within the sixth decade of life, and there was a slight female predominance (55 vs. 45 %). The most common presenting symptom was abdominal pain (N = 47, 45 %), followed by jaundice (N = 24, 23 %) and weight loss (N = 24, 23 %). Only ten patients (10 %) were asymptomatic at presentation; seven (70 %) had suspicious features on EUS. Of the total cohort, few patients had intracystic septations (N = 27, 26 %) or presence of mural nodules (N = 2, 2 %) on EUS. Of 39 patients who had invasive pancreatic ductal adenocarcinoma (PDAC) on final pathology, EUS-fine needle aspiration (EUS-FNA) demonstrated malignancy in only 21 (54 %). An additional seven (18 %) had EUS-FNA findings of atypia or concern for mucinous neoplasm. EUS evaluation of cyst size was correlated with final pathology. Of 70 patients with EUS cyst size <3 cm, 12 (17 %) had a preoperative EUS diagnosis of malignancy. Final pathology revealed 24 (34 %) to have PDAC: 1 of 7 (14 %) patients with cyst size <1 cm, 2 of 19 (11 %) with cyst size 1-2 cm, and 21of 44 (48 %) with cyst size 2-3 cm. Fifteen of 35 (43 %) patients with cyst size >3 cm had PDAC on final pathology. Of the patients with cyst size <3 cm, 16 (23 %) had high-grade dysplasia on final pathology: 3 of 7 (43 %) with cyst size <1 cm, 3 of 19 (16 %) with cyst size 1-2 cm, and 10 of 44 (23 %) with cyst size 2-3 cm. Seven of 35 (20 %) patients with cyst size >3 cm had high-grade dysplasia on final pathology. Although overall survival (OS) at 48 months stratified by EUS cyst size did not significantly differ between groups, patients with PDAC on final pathology had significantly worse OS compared to noninvasive pathology. A total of eight patients (8 %) developed recurrent disease, all of whom had PDAC on final pathology. EUS is a helpful modality for the diagnostic evaluation of SDIPMN. Considering the high incidence of malignancy as well as high-grade dysplasia in SDIPMN greater than 2 cm, EUS features should be used in conjunction with other clinical criteria to guide management decisions. Patients with SDIPMN greater than 2 cm that do not undergo surgical resection may benefit from more intensive surveillance.

Response assessment in neuro-oncology.

PubMed

Quant, Eudocia C; Wen, Patrick Y

2011-02-01

Accuracy and reproducibility in determining response to therapy and tumor progression can be difficult to achieve for nervous system tumors. Current response criteria vary depending on the pathology and have several limitations. Until recently, the most widely used criteria for gliomas were "Macdonald criteria," based on two-dimensional tumor measurements on neuroimaging studies. However, the Response Assessment in Neuro-Oncology (RANO) Working Group has published new recommendations in high-grade gliomas and is working on recommendations for other nervous system tumors. This article reviews current response criteria for high-grade glioma, low-grade glioma, brain metastasis, meningioma, and schwannoma.

Reliability of macroscopic grading of intervertebral disk degeneration in dogs by use of the Thompson system and comparison with low-field magnetic resonance imaging findings.

PubMed

Bergknut, Niklas; Grinwis, Guy; Pickee, Emile; Auriemma, Edoardo; Lagerstedt, Anne-Sofie; Hagman, Ragnvi; Hazewinkel, Herman A W; Meij, Björn P

2011-07-01

To evaluate the reliability of the Thompson system for use in grading the gross pathological changes of intervertebral disk (IVD) degeneration in dogs and to investigate the agreement between gross pathological findings and low-field (0.2-T) magnetic resonance imaging (MRI) findings. Vertebral columns from cadavers of 19 dogs of various ages, breeds, and origins. 182 intervertebral segments were collected from 19 canine cadavers. Sagittal T2-weighted MRI of the T11 through S1 portion of the vertebral column was performed within 24 hours after the dogs were euthanized. The vertebral columns were subsequently divided in the midsagittal plane, and high-resolution photographs were obtained of each intervertebral segment (end plate-disk-end plate). The MRI images and photographs were graded separately in a blinded manner by 4 observers who used both Pfirrmann and Thompson grading criteria. The interobserver agreement for Thompson scores ranged from 0.76 to 0.88, and the intraobserver agreement ranged from 0.88 to 0.94 (Cohen weighted κ analysis). Agreement between scores for the Pfirrmann and Thompson grading criteria was κ = 0.70. Grading of IVD degeneration in dogs by use of the Thompson system resulted in high interobserver and intraobserver agreement, and scores for the Thompson system had substantial agreement with low-field MRI findings graded by use of the Pfirrmann system. This suggested that low-field MRI can be used to diagnose IVD degeneration in dogs.

A binary histologic grading system for ovarian serous carcinoma is an independent prognostic factor: a population-based study of 4317 women diagnosed in Denmark 1978-2006.

PubMed

Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette; Kjaerbye-Thygesen, Anette; Kurman, Robert J; Kjaer, Susanne K

2012-06-01

To evaluate the prognostic significance of histologic grade on survival of ovarian serous cancer in Denmark during nearly 30 years. Using the nationwide Danish Pathology Data Bank, we evaluated 4317 women with ovarian serous carcinoma in 1978-2006. All pathology reports were scrutinized and tumors classified as either low-grade serous carcinomas (LGSC) or high-grade serous carcinomas (HGSC). Tumors in which the original pathology reports were described as well-differentiated were classified as LGSC, and those that were described as moderately or poorly differentiated were classified as HGSC. We obtained histologic slides from the pathology departments for women with a diagnosis of well-differentiated serous carcinoma during 1997-2006, which were then reviewed by expert gynecologic pathologists. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression analysis with follow-up through June 2009. Women with HGSC had a significantly increased risk of dying (HR=1.9; 95% CI: 1.6-2.3) compared with women with LGSC while adjusting for age and stage. Expert review of 171 women originally classified as well-differentiated in 1997-2006 were interpreted as LGSC in 30% of cases, whereas 12% were interpreted as HGSC and 50% as serous borderline ovarian tumors (SBT). Compared with women with confirmed LGSC, women with SBT at review had a significantly lower risk of dying (HR=0.5; 95% CI: 0.22-0.99), and women with HGSC at review had a non-significantly increased risk of dying (HR=1.6; 95% CI: 0.7-3.4). A binary grading system is a significant predictor of survival for ovarian serous carcinoma. Copyright © 2012 Elsevier Inc. All rights reserved.

A comprehensive review of paediatric low-grade diffuse glioma: pathology, molecular genetics and treatment.

PubMed

Ryall, Scott; Tabori, Uri; Hawkins, Cynthia

2017-04-01

Gliomas are the most common central nervous system neoplasms affecting children and can be both high- and low-grade. Paediatric low-grade glioma may be either World Health Organization grade I or grade II. Despite being classified as grade II diffuse astrocytoma, these neoplasms arising in children are distinct clinically and molecularly from their adult counterparts. They do not tend to progress to higher grade lesions and only rarely harbour an IDH mutation. Here, we review the clinical, histologic and molecular features of paediatric grade II diffuse glioma, highlighting their diagnostic criteria, prevalence across brain locations, their most common molecular features and how to test for them, and lastly the current status of therapeutic options available for their treatment.

Predictors of Progression to High-Grade Dysplasia or Adenocarcinoma in Barrett’s Esophagus

PubMed Central

Whitson, Matthew J.; Falk, Gary W.

2015-01-01

Article Synopsis The prevalence of esophageal adenocarcinoma is increasing dramatically. Barrett’s esophagus remains the most well established risk factor for the development of esophageal adenocarcinoma. There are multiple clinical, endoscopic, and pathologic factors that increase the risk of neoplastic progression to high-grade dysplasia or esophageal adenocarcinoma in Barrett’s esophagus. This article will review both risk and protective factors for neoplastic progression in patients with Barrett’s esophagus. PMID:26021196

Molecular and morphologic correlates of the alternative lengthening of telomeres phenotype in high-grade astrocytomas.

PubMed

Nguyen, Doreen N; Heaphy, Christopher M; de Wilde, Roeland F; Orr, Brent A; Odia, Yazmin; Eberhart, Charles G; Meeker, Alan K; Rodriguez, Fausto J

2013-05-01

Recent studies suggest that the telomere maintenance mechanism known as alternative lengthening of telomeres (ALT) is relatively more common in specific glioma subsets and strongly associated with ATRX mutations. We retrospectively examined 116 high-grade astrocytomas (32 pediatric glioblastomas, 65 adult glioblastomas, 19 anaplastic astrocytomas) with known ALT status using tissue microarrays to identify associations with molecular and phenotypic features. Immunohistochemistry was performed using antibodies against ATRX, DAXX, p53 and IDH1(R132H) mutant protein. EGFR amplification was evaluated by fluorescence in situ hybridization (FISH). Almost half of fibrillary and gemistocytic astrocytomas (44%) demonstrated ALT. Conversely all gliosarcomas (n = 4), epithelioid (n = 2), giant cell (n = 2) and adult small cell astrocytomas (n = 7) were ALT negative. The ALT phenotype was positively correlated with the presence of round cells (P = 0.002), microcysts (P < 0.0002), IDH1 mutant protein (P < 0.0001), ATRX protein loss (P < 0.0001), strong P53 immunostaining (P < 0.0001) and absence of EGFR amplification (P = 0.004). There was no significant correlation with DAXX expression. We conclude that ALT represents a specific phenotype in high-grade astrocytomas with distinctive pathologic and molecular features. Future studies are required to clarify the clinical and biological significance of ALT in high-grade astrocytomas. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling.

PubMed

Klein, Eric A; Cooperberg, Matthew R; Magi-Galluzzi, Cristina; Simko, Jeffry P; Falzarano, Sara M; Maddala, Tara; Chan, June M; Li, Jianbo; Cowan, Janet E; Tsiatis, Athanasios C; Cherbavaz, Diana B; Pelham, Robert J; Tenggara-Hunter, Imelda; Baehner, Frederick L; Knezevic, Dejan; Febbo, Phillip G; Shak, Steven; Kattan, Michael W; Lee, Mark; Carroll, Peter R

2014-09-01

Prostate tumor heterogeneity and biopsy undersampling pose challenges to accurate, individualized risk assessment for men with localized disease. To identify and validate a biopsy-based gene expression signature that predicts clinical recurrence, prostate cancer (PCa) death, and adverse pathology. Gene expression was quantified by reverse transcription-polymerase chain reaction for three studies-a discovery prostatectomy study (n=441), a biopsy study (n=167), and a prospectively designed, independent clinical validation study (n=395)-testing retrospectively collected needle biopsies from contemporary (1997-2011) patients with low to intermediate clinical risk who were candidates for active surveillance (AS). The main outcome measures defining aggressive PCa were clinical recurrence, PCa death, and adverse pathology at prostatectomy. Cox proportional hazards regression models were used to evaluate the association between gene expression and time to event end points. Results from the prostatectomy and biopsy studies were used to develop and lock a multigene-expression-based signature, called the Genomic Prostate Score (GPS); in the validation study, logistic regression was used to test the association between the GPS and pathologic stage and grade at prostatectomy. Decision-curve analysis and risk profiles were used together with clinical and pathologic characteristics to evaluate clinical utility. Of the 732 candidate genes analyzed, 288 (39%) were found to predict clinical recurrence despite heterogeneity and multifocality, and 198 (27%) were predictive of aggressive disease after adjustment for prostate-specific antigen, Gleason score, and clinical stage. Further analysis identified 17 genes representing multiple biological pathways that were combined into the GPS algorithm. In the validation study, GPS predicted high-grade (odds ratio [OR] per 20 GPS units: 2.3; 95% confidence interval [CI], 1.5-3.7; p<0.001) and high-stage (OR per 20 GPS units: 1.9; 95% CI, 1.3-3.0; p=0.003) at surgical pathology. GPS predicted high-grade and/or high-stage disease after controlling for established clinical factors (p<0.005) such as an OR of 2.1 (95% CI, 1.4-3.2) when adjusting for Cancer of the Prostate Risk Assessment score. A limitation of the validation study was the inclusion of men with low-volume intermediate-risk PCa (Gleason score 3+4), for whom some providers would not consider AS. Genes representing multiple biological pathways discriminate PCa aggressiveness in biopsy tissue despite tumor heterogeneity, multifocality, and limited sampling at time of biopsy. The biopsy-based 17-gene GPS improves prediction of the presence or absence of adverse pathology and may help men with PCa make more informed decisions between AS and immediate treatment. Prostate cancer (PCa) is often present in multiple locations within the prostate and has variable characteristics. We identified genes with expression associated with aggressive PCa to develop a biopsy-based, multigene signature, the Genomic Prostate Score (GPS). GPS was validated for its ability to predict men who have high-grade or high-stage PCa at diagnosis and may help men diagnosed with PCa decide between active surveillance and immediate definitive treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Endoscopic Ultrasound in Barrett's Oesophagitis with Dysplasia

PubMed Central

Wray, Andrew; Rice, Paul; Love, Mark

2012-01-01

Purpose With the advent of conservative therapies including photodynamic therapy and endoscopic mucosal resection for Barrett's and high grade dysplasia, accurate staging has become increasingly important. We report our experience with endoscopic ultrasound (EUS) in these patients. Materials and Methods Retrospective review of 25 consecutive patients referred for EUS for assessment of Barrett's with high grade dysplasia and /or stricture or polyp. The findings were compared with subsequent surgical pathology, or endoscopy and biopsy follow up. Results Nine patients were found to have invasive tumour on EUS and this was confirmed in all 9 either by oesophagectomy, OGD and oncology follow up, or by endoscopic mucosal resection. Eight patients underwent oesophagectomy, 5 for invasive tumour and 3 for dysplasia only, with pathological agreement with EUS findings in 7 out of 8 cases. The one discrepancy was a EUS case of mucosal thickening only with no invasion, but pathology showed a T1 lesion. Thirteen patients with no evidence of invasion were managed conservatively, with 11 patients being followed up for 6-12 months with serial OGD and biopsy, and no cases of more invasive disease occurring. Therefore, in our experience the sensitivity, specificity and positive predictive value of EUS in complex Barrett's is 90%, 100% and 100% respectively. Conclusion EUS is valuable in the assessment of high grade dysplasia in cases where conservative therapy is being considered, defining those with more deeply invasive tumour for whom radical treatment is the only option. PMID:23526576

Label-free pathological evaluation of grade 3 cancer using Stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Sordillo, Laura A.; Sordillo, Peter P.; Alfano, R. R.

2016-03-01

In this study, Stokes shift spectroscopy (S3) is used for measuring the aggressiveness of malignant tumors. S3 is an optical tool which utilizes the difference between the emission wavelength (λem) and the absorption wavelength (λabs) (the Stokes shift) to give a fixed wavelength shift (Δλs).Our analysis of tumor samples using S3 shows grade 3 (high grade) cancers consistently have increased relative tryptophan content compared to grade 1 or 2 tumors. This technique may be a useful tool in the evaluation of a patient's cancer.

Prostate cancer: from Gleason scoring to prognostic grade grouping.

PubMed

Montironi, Rodolfo; Santoni, Matteo; Mazzucchelli, Roberta; Burattini, Luciano; Berardi, Rossana; Galosi, Andrea B; Cheng, Liang; Lopez-Beltran, Antonio; Briganti, Alberto; Montorsi, Francesco; Scarpelli, Marina

2016-01-01

The Gleason grading system was developed in the late 1960s by Dr. Donald F. Gleason. Due to changes in prostatic adenocarcinoma (PAC) detection and treatment, newer technologies to better characterize prostatic pathology, subsequently described variants of PAC and further data relating various morphologic patterns to prognosis, the application of the Gleason grading system changed substantially in surgical pathology. First in 2005 and more recently in 2014, consensus conferences were held to update PAC grading. Here, we review of the successive changes in the grading of PAC from the original system, with emphasis on the newest prognostic grade grouping.

Infiltration characteristics and influencing factors of retroperitoneal liposarcoma: Novel evidence for extended surgery and a tumor grading system.

PubMed

Wang, Zhen; Wu, Jianhui; Lv, Ang; Li, Chengpeng; Li, Zhongwu; Zhao, Min; Hao, Chunyi

2018-05-13

This study sought to evaluate the infiltration tendency of retroperitoneal liposarcoma (RPLS) from a new pathological angle by exploring the infiltration characteristics, which could provide helpful information to facilitate surgical decision-making and prognosis prediction. Concurrently, we aim to identify significant indicators of infiltration. A total of 61 consecutive patients with RPLS at our institution were retrospectively analyzed. All patients received extended surgery. The tumor infiltration characteristics and influencing factors were studied based on the pathological diagnosis. Univariate and multivariate analyses of organ infiltration (OI) and surrounding fat infiltration (SFI) were performed. OI was found in 95 (28.5%) resected organs from 39 (60.7%) patients, and SFI was found in 119 (35.7%) resected organs from 47 (77%) patients. The tumor infiltrated the serosal layer of 13 organs (13/37, 35.1%), the muscularis layer of 18 organs (18/37, 48.6%) and the submucosa of 6 organs (6/37, 16.2%). The percentage of lipoblasts and the rates of necrosis and mitosis were all significantly higher in high-grade tumors (dedifferentiated, round cell, and pleomorphic). A high lipoblast percentage (≥ 20%) was the only independent risk factor for OI. A recurrent tumor and a high-grade tumor were independent risk factors for SFI. In conclusion, RPLS has a high infiltration tendency, such that it frequently infiltrates organs and surrounding fat tissue. Therefore, extended resection of the tumor and the adjacent organs is recommended. The percentage of lipoblasts was associated with the tumor grade and infiltration characteristics; thus, lipoblast percentage may become a new grading factor for RPLS.

When Does Neoadjuvant Chemotherapy Really Avoid Radiotherapy? Clinical Predictors of Adjuvant Radiotherapy in Cervical Cancer.

PubMed

Papadia, Andrea; Bellati, Filippo; Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Lorusso, Domenica; Donfrancesco, Cristina; Gasparri, Maria Luisa; Raspagliesi, Francesco

2015-12-01

The aim of this study was to identify clinical variables that may predict the need for adjuvant radiotherapy after neoadjuvant chemotherapy (NACT) and radical surgery in locally advanced cervical cancer patients. A retrospective series of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IIB treated with NACT followed by radical surgery was analyzed. Clinical predictors of persistence of intermediate- and/or high-risk factors at final pathological analysis were investigated. Statistical analysis was performed using univariate and multivariate analysis and using a model based on artificial intelligence known as artificial neuronal network (ANN) analysis. Overall, 101 patients were available for the analyses. Fifty-two (51 %) patients were considered at high risk secondary to parametrial, resection margin and/or lymph node involvement. When disease was confined to the cervix, four (4 %) patients were considered at intermediate risk. At univariate analysis, FIGO grade 3, stage IIB disease at diagnosis and the presence of enlarged nodes before NACT predicted the presence of intermediate- and/or high-risk factors at final pathological analysis. At multivariate analysis, only FIGO grade 3 and tumor diameter maintained statistical significance. The specificity of ANN models in evaluating predictive variables was slightly superior to conventional multivariable models. FIGO grade, stage, tumor diameter, and histology are associated with persistence of pathological intermediate- and/or high-risk factors after NACT and radical surgery. This information is useful in counseling patients at the time of treatment planning with regard to the probability of being subjected to pelvic radiotherapy after completion of the initially planned treatment.

[Dedifferentiated chondrosarcoma: radiologic-pathologic correlation].

PubMed

Bierry, G; Feydy, A; Larousserie, F; Pluot, E; Guerini, H; Campagna, R; Dufau-Andreu, C; Anract, P; Babinet, A; Dietemann, J L; Chevrot, A; Drapé, J L

2010-03-01

Dedifferentiated chondrosarcomas are highly malignant tumors characterized by conventional low-grade chondrosarcoma with abrupt transition to foci that have dedifferentiated into a higher-grade noncartilaginous more aggressive sarcoma. The dedifferentiated component, an osteosarcoma or fibrosarcoma, determines the prognosis. Its identification is key for management. A diagnosis of dedifferentiated chondrosarcoma should be suggested by the presence of "tumoral dimorphism" with cartilaginous component and aggressive lytic component invading adjacent soft tissues.

mTOR-Dependent Cell Proliferation in the Brain.

PubMed

Ryskalin, Larisa; Lazzeri, Gloria; Flaibani, Marina; Biagioni, Francesca; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

2017-01-01

The mammalian Target of Rapamycin (mTOR) is a molecular complex equipped with kinase activity which controls cell viability being key in the PI3K/PTEN/Akt pathway. mTOR acts by integrating a number of environmental stimuli to regulate cell growth, proliferation, autophagy, and protein synthesis. These effects are based on the modulation of different metabolic pathways. Upregulation of mTOR associates with various pathological conditions, such as obesity, neurodegeneration, and brain tumors. This is the case of high-grade gliomas with a high propensity to proliferation and tissue invasion. Glioblastoma Multiforme (GBM) is a WHO grade IV malignant, aggressive, and lethal glioma. To date, a few treatments are available although the outcome of GBM patients remains poor. Experimental and pathological findings suggest that mTOR upregulation plays a major role in determining an aggressive phenotype, thus determining relapse and chemoresistance. Among several activities, mTOR-induced autophagy suppression is key in GBM malignancy. In this article, we discuss recent evidence about mTOR signaling and its role in normal brain development and pathological conditions, with a special emphasis on its role in GBM.

mTOR-Dependent Cell Proliferation in the Brain

PubMed Central

Lazzeri, Gloria; Frati, Alessandro

2017-01-01

The mammalian Target of Rapamycin (mTOR) is a molecular complex equipped with kinase activity which controls cell viability being key in the PI3K/PTEN/Akt pathway. mTOR acts by integrating a number of environmental stimuli to regulate cell growth, proliferation, autophagy, and protein synthesis. These effects are based on the modulation of different metabolic pathways. Upregulation of mTOR associates with various pathological conditions, such as obesity, neurodegeneration, and brain tumors. This is the case of high-grade gliomas with a high propensity to proliferation and tissue invasion. Glioblastoma Multiforme (GBM) is a WHO grade IV malignant, aggressive, and lethal glioma. To date, a few treatments are available although the outcome of GBM patients remains poor. Experimental and pathological findings suggest that mTOR upregulation plays a major role in determining an aggressive phenotype, thus determining relapse and chemoresistance. Among several activities, mTOR-induced autophagy suppression is key in GBM malignancy. In this article, we discuss recent evidence about mTOR signaling and its role in normal brain development and pathological conditions, with a special emphasis on its role in GBM. PMID:29259984

Gliomatosis cerebri: clinicopathologic study of 33 cases and comparison of mass forming and diffuse types.

PubMed

Park, S; Suh, Y-L; Nam, D-H; Kim, S T

2009-01-01

Gliomatosis cerebri (GC) is defined as a diffuse neoplastic glial cell infiltration of the brain with the preservation of anatomical architecture and the sparing of neurons and can be classified into Type 1 (diffuse) and Type 2 (mass forming) GCs macroscopically. There is little information on subtypes of GC. The aim of this study was to evaluate the clinicopathologic findings of GCs and to compare the clinicopathologic findings between Type 1 and Type 2 GCs. A total of 33 cases of GC were obtained from pathology file of Samsung Medical Center. The diagnosis was based on magnetic resonance imaging findings and histological confirmation for all patients. Fifteen cases were classified into Type 1 and 18 were Type 2 based on the MR images. Clinical information included patients' age, sex, tumor extent, treatment modality and survival. Pathologic features included the amount of rod cells and cytologic anaplasia such as multinucleated tumor giant cells, endothelial cell proliferation, or mitosis. Immunohistochemical study was performed for GFAP, O1, Gal-C, Ki-67, and p53. Clinicopathologic comparison between subtypes and statistical analysis were performed. Median age at diagnosis was older (56 years) in Type 1 than in Type 2 (44 years). Male to female ratio was about 1.54:1. Mean survival time was shorter (21 months) in Type 2 than in Type 1 GCs (24 months) (p = 0.0447). Histologically, 33 cases of GC were classified into two histologic grades (low and high grade) by cytologic anaplasia. High-grade GC was more common in Type 2 than Type 1 (p = 0.027). Immunohistochemical results demonstrated that the infiltrating tumor cells were undifferentiated cells with astrocytic or oligodendroglial differentiation. Ki-67 labeling index was correlated with subtypes (p = 0.0096). Pathologic features were not correlated with survival. Type 1 and 2 GCs are somewhat different in clinical presentation and pathologic features. The age group, survival time, histologic grade, and Ki-67 labeling index were significantly correlated with subtypes ofGCs. Type 2 GC was correlated with poor survival but histologic grade was not.

Semantic Integrative Digital Pathology: Insights into Microsemiological Semantics and Image Analysis Scalability.

PubMed

Racoceanu, Daniel; Capron, Frédérique

2016-01-01

Being able to provide a traceable and dynamic second opinion has become an ethical priority for patients and health care professionals in modern computer-aided medicine. In this perspective, a semantic cognitive virtual microscopy approach has been recently initiated, the MICO project, by focusing on cognitive digital pathology. This approach supports the elaboration of pathology-compliant daily protocols dedicated to breast cancer grading, in particular mitotic counts and nuclear atypia. A proof of concept has thus been elaborated, and an extension of these approaches is now underway in a collaborative digital pathology framework, the FlexMIm project. As important milestones on the way to routine digital pathology, a series of pioneer international benchmarking initiatives have been launched for mitosis detection (MITOS), nuclear atypia grading (MITOS-ATYPIA) and glandular structure detection (GlaS), some of the fundamental grading components in diagnosis and prognosis. These initiatives allow envisaging a consolidated validation referential database for digital pathology in the very near future. This reference database will need coordinated efforts from all major teams working in this area worldwide, and it will certainly represent a critical bottleneck for the acceptance of all future imaging modules in clinical practice. In line with recent advances in molecular imaging and genetics, keeping the microscopic modality at the core of future digital systems in pathology is fundamental to insure the acceptance of these new technologies, as well as for a deeper systemic, structured comprehension of the pathologies. After all, at the scale of routine whole-slide imaging (WSI; ∼0.22 µm/pixel), the microscopic image represents a structured 'genomic cluster', enabling a naturally structured support for integrative digital pathology approaches. In order to accelerate and structure the integration of this heterogeneous information, a major effort is and will continue to be devoted to morphological microsemiology (microscopic morphology semantics). Besides insuring the traceability of the results (second opinion) and supporting the orchestration of high-content image analysis modules, the role of semantics will be crucial for the correlation between digital pathology and noninvasive medical imaging modalities. In addition, semantics has an important role in modelling the links between traditional microscopy and recent label-free technologies. The massive amount of visual data is challenging and represents a characteristic intrinsic to digital pathology. The design of an operational integrative microscopy framework needs to focus on scalable multiscale imaging formalism. In this sense, we prospectively consider some of the most recent scalable methodologies adapted to digital pathology as marked point processes for nuclear atypia and point-set mathematical morphology for architecture grading. To orchestrate this scalable framework, semantics-based WSI management (analysis, exploration, indexing, retrieval and report generation support) represents an important means towards approaches to integrating big data into biomedicine. This insight reflects our vision through an instantiation of essential bricks of this type of architecture. The generic approach introduced here is applicable to a number of challenges related to molecular imaging, high-content image management and, more generally, bioinformatics. © 2016 S. Karger AG, Basel.

Automated discrimination of lower and higher grade gliomas based on histopathological image analysis.

PubMed

Mousavi, Hojjat Seyed; Monga, Vishal; Rao, Ganesh; Rao, Arvind U K

2015-01-01

Histopathological images have rich structural information, are multi-channel in nature and contain meaningful pathological information at various scales. Sophisticated image analysis tools that can automatically extract discriminative information from the histopathology image slides for diagnosis remain an area of significant research activity. In this work, we focus on automated brain cancer grading, specifically glioma grading. Grading of a glioma is a highly important problem in pathology and is largely done manually by medical experts based on an examination of pathology slides (images). To complement the efforts of clinicians engaged in brain cancer diagnosis, we develop novel image processing algorithms and systems to automatically grade glioma tumor into two categories: Low-grade glioma (LGG) and high-grade glioma (HGG) which represent a more advanced stage of the disease. We propose novel image processing algorithms based on spatial domain analysis for glioma tumor grading that will complement the clinical interpretation of the tissue. The image processing techniques are developed in close collaboration with medical experts to mimic the visual cues that a clinician looks for in judging of the grade of the disease. Specifically, two algorithmic techniques are developed: (1) A cell segmentation and cell-count profile creation for identification of Pseudopalisading Necrosis, and (2) a customized operation of spatial and morphological filters to accurately identify microvascular proliferation (MVP). In both techniques, a hierarchical decision is made via a decision tree mechanism. If either Pseudopalisading Necrosis or MVP is found present in any part of the histopathology slide, the whole slide is identified as HGG, which is consistent with World Health Organization guidelines. Experimental results on the Cancer Genome Atlas database are presented in the form of: (1) Successful detection rates of pseudopalisading necrosis and MVP regions, (2) overall classification accuracy into LGG and HGG categories, and (3) receiver operating characteristic curves which can facilitate a desirable trade-off between HGG detection and false-alarm rates. The proposed method demonstrates fairly high accuracy and compares favorably against best-known alternatives such as the state-of-the-art WND-CHARM feature set provided by NIH combined with powerful support vector machine classifier. Our results reveal that the proposed method can be beneficial to a clinician in effectively separating histopathology slides into LGG and HGG categories, particularly where the analysis of a large number of slides is needed. Our work also reveals that MVP regions are much harder to detect than Pseudopalisading Necrosis and increasing accuracy of automated image processing for MVP detection emerges as a significant future research direction.

Introducing a novel highly prognostic grading scheme based on tumour budding and cell nest size for squamous cell carcinoma of the uterine cervix.

PubMed

Jesinghaus, Moritz; Strehl, Johanna; Boxberg, Melanie; Brühl, Frido; Wenzel, Adrian; Konukiewitz, Björn; Schlitter, Anna M; Steiger, Katja; Warth, Arne; Schnelzer, Andreas; Kiechle, Marion; Beckmann, Matthias W; Noske, Aurelia; Hartmann, Arndt; Mehlhorn, Grit; Koch, Martin C; Weichert, Wilko

2018-04-01

A novel histopathological grading system based on tumour budding and cell nest size has recently been shown to outperform conventional (WHO-based) grading algorithms in several tumour entities such as lung, oral, and oesophageal squamous cell carcinoma (SCC) in terms of prognostic patient stratification. Here, we tested the prognostic value of this innovative grading approach in two completely independent cohorts of SCC of the uterine cervix. To improve morphology-based grading, we investigated tumour budding activity and cell nest size as well as several other histomorphological factors (e.g., keratinization, nuclear size, mitotic activity) in a test cohort (n = 125) and an independent validation cohort (n = 122) of cervical SCC. All parameters were correlated with clinicopathological factors and patient outcome. Small cell nest size and high tumour budding activity were strongly associated with a dismal patient prognosis (p < 0.001 for overall survival [OS], disease-specific survival, and disease-free survival; test cohort) in both cohorts of cervical SCC. A novel grading algorithm combining these two parameters proved to be a highly effective, stage-independent prognosticator in both cohorts (OS: p < 0.001, test cohort; p = 0.001, validation cohort). In the test cohort, multivariate statistical analysis of the novel grade revealed that the hazard ratio (HR) for OS was 2.3 for G2 and 5.1 for G3 tumours compared to G1 neoplasms (p = 0.010). In the validation cohort, HR for OS was 3.0 for G2 and 7.2 for G3 tumours (p = 0.012). In conclusion, our novel grading algorithm incorporating cell nest size and tumour budding allows strongly prognostic histopathological grading of cervical SCC superior to WHO-based grading. Therefore, our data can be regarded as a cross-organ validation of previous results demonstrated for oesophageal, lung, and oral SCC. We suggest this grading algorithm as an additional morphology-based parameter for the routine diagnostic assessment of this tumour entity. © 2018 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.

Gastric B-cell mucosa associated lymphoid tissue lymphoma: a clinicopathological study in 56 patients.

PubMed Central

Castrillo, J M; Montalban, C; Obeso, G; Piris, M A; Rivas, M C

1992-01-01

Clinico-pathological features of 56 patients with primary gastric lymphoma were evaluated retrospectively. All cases were regraded according to a classification of Isaacson et al into high grade and low grade B-cell mucosa associated lymphoid tissue lymphoma. A third group of mixed grade was recognised in 11 patients with low grade who also had occasional areas of high grade. Low grade and mixed grade patients had a 100% actuarial survival at 156 months, which was significantly better (p < 0.01) than that of 52% for patients with high grade disease. Different treatment methods--surgery, chemotherapy, or a combination of both--did not significantly affect survival. Low grade tumours occurred mainly in men with a history of several years, and who presented with non-specific gastric symptoms without remarkable exploratory or laboratory findings: most patients were in stage IE-IIE and achieved remission and cure. High grade can have a shorter history, systemic symptoms, abnormal exploratory and laboratory findings, gastric tumour masses, stage IV disease, and a worse outcome. The only significant prognostic factors for survival were the type of lymphoma and stage IV disease. These findings support the Isaacson classification system which separates two extreme groups of gastric lymphomas with different morphology, behaviour, and outcome. The presence of limited areas of high grade in a specimen showing low grade does not change the outcome but suggests that primary gastric lymphoma forms a continuum between these extreme types. PMID:1446850

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

Testin (TES) as a candidate tumour suppressor and prognostic marker in human astrocytoma.

PubMed

Steponaitis, Giedrius; Kazlauskas, Arunas; Skiriute, Daina; Valiulyte, Indre; Skauminas, Kestutis; Tamasauskas, Arimantas; Vaitkiene, Paulina

2016-11-01

Astrocytomas are one of the most common brain tumours; however, the current methods used to characterize these tumours are inadequate. The establishment of molecular markers may identify variables required to improve tumour characterization and subtyping, and may aid to specify targets for improved treatment with essential prognostic value for patient survival. One such candidate is testin (TES), which was reported to have prognostic value for glioblastoma patients. However, the role of TES protein in gliomagenesis is currently unknown. In the present study, the methylation status of the TES promoter was investigated in post-operative astrocytoma tumours of different malignancy grade, and its association with the survival of astrocytoma patients was evaluated. In addition, the expression of TES protein was investigated in the same set of astrocytoma tumours tissue, and the association of protein expression with glioma patients survival was evaluated. The methylation status of TES was assessed by methylation-specific polymerase chain reaction in 138 different grade astrocytoma samples. Western blot analysis was used to characterize the expression pattern of TES in 86 different grade astrocytoma specimens: 13 of pathological grade I, 31 of pathological grade II, 17 of pathological grade III and 25 of pathological grade IV (glioblastoma). Statistical analyses were conducted to investigate the association between tumour molecular pattern, patient clinical variables and overall survival. The methylation analysis of the TES promoter exhibited a distinct profile between astrocytomas of different malignancy grade (P<0.001). Furthermore, gene promoter methylation was significantly associated with patients' age, survival and pathological grade (P<0.001). The protein expression level of TES was significantly lower in glioblastoma (grade IV astrocytoma) than in lower grade (II-III) astrocytoma tissue (P=0.028 and P=0.04, respectively). Additionally, short overall survival of patients was markedly associated with low TES protein expression (P=0.007). However, no association between TES methylation and TES protein expression was noticed. The present study demonstrated that decreased expression of TES may be important in tumour progression and prognosis in human astrocytomas. TES may be a useful marker for predicting the clinical outcome of astrocytoma patients.

Testin (TES) as a candidate tumour suppressor and prognostic marker in human astrocytoma

PubMed Central

Steponaitis, Giedrius; Kazlauskas, Arunas; Skiriute, Daina; Valiulyte, Indre; Skauminas, Kestutis; Tamasauskas, Arimantas; Vaitkiene, Paulina

2016-01-01

Astrocytomas are one of the most common brain tumours; however, the current methods used to characterize these tumours are inadequate. The establishment of molecular markers may identify variables required to improve tumour characterization and subtyping, and may aid to specify targets for improved treatment with essential prognostic value for patient survival. One such candidate is testin (TES), which was reported to have prognostic value for glioblastoma patients. However, the role of TES protein in gliomagenesis is currently unknown. In the present study, the methylation status of the TES promoter was investigated in post-operative astrocytoma tumours of different malignancy grade, and its association with the survival of astrocytoma patients was evaluated. In addition, the expression of TES protein was investigated in the same set of astrocytoma tumours tissue, and the association of protein expression with glioma patients survival was evaluated. The methylation status of TES was assessed by methylation-specific polymerase chain reaction in 138 different grade astrocytoma samples. Western blot analysis was used to characterize the expression pattern of TES in 86 different grade astrocytoma specimens: 13 of pathological grade I, 31 of pathological grade II, 17 of pathological grade III and 25 of pathological grade IV (glioblastoma). Statistical analyses were conducted to investigate the association between tumour molecular pattern, patient clinical variables and overall survival. The methylation analysis of the TES promoter exhibited a distinct profile between astrocytomas of different malignancy grade (P<0.001). Furthermore, gene promoter methylation was significantly associated with patients' age, survival and pathological grade (P<0.001). The protein expression level of TES was significantly lower in glioblastoma (grade IV astrocytoma) than in lower grade (II–III) astrocytoma tissue (P=0.028 and P=0.04, respectively). Additionally, short overall survival of patients was markedly associated with low TES protein expression (P=0.007). However, no association between TES methylation and TES protein expression was noticed. The present study demonstrated that decreased expression of TES may be important in tumour progression and prognosis in human astrocytomas. TES may be a useful marker for predicting the clinical outcome of astrocytoma patients. PMID:27899997

Characterization of Long Working Distance Optical Coherence Tomography for Imaging of Pediatric Retinal Pathology.

PubMed

Qian, Ruobing; Carrasco-Zevallos, Oscar M; Mangalesh, Shwetha; Sarin, Neeru; Vajzovic, Lejla; Farsiu, Sina; Izatt, Joseph A; Toth, Cynthia A

2017-10-01

We determined the feasibility of fovea and optic nerve head imaging with a long working distance (LWD) swept source optical coherence tomography (OCT) prototype in adults, teenagers, and young children. A prototype swept source OCT system with a LWD (defined as distance from the last optical element of the imaging system to the eye) of 350 mm with custom fixation targets was developed to facilitate imaging of children. Imaging was performed in 49 participants from three age groups: 26 adults, 16 children 13 to 18 years old (teenagers), and seven children under 6 years old (young children) under an approved institutional review board protocol. The imaging goal was to acquire high quality scans of the fovea and optic nerve in each eye in the shortest time possible. OCT B-scans and volumes of the fovea and optic nerve head of each eligible eye were captured and graded based on four categories (lateral and axial centration, contrast, and resolution) and on ability to determine presence or absence of pathology. LWD-OCT imaging was successful in 88 of 94 eligible eyes, including seven of 10 eyes of young children. Of the successfully acquired OCT images, 83% of B-scan and volumetric images, including 86% from young children, were graded as high-quality scans. Pathology was observed in high-quality OCT images. The prototype LWD-OCT system achieved high quality retinal imaging of adults, teenagers, and some young children with and without pathology with reasonable alignment time. The LWD-OCT system can facilitate imaging in children.

Characterization of Long Working Distance Optical Coherence Tomography for Imaging of Pediatric Retinal Pathology

PubMed Central

Qian, Ruobing; Carrasco-Zevallos, Oscar M.; Mangalesh, Shwetha; Sarin, Neeru; Vajzovic, Lejla; Farsiu, Sina; Izatt, Joseph A.; Toth, Cynthia A.

2017-01-01

Purpose We determined the feasibility of fovea and optic nerve head imaging with a long working distance (LWD) swept source optical coherence tomography (OCT) prototype in adults, teenagers, and young children. Methods A prototype swept source OCT system with a LWD (defined as distance from the last optical element of the imaging system to the eye) of 350 mm with custom fixation targets was developed to facilitate imaging of children. Imaging was performed in 49 participants from three age groups: 26 adults, 16 children 13 to 18 years old (teenagers), and seven children under 6 years old (young children) under an approved institutional review board protocol. The imaging goal was to acquire high quality scans of the fovea and optic nerve in each eye in the shortest time possible. OCT B-scans and volumes of the fovea and optic nerve head of each eligible eye were captured and graded based on four categories (lateral and axial centration, contrast, and resolution) and on ability to determine presence or absence of pathology. Results LWD-OCT imaging was successful in 88 of 94 eligible eyes, including seven of 10 eyes of young children. Of the successfully acquired OCT images, 83% of B-scan and volumetric images, including 86% from young children, were graded as high-quality scans. Pathology was observed in high-quality OCT images. Conclusions The prototype LWD-OCT system achieved high quality retinal imaging of adults, teenagers, and some young children with and without pathology with reasonable alignment time. Translational Relevance The LWD-OCT system can facilitate imaging in children. PMID:29057163

Development of a Natural Language Processing Engine to Generate Bladder Cancer Pathology Data for Health Services Research.

PubMed

Schroeck, Florian R; Patterson, Olga V; Alba, Patrick R; Pattison, Erik A; Seigne, John D; DuVall, Scott L; Robertson, Douglas J; Sirovich, Brenda; Goodney, Philip P

2017-12-01

To take the first step toward assembling population-based cohorts of patients with bladder cancer with longitudinal pathology data, we developed and validated a natural language processing (NLP) engine that abstracts pathology data from full-text pathology reports. Using 600 bladder pathology reports randomly selected from the Department of Veterans Affairs, we developed and validated an NLP engine to abstract data on histology, invasion (presence vs absence and depth), grade, the presence of muscularis propria, and the presence of carcinoma in situ. Our gold standard was based on an independent review of reports by 2 urologists, followed by adjudication. We assessed the NLP performance by calculating the accuracy, the positive predictive value, and the sensitivity. We subsequently applied the NLP engine to pathology reports from 10,725 patients with bladder cancer. When comparing the NLP output to the gold standard, NLP achieved the highest accuracy (0.98) for the presence vs the absence of carcinoma in situ. Accuracy for histology, invasion (presence vs absence), grade, and the presence of muscularis propria ranged from 0.83 to 0.96. The most challenging variable was depth of invasion (accuracy 0.68), with an acceptable positive predictive value for lamina propria (0.82) and for muscularis propria (0.87) invasion. The validated engine was capable of abstracting pathologic characteristics for 99% of the patients with bladder cancer. NLP had high accuracy for 5 of 6 variables and abstracted data for the vast majority of the patients. This now allows for the assembly of population-based cohorts with longitudinal pathology data. Published by Elsevier Inc.

The indicating FTA elute cartridge a solid sample carrier to detect high-risk HPV and high-grade cervical lesions.

PubMed

de Bie, Roosmarie P; Schmeink, Channa E; Bakkers, Judith M J E; Snijders, Peter J F; Quint, Wim G V; Massuger, Leon F A G; Bekkers, Ruud L M; Melchers, Willem J G

2011-07-01

The clinically validated high-risk human papillomavirus (hrHPV) Hybrid Capture 2 (HC2) and GP5+/6+-PCR assays were analyzed on an Indicating FTA Elute cartridge (FTA cartridge). The FTA cartridge is a solid dry carrier that allows safe transport of cervical samples. FTA cartridge samples were compared with liquid-based samples for hrHPV and high-grade cervical intraepithelial neoplasia (CIN) detection. One cervical sample was collected in a liquid-based medium, and one was applied to the FTA cartridge. DNA was eluted directly from the FTA cartridge by a simple elution step. HC2 and GP5+/6+-PCR assays were performed on both the liquid-based and the FTA-eluted DNA of 88 women. Overall agreement between FTA and liquid-based samples for the presence of hrHPV was 90.9% with GP5+/6+-PCR and 77.3% with HC2. The sensitivity for high-grade CIN of hrHPV testing on the FTA cartridges was 84.6% with GP5+/6+-PCR and only 53.8% with HC2. By comparison, these sensitivities on liquid-based samples were 92.3% and 100% for GP5+/6+-PCR and HC2, respectively. Therefore, the FTA cartridge shows reasonably good overall agreement for hrHPV detection with liquid-based media when using GP5+/6+-PCR but not HC2 testing. Even with GP5+/6+-PCR, the FTA cartridge is not yet capable of detecting all high-grade CIN lesions. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Value of p16(INK)⁴(a) in the pathology of invasive penile squamous cell carcinomas: A report of 202 cases.

PubMed

Cubilla, Antonio L; Lloveras, Belén; Alejo, Maria; Clavero, Omar; Chaux, Alcides; Kasamatsu, Elena; Monfulleda, Núria; Tous, Sara; Alemany, Laia; Klaustermeier, Joellen; Muñoz, Nubia; Quint, Wim; de Sanjose, Silvia; Bosch, Francisco Xavier

2011-02-01

One third to one half of penile squamous cell carcinomas (SCCs) are related to human papillomavirus (HPV) infection. Viral detection is usually carried out by polymerase chain reaction (PCR) or other molecular methods. In this study, we evaluated p16(INK)⁴(a) immunohistochemical expression, which is simpler and less costly, as a potential marker of high-risk HPV (HR-HPV) infection in penile SCC. We pathologically classified 202 invasive penile carcinomas and performed HPV genotyping by short PCR fragment (SPF)₁₀ PCR and p16(INK)⁴(a) immunohistochemistry. We also evaluated HPV and p16(INK)⁴(a) according to the histologic subtypes of penile SCC. Tumors depicting continuous p16(INK)⁴(a) immunostain in all neoplastic cells were considered positive. HPV and p16(INK)⁴(a) status were compared using classifier performances and concordance indexes. Evidence of HPV (low-risk and high-risk genotypes) was found in 63 cases (31%) by PCR. Fifty-three p16(INK)⁴(a)-positive cases were identified (26%). Overexpression of p16(INK)⁴(a) had a sensitivity of 67% and a specificity of 91% for defining the HPV status. Concordance indexes between p16(INK)⁴(a) and HPV status were high (≥78%) in general cases and in all histologic subtypes of penile SCC. The stain was useful in the differential diagnosis of basaloid and low-grade warty carcinomas. Low-risk HPV genotypes were found in 5 tumors, 4 of which were p16(INK)⁴(a) negative. Basaloid and nonbasaloid high-grade (grade 3) SCCs were more likely to be HR-HPV positive when compared with grades 1 to 2 tumors (P<0.000001 and 0.0417, respectively). p16(INK)⁴(a) overexpression was found to be a reliable marker for HR-HPV and a helpful tool in the differential diagnosis of low-grade verruciform and high-grade solid penile tumors. SCC variants depicting basaloid features were more likely to be HPV and p16(INK)⁴(a) positive than low-grade, keratinizing lesions. We also observed a tendency toward HPV positivity in high-grade nonbasaloid tumors. Our results indicated a concordance between HPV and p16(INK)⁴(a) status and this observation may have diagnostic and prognostic implications.

[Prostate cancer. Part 1: Review of cell kinetics over the years 1966-2015 and future perspectives of the new grading of the International Society of Urological Pathology (ISUP)].

PubMed

Helpap, B; Bubendorf, L

2016-02-01

Using tritium-labeled thymidine histoautoradiography, the AgNOR staining technique and Ki67-MIB-1 immunohistochemistry to study cell kinetics, prostate cancer can be subdivided into slowly, moderately and rapidly proliferating tumors. These are important supplementary methods and prerequisites for a grading as low, intermediate and high-grade in addition to classical histology and cytology. Cytometry of DNA can confirm the cell kinetics of prostate cancer by detection of a predominance of diploid or aneuploid cell nuclei but should only be evaluated together with histological investigations. All histology-based analyses of cell kinetics encompass the classical highly and poorly differentiated glandular and cribriform patterns as well as solid undifferentiated structures and the various subcategories. The malignancy grading of prostate cancer can result from the summation of histological grading and cell kinetic analyses, as long as the named investigations are included. The future perspectives of individualized therapy options, including active surveillance in early low-grade and also for high-grade prostate cancer and new antihormonal treatment in advanced disease, may increasingly rely on tissue biomarkers and advanced technologies for whole genome analysis including next generation sequencing.

DWI-associated entire-tumor histogram analysis for the differentiation of low-grade prostate cancer from intermediate-high-grade prostate cancer.

PubMed

Wu, Chen-Jiang; Wang, Qing; Li, Hai; Wang, Xiao-Ning; Liu, Xi-Sheng; Shi, Hai-Bin; Zhang, Yu-Dong

2015-10-01

To investigate diagnostic efficiency of DWI using entire-tumor histogram analysis in differentiating the low-grade (LG) prostate cancer (PCa) from intermediate-high-grade (HG) PCa in comparison with conventional ROI-based measurement. DW images (b of 0-1400 s/mm(2)) from 126 pathology-confirmed PCa (diameter >0.5 cm) in 110 patients were retrospectively collected and processed by mono-exponential model. The measurement of tumor apparent diffusion coefficients (ADCs) was performed with using histogram-based and ROI-based approach, respectively. The diagnostic ability of ADCs from two methods for differentiating LG-PCa (Gleason score, GS ≤ 6) from HG-PCa (GS > 6) was determined by ROC regression, and compared by McNemar's test. There were 49 LG-tumor and 77 HG-tumor at pathologic findings. Histogram-based ADCs (mean, median, 10th and 90th) and ROI-based ADCs (mean) showed dominant relationships with ordinal GS of Pca (ρ = -0.225 to -0.406, p < 0.05). All above imaging indices reflected significant difference between LG-PCa and HG-PCa (all p values <0.01). Histogram 10th ADCs had dominantly high Az (0.738), Youden index (0.415), and positive likelihood ratio (LR+, 2.45) in stratifying tumor GS against mean, median and 90th ADCs, and ROI-based ADCs. Histogram mean, median, and 10th ADCs showed higher specificity (65.3%-74.1% vs. 44.9%, p < 0.01), but lower sensitivity (57.1%-71.3% vs. 84.4%, p < 0.05) than ROI-based ADCs in differentiating LG-PCa from HG-PCa. DWI-associated histogram analysis had higher specificity, Az, Youden index, and LR+ for differentiation of PCa Gleason grade than ROI-based approach.

Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary.

PubMed

Ahmed, Ahmed Ashour; Etemadmoghadam, Dariush; Temple, Jillian; Lynch, Andy G; Riad, Mohamed; Sharma, Raghwa; Stewart, Colin; Fereday, Sian; Caldas, Carlos; Defazio, Anna; Bowtell, David; Brenton, James D

2010-05-01

Numerous studies have tested the association between TP53 mutations in ovarian cancer and prognosis but these have been consistently confounded by limitations in study design, methodology, and/or heterogeneity in the sample cohort. High-grade serous (HGS) carcinoma is the most clinically important histological subtype of ovarian cancer. As these tumours may arise from the ovary, Fallopian tube or peritoneum, they are collectively referred to as high-grade pelvic serous carcinoma (HGPSC). To identify the true prevalence of TP53 mutations in HGPSC, we sequenced exons 2-11 and intron-exon boundaries in tumour DNA from 145 patients. HGPSC cases were defined as having histological grade 2 or 3 and FIGO stage III or IV. Surprisingly, pathogenic TP53 mutations were identified in 96.7% (n = 119/123) of HGPSC cases. Molecular and pathological review of mutation-negative cases showed evidence of p53 dysfunction associated with copy number gain of MDM2 or MDM4, or indicated the exclusion of samples as being low-grade serous tumours or carcinoma of uncertain primary site. Overall, p53 dysfunction rate approached 100% of confirmed HGPSCs. No association between TP53 mutation and progression-free or overall survival was found. From this first comprehensive mapping of TP53 mutation rate in a homogeneous group of HGPSC patients, we conclude that mutant TP53 is a driver mutation in the pathogenesis of HGPSC cancers. Because TP53 mutation is almost invariably present in HGPSC, it is not of substantial prognostic or predictive significance. Copyright (c) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Primary central chondrosarcoma of long bone, limb girdle and trunk: Analysis of 174 cases by numerical scoring on histology.

PubMed

Konishi, Eiichi; Nakashima, Yasuaki; Mano, Masayuki; Tomita, Yasuhiko; Nagasaki, Ikumitsu; Kubo, Toshikazu; Araki, Nobuhito; Haga, Hironori; Toguchida, Junya; Ueda, Takafumi; Sakuma, Toshiko; Imahori, Masaya; Morii, Eiichi; Yoshikawa, Hideki; Tsukamoto, Yoshitane; Futani, Hiroyuki; Wakasa, Kenichi; Hoshi, Manabu; Hamada, Shinshichi; Takeshita, Hideyuki; Inoue, Takeshi; Aono, Masanari; Kawabata, Kenji; Murata, Hiroaki; Katsura, Kanade; Urata, Yoji; Ueda, Hideki; Yanagisawa, Akio

2015-09-01

The aims of this study were: (i) to elucidate clinicopathological characteristics of pcCHS of long bones (L), limb girdles (LG) and trunk (T) in Japan; (ii) to investigate predictive pathological findings for outcome of pcCHS of L, LG and T, objectively; and (iii) to elucidate a discrepancy of grade between biopsy and resected specimens. Clinicopathological profiles of 174 pcCHS (79 male, 95 female), of L, LG, and T were retrieved. For each case, a numerical score was given to 18 pathological findings. The average age was 50.5 years (15-80 years). Frequently involved sites were femur, humerus, pelvis and rib. The 5-year and 10-year disease-specific survival (DSS) rates [follow-up: 1-258 months (average 65.5)] were 87.0% and 80.4%, respectively. By Cox hazards analysis on pathological findings, age, sex and location, histologically higher grade and older age were unfavorable predictors, and calcification was a favorable predictor in DSS. The histological grade of resected specimen was higher than that of biopsy in 37.7% (26/69 cases). In conclusion, higher histological grade and older age were predictors for poor, but calcification was for good prognosis. Because there was a discrepancy in grade between biopsy and resected specimens, comprehensive evaluation is necessary before definitive operation for pcCHS. © 2015 The Authors. Pathology International published by Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Use of a 2-tier histologic grading system for canine cutaneous mast cell tumors on cytology specimens.

PubMed

Hergt, Franziska; von Bomhard, Wolf; Kent, Michael S; Hirschberger, Johannes

2016-09-01

Mast cell tumors (MCT) represent the most common malignant skin tumor in the dog. Diagnosis of an MCT can be achieved through cytologic examination of a fine-needle aspirate. However, the grade of the tumor is an important prognostic marker and currently requires histologic assessment. Recently a 2-tier histologic grading system based on nuclear features including number of mitoses, multinucleated cells, bizarre nuclei, and karyomegaly was proposed. The aim of this study was to assess if the cytomorphologic criteria proposed in the 2-tier histologic grading system are applicable to cytology specimens. A total of 141 MCT specimens reported as grade I, II, or III according to the Patnaik system with both histologic specimens and fine-needle aspirates available were histologically and cytologically reevaluated in a retrospective study. According to the 2-tier grading system, 38 cases were diagnosed histologically as high-grade and 103 as low-grade MCT. Cytologic grading resulted in 36 high-grade and 105 low-grade tumors. Agreement between histologic and cytologic grading based on the 2-tier grading system was achieved in 133 cases (sensitivity 86.8%, specificity 97.1%, kappa value 0.853), but 5 high-grade tumors on histology were classified as low-grade on cytology. Cytologic grading of MCT in the dog is helpful for initial assessment. However, the reliability of cytology using the 2-tier grading system is considered inadequate at this point. Prospective studies including clinical outcome should be pursued to further determine diagnostic accuracy of cytologic mast cell grading. © 2016 American Society for Veterinary Clinical Pathology.

High Intratumoral Stromal Content Defines Reactive Breast Cancer as a Low-risk Breast Cancer Subtype | Office of Cancer Genomics

Cancer.gov

Improved biomarker tests are required to minimize overdiagnosis and overtreatment of breast cancers. A number of pathologic criteria have been established to differentiate indolent or aggressive behavior, such as Nottingham grade of cancer cells. However, the effects of the tumor microenvironment on patient outcomes have not been integrated into pathologic criteria. In the current study, the Reactive subtype of breast cancer, identified by reverse-phase protein arrays, was demonstrated to indicate a favorable outcome.

Expression of aquaporin8 in human astrocytomas: Correlation with pathologic grade

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

Zhu, Shu-juan; Wang, Ke-jian; Gan, Sheng-wei

2013-10-11

Highlights: •AQP8 is mainly distributed in the cytoplasm of human astrocytoma cells. •AQP8 over-expressed in human astrocytomas, especially glioblastoma. •The up-regulation of AQP8 is related to the pathological grade of human astrocytomas. •AQP8 may contribute to the growth and proliferation of astrocytomas. -- Abstract: Aquaporin8 (AQP8), a member of the aquaporin (AQP) protein family, is weakly distributed in mammalian brains. Previous studies on AQP8 have focused mainly on the digestive and the reproductive systems. AQP8 has a pivotal role in keeping the fluid and electrolyte balance. In this study, we investigated the expression changes of AQP8 in 75 cases ofmore » human brain astrocytic tumors using immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction. The results demonstrated that AQP8 was mainly distributed in the cytoplasm of astrocytoma cells. The expression levels and immunoreactive score of AQP8 protein and mRNA increased in low-grade astrocytomas, and further increased in high-grade astrocytomas, especially in glioblastoma. Therefore, AQP8 may contribute to the proliferation of astrocytomas, and may be a biomarker and candidate therapy target for patients with astrocytomas.« less

Automated Processing of Dynamic Contrast-Enhanced MRI: Correlation of Advanced Pharmacokinetic Metrics with Tumor Grade in Pediatric Brain Tumors.

PubMed

Vajapeyam, S; Stamoulis, C; Ricci, K; Kieran, M; Poussaint, T Young

2017-01-01

Pharmacokinetic parameters from dynamic contrast-enhanced MR imaging have proved useful for differentiating brain tumor grades in adults. In this study, we retrospectively reviewed dynamic contrast-enhanced perfusion data from children with newly diagnosed brain tumors and analyzed the pharmacokinetic parameters correlating with tumor grade. Dynamic contrast-enhanced MR imaging data from 38 patients were analyzed by using commercially available software. Subjects were categorized into 2 groups based on pathologic analyses consisting of low-grade (World Health Organization I and II) and high-grade (World Health Organization III and IV) tumors. Pharmacokinetic parameters were compared between the 2 groups by using linear regression models. For parameters that were statistically distinct between the 2 groups, sensitivity and specificity were also estimated. Eighteen tumors were classified as low-grade, and 20, as high-grade. Transfer constant from the blood plasma into the extracellular extravascular space (K trans ), rate constant from extracellular extravascular space back into blood plasma (K ep ), and extracellular extravascular volume fraction (V e ) were all significantly correlated with tumor grade; high-grade tumors showed higher K trans , higher K ep , and lower V e . Although all 3 parameters had high specificity (range, 82%-100%), K ep had the highest specificity for both grades. Optimal sensitivity was achieved for V e , with a combined sensitivity of 76% (compared with 71% for K trans and K ep ). Pharmacokinetic parameters derived from dynamic contrast-enhanced MR imaging can effectively discriminate low- and high-grade pediatric brain tumors. © 2017 by American Journal of Neuroradiology.

Sonographic appearance of anal cushions of hemorrhoids

PubMed Central

Aimaiti, Adilijiang; A Ba Bai Ke Re, Ma Mu Ti Jiang; Ibrahim, Irshat; Chen, Hui; Tuerdi, Maimaitituerxun; Mayinuer

2017-01-01

AIM To evaluate the diagnostic value of different sonographic methods in hemorrhoids. METHODS Forty-two healthy volunteers and sixty-two patients with grades I-IV hemorrhoids received two different sonographic examinations from January 2013 to January 2016 at the First and Second Hospitals of Xinjiang Medical University in a prospective way. We analyzed the ultrasonographic findings of these participants and evaluated the outcomes. Resected grades III and IV hemorrhoid tissues were pathologically examined. The concordance of ultrasonographic results with pathology results was assessed with the Cohen’s kappa coefficient. RESULTS All healthy volunteers and all patients had no particular complications related to sonography. There were no statistically significant differences between the participants regarding age (P = 0.5919), gender (P = 0.4183), and persistent symptoms (P > 0.8692). All healthy control participants had no special findings. However, 30 patients with hemorrhoids showed blood signals around the dentate line on ultrasonography. When grades I and II hemorrhoids were analyzed, there were no significant differences between transrectal ultrasound (TRUS), transperianal ultrasound (TPUS), and transvaginal ultrasound (TVUS) (P > 0.05). Grades III and IV hemorrhoids revealed blood flow with different directions which could be observed as a “mosaic pattern”. In patients with grades III and IV hemorrhoids, the number of patients with “mosaic pattern” as revealed by TRUS, TPUS and TVUS was 22, 12, and 4, respectively. Patients with grades III and IV disease presented with a pathologically abnormal cushion which usually appeared as a “mosaic pattern” in TPUS and an arteriovenous fistula in pathology. Subepithelial vessels of resected grades III and IV hemorrhoid tissues were manifested by obvious structural impairment and retrograde and ruptured changes of internal elastic lamina. Some parts of the Trietz’s muscle showed hypertrophy and distortion. Arteriovenous fistulas and venous dilatation were obvious in the anal cushion of hemorhoidal tissues. After pathological results with arteriovenous fistulas were taken as the standard reference, we evaluated the compatibility between the two methods according to the Cohen’s kappa co-efficiency calculation. The compatibility (Cohein kappa co-efficiency value) between “mosaic pattern” in the TPUS and arteriovenous fistula in pathology was very good (ĸ = 0.8939). When compared between different groups, TRUS presented the advantage that the mosaic pattern could be confirmed in more patients, especially for group A. There was a statistical difference when comparing group A with group B or C (P < 0.05 for both). There were obvious statistical differences between group A and group B with regard to the vessel diameter and blood flow velocity measured by TRUS (P < 0.05). CONCLUSION Patients with grades III and IV hemorrhoids present with a pathologically abnormal cushion which usually appears as a “mosaic pattern” in sonography, which is in accord with an arteriovenous fistula in pathology. There are clearly different hemorrhoid structures shown by sonography. “Mosaic pattern” may be a parameter for surgical indication of grades III and IV hemorrhoids. PMID:28611519

Sonographic appearance of anal cushions of hemorrhoids.

PubMed

Aimaiti, Adilijiang; A Ba Bai Ke Re, Ma Mu Ti Jiang; Ibrahim, Irshat; Chen, Hui; Tuerdi, Maimaitituerxun; Mayinuer

2017-05-28

To evaluate the diagnostic value of different sonographic methods in hemorrhoids. Forty-two healthy volunteers and sixty-two patients with grades I-IV hemorrhoids received two different sonographic examinations from January 2013 to January 2016 at the First and Second Hospitals of Xinjiang Medical University in a prospective way. We analyzed the ultrasonographic findings of these participants and evaluated the outcomes. Resected grades III and IV hemorrhoid tissues were pathologically examined. The concordance of ultrasonographic results with pathology results was assessed with the Cohen's kappa coefficient. All healthy volunteers and all patients had no particular complications related to sonography. There were no statistically significant differences between the participants regarding age ( P = 0.5919), gender ( P = 0.4183), and persistent symptoms ( P > 0.8692). All healthy control participants had no special findings. However, 30 patients with hemorrhoids showed blood signals around the dentate line on ultrasonography. When grades I and II hemorrhoids were analyzed, there were no significant differences between transrectal ultrasound (TRUS), transperianal ultrasound (TPUS), and transvaginal ultrasound (TVUS) ( P > 0.05). Grades III and IV hemorrhoids revealed blood flow with different directions which could be observed as a "mosaic pattern". In patients with grades III and IV hemorrhoids, the number of patients with "mosaic pattern" as revealed by TRUS, TPUS and TVUS was 22, 12, and 4, respectively. Patients with grades III and IV disease presented with a pathologically abnormal cushion which usually appeared as a "mosaic pattern" in TPUS and an arteriovenous fistula in pathology. Subepithelial vessels of resected grades III and IV hemorrhoid tissues were manifested by obvious structural impairment and retrograde and ruptured changes of internal elastic lamina. Some parts of the Trietz's muscle showed hypertrophy and distortion. Arteriovenous fistulas and venous dilatation were obvious in the anal cushion of hemorhoidal tissues. After pathological results with arteriovenous fistulas were taken as the standard reference, we evaluated the compatibility between the two methods according to the Cohen's kappa co-efficiency calculation. The compatibility (Cohein kappa co-efficiency value) between "mosaic pattern" in the TPUS and arteriovenous fistula in pathology was very good (ĸ = 0.8939). When compared between different groups, TRUS presented the advantage that the mosaic pattern could be confirmed in more patients, especially for group A. There was a statistical difference when comparing group A with group B or C ( P < 0.05 for both). There were obvious statistical differences between group A and group B with regard to the vessel diameter and blood flow velocity measured by TRUS ( P < 0.05). Patients with grades III and IV hemorrhoids present with a pathologically abnormal cushion which usually appears as a "mosaic pattern" in sonography, which is in accord with an arteriovenous fistula in pathology. There are clearly different hemorrhoid structures shown by sonography. "Mosaic pattern" may be a parameter for surgical indication of grades III and IV hemorrhoids.

[Prostate cancer. Part 2: Review of the various tumor grading systems over the years 1966-2015 and future perspectives of the new grading of the International Society of Urological Pathology (ISUP)].

PubMed

Helpap, B; Bubendorf, L; Kristiansen, G

2016-02-01

The continued development of methods in needle biopsies and radical prostatectomy for treatment of prostate cancer has given special emphasis to the question of the prognostic relevance of the various systems of grading. The classical purely histological grading system of Gleason has been modified several times in the past decades and cleared the way for a new grading system by the prognostic grading of Epstein. Assessment of the old and also modified combined histological and cytological grading of Mostofi, the World health Organization (WHO) and the urologic-pathological working group of prostate cancer in connection with the Gleason grading (combined Gleason-Helpap grading), has led to considerably improved rates of concordance between biopsy and radical prostatectomy and to improved estimations of prognosis beside its contribution to the development of a more practicable grading system for clinical use.

Computational Pathology to Discriminate Benign from Malignant Intraductal Proliferations of the Breast

PubMed Central

Oh, Eun-Yeong; Lerwill, Melinda F.; Brachtel, Elena F.; Jones, Nicholas C.; Knoblauch, Nicholas W.; Montaser-Kouhsari, Laleh; Johnson, Nicole B.; Rao, Luigi K. F.; Faulkner-Jones, Beverly; Wilbur, David C.; Schnitt, Stuart J.; Beck, Andrew H.

2014-01-01

The categorization of intraductal proliferative lesions of the breast based on routine light microscopic examination of histopathologic sections is in many cases challenging, even for experienced pathologists. The development of computational tools to aid pathologists in the characterization of these lesions would have great diagnostic and clinical value. As a first step to address this issue, we evaluated the ability of computational image analysis to accurately classify DCIS and UDH and to stratify nuclear grade within DCIS. Using 116 breast biopsies diagnosed as DCIS or UDH from the Massachusetts General Hospital (MGH), we developed a computational method to extract 392 features corresponding to the mean and standard deviation in nuclear size and shape, intensity, and texture across 8 color channels. We used L1-regularized logistic regression to build classification models to discriminate DCIS from UDH. The top-performing model contained 22 active features and achieved an AUC of 0.95 in cross-validation on the MGH data-set. We applied this model to an external validation set of 51 breast biopsies diagnosed as DCIS or UDH from the Beth Israel Deaconess Medical Center, and the model achieved an AUC of 0.86. The top-performing model contained active features from all color-spaces and from the three classes of features (morphology, intensity, and texture), suggesting the value of each for prediction. We built models to stratify grade within DCIS and obtained strong performance for stratifying low nuclear grade vs. high nuclear grade DCIS (AUC = 0.98 in cross-validation) with only moderate performance for discriminating low nuclear grade vs. intermediate nuclear grade and intermediate nuclear grade vs. high nuclear grade DCIS (AUC = 0.83 and 0.69, respectively). These data show that computational pathology models can robustly discriminate benign from malignant intraductal proliferative lesions of the breast and may aid pathologists in the diagnosis and classification of these lesions. PMID:25490766

A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.

PubMed

Critchley-Thorne, Rebecca J; Duits, Lucas C; Prichard, Jeffrey W; Davison, Jon M; Jobe, Blair A; Campbell, Bruce B; Zhang, Yi; Repa, Kathleen A; Reese, Lia M; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory; DeMarshall, Maureen; Foxwell, Tyler; Zaidi, Ali H; Lansing Taylor, D; Rustgi, Anil K; Bergman, Jacques J G H M; Falk, Gary W

2016-06-01

Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia. We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies. Data were collected from Barrett's esophagus patients at four institutions. Patients who progressed to HGD or EAC in ≥1 year (n = 79) were matched with patients who did not progress (n = 287). Biopsies were assigned randomly to training or validation sets. Immunofluorescence analyses were performed for 14 biomarkers and quantitative biomarker and morphometric features were analyzed. Prognostic features were selected in the training set and combined into classifiers. The top-performing classifier was assessed in the validation set. A 3-tier, 15-feature classifier was selected in the training set and tested in the validation set. The classifier stratified patients into low-, intermediate-, and high-risk classes [HR, 9.42; 95% confidence interval, 4.6-19.24 (high-risk vs. low-risk); P < 0.0001]. It also provided independent prognostic information that outperformed predictions based on pathology analysis, segment length, age, sex, or p53 overexpression. We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables. The test has the potential to improve upon histologic analysis as an objective method to risk stratify Barrett's esophagus patients. Cancer Epidemiol Biomarkers Prev; 25(6); 958-68. ©2016 AACR. ©2016 American Association for Cancer Research.

Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial.

PubMed

Mackay, Alan; Burford, Anna; Molinari, Valeria; Jones, David T W; Izquierdo, Elisa; Brouwer-Visser, Jurriaan; Giangaspero, Felice; Haberler, Christine; Pietsch, Torsten; Jacques, Thomas S; Figarella-Branger, Dominique; Rodriguez, Daniel; Morgan, Paul S; Raman, Pichai; Waanders, Angela J; Resnick, Adam C; Massimino, Maura; Garrè, Maria Luisa; Smith, Helen; Capper, David; Pfister, Stefan M; Würdinger, Thomas; Tam, Rachel; Garcia, Josep; Thakur, Meghna Das; Vassal, Gilles; Grill, Jacques; Jaspan, Tim; Varlet, Pascale; Jones, Chris

2018-05-14

The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8 + tumor-infiltrating lymphocytes, and longer survival with the addition of BEV. Histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. Future clinical trials will need to take into account the diversity represented by the term "HGG" in the pediatric population. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

CD 10 expression intensity in various grades and stages of urothelial carcinoma of urinary bladder.

PubMed

Atique, Muhammad; Abbasi, Muhammad Sajjad; Jamal, Shahid; Khadim, Muhammad Tahir; Akhtar, Farhan; Jamal, Nighat

2014-05-01

To evaluate CD10 expression in urothelial carcinoma of the urinary bladder and the association of immunohistochemical (IHC) CD10 expression intensity with grade and stage. Descriptive cross-sectional analytical study. Armed Forces Institute of Pathology, Rawalpindi, from January to December 2011. Fifty consecutive cases of urothelial bladder carcinomas, obtained through transurethral resections, were included in this study. Hematoxylin-eosin (HE) stained sections from each case were re-evaluated histopathologically according to WHO 2004 grading system. The TNM system was used for pathologic staging. On selected slides IHC CD10 marker was applied and a semiquantitative scoring for its expression based on the percentage of positive cells and intensity was performed. Data was entered and analysed on SPSS version 17. Fisher's exact test was used to compare grades, stages of urothelial carcinoma with CD 10 expression and age groups. P < 0.05 was taken as level of significance. Urothelial carcinoma was more common in males. The male to female ratio was 9:1. The older patients > 50 years had higher grade and stage as compared to the younger patients. All cases of high grade urothelial carcinoma showed higher positivity for CD 10. Twenty cases (86.95%) of high grade urothelial carcinoma were positive with +2 immunostaining while 3 cases (13.04 %) were positive with +1 staining. None of the tumors of stage pTa was positive for CD 10 expression. Of all patients with stage pT 1 tumor, 1 case (5.3%) was CD 10 negative and 17 cases (89.9%) were CD 10 positive having +1 staining with 5 - 50% staining and 1 case (5.3%) had +2 staining with more then 50% expression. Out of all patients with stage pT 2, no tumor was CD 10 negative, 3 (13.6%) patients were CD 10 positive with +1 staining and 19 (86.4%) with stage pT 2 tumor had stained positive with +2 staining. CD 10 expression was greater in high grade and invasive urothelial carcinomas; it may be associated with tumor progression in bladder cancer pathogenesis.

Pathological video-game use among youth ages 8 to 18: a national study.

PubMed

Gentile, Douglas

2009-05-01

Researchers have studied whether some youth are "addicted" to video games, but previous studies have been based on regional convenience samples. Using a national sample, this study gathered information about video-gaming habits and parental involvement in gaming, to determine the percentage of youth who meet clinical-style criteria for pathological gaming. A Harris poll surveyed a randomly selected sample of 1,178 American youth ages 8 to 18. About 8% of video-game players in this sample exhibited pathological patterns of play. Several indicators documented convergent and divergent validity of the results: Pathological gamers spent twice as much time playing as nonpathological gamers and received poorer grades in school; pathological gaming also showed comorbidity with attention problems. Pathological status significantly predicted poorer school performance even after controlling for sex, age, and weekly amount of video-game play. These results confirm that pathological gaming can be measured reliably, that the construct demonstrates validity, and that it is not simply isomorphic with a high amount of play.

Prospective Evaluation of Intraprostatic Inflammation and Focal Atrophy as a Predictor of Risk of High-Grade Prostate Cancer and Recurrence after Prostatectomy

DTIC Science & Technology

2015-08-01

average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data ...SELECT data (incident prostate cancer). We found that the odds of low-grade prostate cancer tended to increase with the number of biopsy cores with...merged pathology-PCPT-SELECT data from the review of the H&E stained slide images (Task 7a), and performed the statistical analysis of the merged

LpMab-23-recognizing cancer-type podoplanin is a novel predictor for a poor prognosis of early stage tongue cancer.

PubMed

Miyazaki, Akihiro; Nakai, Hiromi; Sonoda, Tomoko; Hirohashi, Yoshihiko; Kaneko, Mika K; Kato, Yukinari; Sawa, Yoshihiko; Hiratsuka, Hiroyoshi

2018-04-20

We report that the reactivity of a novel monoclonal antibody LpMab-23 for human cancer-type podoplanin (PDPN) is a predictor for a poor prognosis of tongue cancer. The association between LpMab-23-recognizing cancer-type PDPN expression and clinical/pathological features were analyzed on 60 patients with stage I and II tongue cancer treated with transoral resection of the primary tumor. In the mode of invasion, the LpMab-23-dull/negative cases were significantly larger in cases with low-grade malignancies and without late cervical lymph node metastasis, than in cases with high-grade malignancies and the metastasis. In the high-grade malignant cases, LpMab-23-positive cases were significantly larger than LpMab-23-dull/negative cases. The Kaplan-Meier curves of the five-year metastasis-free survival rate (MFS) were significantly lower in the LpMab-23 positive patients than in LpMab-23 dull/negative patients. The LpMab-23-dull/negative cases showed the highest MFS in all of the clinical/pathological features and particularly, the MFS of the LpMab-23 positive cases decreased to less than 60% in the first year. In the Cox proportional hazard regression models a comparison of the numbers of LpMab-23 dull/negative with positive cases showed the highest hazard ratio with statistical significance in all of the clinical/pathological features. LpMab-23 positive cases may be considered to present a useful predictor of poor prognosis for early stage tongue cancer.

Grade classification of neuroepithelial tumors using high-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and pattern recognition.

PubMed

Chen, WenXue; Lou, HaiYan; Zhang, HongPing; Nie, Xiu; Lan, WenXian; Yang, YongXia; Xiang, Yun; Qi, JianPin; Lei, Hao; Tang, HuiRu; Chen, FenEr; Deng, Feng

2011-07-01

Clinical data have shown that survival rates vary considerably among brain tumor patients, according to the type and grade of the tumor. Metabolite profiles of intact tumor tissues measured with high-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy (HRMAS (1)H NMRS) can provide important information on tumor biology and metabolism. These metabolic fingerprints can then be used for tumor classification and grading, with great potential value for tumor diagnosis. We studied the metabolic characteristics of 30 neuroepithelial tumor biopsies, including two astrocytomas (grade I), 12 astrocytomas (grade II), eight anaplastic astrocytomas (grade III), three glioblastomas (grade IV) and five medulloblastomas (grade IV) from 30 patients using HRMAS (1)H NMRS. The results were correlated with pathological features using multivariate data analysis, including principal component analysis (PCA). There were significant differences in the levels of N-acetyl-aspartate (NAA), creatine, myo-inositol, glycine and lactate between tumors of different grades (P<0.05). There were also significant differences in the ratios of NAA/creatine, lactate/creatine, myo-inositol/creatine, glycine/creatine, scyllo-inositol/creatine and alanine/creatine (P<0.05). A soft independent modeling of class analogy model produced a predictive accuracy of 87% for high-grade (grade III-IV) brain tumors with a sensitivity of 87% and a specificity of 93%. HRMAS (1)H NMR spectroscopy in conjunction with pattern recognition thus provides a potentially useful tool for the rapid and accurate classification of human brain tumor grades.

A Pilot Study of the Immunologic, Virologic, and Pathologic Consequences of Intra-anal 5% Imiquimod in HIV-1-Infected Men With High-Grade Squamous Intraepithelial Lesions.

PubMed

Cranston, Ross D; Baker, Jonathan R; Siegel, Aaron; Brand, Rhonda M; Janocko, Laura; McGowan, Ian

2018-03-01

Imiquimod can be used to treat internal anal high-grade squamous intraepithelial lesions. In HIV-1-infected individuals there is a theoretical concern for increased HIV replication in anorectal tissue secondary to imiquimod-induced mucosal inflammation. The purpose of this study was to assess local virologic, immunologic, and pathologic effects of imiquimod treatment in HIV-infected individuals. This was a pilot study at a single academic center. The study was conducted at the University of Pittsburgh Anal Dysplasia Clinic. HIV-1-infected individuals with biopsy-confirmed internal anal high-grade squamous intraepithelial lesions were included. Imiquimod cream was prescribed for intra-anal use 3 times per week for 9 weeks. Anal human papillomavirus typing, anal and rectal tissue HIV-1 RNA and DNA quantification, cytokine gene expression, and anal histology were measured. Nine evaluable participants (1 participant was lost to follow-up) were all white men with a median age of 46 years (interquartile range = 12 y) and a median CD4 T-cell count of 480 cells per cubic millimeter (interquartile range = 835). All were taking antiretroviral therapy, and 7 of 9 had HIV-1 RNA <50 copies per milliliter. The median dose of imiquimod used was 27.0 (interquartile range = 3.5), and there was a median of 11 days (interquartile range = 10 d) from last dose to assessment. There was no progression to cancer, no significant change in the number of human papillomavirus types detected, and no significant change in quantifiable cytokines/HIV-1 RNA or DNA levels in anal or rectal tissue. Seven (35%) of 20 high-grade lesions resolved to low-grade squamous intraepithelial lesions. The study was limited by the small number of participants and variable time to final assessment. Intra-anal imiquimod showed no evidence of immune activation or increase in HIV-1 viral replication in anal and rectal tissue and confirmed efficacy for intra-anal high-grade squamous intraepithelial lesion treatment morbidity. See Video Abstract at http://links.lww.com/DCR/A498.

Validation of International Society of Urological Pathology (ISUP) grading for prostatic adenocarcinoma in thin core biopsies using TROG 03.04 'RADAR' trial clinical data.

PubMed

Delahunt, B; Egevad, L; Srigley, J R; Steigler, A; Murray, J D; Atkinson, C; Matthews, J; Duchesne, G; Spry, N A; Christie, D; Joseph, D; Attia, J; Denham, J W

2015-10-01

In 2014 a consensus conference convened by the International Society of Urological Pathology (ISUP) adopted amendments to the criteria for Gleason grading and scoring (GS) for prostatic adenocarcinoma. The meeting defined a modified grading system based on 5 grading categories (grade 1, GS 3+3; grade 2, GS 3+4; grade 3, GS 4+3; grade 4, GS 8; grade 5, GS 9-10). In this study we have evaluated the prognostic significance of ISUP grading in 496 patients enrolled in the TROG 03.04 RADAR Trial. There were 19 grade 1, 118 grade 2, 193 grade 3, 88 grade 4 and 79 grade 5 tumours in the series, with follow-up for a minimum of 6.5 years. On follow-up 76 patients experienced distant progression of disease, 171 prostate specific antigen (PSA) progression and 39 prostate cancer deaths. In contrast to the 2005 modified Gleason system (MGS), the hazards of the distant and PSA progression endpoints, relative to grade 2, were significantly greater for grades 3, 4 and 5 of the 2014 ISUP grading scheme. Comparison of predictive ability utilising Harrell's concordance index, showed 2014 ISUP grading to significantly out-perform 2005 MGS grading for each of the three clinical endpoints.

Incidence of Anal Dysplasia in a Population of High-Risk Women: Observations at a Cervical Pathology Unit.

PubMed

Oliver-Pérez, María de Los Reyes; Bravo Violeta, Victoria; Legorburu Alonso, Beatriz; Betancor Pérez, Diana; Bebia Conesa, Vicente; Jiménez López, Jesús S

2017-10-01

This study aimed to evaluate the incidence of anal dysplasia in women at high risk of developing those lesions and to assess the relationships between positive anal cytology and different risk factors. We performed an observational cross-sectional study involving a patient survey and chart review. The study was conducted at the cervical pathology unit at the Hospital Universitario 12 de Octubre, Madrid, Spain, from 2011 to 2015. Patients were 215 women aged 18 to 65 years old with risk factors for anal dysplasia, for whom anal evaluation was indicated. Anal cytology was performed in all patients. High-resolution anoscopy and anal biopsy were used to investigate abnormalities. All patients completed a survey regarding sexual practices. The patients' demographic and clinical data were collected by using a retrospective chart review. The main outcome measure was the incidence of anal dysplasia in this population. Of the 215 patients, 45 (21.0%) presented with cytological abnormalities (atypical squamous cells of undetermined significance, 13.5%; low-grade squamous intraepithelial lesion, 5.6%; high-grade squamous intraepithelial lesion, 1.9%). Anoscopy was performed in 31 patients (14.4%) and 2 patients (0.9%) had abnormal findings. One case (0.5%) of low-grade anal intraepithelial neoplasia was identified. Only immunosuppression (p = .01) and smoking status (p = .02) were significantly correlated with positive anal cytology results. Limitations of the study include the small single-center sample, a lack of controls, the retrospective design, potential survey response biases, and the nonstandardized survey. The incidence of abnormal cytological findings was 21.0%, whereas low-grade anal intraepithelial was confirmed in 0.5% of the patients. There is a higher incidence of cytological abnormalities among immunosuppressed women and smokers.

Automated high-grade prostate cancer detection and ranking on whole slide images

NASA Astrophysics Data System (ADS)

Huang, Chao-Hui; Racoceanu, Daniel

2017-03-01

Recently, digital pathology (DP) has been largely improved due to the development of computer vision and machine learning. Automated detection of high-grade prostate carcinoma (HG-PCa) is an impactful medical use-case showing the paradigm of collaboration between DP and computer science: given a field of view (FOV) from a whole slide image (WSI), the computer-aided system is able to determine the grade by classifying the FOV. Various approaches have been reported based on this approach. However, there are two reasons supporting us to conduct this work: first, there is still room for improvement in terms of detection accuracy of HG-PCa; second, a clinical practice is more complex than the operation of simple image classification. FOV ranking is also an essential step. E.g., in clinical practice, a pathologist usually evaluates a case based on a few FOVs from the given WSI. Then, makes decision based on the most severe FOV. This important ranking scenario is not yet being well discussed. In this work, we introduce an automated detection and ranking system for PCa based on Gleason pattern discrimination. Our experiments suggested that the proposed system is able to perform high-accuracy detection ( 95:57% +/- 2:1%) and excellent performance of ranking. Hence, the proposed system has a great potential to support the daily tasks in the medical routine of clinical pathology.

A survey of liver pathology in needle biopsies from HBsAg and anti-HBe positive individuals.

PubMed

ter Borg, F; ten Kate, F J; Cuypers, H T; Leentvaar-Kuijpers, A; Oosting, J; Wertheim-van Dillen, P M; Honkoop, P; Rasch, M C; de Man, R A; van Hattum, J; Chamuleau, R A; Tytgat, G N; Jones, E A

2000-07-01

To use laboratory data and liver biopsies, prospectively obtained from hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-HBe) positive patients, for the assessment of: (1) the relation between biopsy length/number of portal tracts and sampling error; (2) the relation between the severity of piecemeal necrosis and the new grading terminology (minimal, mild, moderate, and severe chronic hepatitis); and (3) liver pathology, which has not been studied in patients with this specific serological profile. The study group (n = 174) included 104 patients with normal aminotransferase concentrations and no cases with clinically apparent cirrhosis. The specimen length and number of portal tracts were measured at light microscopy examination. Sampling error analysis was related to the discrepancies between aminotransferase concentrations versus histological grade. Detailed histological scorings were undertaken by the reference pathologist and compared with laboratory and hepatitis B virus (HBV) DNA precore sequence data. Sampling error seemed to be a constant feature, even for biopsies > or = 20 mm, but increased dramatically in biopsies < 5 mm long and/or containing less than four portal tracts. Between 25% and 30% of biopsies, graded as "mild" or "moderate" activity showed features of moderate and severe piecemeal necrosis, respectively. Ten per cent of the patients with normal aminotransferase values had stage III-IV hepatic fibrosis, and 20% had piecemeal necrosis. Only cytoplasmic, not nuclear, core antigen expression was a strong predictor of high hepatitis B viraemia. There was no association between precore stop codon mutations, grade/stage of liver disease, and hepatitis B core antigen (HBcAg) expression. The specimen available for light microscopical examination should be > 5 mm long and should contain more than four portal tracts. In addition, the new grading terminology might give the clinician an inappropriately mild impression of the severity of piecemeal necrosis. Furthermore, even in the presence of normal aminotransferase concentrations, considerable liver pathology can be found in 10-20% of HBsAg and anti-HBe positive individuals; such pathology is not associated with the occurrence of precore stop codon mutations.

Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin's lymphomas

PubMed Central

Vacca, A; Ribatti, D; Ruco, L; Giacchetta, F; Nico, B; Quondamatteo, F; Ria, R; Iurlaro, M; Dammacco, F

1999-01-01

Node biopsies of 30 benign lymphadenopathies and 71 B-cell non-Hodgkin's lymphomas (B-NHLs) were investigated for microvessel and macrophage counts using immunohistochemistry and morphometric analysis. Both counts were significantly higher in B-NHL. Moreover, when these were grouped into low-grade and high-grade lymphomas, according to the Kiel classification and Working Formulation (WF), statistically significant higher counts were found in the high-grade tumours. Immunohistochemistry and electron microscopy revealed a close spatial association between microvessels and macrophages. Overall, the results suggest that, in analogy to what has already been shown in solid tumours, angiogenesis occurring in B-NHLs increases with tumour progression, and that macrophages promote the induction of angiogenesis via the release of their angiogenic factors. © 1999 Cancer Research Campaign PMID:10070898

Processing of fallopian tube, ovary, and endometrial surgical pathology specimens: A survey of U.S. laboratory practices.

PubMed

Samimi, Goli; Trabert, Britton; Duggan, Máire A; Robinson, Jennifer L; Coa, Kisha I; Waibel, Elizabeth; Garcia, Edna; Minasian, Lori M; Sherman, Mark E

2018-03-01

Many high-grade serous carcinomas initiate in fallopian tubes as serous tubal intraepithelial carcinoma (STIC), a microscopic lesion identified with specimen processing according to the Sectioning and Extensive Examination of the Fimbria protocol (SEE-Fim). Given that the tubal origin of these cancers was recently recognized, we conducted a survey of pathology practices to assess processing protocols that are applied to gynecologic surgical pathology specimens in clinical contexts in which finding STIC might have different implications. We distributed a survey electronically to the American Society for Clinical Pathology list-serve to determine practice patterns and compared results between practice types by chi-square (χ2) tests for categorical variables. Free text comments were qualitatively reviewed. Survey responses were received from 159 laboratories (72 academic, 87 non-academic), which reported diverse specimen volumes and percentage of gynecologic samples. Overall, 74.1% of laboratories reported performing SEE-Fim for risk-reducing surgical specimens (82.5% academic versus 65.7% non-academic, p < 0.05). In specimens from surgery for benign indications in which initial microscopic sections showed an unanticipated suspicious finding, 75.9% of laboratories reported using SEE-Fim to process the remainder of the specimen (94.8% academic versus 76.4% non-academic, p < 0.01), and 84.6% submitted the entire fimbriae. Changes in the theories of pathogenesis of high-grade serous carcinoma have led to implementation of pathology specimen processing protocols that include detailed analysis of the fallopian tubes. These results have implications for interpreting trends in cancer incidence data and considering the feasibility of developing a bank of gynecologic tissues containing STIC or early cancer precursors. Published by Elsevier Inc.

[Pap smear for mass screening: Results of an African experiment].

PubMed

Somé, O-R; Zongo, N; Ka, S; Wardini, R; Dem, A

2016-06-01

To assess the impact of smear test in the fight against cervix uteri cancer in Senegal. This was a descriptive cross-sectional study of 1836 Pap smears performed in patients over 15 years during several screening campaigns in Senegal conducted between June 2010 and June 2012. We analyzed epidemiological data, pathological smears, and the proposed management. In 69% of cases, the women were less than 45 years old. They were mostly multiparous and did not use contraceptive methods before. The smears were interpreted in 91.4% (n=1661) and were pathological in 5.2% of cases. They revealed mainly atypical squamous cells of undetermined significance, squamous intraepithelial low-grade lesions, and squamous intraepithelial high-grade lesions, respectively in 2.5% (n=46), 1.7% (n=30) and 1% (n=19) of cases. Multiparity, early marriages were the main risk factors. Patients with pathological smars had colposcopy with cryotherapy (23 cases), and colposcopy and biopsy (13 cases). A hysterectomy was performed in 4 cases. The pathological smear rate found in this study confirms the interest to continue cervical cancer screening with this practice. Strengthening of its geographical and financial access through a national prevention program will effectively help to lower cases of cervical cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Ultra wide field fluorescein angiography can detect macular pathology in central retinal vein occlusion.

PubMed

Tsui, Irena; Franco-Cardenas, Valentina; Hubschman, Jean-Pierre; Yu, Fei; Schwartz, Steven D

2012-01-01

The purpose of this study was to evaluate whether ultra wide field fluorescein angiography (UWFFA), a tool established for the detection of peripheral non-perfusion, can also detect macular pathology. A retrospective imaging review was performed on patients with central retinal vein occlusion. UWFFA was graded for angiographic leakage (petalloid and/or diffuse leakage) and presence of abnormalities in the foveal avascular zone and was then correlated to spectral-domain optical coherence tomography (SD-OCT). Sixty-six eyes met inclusion criteria. Intergrader agreement was highly reliable for grading macular leakage on UWFFA (kappa = 0.75) and moderately reliable for the evaluation of an abnormal foveal avascular zone (kappa = 0.43). Angiographic leakage on UWFFA correlated to macular edema on SD-OCT (P > .0001), and abnormalities in the foveal avascular zone on UWFFA correlated to ganglion cell layer atrophy on SD-OCT (P = .0002). Intergrader reliability in grading UWFFA was better when assessing macular leakage than when assessing macular ischemia. UWFFA findings correlated to macular edema and signs of macular ischemia on SD-OCT. Copyright 2012, SLACK Incorporated.

Disseminated Oligodendroglial-like Leptomeningeal Tumor in the Adult: Case Report and Review of the Literature.

PubMed

Fiaschi, Pietro; Badaloni, Filippo; Cagetti, Bernarda; Bruzzone, Luca; Marucci, Gianluca; Dellachà, Anna; Pavanello, Marco; Ganci, Giuseppe; Padolecchia, Riccardo; Valsania, Valtero

2018-06-01

Diffuse leptomeningeal glioneuronal tumor (DLGNT) was recently added to the World Health Organization classification of central nervous system tumors. DLGNT is a rare entity that occurs more commonly in pediatric patients, but occasional cases have been reported in adults. This tumor has been recognized as a distinct pathologic entity; however, its biologic behavior remains unclear. It is considered an indolent neoplasm, although considerable morbidity has been reported. For this reason, further characterization and collection of evidence are crucial. In this article, we reported a case of a 36-year-old woman with a DLGNT characterized by rapid, aggressive behavior. We also performed a review of the literature for reported cases of low-grade and high-grade forms involving adults and children. DLGNTs should no longer be considered only as low-grade tumors affecting pediatric patients. The spectrum of presentations also includes aggressive tumors affecting adults. Further clinical and pathologic data supported by cytogenetic and molecular investigations are mandatory to better characterize DLGNTs. Copyright © 2018 Elsevier Inc. All rights reserved.

Inter-observer variability between general pathologists and a specialist in breast pathology in the diagnosis of lobular neoplasia, columnar cell lesions, atypical ductal hyperplasia and ductal carcinoma in situ of the breast

PubMed Central

2014-01-01

Background This study aimed to assess inter-observer variability between the original diagnostic reports and later review by a specialist in breast pathology considering lobular neoplasias (LN), columnar cell lesions (CCL), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) of the breast. Methods A retrospective, observational, cross-sectional study was conducted. A total of 610 breast specimens that had been formally sent for consultation and/or second opinions to the Breast Pathology Laboratory of Federal University of Minas Gerais were analysed between January 2005 and December 2010. The inter-observer variability between the original report and later review was compared regarding the diagnoses of LN, CCL, ADH, and DCIS. Statistical analyses were conducted using the Kappa index. Results Weak correlations were observed for the diagnoses of columnar cell change (CCC; Kappa = 0.38), columnar cell hyperplasia (CCH; Kappa = 0.32), while a moderate agreement (Kappa = 0.47) was observed for the diagnoses of flat epithelial atypia (FEA). Good agreement was observed in the diagnoses of atypical lobular hyperplasia (ALH; Kappa = 0.62) and lobular carcinoma in situ (LCIS; Kappa = 0.66). However, poor agreement was observed for the diagnoses of pleomorphic LCIS (Kappa = 0.22). Moderate agreement was observed for the diagnoses of ADH (Kappa = 0.44), low-grade DCIS (Kappa = 0.47), intermediate-grade DCIS (Kappa = 0.45), and DCIS with microinvasion (Kappa = 0.56). Good agreement was observed between the diagnoses of high-grade DCIS (Kappa = 0.68). Conclusions According to our data, the best diagnostic agreements were observed for high-grade DCIS, ALH, and LCIS. CCL without atypia and pleomorphic LCIS had the worst agreement indices. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1640072350119725. PMID:24948027

Inter-observer variability between general pathologists and a specialist in breast pathology in the diagnosis of lobular neoplasia, columnar cell lesions, atypical ductal hyperplasia and ductal carcinoma in situ of the breast.

PubMed

Gomes, Douglas S; Porto, Simone S; Balabram, Débora; Gobbi, Helenice

2014-06-19

This study aimed to assess inter-observer variability between the original diagnostic reports and later review by a specialist in breast pathology considering lobular neoplasias (LN), columnar cell lesions (CCL), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) of the breast. A retrospective, observational, cross-sectional study was conducted. A total of 610 breast specimens that had been formally sent for consultation and/or second opinions to the Breast Pathology Laboratory of Federal University of Minas Gerais were analysed between January 2005 and December 2010. The inter-observer variability between the original report and later review was compared regarding the diagnoses of LN, CCL, ADH, and DCIS. Statistical analyses were conducted using the Kappa index. Weak correlations were observed for the diagnoses of columnar cell change (CCC; Kappa=0.38), columnar cell hyperplasia (CCH; Kappa=0.32), while a moderate agreement (Kappa=0.47) was observed for the diagnoses of flat epithelial atypia (FEA). Good agreement was observed in the diagnoses of atypical lobular hyperplasia (ALH; Kappa=0.62) and lobular carcinoma in situ (LCIS; Kappa=0.66). However, poor agreement was observed for the diagnoses of pleomorphic LCIS (Kappa=0.22). Moderate agreement was observed for the diagnoses of ADH (Kappa=0.44), low-grade DCIS (Kappa=0.47), intermediate-grade DCIS (Kappa=0.45), and DCIS with microinvasion (Kappa=0.56). Good agreement was observed between the diagnoses of high-grade DCIS (Kappa=0.68). According to our data, the best diagnostic agreements were observed for high-grade DCIS, ALH, and LCIS. CCL without atypia and pleomorphic LCIS had the worst agreement indices. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1640072350119725.

Pathologic audit of 164 consecutive cases of vulvar intraepithelial neoplasia.

PubMed

Scurry, James; Campion, Michael; Scurry, Bonnie; Kim, Soo Nyung; Hacker, Neville

2006-04-01

There are 2 types of vulvar intraepithelial neoplasia (VIN): warty-basaloid and differentiated. Differentiated VIN is uncommon and seldom diagnosed prior to carcinoma and, traditionally, is not graded. There are currently 3 grading systems for warty-basaloid VIN: the World Health Organization (WHO) 3 grade system of VIN 1-3, a 2 grade system of low and high grade vulvar intraepithelial lesions, and the revised International Society for the Study of Vulvovaginal Disease (ISSVD) classification which has no grading of VIN. According to the ISSVD, VIN 1 should be abolished and VIN 2 and 3 combined into a single category, simply termed warty-basaloid VIN. To determine the best system for grading warty-basaloid VIN and learn more about differentiated VIN, we reviewed the pathology of 164 consecutive women with VIN. Of these, 134 (82.3%) had warty-basaloid VIN, 29 (18.2%) had differentiated VIN, and 1 had both. Of warty-basaloid VIN cases, 4 had VIN 1, 13 VIN 2, and 118 VIN 3 when graded according to the WHO. All VIN 1 occurred in condylomata acuminata. VIN 2 and 3 were distinguished only by degree of abnormality. Differentiated VIN was diagnosed before SCC in only 7 cases (26.7%). Because the only VIN 1 cases seen were in condylomata acuminata and because VIN 2 and 3 were difficult to distinguish and there appears little clinical reason to do so, our study supports the ISSVD proposal that VIN 1 be abolished and VIN 2 and 3 be combined. There needs to be more clinical awareness of vulvar conditions, so that differentiated VIN is biopsied before cancer has supervened.

Bcl-2 protein expression in mucoepidermoid carcinoma of salivary glands: a single institution experience.

PubMed

Janjua, Omer Sefvan; Qureshi, Sana Mehmood; Khan, Tariq Sarfraz; Alamgir, Wajiha

2012-01-01

Mucoepidermoid carcinoma is the most common salivary gland tumor with varying behavior among different histopathological grades. The objective of this study was to determine the expression of Bcl-2 protein in mucoepidermoid carcinoma (MEC) and to correlate with histological grades. The records of 40 cases of MEC were collected from the histopathology department. Fresh slides were prepared and fresh diagnoses were made using the grading criteria for MEC. Immunohistochemical markers for Bcl-2 were applied and the results analyzed using the chi-square test. Of 40 cases, 20 were males and 20 were females. The range in age of the patients was 6 to 67 years mean (SD) was 42.6 (1.85) years. Twenty-two were low grade (55%), 11 high grade (27.5%) and 7 (17.5%) were intermediate grade MEC. Among these 40 cases, Bcl-2 expression was positive in 24 cases and negative in 16 cases. In 22 cases of low-grade MEC, 19 were positive while only 3 were negative. In high-grade tumors, all 11 cases were found to have a negative expression of Bcl-2 protein. In intermediate-grade MEC, 5 cases showed positive expression while only 2 cases showed negative expression. Bcl-2 protein expression showed positive expression in low-grade and negative expression in high-grade MEC. Intermediate grade showed more than 50% positive results for Bcl-2. Correlation between grades of MEC and expression of Bcl-2 is statistically significant and can be used for the depicting the prognosis of MEC along with other prognostic and clinico-pathological parameters.

Frozen section pathology for decision making in parotid surgery.

PubMed

Olsen, Kerry D; Moore, Eric J; Lewis, Jean E

2013-12-01

For parotid lesions, the high accuracy and utility of intraoperative frozen section (FS) pathology, compared with permanent section pathology, facilitates intraoperative decision making about the extent of surgery required. To demonstrate the accuracy and utility of FS pathology of parotid lesions as one factor in intraoperative decision making. Retrospective review of patients undergoing parotidectomy at a tertiary care center. Evaluation of the accuracy of FS pathology for parotid surgery by comparing FS pathology results with those of permanent section. Documented changes from FS to permanent section in 1339 parotidectomy pathology reports conducted from January 1, 2000, through December 31, 2009, included 693 benign and 268 primary and metastatic malignant tumors. Changes in diagnosis were found from benign to malignant (n = 11) and malignant to benign (n = 2). Sensitivity and specificity of a malignant diagnosis were 98.5% and 99.0%, respectively. Other changes were for lymphoma vs inflammation or lymphoma typing (n = 89) and for confirmation of or change in tumor type for benign (n = 36) or malignant (n = 69) tumors. No case changed from low- to high-grade malignant tumor. Only 4 cases that changed from FS to permanent section would have affected intraoperative decision making. Three patients underwent additional surgery 2 to 3 weeks later. Overall, only 1 patient was overtreated (lymphoma initially deemed carcinoma). Frozen section pathology for parotid lesions has high accuracy and utility in intraoperative decision making, facilitating timely complete procedures.

High apoptotic index in urine cytology is associated with high-grade urothelial carcinoma.

PubMed

Yang, Chi-Shun; Chen, Shaoxiong; Cramer, Harvey M; Wu, Howard H

2016-08-01

The significance of apoptosis and its association with high-grade urothelial carcinoma (HGUC) in urine cytology has yet to be determined. A computerized search of the study laboratory information system was performed over a 3-year period for all urine cytology specimens processed using the SurePath liquid-based preparation technique. Only those cases with correlating surgical pathology obtained within 6 months after the urine cytologic samples were included in the current study. Cases from ileal conduit samples were excluded. A semiquantitative numerical scoring system (apoptotic index) was used to assess the amount of pyknosis or karyorrhexis, with 0 indicating none, 1 indicating < 10 per 10 high-power fields, 2 indicating 10 to 30 per 10 high-power fields, and 3 indicating > 30 per 10 high-power fields. Statistical analysis using the Pearson chi-square test was performed. A total of 228 cases including 105 benign cases, 79 cases of HGUC, and 44 cases of low-grade urothelial carcinoma (LGUC) diagnosed on follow-up surgical pathology were selected. A score of 0 was observed in 70 benign, 11 HGUC, and 8 LGUC cases; a score of 1 was observed in 31 benign, 21 HGUC, and 23 LGUC cases; a score of 2 was observed in 3 benign, 27 HGUC, and 9 LGUC cases; and a score of 3 was observed in 1 benign, 20 HGUC, and 4 LGUC cases. Excluding ileal conduit urine specimens, the finding of a high apoptotic index (score ≥ 2) with the presence of pyknosis or karyorrhexis in ≥10 per 10 high-power fields in the urine cytology appears to be significantly associated with HGUC (P<.05). Cancer Cytopathol 2016;124:546-51. © 2016 American Cancer Society. © 2016 American Cancer Society.

B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma.

PubMed

Snuderl, Matija; Kolman, Olga K; Chen, Yi-Bin; Hsu, Jessie J; Ackerman, Adam M; Dal Cin, Paola; Ferry, Judith A; Harris, Nancy Lee; Hasserjian, Robert P; Zukerberg, Lawrence R; Abramson, Jeremy S; Hochberg, Ephraim P; Lee, Hang; Lee, Alfred I; Toomey, Christiana E; Sohani, Aliyah R

2010-03-01

B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as "double-hit" lymphomas (DHL), are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathologic features overlapping with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and B-lymphoblastic lymphoma/leukemia (B-LBL). The clinical and pathologic spectrum of this rare entity, including comparison to other high-grade B-cell neoplasms, has not been well defined. We conducted a retrospective analysis of clinical and pathologic features of 20 cases of DHL seen at our institution during a 5-year period. In addition, we carried out case-control comparisons of DHL with BL and International Prognostic Index (IPI)-matched DLBCL. The 11 men and 9 women had a median age of 63.5 years (range 32 to 91). Six patients had a history of grade 1 to 2 follicular lymphoma; review of the prior biopsy specimens in 2 of 5 cases revealed blastoid morphology. Eighteen patients had Ann Arbor stage 3 or 4 disease and all had elevated serum lactate dehydrogenase (LDH) levels at presentation. Extranodal disease was present in 17/20 (85%), bone marrow involvement in 10/17 (59%) and central nervous system (CNS) disease in 5/11 (45%). Nineteen patients were treated with combination chemotherapy, of whom 18 received rituximab and 14 received CNS-directed therapy. Fourteen patients (70%) died within 8 months of diagnosis. Median overall survival in the DHL group (4.5 mo) was inferior to both BL (P=0.002) and IPI-matched DLBCL (P=0.04) control patients. Twelve DHL cases (60%) were classified as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, 7 cases (35%) as DLBCL, not otherwise specified, and 1 case as B-LBL. Distinguishing features from BL included expression of Bcl2 (P<0.0001), Mum1/IRF4 (P=0.006), Ki-67 <95% (P<0.0001), and absence of EBV-EBER (P=0.006). DHL commonly contained the t(8;22) rather than the t(8;14) seen in most BL controls (P=0.001), and exhibited a higher number of chromosomal aberrations (P=0.0009). DHL is a high-grade B-cell neoplasm with a poor prognosis, resistance to multiagent chemotherapy, and clinical and pathologic features distinct from other high-grade B-cell neoplasms. Familiarity with the morphologic and immunophenotypic spectrum of DHL is important in directing testing to detect concurrent IGH-BCL2 and MYC rearrangements when a karyotype is unavailable. The aggressive clinical behavior and combination of genetic abnormalities seen in these cases may warrant categorization as a separate entity in future classifications and call for novel therapeutic approaches.

In phyllodes tumour of the breast expression of c-kit but not of ALDH1A1 is associated with adverse clinico-pathological features.

PubMed

Chougule, Abhijit; Bal, Amanjit; Das, Ashim; Kohli, Pavneet Singh; Singh, Gurpreet

2016-12-01

Attempts at identification of an ideal prognostic/predictive biomarker in phyllodes tumour (PT) have not been fruitful so far. Studies evaluating c-kit expression in PT have shown contradictory results. Recently aldehyde dehydrogenase 1A1 (ALDH1A1) was proposed as a stem cell marker for malignant PT but its expression has not been studied in benign and borderline tumours. We aimed to evaluate expression and prognostic significance of c-kit and ALDH1A1 in different grades of PT. Epithelial and stromal c-kit and ALDH1A1 expression were studied in 104 PT cases (86 primary and 18 recurrent tumours) and compared with different clinico-pathological features and recurrence rates. Stromal c-kit expression at 1 % cutoff correlated with increasing tumour grade, larger tumour size, hypercellularity, nuclear atypia, stromal overgrowth, infiltrative margins and mitotic count. These associations, however, were lost with higher (5 or 10 %) cutoffs. Conversely, decreased c-kit expression in the epithelial component correlated with increasing tumour grade, regardless of the cutoffs used. Stromal ALDH1A1 expression did not have significant associations with tumour grade or other adverse clinico-pathological features, regardless of different cutoffs. None of the cases showed significant epithelial ALDH1A1 expression. Expression of c-kit was associated with poorer overall survival (p = 0.011), while ALDH1A1 expression was associated with shorter recurrence-free survival (p = 0.036). In conclusion, c-kit expression was associated with higher tumour grade and adverse clinico-pathological features. However, these associations are cutoff dependent, partly explaining the variability in previously reported studies. ALDH1A1 expression did not have significant correlations with tumour grade and adverse clinico-pathological variables.

Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma.

PubMed

Ayadi, Lobna; Khabir, Abdelmajid; Amouri, Habib; Karray, Sondes; Dammak, Abdallah; Guermazi, Mohamed; Boudawara, Tahya

2008-10-22

Breast carcinoma is a disease with a tremendous heterogeneity in its clinical behavior. Newer prognostic factors and predictors of response to therapy are needed. The aim of this study was to evaluate the expression of HER-2, estrogen receptor (ER) and progesterone receptors (PR) in breast carcinoma and to compare it with other prognostic parameters such as histological type and grade, tumor size, patients' age, and lymph node metastases. This is a retrospective study conducted in the department of pathology at Sfax University Hospital. Confirmed 155 Cases of breast carcinoma were reviewed in the period between January 2000 and December 2004. We used immunohistochemistry to evaluate the expression of HER-2, ER, and PR receptor and Chi-square and Fisher exact test to correlate immunohistochemical findings with prognostic parameters for breast carcinoma such as patients' age, tumor size, histological type, histological grade and lymph node status. The mean age of patients was 51.5 years, ranging from 22 to 89 years. 80 (51.6%) of the patients were below 50 years. The percentage of expression of HER-2, ER and PR was 26, 59.4, and 52.3%, respectively. HER-2 was over-expressed (3+) in 18.1% of the cases, was inversely related to ER expression (p = 0.00) and to PR expression (p = 0.048). This over-expression was also associated with a high tumor grade with marginal significance (p = 0.072). A negative correlation was noted between ER and PR expression and SBR grade (p = 0.000) and ER and age (p = 0.002). HER-2 over-expression was observed in 18.1% of Tunisian breast carcinoma affecting female patients. This group presents apparently an aggressive form of breast carcinoma with high histological grade and negative ER.

Dedifferentiated liposarcoma of the lower extremity with low-grade dedifferentiation and low-grade osteosarcomatous component.

PubMed

Zajicek, Anna K; Bridge, Julia A; Akers, Joshua W; McGarry, Sean V; Walker, Craig W

2017-02-01

Dedifferentiated liposarcoma can arise de novo or as a complication of a preexisting well-differentiated liposarcoma. We describe the radiologic and pathologic features of a long-standing liposarcoma with multiple recurrences in a 59-year-old male. Imaging demonstrated a heterogeneous fat-containing mass in the anterior thigh. The adjacent proximal femur showed irregular cortical new bone, eventually followed by intramedullary osteoblastic involvement and pathologic fracture. Histologic assessment at resection revealed dedifferentiated liposarcoma with low-grade osteosarcomatous component. The patient subsequently developed metastatic lesions in the lungs containing osteoid and osteoblastic bone metastases. We discuss the radiologic and pathologic features of this rare entity that, to our knowledge, has previously been reported to directly involve osseous structures in only one other case and discuss the potential pitfalls in diagnosis.

Analyses of atypical glandular cells re-defined by the 2006 Bethesda System: histologic outcomes and clinical implication of follow-up management.

PubMed

Ulker, V; Numanoglu, C; Akyol, A; Kuru, O; Akbayir, O; Erim, A; Ongut, C

2013-01-01

To evaluate the histopathology and the long-term follow-up outcome of women who had atypical glandular cells on Pap smears. All women with atypical glandular cells (AGC) who underwent colposcopic and histopathologic evaluation between January 2005 and October 2010 were reviewed. Patient data were examined up to October 2012, allowing for at least two years of follow-up for all patients. Forty-four women with AGC Pap test underwent histologic follow-up during the study period. Overall, upon reclassification of smears, 35 (79.5%) cases were diagnosed with AGC "not otherwise specified" (NOS) and nine (20.5%) with AGC "favour neoplasia". Seven out of nine patients (77.7%) with AGC "favour neoplasia" had significant pathology. On the other hand, only 11 out of 35 cases (31.4%) with AGC "NOS" had significant pathology. Significant correlation was found between AGC "favour neoplasia" smears and a significant pathology (p: 0.01). Of the 44 patients, 18 (40.9%) had significant pathology. Eight patients (18.2%) had low grade cervical intraepithelial neoplasia (CIN 1), four (9%) had high-grade cervical intraepithelial neoplasia (CIN 2/3), one (2.2%) had microinvasive squamous cell carcinoma of uterine cervix, one (2.2%) had cervical adenocarcinoma in situ, one (2.2%) had cervical adenocarcinoma, one (2.2%) had endometrial adenocarcinoma, and two (4.5%) had endometrial hyperplasia. Reporting AGC in the population is clinically significant due to the high prevalence of underlying preinvasive and invasive diseases (40.9%). The subtypes of the AGC category are significant predictor of such lesions.

White-nose syndrome pathology grading in Nearctic and Palearctic bats

PubMed Central

Pikula, Jiri; Amelon, Sybill K.; Bandouchova, Hana; Bartonička, Tomáš; Berkova, Hana; Brichta, Jiri; Hooper, Sarah; Kokurewicz, Tomasz; Kolarik, Miroslav; Köllner, Bernd; Kovacova, Veronika; Linhart, Petr; Piacek, Vladimir; Turner, Gregory G.; Zukal, Jan; Martínková, Natália

2017-01-01

While white-nose syndrome (WNS) has decimated hibernating bat populations in the Nearctic, species from the Palearctic appear to cope better with the fungal skin infection causing WNS. This has encouraged multiple hypotheses on the mechanisms leading to differential survival of species exposed to the same pathogen. To facilitate intercontinental comparisons, we proposed a novel pathogenesis-based grading scheme consistent with WNS diagnosis histopathology criteria. UV light-guided collection was used to obtain single biopsies from Nearctic and Palearctic bat wing membranes non-lethally. The proposed scheme scores eleven grades associated with WNS on histopathology. Given weights reflective of grade severity, the sum of findings from an individual results in weighted cumulative WNS pathology score. The probability of finding fungal skin colonisation and single, multiple or confluent cupping erosions increased with increase in Pseudogymnoascus destructans load. Increasing fungal load mimicked progression of skin infection from epidermal surface colonisation to deep dermal invasion. Similarly, the number of UV-fluorescent lesions increased with increasing weighted cumulative WNS pathology score, demonstrating congruence between WNS-associated tissue damage and extent of UV fluorescence. In a case report, we demonstrated that UV-fluorescence disappears within two weeks of euthermy. Change in fluorescence was coupled with a reduction in weighted cumulative WNS pathology score, whereby both methods lost diagnostic utility. While weighted cumulative WNS pathology scores were greater in the Nearctic than Palearctic, values for Nearctic bats were within the range of those for Palearctic species. Accumulation of wing damage probably influences mortality in affected bats, as demonstrated by a fatal case of Myotis daubentonii with natural WNS infection and healing in Myotis myotis. The proposed semi-quantitative pathology score provided good agreement between experienced raters, showing it to be a powerful and widely applicable tool for defining WNS severity. PMID:28767673

White-nose syndrome pathology grading in Nearctic and Palearctic bats.

PubMed

Pikula, Jiri; Amelon, Sybill K; Bandouchova, Hana; Bartonička, Tomáš; Berkova, Hana; Brichta, Jiri; Hooper, Sarah; Kokurewicz, Tomasz; Kolarik, Miroslav; Köllner, Bernd; Kovacova, Veronika; Linhart, Petr; Piacek, Vladimir; Turner, Gregory G; Zukal, Jan; Martínková, Natália

2017-01-01

While white-nose syndrome (WNS) has decimated hibernating bat populations in the Nearctic, species from the Palearctic appear to cope better with the fungal skin infection causing WNS. This has encouraged multiple hypotheses on the mechanisms leading to differential survival of species exposed to the same pathogen. To facilitate intercontinental comparisons, we proposed a novel pathogenesis-based grading scheme consistent with WNS diagnosis histopathology criteria. UV light-guided collection was used to obtain single biopsies from Nearctic and Palearctic bat wing membranes non-lethally. The proposed scheme scores eleven grades associated with WNS on histopathology. Given weights reflective of grade severity, the sum of findings from an individual results in weighted cumulative WNS pathology score. The probability of finding fungal skin colonisation and single, multiple or confluent cupping erosions increased with increase in Pseudogymnoascus destructans load. Increasing fungal load mimicked progression of skin infection from epidermal surface colonisation to deep dermal invasion. Similarly, the number of UV-fluorescent lesions increased with increasing weighted cumulative WNS pathology score, demonstrating congruence between WNS-associated tissue damage and extent of UV fluorescence. In a case report, we demonstrated that UV-fluorescence disappears within two weeks of euthermy. Change in fluorescence was coupled with a reduction in weighted cumulative WNS pathology score, whereby both methods lost diagnostic utility. While weighted cumulative WNS pathology scores were greater in the Nearctic than Palearctic, values for Nearctic bats were within the range of those for Palearctic species. Accumulation of wing damage probably influences mortality in affected bats, as demonstrated by a fatal case of Myotis daubentonii with natural WNS infection and healing in Myotis myotis. The proposed semi-quantitative pathology score provided good agreement between experienced raters, showing it to be a powerful and widely applicable tool for defining WNS severity.

A survey study on student preferences regarding pathology teaching in Germany: a call for curricular modernization.

PubMed

Herrmann, Florian E M; Lenski, Markus; Steffen, Julius; Kailuweit, Magdalena; Nikolaus, Marc; Koteeswaran, Rajasekaran; Sailer, Andreas; Hanszke, Anna; Wintergerst, Maximilian; Dittmer, Sissi; Mayr, Doris; Genzel-Boroviczény, Orsolya; Eley, Diann S; Fischer, Martin R

2015-06-02

Pathology is a discipline that provides the basis of the understanding of disease in medicine. The past decades have seen a decline in the emphasis laid on pathology teaching in medical schools and outdated pathology curricula have worsened the situation. Student opinions and thoughts are central to the questions of whether and how such curricula should be modernized. A survey was conducted among 1018 German medical students regarding their preferences in pathology teaching modalities and their satisfaction with lecture-based courses. A qualitative analysis was performed comparing a recently modernized pathology curriculum with a traditional lecture-based curriculum. The differences in modalities of teaching used were investigated. Student satisfaction with the lecture-based curriculum positively correlated with student grades (spearman's correlation coefficient 0.24). Additionally, students with lower grades supported changing the curriculum (spearman's correlation coefficient 0.47). The majority supported virtual microscopy, autopsies, seminars and podcasts as preferred didactic methods. The data supports the implementation of a pathology curriculum where tutorials, autopsies and supplementary computer-based learning tools play important roles.

Evaluating the apparent diffusion coefficient in MRI studies as a means of determining paediatric brain tumour stages.

PubMed

Domínguez-Pinilla, N; Martínez de Aragón, A; Diéguez Tapias, S; Toldos, O; Hinojosa Bernal, J; Rigal Andrés, M; González-Granado, L I

2016-09-01

The apparent diffusion coefficient (ADC) in MRI seems to be related to cellularity in brain tumours. Its utility as a tool for distinguishing between histological types and tumour stages remains controversial. We retrospectively evaluated children diagnosed with CNS tumours between January 2008 and December 2013. Data collected were age, sex, histological diagnosis, and location of the tumour. We evaluated the ADC and ADC ratio and correlated those values with histological diagnoses. The study included 55 patients with a median age of 6 years. Histological diagnoses were pilocytic astrocytoma (40%), anaplastic ependymoma (16.4%), ganglioglioma (10.9%), glioblastoma (7.3%), medulloblastoma (5.5%), and other (20%). Tumours could also be classified as low-grade (64%) or high-grade (36%). Mean ADC was 1.3 for low-grade tumours and 0.9 for high-grade tumours (p=.004). Mean ADC ratios were 1.5 and 1.2 for low and high-grade tumours respectively (p=.025). There were no significant differences in ADC/ADC ratio between different histological types. ADC and ADC ratio may be useful in imaging-study based differential diagnosis of low and high-grade tumours, but they are not a substitute for an anatomical pathology study. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

An approach to the diagnosis of flat intraepithelial lesions of the urinary bladder using the World Health Organization/ International Society of Urological Pathology consensus classification system.

PubMed

Amin, Mahul B; McKenney, Jesse K

2002-07-01

The classification of flat urothelial (transitional cell) lesions with atypia has historically varied in its application from institution to institution with no fewer than six major nomenclature systems proposed in the past 25 years. In 1998, the World Health Organization/ International Society of Urological Pathology (WHO/ISUP) published a consensus classification that included the following categories for flat urinary bladder lesions: reactive atypia, atypia of unknown significance, dysplasia (low-grade intraepithelial neoplasia), and carcinoma in situ (high-grade intraepithelial neoplasia). This classification expands the definition traditionally used for urothelial carcinoma in situ, basing its diagnosis primarily on the severity of cytologic changes. In proposing the classification system for flat lesions of the bladder with atypia, it was hoped that consistent use of uniform diagnostic terminology would ultimately aid in a better understanding of the biology of these lesions. In this review, the authors discuss the history of the concept of flat urothelial neoplasia, the rationale and histologic criteria for the WHO/ISUP diagnostic categories, an approach to the diagnosis of flat lesions, and problems and pitfalls associated with their recognition in routine surgical pathology specimens.

Accuracy of Computed Tomography for Predicting Pathologic Nodal Extracapsular Extension in Patients With Head-and-Neck Cancer Undergoing Initial Surgical Resection

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

Prabhu, Roshan S., E-mail: roshansprabhu@gmail.com; Winship Cancer Institute, Emory University, Atlanta, Georgia; Magliocca, Kelly R.

2014-01-01

Purpose: Nodal extracapsular extension (ECE) in patients with head-and-neck cancer increases the loco-regional failure risk and is an indication for adjuvant chemoradiation therapy (CRT). To reduce the risk of requiring trimodality therapy, patients with head-and-neck cancer who are surgical candidates are often treated with definitive CRT when preoperative computed tomographic imaging suggests radiographic ECE. The purpose of this study was to assess the accuracy of preoperative CT imaging for predicting pathologic nodal ECE (pECE). Methods and Materials: The study population consisted of 432 consecutive patients with oral cavity or locally advanced/nonfunctional laryngeal cancer who underwent preoperative CT imaging before initialmore » surgical resection and neck dissection. Specimens with pECE had the extent of ECE graded on a scale from 1 to 4. Results: Radiographic ECE was documented in 46 patients (10.6%), and pECE was observed in 87 (20.1%). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 43.7%, 97.7%, 82.6%, and 87.3%, respectively. The sensitivity of radiographic ECE increased from 18.8% for grade 1 to 2 ECE, to 52.9% for grade 3, and 72.2% for grade 4. Radiographic ECE criteria of adjacent structure invasion was a better predictor than irregular borders/fat stranding for pECE. Conclusions: Radiographic ECE has poor sensitivity, but excellent specificity for pECE in patients who undergo initial surgical resection. PPV and NPV are reasonable for clinical decision making. The performance of preoperative CT imaging increased as pECE grade increased. Patients with resectable head-and-neck cancer with radiographic ECE based on adjacent structure invasion are at high risk for high-grade pECE requiring adjuvant CRT when treated with initial surgery; definitive CRT as an alternative should be considered where appropriate.« less

Cancer Staging

MedlinePlus

... cancer described by this staging system in your pathology report, unless you have a cancer for which ... adult and childhood cancers. Related Resources Tumor Grade Pathology Reports Posted: March 9, 2015 Most text on ...

Biochemical metabolic changes assessed by 31P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

PubMed Central

Yu, Ri-Sheng; Hao, Liang; Dong, Fei; Mao, Jian-Shan; Sun, Jian-Zhong; Chen, Ying; Lin, Min; Wang, Zhi-Kang; Ding, Wen-Hong

2009-01-01

AIM: To compare the features of biochemical metabolic changes detected by hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) with the liver damage score (LDS) and pathologic changes in rabbits and to investigate the diagnostic value of 31P MRS in acute hepatic radiation injury. METHODS: A total of 30 rabbits received different radiation doses (ranging 5-20 Gy) to establish acute hepatic injury models. Blood biochemical tests, 31P MRS and pathological examinations were carried out 24 h after irradiation. The degree of injury was evaluated according to LDS and pathology. Ten healthy rabbits served as controls. The MR examination was performed on a 1.5 T imager using a 1H/31P surface coil by the 2D chemical shift imaging technique. The relative quantities of phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured. The data were statistically analyzed. RESULTS: (1) Relative quantification of phosphorus metabolites: (a) ATP: there were significant differences (P < 0.05) (LDS-groups: control group vs mild group vs moderate group vs severe group, 1.83 ± 0.33 vs 1.55 ± 0.24 vs 1.27 ± 0.09 vs 0.98 ± 0.18; pathological groups: control group vs mild group vs moderate group vs severe group, 1.83 ± 0.33 vs 1.58 ± 0.25 vs 1.32 ± 0.07 vs 1.02 ± 0.18) of ATP relative quantification among control group, mild injured group, moderate injured group, and severe injured group according to both LDS grading and pathological grading, respectively, and it decreased progressively with the increased degree of injury (r = -0.723, P = 0.000). (b) PME and Pi; the relative quantification of PME and Pi decreased significantly in the severe injured group, and the difference between the control group and severe injured group was significant (P < 0.05) (PME: LDS-control group vs LDS-severe group, 0.86 ± 0.23 vs 0.58 ± 0.22, P = 0.031; pathological control group vs pathological severe group, 0.86 ± 0.23 vs 0.60 ± 0.21, P = 0.037; Pi: LDS-control group vs LDS-severe group, 0.74 ± 0.18 vs 0.43 ± 0.14, P = 0.013; pathological control group vs pathological severe group, 0.74 ± 0.18 vs 0.43 ± 0.14, P = 0.005) according to LDS grading and pathological grading, respectively. (c) PDE; there were no significant differences among groups according to LDS grading, and no significant differences between the control group and experimental groups according to pathological grading. (2) The ratio of relative quantification of phosphorus metabolites: significant differences (P < 0.05) (LDS-moderate group and LDS-severe group vs LDS-control group and LDS-mild group, 1.94 ± 0.50 and 1.96 ± 0.72 vs 1.43 ± 0.31 and 1.40 ± 0.38) were only found in PDE/ATP between the moderate injured group, the severe injured group and the control group, the mild injured group. No significant difference was found in other ratios of relative quantification of phosphorus metabolites. CONCLUSION: 31P MRS is a useful method to evaluate early acute hepatic radiation injury. The relative quantification of hepatic ATP levels, which can reflect the pathological severity of acute hepatic radiation injury, is correlated with LDS. PMID:19522022

Treatment of AIDS related non-Hodgkin's lymphoma with combination mitoguazone dihydrochloride and low dose CHOP chemotherapy: results of a phase II study.

PubMed

Tulpule, Anil; Espina, Byron M; Pedro Santabarbara, A B; Palmer, Maria; Schiflett, Joanne; Boswell, William; Smith, Susan; Levine, Alexandra M

2004-01-01

To evaluate the response and side effects of combination therapy with low dose CHOP chemotherapy and mitoguazone dihydrochloride in patients with non-Hodgkin's lymphoma associated with the acquired immunodeficiency syndrome (AIDS-NHL). Eighteen patients newly diagnosed with intermediate or high-grade AIDS-NHL were treated with low dose CHOP as follows: day 1, cyclophosphamide 350 mg/m(2), intravenously (IV); doxorubicin 25mg/m(2) IV; vincristine 2mg IV; and prednisone 100mg given orally on days 1 through 5. In addition, mitoguazone dihydrochloride was given at a dose of 600 mg/m(2) IV on days 1 and 15 of each 28-day treatment cycle. Seventeen males and one female patient were accrued. Twelve patients had high-grade pathologies while the remainder had an intermediate grade pathology (diffuse large cell). The median CD4+ lymphocyte count was 98/dl (range 1-924). Three patients (17%) reported an AIDS-defining illness prior to lymphoma diagnosis. Of 14 evaluable patients, 6 (43%) achieved a complete remission and 5 (35%) a partial remission. The median failure free and overall survival times were 6.5 and 8.4 months, respectively. Major toxicity was hematologic with grade 3 or 4 neutropenia in 72%; two patients died of neutropenic sepsis. Mitoguazone in combination with low dose CHOP is a safe regimen, associated with a response rate of 79% (CR 43%, PR 36%, 95% CI=49-95%). These preliminary results suggest no major improvement in terms of response over use of CHOP without mitoguazone.

Effect of Lecture Attendance and Prerequisite Academic Outcomes on Dental Students' Oral Pathology Performance.

PubMed

Shumway, Brian S; Bernstein, Mark L; Qian, Chen; Kulkarni, Manjiri Y; Rai, Shesh N

2018-03-01

Decreased lecture attendance in undergraduate and health science professions education has been noted throughout the world. The limited study of the effect of lecture attendance on dental students' performance has yielded mixed results, with some studies finding a positive effect and others reporting no association. The aim of this study was to evaluate the effect of lecture attendance on dental students' final grades in an oral pathology course at one U.S. dental school. Due to a curriculum change, second- and third-year students (N=233) were concurrently enrolled in the spring 2016 oral pathology (OP) course. Students' course grades were compared to attendance percentage (Att), grades in prerequisite basic science (PBS) courses, and Academic Average and Total Science (TS) scores on the Dental Admission Test. The results showed that both Att (p=0.011) and TS score (p<0.001) were significant predictors of OP grade, while race, gender, and age were not. Students' grades in OP were moderately to strongly correlated with their grades in all PBS courses (p<0.001). These results suggest that lecture attendance in OP should be encouraged but viewed in light of the finding that it was not as strongly correlated as PBS course performance and was a weaker predictor than TS score. Students with lower TS scores and PBS course grades should be encouraged to use additional supports such as tutoring to improve their performance in OP.

Regarding the Focal Treatment of Prostate Cancer: Inference of the Gleason Grade From Magnetic Resonance Spectroscopic Imaging

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

Brame, Ryan S.; Zaider, Marco; Zakian, Kristen L.

2009-05-01

Purpose: To quantify, as a function of average magnetic resonance spectroscopy (MRS) score and tumor volume, the probability that a cancer-suspected lesion has an elevated Gleason grade. Methods and Materials: The data consist of MRS imaging ratios R stratified by patient, lesion (contiguous abnormal voxels), voxels, biopsy and pathologic Gleason grade, and lesion volume. The data were analyzed using a logistic model. Results: For both low and high Gleason score biopsy lesions, the probability of pathologic Gleason score {>=}4+3 increases with lesion volume. At low values of R a lesion volume of at least 15-20 voxels is needed to reachmore » a probability of success of 80%; the biopsy result helps reduce the prediction uncertainty. At larger MRS ratios (R > 6) the biopsy result becomes essentially uninformative once the lesion volume is >12 voxels. With the exception of low values of R, for lesions with low Gleason score at biopsy, the MRS ratios serve primarily as a selection tool for assessing lesion volumes. Conclusions: In patients with biopsy Gleason score {>=}4+3, high MRS imaging tumor volume and (creatine + choline)/citrate ratio may justify the initiation of voxel-specific dose escalation. This is an example of biologically motivated focal treatment for which intensity-modulated radiotherapy and especially brachytherapy are ideally suited.« less

Is Needle Biopsy Clinically Useful in Preoperative Grading of Central Chondrosarcoma of the Pelvis and Long Bones?

PubMed

Roitman, Pablo D; Farfalli, Germán L; Ayerza, Miguel A; Múscolo, D Luis; Milano, Federico E; Aponte-Tinao, Luis A

2017-03-01

Central chondrosarcoma of bone is graded on a scale of 1 to 3 according to histological criteria. Clinically, these tumors can be divided into low-grade (Grade 1) and high-grade (Grade 2, Grade 3, and dedifferentiated) chondrosarcomas. Although en bloc resection has been the most widely used treatment, it has become generally accepted that in selected patients with low-grade chondrosarcomas of long bones, curettage is safe and effective. This approach requires an accurate preoperative estimation of grade to avoid under- or overtreatment, but prior reports have indicated that both imaging and biopsy do not always give an accurate prediction of grade. (1) What is the concordance of image-guided needle preoperative biopsy and postoperative grading in central (intramedullary) chondrosarcomas of long bones, and how does this compare with the concordance of image-guided needle preoperative biopsy and postoperative grading in central pelvic chondrosarcomas? (2) What is the concordance of preoperative image-guided needle biopsy and postoperative findings in differentiating low-grade from high-grade central chondrosarcomas of long bones, and how does this compare with the concordance in central pelvic chondrosarcomas? Between 1997 and 2014, in our institution, we treated 126 patients for central chondrosarcomas located in long bones and the pelvis. Of these 126 cases, 41 were located in the pelvis and the remaining 85 cases were located in long bones. This study considers 39 (95%) and 40 (47%) of them, respectively. We included all cases in which histological information was complete regarding preoperative and postoperative tumor grading. We excluded all cases with incomplete data sets or nondiagnostic preoperative biopsies. To evaluate the needle biopsy accuracy, we compared the histological tumor grade, obtained from the preoperative biopsy, with the final histological grade obtained from the postoperative surgical specimen. The weighted and nonweighted kappa statistics were used to evaluate the agreement. Concordance between the preoperative biopsy and the final pathological analysis in terms of histological grade was much higher in long-bone chondrosarcoma than in pelvic chondrosarcoma (83% [33 of 40] versus 36% [14 of 39]; odds ratio, 8, 48). Likewise, the weighted kappa coefficients were higher in long-bone chondrosarcoma than in pelvic chondrosarcoma for the determination of histological grade (0.63; 95% confidence interval [CI], 0.34-0.91 versus 0.12; -0.32 to 0.57; p < 0.001). When categorizing the lesions as low grade or high grade, concordance between the preoperative biopsy and the final pathological analysis was much higher in long-bone chondrosarcoma than in pelvic chondrosarcoma (90% [36 of 40] versus 67% [26 of 39]; odds ratio, 4, 5). Likewise, the weighted kappa coefficients were higher in long-bone chondrosarcoma than in pelvic chondrosarcoma (0.73; 95% CI, 0.51-0.94 versus 0.26; 0.04-0.48; p < 0.001). Image-guided needle biopsy, when performed by a specialist radiologist and evaluated by an experienced bone pathologist, is a useful tool in determining the histological grade of long-bone chondrosarcomas allowing identification of true low-grade tumors. The histological grade should be correlated with imaging and the clinical presentation, but under these circumstances, experienced tumor surgeons may use this information in planning surgical treatment. The same appears not to be true for pelvic lesions, in which histological grade established by needle biopsy should be interpreted with caution. Level III, diagnostic study.

Anal study in immunocompetent women with human papillomavirus related lower genital tract pathology.

PubMed

Donaire, Concepción; Reillo, Marcos; Martínez-Escoriza, Juan C; López-Fernández, José A

2017-04-01

To estimate the prevalence of anal dysplasia in immunocompetent women with cervical intraepithelial dysplasia. We did a prospective cohort study, in which we enrolled 166 women with gynecological pathology related to human papilloma virus (HPV) infection. All patients underwent an anal cytology and HPV detection. Statistical analysis with a 95% confidence interval was used for prevalence calculations. A Χ2 test and Fisher's exact one were used to determine differences between groups of qualitative variables. Differences between normally distributed and non-normally distributed groups in quantitative variables were accounted for using Student's t-test or Mann-Whitney's U test, respectively. Out of the 166 patients studied, high risk HPV in the anal canal was detected in 107 (64.46%) cases. The most prevalent genotype observed was non 16/18 high risk HPV, present in 54 (50.47%) patients. There was no a significant association with smoking, use of condom, anal intercourse, or anal benign pathology. However, a significant correlation between the presence of high risk HPV in the anal canal and the antecedent of condylomas was observed (p=0.047) (CI95%: 1.00%-12.58%). Women with cervical intraepithelial neoplasia (CIN) grade 1 had a significantly increased presence of high risk HPV in the anal canal (p=0.044). Out of the 166 women, 6 (3.61%) had abnormal anal cytology results, and were referred to high-resolution anoscopy. Anal biopsy was performed in these six cases. In 2 patients the biopsy reported low-grade Anal Intraepithelial Neoplasia: 1.20% (0.15%-4.28%). Women with cervical intraepithelial dysplasia have 1.20% prevalence of anal intraepithelial neoplasia, so that it does not seem necessary to screen this population. Copyright © 2017 Elsevier B.V. All rights reserved.

The Association Between Rotator Cuff Muscle Fatty Infiltration and Glenoid Morphology in Glenohumeral Osteoarthritis.

PubMed

Donohue, Kenneth W; Ricchetti, Eric T; Ho, Jason C; Iannotti, Joseph P

2018-03-07

Glenoid morphology and rotator cuff muscle quality are important anatomic factors that can impact longevity of the glenoid component following total shoulder arthroplasty (TSA). We hypothesized that rotator cuff muscle fatty infiltration is associated with increased pathologic glenoid bone loss in glenohumeral osteoarthritis (OA). We retrospectively reviewed 190 preoperative computed tomography (CT) scans of 175 patients (mean age, 66 years; range, 44 to 90 years) who underwent TSA for the treatment of primary glenohumeral OA. Two-dimensional orthogonal CT images were reformatted in the plane of the scapula from 3-dimensional images. Pathologic joint-line medialization was defined with use of the glenoid vault model. Pathologic glenoid version was measured directly. Glenoid morphology was graded according to a modified Walch classification (subtypes A1, A2, B1, B2, B3, C1, and C2). Rotator cuff muscle fatty infiltration was assessed and assigned a Goutallier score on the sagittal CT slice just medial to the spinoglenoid notch for each muscle. There was a significant difference in the Goutallier score for the supraspinatus, infraspinatus, and teres minor muscles between Walch subtypes (p ≤ 0.05). High-grade posterior rotator cuff muscle fatty infiltration was present in 55% (21) of 38 B3 glenoids compared with 8% (3) of 39 A1 glenoids. Increasing joint-line medialization was associated with increasing fatty infiltration of all rotator cuff muscles (p ≤ 0.05). Higher fatty infiltration of the infraspinatus, teres minor, and combined posterior rotator cuff muscles was associated with increasing glenoid retroversion (p ≤ 0.05). After controlling for joint-line medialization and retroversion, B3 glenoids were more likely to have fatty infiltration of the supraspinatus and infraspinatus muscles than B2 glenoids were. High-grade rotator cuff muscle fatty infiltration is associated with B3 glenoids, increased pathologic glenoid retroversion, and increased joint-line medialization. Additional studies are needed to determine the causal relationship between these muscle changes and glenoid wear, whether these muscle changes independently affect clinical and radiographic outcomes in anatomic TSA, and whether fatty infiltration can improve postoperatively with correction of pathologic version and/or joint-line restoration. This study investigates the association between different patterns of glenoid bone loss and rotator cuff muscle fatty infiltration. Both factors have been shown to affect clinical outcome following TSA.

Small Renal Masses in Close Proximity to the Collecting System and Renal Sinus Are Enriched for Malignancy and High Fuhrman Grade and Should Be Considered for Early Intervention.

PubMed

Correa, Andres F; Toussi, Amir; Amin, Milon; Hrebinko, Ronald L; Gayed, Bishoy A; Parwani, Anil V; Maranchie, Jodi K

2018-02-05

Recent reports show a correlation between renal tumor radiographic characteristics and pathologic features. We hypothesize that a more central location within the relatively hypoxic renal medulla might confer a more aggressive tumor phenotype. To test this, radiographic tumor characteristics were compared with tumor grade and histology. We retrospectively reviewed renal masses <4 cm in diameter that underwent resection between 2008 and 2013. Tumor location was recorded using standard R.E.N.A.L. Nephrometry Score. Multivariate logistic regression was performed to compare independent anatomic features with incidence of malignancy and high nuclear grade. A total of 334 renal tumors had information available for analysis. Univariate analysis showed that increasing endophycity and proximity to the collecting system (<4 mm) were predictors of malignancy and high-grade features. In multivariate analysis, proximity to the collecting system <4 mm remained the as the only anatomical variable predictive of malignancy (odds ratio [OR], 3.58; 95% confidence interval [CI], 1.06-12.05; P = .04) and high nuclear grade (OR, 2.81; 95% CI, 1.44-5.51; P = .003). Malignancy and high tumor grade occur with much greater frequency when tumors are located deep in the kidney, in close proximity to the collecting system and renal sinus. Ninety-six percent of small renal masses in this region were cancers and nearly half were Fuhrman Grade 3 or 4, suggesting that these small centrally located tumors should be targeted for early intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Data bank of optical properties of biological tissue and blood in the visible and near infrared spectral region

NASA Astrophysics Data System (ADS)

Khairullina, Alphiya Y.; Bui, Lilia; Oleinik, Tatiana V.; Artishevsky, Nelli; Prigoun, Natalia; Sevkovsky, Jakov; Mokhort, Tatiana

1996-12-01

The data bank contains optical, ordinary biochemical and biophysical information on 120 venous blood samples of donors, healthy persons, patients with high pathology, 60 tissue samples. The optical parameters include diffuse reflection R((lambda) ) and transmission T((lambda) ) coefficients for optically thick layers, the absorption K((lambda) ) and extinction (epsilon) ((lambda) ) spectra, oxygenation degree CO2, parameter p determined by sizes and shapes of cells and their aggregates, refractive index of a disperse phase relative to surrounding media, and cooperative effects at high relative concentration. The peculiarities in absorption K((lambda) spectra are connected with different pathologies. It is shown from K((lambda) ) that the grade of pathology connected with the concentration of hemoglobin and mithohondrion together with oxygenation degree of blood and tissues, with the pathological hemoglobin's forms and its decomposition products of different levels. Parameter p is an important diagnostic parameter. We consider that it is necessary to include the oxygenation degree and erythrocyte's aggregation parameter to extend the range of common diagnostic parameters of blood by the first rota.

Non-Hodgkin's lymphomas in Turkey: eighteen years' experience at the Hacettepe University.

PubMed

Barista, I; Tekuzman, G; Firat, D; Baltali, E; Kansu, E; Kars, A; Ozisik, Y; Ruacan, S; Uzunalimoğlu, B; Karaağaoğlu, E

1994-12-01

In this retrospective study, 470 patients with non-Hodgkin's lymphoma (NHL) who had been followed in the Hacettepe University Medical Oncology Department between 1973 and 1990, were evaluated to establish their epidemiologic, clinical and therapeutic characteristics. Out of 470 patients, 302 (62.2%) were male and 168 (37.8%) were female. The ages ranged from 16 to 85, with a median of 44 years. Constitutional symptoms were present in 46.4% of the patients. According to the Working Formulation, low, intermediate, and high-grade lymphomas comprised 33.4%, 54.9%, and 12.7%, respectively. The most common extranodal presentation was gastrointestinal. The chemotherapy regimens most commonly used were CVP (cyclophosphamide, vincristine, prednisone), BCNOP (bleomycin, cyclophosphamide, mitoxantrone, vincristine, prednisone), CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and CHOP-Bleo (cyclophosphamide, doxorubicin, vincristine, prednisone, bleomycin). The response rates and the survival figures attained with these regimens were not statistically significantly different (P > 0.05). In the Cox multivariate model, pathologic grade, leukopenia, responsiveness to chemotherapy, bone marrow involvement and age were the important factors influencing the disease-free survival, while responsiveness to chemotherapy, age, presence of constitutional symptoms, pathologic grade, extranodal presentation and stage were the important factors influencing the overall survival. The distribution of NHL according to grade and stage was similar to that in western societies, while constitutional symptoms and lymphomas of the small intestine including immunoproliferative small intestinal disease were more common in Turkey.

Correlation of four potential biomarkers of liver fibrosis with liver function and grade of hepatic fibrosis in a neonatal cholestatic rat model.

PubMed

Tang, Ning; Zhang, Yaping; Liu, Zeyu; Ai, Xuemei; Liang, Qinghong

2017-07-01

The present study investigated the correlation between four serum biomarkers of liver fibrosis, liver function and pathological hepatic fibrosis grade in neonatal cholestatic rats. A total of 38 Sprague‑Dawley rats, aged 3 weeks, were randomly assigned to the experimental group (EG), control group (CG) and the blank control group (BCG). EG received intragastric administration of 1% α‑naphthylisothiocyanate, 75 mg/kg, to induce acute cholestasis liver injury, CG and BCG were set as control groups. Blood samples from all groups were collected 48 h following the procedure. The levels of liver function markers, and four biomarkers of liver fibrosis in serum, were measured and sections of liver tissue were stained for pathological analysis. The results of the present study demonstrated that the degree of hepatic fibrosis in EG, in the serum levels or by pathological analysis, was markedly more evident compared with the CG. Several indices of four biomarkers for liver fibrosis in serum were identified and correlated with the levels of liver function markers. The pathological hepatic fibrosis grade was correlated with γ‑glutamyl transferase (γ‑GT) and Hyaluronic acid (HA). Therefore, HA and γ‑GT were positively correlated with the grade of hepatic fibrosis, indicating their efficacy as biomarkers of infantile cholestatic hepatic fibrosis.

Pathological Gleason prediction through gland ring morphometry in immunofluorescent prostate cancer images

NASA Astrophysics Data System (ADS)

Scott, Richard; Khan, Faisal M.; Zeineh, Jack; Donovan, Michael; Fernandez, Gerardo

2016-03-01

The Gleason score is the most common architectural and morphological assessment of prostate cancer severity and prognosis. There have been numerous quantitative techniques developed to approximate and duplicate the Gleason scoring system. Most of these approaches have been developed in standard H and E brightfield microscopy. Immunofluorescence (IF) image analysis of tissue pathology has recently been proven to be extremely valuable and robust in developing prognostic assessments of disease, particularly in prostate cancer. There have been significant advances in the literature in quantitative biomarker expression as well as characterization of glandular architectures in discrete gland rings. In this work we leverage a new method of segmenting gland rings in IF images for predicting the pathological Gleason; both the clinical and the image specific grade, which may not necessarily be the same. We combine these measures with nuclear specific characteristics as assessed by the MST algorithm. Our individual features correlate well univariately with the Gleason grades, and in a multivariate setting have an accuracy of 85% in predicting the Gleason grade. Additionally, these features correlate strongly with clinical progression outcomes (CI of 0.89), significantly outperforming the clinical Gleason grades (CI of 0.78). This work presents the first assessment of morphological gland unit features from IF images for predicting the Gleason grade.

Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer.

PubMed

Moran-Jones, Kim; Gloss, Brian S; Murali, Rajmohan; Chang, David K; Colvin, Emily K; Jones, Marc D; Yuen, Samuel; Howell, Viive M; Brown, Laura M; Wong, Carol W; Spong, Suzanne M; Scarlett, Christopher J; Hacker, Neville F; Ghosh, Sue; Mok, Samuel C; Birrer, Michael J; Samimi, Goli

2015-12-29

Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer.

Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer

PubMed Central

Moran-Jones, Kim; Gloss, Brian S.; Murali, Rajmohan; Chang, David K.; Colvin, Emily K.; Jones, Marc D.; Yuen, Samuel; Howell, Viive M.; Brown, Laura M.; Wong, Carol W.; Spong, Suzanne M.; Scarlett, Christopher J.; Hacker, Neville F.; Ghosh, Sue; Mok, Samuel C.; Birrer, Michael J.; Samimi, Goli

2015-01-01

Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer. PMID:26575166

Clear cell renal cell carcinoma: validation of World Health Organization/International Society of Urological Pathology grading.

PubMed

Dagher, Julien; Delahunt, Brett; Rioux-Leclercq, Nathalie; Egevad, Lars; Srigley, John R; Coughlin, Geoffrey; Dunglinson, Nigel; Gianduzzo, Troy; Kua, Boon; Malone, Greg; Martin, Ben; Preston, John; Pokorny, Morgan; Wood, Simon; Yaxley, John; Samaratunga, Hemamali

2017-12-01

In 2012, the International Society of Urological Pathology (ISUP) introduced a novel grading system for clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma. This system is incorporated into the latest World Health Organization renal tumour classification, being designated WHO/ISUP grading. This study was undertaken to compare WHO/ISUP and Fuhrman grading and to validate WHO/ISUP grading as a prognostic parameter in a series of clear cell RCC. Analysis of 681 cases of ccRCC showed that 144 tumours could not be assigned a Fuhrman grade on the basis of ambiguous grading features. The application of WHO/ISUP grading resulted in a general down-grading of cases when compared with Fuhrman grading. In a sub-group of 374 cases, for which outcome data were available, 9.3% were WHO/ISUP grade 1, 50.3% were grade 2, 24.1% grade 3 and 16.3% grade 4, while the distribution of Fuhrman grades was 0.4% grade 1, 48.7% grade 2, 29.4% grade 3 and 21.5% grade 4. There were no recurrence/metastases amongst patients with WHO/ISUP grade 1 tumours and there was a significant difference in outcome for WHO/ISUP grades 2, 3 and 4. For Fuhrman grading the cancer-free survival was not significantly different for grade 2 and grade 3 tumours. On multivariate analysis WHO/ISUP grade and pT staging category were found to retain prognostic significance. The study demonstrates that FG cannot be applied in >20% of cases of ccRCC and the WHO/ISUP provides superior prognostic information. © 2017 John Wiley & Sons Ltd.

Preoperative easily misdiagnosed telangiectatic osteosarcoma: clinical-radiologic-pathologic correlations.

PubMed

Gao, Zhen-Hua; Yin, Jun-Qiang; Liu, Da-Wei; Meng, Quan-Fei; Li, Jia-Ping

2013-12-11

To describe the clinical, imaging, and pathologic characteristics and diagnostic methods of telangiectatic osteosarcoma (TOS) for improving the diagnostic level. The authors retrospectively reviewed patient demographics, serum alkaline phosphatase (AKP) levels, preoperative biopsy pathologic reports, pathologic materials, imaging findings, and treatment outcomes from 26 patients with TOS. Patient images from radiography (26 cases) and magnetic resonance (MR) imaging (22 cases) were evaluated by 3 authors in consensus for intrinsic characteristics. There were 15 male and 11 female patients in the study, with an age of 9-32 years (mean age 15.9 years). Eighteen of 26 patients died of lung metastases within 5 years of follow-up. The distal femur was affected more commonly (14 cases, 53.8%). Regarding serum AKP, normal (8 cases) or mildly elevated (18 cases) levels were found before preoperative chemotherapy. Radiographs showed geographic bone lysis without sclerotic margin (26 cases), cortical destruction (26 cases), periosteal new bone formation (24 cases), soft-tissue mass (23 cases), and matrix mineralization (4 cases). The aggressive radiographic features of TOS simulated the appearance of conventional high-grade intramedullary osteosarcoma, though different from aneurysmal bone cyst. MR images demonstrated multiple big (16 cases) or small (6 cases) cystic spaces, fluid-fluid levels (14 cases), soft-tissue mass (22 cases), and thick peripheral and septal enhancement (22 cases). Nine of 26 cases were misdiagnosed as aneurysmal bone cysts by preoperative core-needle biopsy, owing to the absence of viable high-grade sarcomatous cells in the small tissue samples. The aggressive growth pattern with occasional matrix mineralization, and multiple big or small fluid-filled cavities with thick peripheral, septal, and nodular tissue surrounding the fluid-filled cavities are characteristic imaging features of TOS, and these features are helpful in making the correct preoperative diagnosis of TOS.

Phase II trial of cystemustine, a new nitrosourea, as treatment of high-grade brain tumors in adults.

PubMed

Roche, H; Cure, H; Adenis, A; Fargeot, P; Terret, C; Lentz, M A; Madelmont, J C; Fumoleau, P; Hanausk, A; Chollet, P

2000-09-01

This study included 39 patients (37 evaluable, of whom 30 patients with recurrent gliomas and 7 patients with gliomas untreated by radiotherapy); they were enrolled into a phase II trial using a new nitrosourea, cystemustine, administrated every 2 weeks at 60 mg/m2 as a 15 min-infusion. Pathology at inclusion was (WHO classification): 14 glioblastomas, 20 grade 3-4 astrocytomas and 3 grade 3 oligodendrogliomas. Four partial responses have been obtained, giving an overall response rate of 10.8%. Four additional patients had a partial response, which for various reasons was not confirmed 4 weeks later; 12 patients had a stable disease for at least 8 weeks, 15 patients had progressive disease. Of the 4 responses, 2 were with a grade 3 oligodendroglioma and 2 glioblastoma. Toxicity (WHO grading) was mainly hematological: leukopenia (16.2% grade 3-4), neutropenia (29.7% grade 3-4), thrombopenia (27% grade 3-4). No other toxicity greater than grade 2 was observed. In conclusion, cystemustine at 60 mg/m2 has moderate clinical activity in relapsing glioma. Our results warrant further investigation of this agent with an increased dose or modified scheme.

Primary dedifferentiated liposarcoma of the axilla arising in a mixed, well-differentiated and myxoid liposarcoma.

PubMed

Campbell, Garth S; Lawrence, Thomas J; Porter, Scott E; Rezeanu, Luminita

2012-01-01

We describe a case of mixed liposarcoma of the axilla presenting as a high grade undifferentiated sarcoma with areas of well-differentiated and myxoid liposarcoma. MRI demonstrated a lobulated, septated intermuscular mass with marked heterogeneous gadolinium enhancement. A small focus of the tumor demonstrated fat suppressed signal more characteristic of well-differentiated liposarcoma. Pathologic analysis following wide local excision revealed a large, high grade sarcomatous component with highly pleomorphic cells with a thin rim of well-differentiated and myxoid liposarcoma on histologic examination. Dedifferentiated liposarcomas arising outside of the retroperitoneum are very rare, as are dedifferentiated liposarcomas arising from a histologically mixed liposarcoma. In this regard, this case illustrates an unusual combination of tumor location and histology which, to our knowledge, has not previously been reported.

Primary Dedifferentiated Liposarcoma of the Axilla Arising in a Mixed, Well-differentiated and Myxoid Liposarcoma

PubMed Central

Campbell, Garth S.; Lawrence, Thomas J.; Porter, Scott E.; Rezeanu, Luminita

2012-01-01

We describe a case of mixed liposarcoma of the axilla presenting as a high grade undifferentiated sarcoma with areas of well-differentiated and myxoid liposarcoma. MRI demonstrated a lobulated, septated intermuscular mass with marked heterogeneous gadolinium enhancement. A small focus of the tumor demonstrated fat suppressed signal more characteristic of well-differentiated liposarcoma. Pathologic analysis following wide local excision revealed a large, high grade sarcomatous component with highly pleomorphic cells with a thin rim of well-differentiated and myxoid liposarcoma on histologic examination. Dedifferentiated liposarcomas arising outside of the retroperitoneum are very rare, as are dedifferentiated liposarcomas arising from a histologically mixed liposarcoma. In this regard, this case illustrates an unusual combination of tumor location and histology which, to our knowledge, has not previously been reported. PMID:22690275

Yield of Cytology Surveillance After High-Grade Vulvar Intraepithelial Neoplasia or Cancer.

PubMed

Kuroki, Lindsay M; Frolova, Antonina I; Wu, Ningying; Liu, Jingxia; Powell, Matthew; Thaker, Premal H; Massad, L Stewart

2017-07-01

The aim of the study was to estimate the risk of high-grade cervical and vaginal intraepithelial neoplasia (CIN/VAIN 2+) and cancer among women treated surgically for high-grade vulvar intraepithelial neoplasia (HGVIN) and vulvar cancer. We performed a retrospective cohort study of women who underwent surgery for HGVIN/vulvar cancer between 2006 and 2010. Univariate and multivariate analyses using stepwise selection were used to identify correlates of abnormal cytology after treatment for VIN and vulvar cancer. Among 191 women under surveillance for a median of 3.7 years who underwent treatment for HGVIN/vulvar cancer, primary vulvar lesions included VIN 2 (10, 5%), VIN 3 (102, 53%), and carcinoma (79, 41%). During follow-up, 71 (37%) had abnormal cytology, including 47 (25%) low grade, 23 (12%) high grade, and 1 (0.5%) carcinoma. Subsequent risk for VAIN 2+ was 11% (6/57) after previous hysterectomy and 8% for CIN 2+ (10/124) with intact cervix. Overall risk for CIN 3+ was 5%. Correlates of high-grade cytology after treatment for HGVIN/vulvar cancer included nonwhite race (odds ratio [OR] = 3.3, 95% CI = 1.50-7.36), immunodeficiency (OR = 4.2, 95% CI = 1.76-9.94), and previous abnormal cytology (OR = 2.7, 95% CI = 1.29-5.78). Stepwise multivariate analysis revealed immunosuppression as the only significant correlate of high-grade cytology after vulvar treatment (adjusted OR = 3.7, 95% CI = 1.26-10.83). Women with HGVIN/cancer should have cervical/vaginal cytology before vulvar surgery. Those with a negative cervical or vaginal cytology result should undergo cytology testing at 1- to 3-year intervals, based on the threshold for CIN 3+ set forth by the American Society for Colposcopy and Cervical Pathology.

Does the Fuhrman or World Health Organization/International Society of Urological Pathology Grading System Apply to the Xp11.2 Translocation Renal Cell Carcinoma?: A 10-Year Single-Center Study.

PubMed

Liu, Ning; Gan, Weidong; Qu, Feng; Wang, Zhen; Zhuang, Wenyuan; Agizamhan, Sezim; Xu, Linfeng; Yin, Juanjuan; Guo, Hongqian; Li, Dongmei

2018-04-01

The Fuhrman and World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading systems are widely used to predict survival for patients with conventional renal cell carcinoma. To determine the validity of nuclear grading systems (both the Fuhrman and the WHO/ISUP) and the individual components of the Fuhrman grading system in predicting the prognosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC), we identified and followed up 47 patients with Xp11.2 tRCC in our center from January 2007 to June 2017. The Fuhrman and WHO/ISUP grading was reassigned by two pathologists. Nuclear size and shape were determined for each case based on the greatest degree of nuclear pleomorphism using image analysis software. Univariate and multivariate analyses were performed to evaluate the capacity of the grading systems and nuclear parameters to predict overall survival and progression-free survival. On univariate Cox regression analysis, the parameters of nuclear size were associated significantly with overall survival and progression-free survival, whereas the grading systems and the parameters of nuclear shape failed to reach a significant correlation. On multivariate analysis, however, none of the parameters was associated independently with survival. Our findings indicate that neither the Fuhrman nor the WHO/ISUP grading system is applicable to Xp11.2 tRCC. The assessment of nuclear size instead may be novel outcome predictors for patients with Xp11.2 tRCC. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Three-Dimensional Printed Modeling of Diffuse Low-Grade Gliomas and Associated White Matter Tract Anatomy.

PubMed

Thawani, Jayesh P; Singh, Nickpreet; Pisapia, Jared M; Abdullah, Kalil G; Parker, Drew; Pukenas, Bryan A; Zager, Eric L; Verma, Ragini; Brem, Steven

2017-04-01

Diffuse low-grade gliomas (DLGGs) represent several pathological entities that infiltrate and invade cortical and subcortical structures in the brain. To describe methods for rapid prototyping of DLGGs and surgically relevant anatomy. Using high-definition imaging data and rapid prototyping technologies, we were able to generate 3 patient DLGGs to scale and represent the associated white matter tracts in 3 dimensions using advanced diffusion tensor imaging techniques. This report represents a novel application of 3-dimensional (3-D) printing in neurosurgery and a means to model individualized tumors in 3-D space with respect to subcortical white matter tract anatomy. Faculty and resident evaluations of this technology were favorable at our institution. Developing an understanding of the anatomic relationships existing within individuals is fundamental to successful neurosurgical therapy. Imaging-based rapid prototyping may improve on our ability to plan for and treat complex neuro-oncologic pathology. Copyright © 2017 by the Congress of Neurological Surgeons

Prognostic significance of extensive necrosis in renal cell carcinoma.

PubMed

Collins, Jennifer; Epstein, Jonathan I

2017-08-01

Few studies using the current classification of renal cell carcinoma (RCC) have looked at a large number of cases with near total necrosis. We identified 21 cases of resections of RCC with >90% necrosis from the archives of Johns Hopkins Hospital between 2000 and 2015. Patients' mean age was 59 years (43-77) with 16 men (76%); 12 cases (57%) were papillary RCC, 4 clear cell papillary RCC (19%), 4 clear cell RCC (19%), and 1 unclassified with sarcomatoid differentiation (5%). International Society of Urological Pathology (ISUP) nucleolar grade was grade 1 (9 cases) or grade 2 (9 cases). Two cases were ISUP nucleolar grade 3, and 1 case was grade 4. Pathological stage was low (pT1-2) in 20 (95%) with the unclassified RCC with sarcomatoid differentiation RCC stage pT3a. Mean tumor size was 6.3 cm (1.2-17). In 52% (11) of cases, it was difficult to identify viable tumor, requiring multiple sections; 4 cases of papillary RCC were diagnosed in part due to necrotic tumor "ghost" architecture. Follow-up was available in 17 cases (81%) with a mean follow-up of 59 months. Thirteen patients (62%) are alive without disease. The patient with unclassified carcinoma with sarcomatoid differentiation died of cancer, and 2 died due to causes unrelated to cancer. One patient (5%) with low-grade clear cell RCC developed metastases but had a contralateral RCC. In the setting of a low-grade RCC, extensive necrosis does not have an adverse prognosis. In summary, our data, together with a prior study from our institution, comprise one of the largest cohorts of extensively (>90%) necrotic RCCs and suggests that in the setting of a low-grade RCC, it portends a good prognosis (only 2/36 cases showing progression (6%) on follow-up). However, we did identify a single case of high-grade RCC with an adverse prognosis and therefore, careful attention to tumor grade and classification is critical. The presence of tumor necrosis as a prognosticator in RCCs is complex, and despite its well-accepted role as an indicator of poor prognosis, our data would suggest otherwise under specific conditions. Importantly, in diagnosing a renal mass with extensive cystic necrosis, careful and extensive sampling to identify small foci of viable tumor or "ghost" architecture may be necessary for classification. As such, evaluation of its presence should not only be quantitative, but critical attention should be made to tumor grade and stage, whereby in high-grade carcinomas, necrosis likely imparts a worse prognosis; however, in low-grade carcinomas with extensive necrosis, the histological subtype, grade, and stage drive prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical characteristics associated with the intracranial dissemination of gliomas.

PubMed

Cai, Xu; Qin, Jun-Jie; Hao, Shu-Yu; Li, Huan; Zeng, Chun; Sun, Sheng-Jun; Yu, Lan-Bing; Gao, Zhi-Xian; Xie, Jian

2018-03-01

Glioma is the most common malignant tumor of the brain and the intracranial dissemination of gliomas is the late stage of the development of the tumor. However, there is little research in literature on the occurrence of intracranial dissemination of gliomas. In order to provide a reference for clinical work, we carried out this study on intracranial dissemination of glioma. A total of 629 patients with gliomas received tumor resection by the same surgeon from August 2010 to September 2015 were included in this study. The authors performed a retrospective review of the patients and the information regarding clinical features, histopathological results, molecular pathologic results and clinical outcomes was collected and analyzed. In this retrospective study, we found that the intracranial dissemination phenomenon occurred in 53 patients (8.43%). We analyzed the clinical characteristics of patients and found that the age at diagnosis (P = 0.011), WHO grade of the tumor (P < 0.001), and involvement of the corpus callosum (P = 0.010) were associated with the occurrence of dissemination. The higher grade of the tumor, the more prone to disseminate. Deletion of 1p/19q had no significant correlation with the intracranial dissemination. MMP9, Ki-67, and EGFR were highly expressed in tumor cells that caused dissemination, and the level of Ki-67 expression had significance in statistics (P < 0.01). In our study, older age (>40 years), high pathological grade, invasion of the corpus callosum and high levels of Ki-67 expression were risk factors associated with the intracranial dissemination of gliomas. Copyright © 2018 Elsevier B.V. All rights reserved.

Prognostic Factors and Expression of MDM2 in Patients with Primary Extremity Liposarcoma

PubMed Central

Júnior, Rosalvo Zósimo Bispo; de Camargo, Olavo Pires; de Oliveira, Cláudia Regina G. C. M.; Filippi, Renée Zon; Baptista, André Mathias; Caiero, Marcelo Tadeu

2008-01-01

OBJECTIVE The objective of this study was to investigate MDM2 (murine double minute 2) protein expression and evaluate its relationship with some anatomical and pathological aspects, aiming also to identify prognostic factors concerning local recurrence-free survival, metastasis-free survival and overall survival in patients with primary liposarcomas of the extremities. MATERIALS AND METHODS Of 50 patients with primary liposarcomas of the extremities admitted to a Reference Service, between 1968 and 2004, 25 were enrolled in the study, following eligibility and exclusion criteria. RESULTS The adverse factors that influenced the risk for local recurrence in the univariant analysis included male sex (P = 0.023), pleomorphic histological subtype (P = 0.027), and high histological grade (P = 0.007). Concerning metastasis-free survival, age less than 50 years (P = 0.040), male sex (P = 0.040), pleomorphic subtype (P < 0.001), and high histological grade (P = 0.003) had a worse prognosis. Adverse factors for overall survival were age under 50 years (P = 0.040), male sex (P = 0.040), pleomorphic subtype (P < 0.001), and high histological grade (P = 0.003). CONCLUSIONS There was no correlation between immunohistochemically observed MDM2 protein expressions and the anatomical and pathological variables studied. The immunohistochemical expression of MDM2 protein was not considered to have a prognostic value for any of the surviving patients in this study (local recurrence-free survival, metastasis-free survival, or overall survival). The immunoexpression of MDM2 protein was a frequent event in the different subtypes of liposarcomas. PMID:18438568

Pediatric intramedullary spinal cord lesions: Pathological spectrum and outcome of surgery

PubMed Central

Sahu, Rajni Kant; Das, Kuntal Kanti; Bhaisora, Kamlesh Singh; Singh, Amit Kumar; Mehrotra, Anant; Srivastava, Arun Kumar; Sahu, Rabi Narayan; Jaiswal, Awadhesh Kumar; Behari, Sanjay

2015-01-01

Background: Pediatric intramedullary spinal cord lesions are not only rare but also different from adults in a number of aspects. We aimed to study the incidence and the frequencies of various pediatric intramedullary mass lesions, their outcome to treatment and the factors determining their outcome of treatment. Materials and Methods: Thirty-one consecutive children (aged 1–18 years, mean 11.1 years, male: female = 1.8:1) with pathologically proven intramedullary spinal cord lesions treated at our center were studied. Clinico-radiological, histopathological, operative, and outcome data were reviewed retrospectively. The functional status was assessed using the modified McCormick grading system. Results: Gross total tumor excision was performed in 19 patients (61.3%), subtotal in 9 patients (29%), partial excision was performed in 2 (6.5%) patient, and only biopsy was performed in 1 patient (6.5%). There was one peroperative death, 2 patients died at follow-up. Complications included wound related complications (n = 4), transient deterioration in the motor power, and respiratory complication requiring a tracheostomy. Six patients showed recurrence at a mean follow-up of 16.4 months. Developmental tumors, high-grade ependymomas, and incompletely excised grade 2 ependymomas showed a tendency to recur. Conclusions: Children constituted nearly 1/5th (17.4%) of intramedullary spinal cord tumors. Astrocytomas and ependymomas taken together constituted the most common intramedullary spinal lesions in children; however, developmental tumors predominated in the first decade. Children usually presented in good functional grades preoperatively and maintained good grades after surgery. Functional outcome was dependent on the preoperative neurological status and histopathology of the lesions. PMID:26557160

Readability of the Most Commonly Accessed Online Patient Education Materials Pertaining to Pathology of the Hand.

PubMed

Akinleye, Sheriff D; Garofolo-Gonzalez, Garret; Montuori, Michael; Culbertson, Maya Deza; Hashem, Jennifer; Edelstein, David Marc

2017-08-01

The American Medical Association (AMA) and National Institutes of Health (NIH) recommend that patient education materials be written at no higher than a sixth-grade reading level. We examined 100 online educational materials for the 10 hand conditions most commonly treated by hand surgeons, as reported by the American Society for Surgery of the Hand. The listed conditions were carpal tunnel syndrome, basal joint arthritis of the thumb, de Quervain syndrome, Dupuytren's contracture, ganglion cysts, hand fractures, trigger finger, extensor tendon injuries, flexor tendon injuries, and mallet finger. Following a Google search for each condition, we analyzed the 10 most visited websites for each disorder utilizing the Flesch-Kincaid formula. The average grade reading level of the 100 websites studied was 9.49 with a reading ease of 53.03 ("fairly difficult high school"). Only 29% of the websites were at or below the national average of an eighth-grade reading level. Carpal tunnel syndrome had the highest average grade reading level at 10.32 (standard deviation: 1.52), whereas hand fractures had the lowest at 8.14 (2.03). Every hand condition in this study had an average readability at or above the ninth-grade reading level. The most frequently accessed materials for common maladies of the hand exceed both the readability limits recommended by the AMA and NIH, and the average reading ability of most US adults. Therefore, the most commonly accessed websites pertaining to hand pathology may not be comprehended by the audience for which it is intended.

Pathological and 3 Tesla Volumetric Magnetic Resonance Imaging Predictors of Biochemical Recurrence after Robotic Assisted Radical Prostatectomy: Correlation with Whole Mount Histopathology.

PubMed

Tan, Nelly; Shen, Luyao; Khoshnoodi, Pooria; Alcalá, Héctor E; Yu, Weixia; Hsu, William; Reiter, Robert E; Lu, David Y; Raman, Steven S

2018-05-01

We sought to identify the clinical and magnetic resonance imaging variables predictive of biochemical recurrence after robotic assisted radical prostatectomy in patients who underwent multiparametric 3 Tesla prostate magnetic resonance imaging. We performed an institutional review board approved, HIPAA (Health Insurance Portability and Accountability Act) compliant, single arm observational study of 3 Tesla multiparametric magnetic resonance imaging prior to robotic assisted radical prostatectomy from December 2009 to March 2016. Clinical, magnetic resonance imaging and pathological information, and clinical outcomes were compiled. Biochemical recurrence was defined as prostate specific antigen 0.2 ng/cc or greater. Univariate and multivariate regression analysis was performed. Biochemical recurrence had developed in 62 of the 255 men (24.3%) included in the study at a median followup of 23.5 months. Compared to the subcohort without biochemical recurrence the subcohort with biochemical recurrence had a greater proportion of patients with a high grade biopsy Gleason score, higher preoperative prostate specific antigen (7.4 vs 5.6 ng/ml), intermediate and high D'Amico classifications, larger tumor volume on magnetic resonance imaging (0.66 vs 0.30 ml), higher PI-RADS® (Prostate Imaging-Reporting and Data System) version 2 category lesions, a greater proportion of intermediate and high grade radical prostatectomy Gleason score lesions, higher pathological T3 stage (all p <0.01) and a higher positive surgical margin rate (19.3% vs 7.8%, p = 0.016). On multivariable analysis only tumor volume on magnetic resonance imaging (adjusted OR 1.57, p = 0.016), pathological T stage (adjusted OR 2.26, p = 0.02), positive surgical margin (adjusted OR 5.0, p = 0.004) and radical prostatectomy Gleason score (adjusted OR 2.29, p = 0.004) predicted biochemical recurrence. In this cohort tumor volume on magnetic resonance imaging and pathological variables, including Gleason score, staging and positive surgical margins, significantly predicted biochemical recurrence. This suggests an important new imaging biomarker. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Disseminated pleomorphic myofibrosarcoma in a grizzly bear (Ursus arctos horribilis).

PubMed

Mete, A; Woods, L; Famini, D; Anderson, M

2012-01-01

The pathological and diagnostic features of a widely disseminated pleomorphic high-grade myofibroblastic sarcoma are described in a 23-year-old male brown bear (Ursus arctos horribilis). Firm, solid, white to tan neoplastic nodules, often with cavitated or soft grey-red necrotic centres, were observed throughout most internal organs, subcutaneous tissues and skeletal muscles on gross examination. Microscopically, the tumour consisted of pleomorphic spindle cells forming interlacing fascicles with a focal storiform pattern with large numbers of bizarre polygonal multinucleate cells, frequently within a collagenous stroma. Immunohistochemistry, Masson's trichrome stain and transmission electron microscopy designated the myofibroblast as the cell of origin. This is the first case of a high-grade myofibrosarcoma in a grizzly bear. Published by Elsevier Ltd.

Anti-inflammatory use may not negatively impact oncologic outcomes following intravesical BCG for high-grade non-muscle-invasive bladder cancer.

PubMed

Singla, Nirmish; Haddad, Ahmed Q; Passoni, Niccolo M; Meissner, Matthew; Lotan, Yair

2017-01-01

To evaluate whether anti-inflammatory agents affect outcomes in patients receiving intravesical BCG therapy for high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). We reviewed the records of 203 patients in a prospective database of HG NMIBC from 2006 to 2012 at a single institution. Patients who had muscle-invasive disease (n = 32), low-grade pathology (n = 4), underwent early cystectomy within 3 months (n = 25), had <3 months of follow-up (n = 11), or did not receive an induction course of intravesical BCG (n = 32) were excluded. Clinicopathologic data were tabulated including demographics, comorbidities, pathologic stage and grades, intravesical therapy, and concomitant use of aspirin, NSAIDs, COX inhibitors, and statins. Multivariate Cox regression analysis explored predictive factors for recurrence, progression (stage progression or progression to cystectomy), cancer-specific survival (CSS), and overall survival (OS). Ninety-nine patients with HG NMIBC who received at least one induction course of intravesical BCG were identified, with median follow-up of 31.4 months. There were 20 (20.2 %) deaths, including 6 (6.1 %) patients with bladder cancer-related mortality. 13 % patients experienced tumor progression and 27 % underwent cystectomy following failure of intravesical therapy. Anti-inflammatory use included statins (65 %), aspirin (63 %), or non-aspirin NSAIDs/COX inhibitors (26 %). Anti-inflammatory use was not significantly predictive of recurrence, progression, or mortality outcomes on Cox regression. CIS stage was associated with higher progression, while age, BMI, and Charlson score were independent predictors of overall mortality. Despite speculation of inhibitory effects on BCG immunomodulation there was no evidence that anti-inflammatory agents impacted oncologic outcomes in patients receiving BCG for HG NMIBC.

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

PubMed

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

2012-12-01

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

Accuracy of reading liquid based cytology slides using the ThinPrep Imager compared with conventional cytology: prospective study

PubMed Central

d'Assuncao, Jefferson; Irwig, Les; Macaskill, Petra; Chan, Siew F; Richards, Adele; Farnsworth, Annabelle

2007-01-01

Objective To compare the accuracy of liquid based cytology using the computerised ThinPrep Imager with that of manually read conventional cytology. Design Prospective study. Setting Pathology laboratory in Sydney, Australia. Participants 55 164 split sample pairs (liquid based sample collected after conventional sample from one collection) from consecutive samples of women choosing both types of cytology and whose specimens were examined between August 2004 and June 2005. Main outcome measures Primary outcome was accuracy of slides for detecting squamous lesions. Secondary outcomes were rate of unsatisfactory slides, distribution of squamous cytological classifications, and accuracy of detecting glandular lesions. Results Fewer unsatisfactory slides were found for imager read cytology than for conventional cytology (1.8% v 3.1%; P<0.001). More slides were classified as abnormal by imager read cytology (7.4% v 6.0% overall and 2.8% v 2.2% for cervical intraepithelial neoplasia of grade 1 or higher). Among 550 patients in whom imager read cytology was cervical intraepithelial neoplasia grade 1 or higher and conventional cytology was less severe than grade 1, 133 of 380 biopsy samples taken were high grade histology. Among 294 patients in whom imager read cytology was less severe than cervical intraepithelial neoplasia grade 1 and conventional cytology was grade 1 or higher, 62 of 210 biopsy samples taken were high grade histology. Imager read cytology therefore detected 71 more cases of high grade histology than did conventional cytology, resulting from 170 more biopsies. Similar results were found when one pathologist reread the slides, masked to cytology results. Conclusion The ThinPrep Imager detects 1.29 more cases of histological high grade squamous disease per 1000 women screened than conventional cytology, with cervical intraepithelial neoplasia grade 1 as the threshold for referral to colposcopy. More imager read slides than conventional slides were satisfactory for examination and more contained low grade cytological abnormalities. PMID:17604301

What Happened to the "Superior Abilities" in Adults with Dyslexia and High IQs? A Behavioral and Neurological Illustration

ERIC Educational Resources Information Center

Gilger, Jeffrey W.; Olulade, Olumide A.

2013-01-01

Observable behavior, such as test scores, is the gold standard by which we make judgments about levels of function, grade placements, and the presence/absence of pathology. Individual differences in test performance have long intrigued researchers and clinicians, and some have noted how people can come up with essentially the same answers using…

Quantitative assessment of hTERT mRNA expression in dysplastic nodules of HBV-related hepatocarcinogenesis.

PubMed

Oh, Bong-Kyeong; Kim, Young-Joo; Park, Young Nyun; Choi, Jinsub; Kim, Kyung Sik; Park, Chanil

2006-04-01

Telomerase reverse transcriptase (hTERT) is the rate-limiting determinant of telomerase, which is critical for carcinogenesis. Dysplastic nodules (DNs) appear to be preneoplastic lesions of hepatocellular carcinomas (HCCs). In this study, in order to characterize DNs, hTERT mRNA, hTERT gene dosage, and mRNA for c-myc, a transcriptional activator of hTERT were studied in human multi-step hepatocarcinogenesis. Fifty four hepatic nodules including 5 large regenerative nodules, 14 low-grade DNs, 7 high-grade DNs, 11 DNs with HCC foci and 17 HCCs, 23 livers with chronic hepatitis/cirrhosis, and 6 normal livers were examined. Transcript levels were measured by real-time quantitative RT-PCR and gene dosages by real-time PCR and Southern blotting. The hTERT mRNA levels increased with the progression of hepatocarcinogenesis, and a significant induction in the transition between low- and high-grade DNs was seen. Most high-grade DNs strongly expressed hTERT mRNA at levels similar to those of HCCs. Twenty-one percent of low-grade DNs had high levels of hTERT mRNA, up to those of high-grade DNs and there was no difference in the pathological features between low-grade DNs with and without increased hTERT mRNA levels. No correlation was found between hTERT mRNA levels, hTERT gene dosage, and c-myc mRNA levels. These results suggest that the induction of hTERT mRNA is an important early event and that its measurement by real-time quantitative RT-PCR is a useful tool to detect premalignant/malignant tendencies in hepatic nodules. However, hTERT gene dosage and c-myc expression are not the main mechanisms regulating hTERT expression in hepatocarcinogenesis.

Anisotropy of anomalous diffusion improves the accuracy of differentiating low- and high-grade cerebral gliomas.

PubMed

Xu, Boyan; Su, Lu; Wang, Zhenxiong; Fan, Yang; Gong, Gaolang; Zhu, Wenzhen; Gao, Peiyi; Gao, Jia-Hong

2018-04-17

Anomalous diffusion model has been introduced and shown to be beneficial in clinical applications. However, only the directionally averaged values of anomalous diffusion parameters were investigated, and the anisotropy of anomalous diffusion remains unexplored. The aim of this study was to demonstrate the feasibility of using anisotropy of anomalous diffusion for differentiating low- and high-grade cerebral gliomas. Diffusion MRI images were acquired from brain tumor patients and analyzed using the fractional motion (FM) model. Twenty-two patients with histopathologically confirmed gliomas were selected. An anisotropy metric for the FM-related parameters, including the Noah exponent (α) and the Hurst exponent (H), was introduced and their values were statistically compared between the low- and high-grade gliomas. Additionally, multivariate logistic regression analysis was performed to assess the combination of the anisotropy metric and the directionally averaged value for each parameter. The diagnostic performances for grading gliomas were evaluated using a receiver operating characteristic (ROC) analysis. The Hurst exponent H was more anisotropic in high-grade than in low-grade gliomas (P = 0.015), while no significant difference was observed for the anisotropy of α. The ROC analysis revealed that larger areas under the ROC curves were produced for the combination of α (1) and the combination of H (0.813) compared with the directionally averaged α (0.979) and H (0.594), indicating an improved performance for tumor differentiation. The anisotropy of anomalous diffusion can provide distinctive information and benefit the differentiation of low- and high-grade gliomas. The utility of anisotropic anomalous diffusion may have an improved effect for investigating pathological changes in tissues. Copyright © 2018 Elsevier Inc. All rights reserved.

Expression of P-Akt, NFkappaB and their correlation with human papillomavirus infection in cervical carcinoma.

PubMed

Du, C X; Wang, Y

2012-01-01

To investigate the expression of P-Akt and NFkappaB and their correlation with human papillomavirus (HPV) infection in cervical carcinoma. Expression of P-Akt and NFkappaB was detected by an immunohistochemical SP technique with HPV DNA detetion by PCR in 26 cases of cervical carcinoma tissues, 18 cases of cervical intraepithelial neoplasia tissues (CINI / n = 5, CINII / n = 3, CINIII / n = 10) and 19 cases of chronic cervicitis tissues. The different expressions of P-Akt and NFkappaB were compared in different pathological types of cervical carcinoma (cervical squamous cell carcinoma, cervical adenocarcinoma), different pathological grading (high, medium, poorly differentiated) and different clinical stage (FIGO I to IV). The relationships between P-Akt and NFkappaB, respectively, with HPV infection in cervical carcinoma were analyzed. The positive expression rate of P-Akt in chronic cervicitis tissues, CIN and cervical carcinoma tissues was 21.05%, 66.67%, and 92.31%, respectively. There was no obvious difference in the expression of P-Akt in cervical carcinoma in different pathological types or in pathological grading and no obvious difference in different clinical stages. The positive expression rate of NFkappaB in chronic cervicitis tissues, CIN and cervical carcinoma tissues was 10.52%, 72.22% and 96.15%, respectively; there was no statistically significant difference among the groups for different pathological types and there was no obvious difference in different pathological grading or different clinical stage. There was an obviously positive correlation between P-Akt and NFkappaB expression rate and degree of disease (r = 0.998, p < 0.05). Cervical carcinoma and CIN cases totaled 44; the positive expression rate of P-Akt was 87.55% in 32 cases of positive HPV-DNA of the 44 cases, and the positive expression rate of P-Akt was only 16.70% in 12 cases of negative HPV-DNA of the 44 cases. The positive expression rate of NFkappaB was obviously higher in the HPV DNA positive than in the HPV-DNA negative cases. There was a statistically significant difference among the groups (p < 0.05). The positive expression rate of P-Akt and NFkappaB was closely related with cervical disease extent, and closely related with HPV infection in cervical carcinoma. This study suggests that P-Akt and NFkappaB more probably play an important role in the occurrence of cervical carcinoma.

Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma

PubMed Central

Ayadi, Lobna; Khabir, Abdelmajid; Amouri, Habib; Karray, Sondes; Dammak, Abdallah; Guermazi, Mohamed; Boudawara, Tahya

2008-01-01

Background Breast carcinoma is a disease with a tremendous heterogeneity in its clinical behavior. Newer prognostic factors and predictors of response to therapy are needed. The aim of this study was to evaluate the expression of HER-2, estrogen receptor (ER) and progesterone receptors (PR) in breast carcinoma and to compare it with other prognostic parameters such as histological type and grade, tumor size, patients' age, and lymph node metastases. Patients and methods This is a retrospective study conducted in the department of pathology at Sfax University Hospital. Confirmed 155 Cases of breast carcinoma were reviewed in the period between January 2000 and December 2004. We used immunohistochemistry to evaluate the expression of HER-2, ER, and PR receptor and Chi-square and Fisher exact test to correlate immunohistochemical findings with prognostic parameters for breast carcinoma such as patients' age, tumor size, histological type, histological grade and lymph node status. Results The mean age of patients was 51.5 years, ranging from 22 to 89 years. 80 (51.6%) of the patients were below 50 years. The percentage of expression of HER-2, ER and PR was 26, 59.4, and 52.3%, respectively. HER-2 was over-expressed (3+) in 18.1% of the cases, was inversely related to ER expression (p = 0.00) and to PR expression (p = 0.048). This over-expression was also associated with a high tumor grade with marginal significance (p = 0.072). A negative correlation was noted between ER and PR expression and SBR grade (p = 0.000) and ER and age (p = 0.002). Conclusion HER-2 over-expression was observed in 18.1% of Tunisian breast carcinoma affecting female patients. This group presents apparently an aggressive form of breast carcinoma with high histological grade and negative ER. PMID:18945339

Modern Problems: Sociology Units. An Experimental Program for Grade 12.

ERIC Educational Resources Information Center

Carlson, Marshall; Fennig, Lois

GRADES OR AGES: Grade 12. SUBJECT MATTER: Sociology; modern problems. ORGANIZATION AND PHYSICAL APPEARANCE: The guide contains two units, one on the problems of minority groups and the other on social pathology. Sub-sections of unit 2 include crime and criminals, criminal investigation, gun control, U.S. criminal law, criminal procedure,…

[Guidelines for adult diffuse gliomas WHO grade II, III and IV: pathology and biology. Société franc¸aise de neuropathologie . Réseau de neuro-oncologie pathologique].

PubMed

Figarella-Branger, Dominique; Labrousse, François; Mohktari, Karima

2012-10-01

Pathological diagnosis plays a major role in the therapeutic management of adult diffuse gliomas. It is based on the histopathological analysis of a representative specimen. Therefore pathologists might be aware of the neuroradiological features of the lesions. Pathologists play a major role in the management of biological resources. Pathologists should classify adult gliomas according to WHO 2007 classification (histological subtype and grade). In addition, in order to provide the histomolecular classification of adult gliomas, search for molecular markers of diagnostic, prognostic or predictive of therapeutic responses must be performed by appropriate and validated immunohistochemical and molecular techniques. In all diffuse gliomas, whatever their grade, search for IDH1 R132H and P53 expression is required. Search for IDH1 minor mutations and IDH2 mutations is required in grade II and III IDH1 R132H negative gliomas whereas 1p19q codeletion should be searched for in grade II and III gliomas with an oligodendroglial component. Search for EGFR amplification and MGMT promoter methylation is recommended. It is strongly recommended to fill the standardized form for pathology and molecular features (validated by the French Society of Neuropathology) in all adult diffuse gliomas. Copyright © 2012. Published by Elsevier Masson SAS.

Primary central chondrosarcoma of long bone, limb girdle and trunk: Analysis of 174 cases by numerical scoring on histology

PubMed Central

Nakashima, Yasuaki; Mano, Masayuki; Tomita, Yasuhiko; Nagasaki, Ikumitsu; Kubo, Toshikazu; Araki, Nobuhito; Haga, Hironori; Toguchida, Junya; Ueda, Takafumi; Sakuma, Toshiko; Imahori, Masaya; Morii, Eiichi; Yoshikawa, Hideki; Tsukamoto, Yoshitane; Futani, Hiroyuki; Wakasa, Kenichi; Hoshi, Manabu; Hamada, Shinshichi; Takeshita, Hideyuki; Inoue, Takeshi; Aono, Masanari; Kawabata, Kenji; Murata, Hiroaki; Katsura, Kanade; Urata, Yoji; Ueda, Hideki; Yanagisawa, Akio

2015-01-01

The aims of this study were: (i) to elucidate clinicopathological characteristics of pcCHS of long bones (L), limb girdles (LG) and trunk (T) in Japan; (ii) to investigate predictive pathological findings for outcome of pcCHS of L, LG and T, objectively; and (iii) to elucidate a discrepancy of grade between biopsy and resected specimens. Clinicopathological profiles of 174 pcCHS (79 male, 95 female), of L, LG, and T were retrieved. For each case, a numerical score was given to 18 pathological findings. The average age was 50.5 years (15–80 years). Frequently involved sites were femur, humerus, pelvis and rib. The 5‐year and 10‐year disease‐specific survival (DSS) rates [follow‐up: 1–258 months (average 65.5)] were 87.0% and 80.4%, respectively. By Cox hazards analysis on pathological findings, age, sex and location, histologically higher grade and older age were unfavorable predictors, and calcification was a favorable predictor in DSS. The histological grade of resected specimen was higher than that of biopsy in 37.7% (26/69 cases). In conclusion, higher histological grade and older age were predictors for poor, but calcification was for good prognosis. Because there was a discrepancy in grade between biopsy and resected specimens, comprehensive evaluation is necessary before definitive operation for pcCHS. PMID:26126783

Non-Hodgkin's lymphomas of the tonsil: a retrospective analysis of twenty-eight patients with primary tonsillary lymphoma.

PubMed

Barişta, I; Tekuzman, G; Güllü, I; Baltali, E; Kars, A; Ozişik, Y; Güler, N; Celik, I; Atahan, I L; Firat, D

1995-01-01

To analyze the clinical and therapeutic aspects of patients with primary tonsillary non-Hodgkin's lymphoma. Twenty-eight patients with primary tonsillary non-Hodgkin's lymphoma who had been followed in the Hacettepe Oncology Institute between 1974 and 1992 were retrospectively analyzed. Fifteen patients were male, 13 were female. Median age was 55 years. Constitutional symptoms were present in 10 patients (35.7%). Stages according to the Ann Arbor classification were I and II in 12 and 16 patients, respectively. According to the Rappaport classification, poorly differentiated lymphocytic was the most common pathologic subgroup (42.9%). Grades according to the Working Formulation were low, intermediate and high in 3, 22 and 3 patients, respectively. Twenty-two patients had received chemotherapy. Cyclophosphamide, vincristine and prednisone (CVP), and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were the regimens most commonly employed. Eighteen patients received radiotherapy to Waldeyer's ring and neck. Eight patients achieved remission with chemotherapy plus radio-therapy, 7 patients with chemotherapy alone, and 5 patients with radiotherapy alone. In addition to the 20 patients who achieved complete remission, 3 patients achieved partial remission; the overall response rate was 82.1%. The response rates and survival attained with the combined modality, chemotherapy, or radiotherapy alone were not statistically different (P > 0.05). The median follow-up was 14 months. Overall and disease-free survival at 5 years were 62.6% and 77.6%, respectively. Pathologic grade was the most important prognostic factor influencing overall survival in the Cox multivariate model. Poorly differentiated lymphocytic lymphomas were the most common pathologic subtype, and pathologic grade was the most important prognostic factor to influence survival in the present study. Although combined modality treatment did not appear to be superior to chemotherapy or radiotherapy alone, a larger number of patients is needed to draw definite conclusions.

Bronchoalveolar carcinoma: clinical, radiologic, and pathologic factors and survival.

PubMed

Okubo, K; Mark, E J; Flieder, D; Wain, J C; Wright, C D; Moncure, A C; Grillo, H C; Mathisen, D J

1999-10-01

The principal feature of bronchoalveolar carcinoma is that it spreads along airways or aerogenously with multifocality, but many issues are unresolved. We studied 119 patients with pathologically confirmed bronchoalveolar carcinoma. Symptoms, smoking status, radiologic findings, the size of tumor, operative procedures, and complications were reviewed. We studied the pathologic features: presence or absence of aerogenous spread, patterns of growth, cell type, nuclear grade, mitosis, rate of bronchoalveolar carcinoma in adenocarcinoma, and lymphocyte infiltration. The correlation among clinical, radiologic, and pathologic findings was examined, and the factors affecting survival were analyzed. Symptomatic patients had more infiltrative radiographic features, and asymptomatic patients tended to have more mass-like features (P <.0001). Tumors with radiographically infiltrating lesions tended to have mucinous histologic features (P =.006). Tumors with mass lesions by radiograph tended to have nonmucinous and sclerosing histologic features (P =.003). Aerogenous spread was seen in 94% of specimens. The presence of a variety of cell types suggested multiple clonal origin. The overall survival in those patients undergoing resection was 69.1% at 5 years and 56.5% at 10 years. The significant factors affecting survival were radiologic presence of a mass or infiltrate, pathologic findings of the presence of sclerosis, association with a scar, the rate of bronchoalveolar carcinoma in adenocarcinoma, lymphocyte infiltration grade, nodal involvement, and status of complete resection. Mitosis or nuclear grade of tumor cells did not correlate with survival. Bronchoalveolar carcinoma showed good overall survival with appropriate surgical procedures. Certain radiologic or pathologic findings correlated with survival. These findings may enhance the ability to predict long-term survival.

A natural language processing program effectively extracts key pathologic findings from radical prostatectomy reports.

PubMed

Kim, Brian J; Merchant, Madhur; Zheng, Chengyi; Thomas, Anil A; Contreras, Richard; Jacobsen, Steven J; Chien, Gary W

2014-12-01

Natural language processing (NLP) software programs have been widely developed to transform complex free text into simplified organized data. Potential applications in the field of medicine include automated report summaries, physician alerts, patient repositories, electronic medical record (EMR) billing, and quality metric reports. Despite these prospects and the recent widespread adoption of EMR, NLP has been relatively underutilized. The objective of this study was to evaluate the performance of an internally developed NLP program in extracting select pathologic findings from radical prostatectomy specimen reports in the EMR. An NLP program was generated by a software engineer to extract key variables from prostatectomy reports in the EMR within our healthcare system, which included the TNM stage, Gleason grade, presence of a tertiary Gleason pattern, histologic subtype, size of dominant tumor nodule, seminal vesicle invasion (SVI), perineural invasion (PNI), angiolymphatic invasion (ALI), extracapsular extension (ECE), and surgical margin status (SMS). The program was validated by comparing NLP results to a gold standard compiled by two blinded manual reviewers for 100 random pathology reports. NLP demonstrated 100% accuracy for identifying the Gleason grade, presence of a tertiary Gleason pattern, SVI, ALI, and ECE. It also demonstrated near-perfect accuracy for extracting histologic subtype (99.0%), PNI (98.9%), TNM stage (98.0%), SMS (97.0%), and dominant tumor size (95.7%). The overall accuracy of NLP was 98.7%. NLP generated a result in <1 second, whereas the manual reviewers averaged 3.2 minutes per report. This novel program demonstrated high accuracy and efficiency identifying key pathologic details from the prostatectomy report within an EMR system. NLP has the potential to assist urologists by summarizing and highlighting relevant information from verbose pathology reports. It may also facilitate future urologic research through the rapid and automated creation of large databases.

Significance of perivascular tumour cells defined by CD109 expression in progression of glioma.

PubMed

Shiraki, Yukihiro; Mii, Shinji; Enomoto, Atsushi; Momota, Hiroyuki; Han, Yi-Peng; Kato, Takuya; Ushida, Kaori; Kato, Akira; Asai, Naoya; Murakumo, Yoshiki; Aoki, Kosuke; Suzuki, Hiromichi; Ohka, Fumiharu; Wakabayashi, Toshihiko; Todo, Tomoki; Ogawa, Seishi; Natsume, Atsushi; Takahashi, Masahide

2017-12-01

In the progression of glioma, tumour cells often exploit the perivascular microenvironment to promote their survival and resistance to conventional therapies. Some of these cells are considered to be brain tumour stem cells (BTSCs); however, the molecular nature of perivascular tumour cells has not been specifically clarified because of the complexity of glioma. Here, we identified CD109, a glycosylphosphatidylinositol-anchored protein and regulator of multiple signalling pathways, as a critical regulator of the progression of lower-grade glioma (World Health Organization grade II/III) by clinicopathological and whole-genome sequencing analysis of tissues from human glioma. The importance of CD109-positive perivascular tumour cells was confirmed not only in human lower-grade glioma tissues but also in a mouse model that recapitulated human glioma. Intriguingly, BTSCs isolated from mouse glioma expressed high levels of CD109. CD109-positive BTSCs exerted a proliferative effect on differentiated glioma cells treated with temozolomide. These data reveal the significance of tumour cells that populate perivascular regions during glioma progression, and indicate that CD109 is a potential therapeutic target for the disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Predictive model for inflammation grades of chronic hepatitis B: Large-scale analysis of clinical parameters and gene expressions.

PubMed

Zhou, Weichen; Ma, Yanyun; Zhang, Jun; Hu, Jingyi; Zhang, Menghan; Wang, Yi; Li, Yi; Wu, Lijun; Pan, Yida; Zhang, Yitong; Zhang, Xiaonan; Zhang, Xinxin; Zhang, Zhanqing; Zhang, Jiming; Li, Hai; Lu, Lungen; Jin, Li; Wang, Jiucun; Yuan, Zhenghong; Liu, Jie

2017-11-01

Liver biopsy is the gold standard to assess pathological features (eg inflammation grades) for hepatitis B virus-infected patients although it is invasive and traumatic; meanwhile, several gene profiles of chronic hepatitis B (CHB) have been separately described in relatively small hepatitis B virus (HBV)-infected samples. We aimed to analyse correlations among inflammation grades, gene expressions and clinical parameters (serum alanine amino transaminase, aspartate amino transaminase and HBV-DNA) in large-scale CHB samples and to predict inflammation grades by using clinical parameters and/or gene expressions. We analysed gene expressions with three clinical parameters in 122 CHB samples by an improved regression model. Principal component analysis and machine-learning methods including Random Forest, K-nearest neighbour and support vector machine were used for analysis and further diagnosis models. Six normal samples were conducted to validate the predictive model. Significant genes related to clinical parameters were found enriching in the immune system, interferon-stimulated, regulation of cytokine production, anti-apoptosis, and etc. A panel of these genes with clinical parameters can effectively predict binary classifications of inflammation grade (area under the ROC curve [AUC]: 0.88, 95% confidence interval [CI]: 0.77-0.93), validated by normal samples. A panel with only clinical parameters was also valuable (AUC: 0.78, 95% CI: 0.65-0.86), indicating that liquid biopsy method for detecting the pathology of CHB is possible. This is the first study to systematically elucidate the relationships among gene expressions, clinical parameters and pathological inflammation grades in CHB, and to build models predicting inflammation grades by gene expressions and/or clinical parameters as well. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gleason Score Determination with Transrectal Ultrasound-Magnetic Resonance Imaging Fusion Guided Prostate Biopsies--Are We Gaining in Accuracy?

PubMed

Lanz, Camille; Cornud, François; Beuvon, Frédéric; Lefèvre, Arnaud; Legmann, Paul; Zerbib, Marc; Delongchamps, Nicolas Barry

2016-01-01

We evaluated the accuracy of prostate magnetic resonance imaging- transrectal ultrasound targeted biopsy for Gleason score determination. We selected 125 consecutive patients treated with radical prostatectomy for a clinically localized prostate cancer diagnosed on magnetic resonance imaging-transrectal ultrasound targeted biopsy and/or systematic biopsy. On multiparametric magnetic resonance imaging each suspicious area was graded according to PI-RADS™ score. A correlation analysis between multiparametric magnetic resonance imaging and pathological findings was performed. Factors associated with determining the accuracy of Gleason score on targeted biopsy were statistically assessed. Pathological analysis of radical prostatectomy specimens detected 230 tumor foci. Multiparametric magnetic resonance imaging detected 151 suspicious areas. Of these areas targeted biopsy showed 126 cancer foci in 115 patients, and detected the index lesion in all of them. The primary Gleason grade, secondary Gleason grade and Gleason score of the 126 individual tumors were determined accurately in 114 (90%), 75 (59%) and 85 (67%) cases, respectively. Maximal Gleason score was determined accurately in 80 (70%) patients. Gleason score determination accuracy on targeted biopsy was significantly higher for low Gleason and high PI-RADS score tumors. Magnetic resonance imaging-transrectal ultrasound targeted biopsy allowed for an accurate estimation of Gleason score in more than two-thirds of patients. Gleason score misclassification was mostly due to a lack of accuracy in the determination of the secondary Gleason grade. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Genomic Biomarkers for the Prediction of Stage and Prognosis of Upper Tract Urothelial Carcinoma.

PubMed

Bagrodia, Aditya; Cha, Eugene K; Sfakianos, John P; Zabor, Emily C; Bochner, Bernard H; Al-Ahmadie, Hikmat A; Solit, David B; Coleman, Jonathan A; Iyer, Gopa; Scott, Sasinya N; Shah, Ronak; Ostrovnaya, Irina; Lee, Byron; Desai, Neil B; Ren, Qinghu; Rosenberg, Jonathan E; Dalbagni, Guido; Bajorin, Dean F; Reuter, Victor E; Berger, Michael F

2016-06-01

Genomic characterization of radical nephroureterectomy specimens in patients with upper tract urothelial carcinoma may allow for thoughtful integration of systemic and targeted therapies. We sought to determine whether genomic alterations in upper tract urothelial carcinoma are associated with adverse pathological and clinical outcomes. Next generation exon capture sequencing of 300 cancer associated genes was performed in 83 patients with upper tract urothelial carcinoma. Genomic alterations were assessed individually and also grouped into core signal transduction pathways or canonical cell functions for association with clinicopathological outcomes. Binary outcomes, including grade (high vs low), T stage (pTa/T1/T2 vs pT3/T4) and organ confined status (pT2 or less and N0/Nx vs greater than pT2 or N+) were assessed with the Kruskal-Wallis and Fisher exact tests as appropriate. Associations between alterations and survival were estimated using the Kaplan-Meier method and Cox regression. Of the 24 most commonly altered genes in 9 pathways TP53/MDM2 alterations and FGFR3 mutations were the only 2 alterations uniformly associated with high grade, advanced stage, nonorgan confined disease, and recurrence-free and cancer specific survival. TP53/MDM2 alterations were associated with adverse clinicopathological outcomes whereas FGFR3 mutations were associated with favorable outcomes. We created a risk score using TP53/MDM2 and FGFR3 status that was able to discriminate between adverse pathological and clinical outcomes, including in the subset of patients with high grade disease. The study is limited by small numbers and lack of validation. Our data indicate that specific genomic alterations in radical nephroureterectomy specimens correlate with tumor grade, stage and cancer specific survival outcomes. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Prevalence of altered mismatch repair protein nuclear expression detected by immunohistochemistry on adenomas with high-grade dysplasia and features associated with this risk in a population-based study].

PubMed

Basterra, Marta; Gomez, Marta; Mercado, María Del Rosario; Irisarri, Rebeca; Amorena, Edurne; Arrospide, Arantzazu; Montes, Marta; Aisa, Gregorio; Cambra, Koldo Iñaki; Urman, Jesús

2016-10-01

Alteration of mismatch repair system protein expression detected by immunohistochemistry (IHQ) in tumoural tissue is a useful technique for Lynch Syndrome (LS) screening. A recent review proposes LS screening through immunohistochemical study not only in all diagnosed cases of colorectal cancer (CRC) but also in advanced adenomas, especially in young patients. To assess the prevalence of altered IHQ carried out in all adenomas with high-grade dysplasia (HGD) diagnosed in our community in 2011, as well as the variables associated with this alteration. We included all the cases of adenomatous polyps with HGD diagnosed in the three public pathology laboratories of Navarre during 2011 and performed a statistical study to assess the association between different patient and lesion characteristics and altered IHQ results. A total of 213 colonic adenomas with HGD were diagnosed, and 26 (12.2%) cases were excluded from the final analysis (2 known LS, 22 without IHQ study and 2 with inconclusive IHQ studies). The final number of adenomas included was 187. Pathologic results were found in 10 cases (5.35%)-6 cases in MLH1 and PMS2, 2 cases in PMS2, 1 case in MSH6 and 1 case in MSH2 and MSH6. The factors showing a statistically significant association with the presence of abnormal proteins were the synchronous presence of CRC, the presence of only one advanced adenoma, proximal location of HGD and age <50 years. The percentage of pathologic nuclear expression found in IHQ is high. Consequently, screening of all diagnosed HGD could be indicated, especially in young patients, with a single AA and proximal HGD. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

Adenoid Cystic Carcinoma of the Uterine Cervix: A Report of 2 Cases

PubMed Central

Kharmoum, Jinane; Ech-Charif, Soumaya; El Khannoussi, Basma

2017-01-01

Adenoid cystic carcinoma is malignant tumor that exceptionally occurs in the uterine cervix. It is mostly seen in postmenopausal women and has an aggressive clinical course. We report two cases of an adenoid cystic carcinoma associated with a high grade squamous intraepithelial lesion and invasive squamous cell carcinoma of the uterine cervix and discuss briefly its clinical and pathological characteristics. PMID:28348909

ESR1, ERBB2, and Ki67 mRNA expression predicts stage and grade of non-muscle-invasive bladder carcinoma (NMIBC).

PubMed

Breyer, Johannes; Wirtz, Ralph M; Laible, Mark; Schlombs, Kornelia; Erben, Philipp; Kriegmair, Maximilian Christian; Stoehr, Robert; Eidt, Sebastian; Denzinger, Stefan; Burger, Maximilian; Hartmann, Arndt; Otto, Wolfgang

2016-11-01

Pathological staging and grading are crucial for risk assessment in non-muscle-invasive bladder cancer (NMIBC). Molecular grading might support pathological evaluation and minimize interobserver variability. In this study, the well-established breast cancer markers ESR1, PGR, ERBB2, and MKI67 were evaluated as potential molecular markers to support grading and staging in NMIBC. We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with NMIBC. Messenger RNA (mRNA) expression of the aforementioned markers was measured by single-step reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) using RNA-specific TaqMan assays. Relative gene expression was determined by normalization to two reference genes (CALM2 and B2M) using the 40 -ΔΔCT method and correlated to histopathological stage and grade. Pathological assessment was performed by an experienced uropathologist. Statistical analysis was performed using the SAS software JMP 9.0.0 version and GraphPad Prism 5.04. Of 381 cases of NMIBC, samples of 100 pTa and 255 pT1 cases were included in the final study. Spearman rank correlation revealed significant correlations between grade and expression of MKI67 (r = 0.52, p < 0.0001), ESR1 (r = 0.25, p < 0.0001), and ERBB2 (r = 0.18, p = 0.0008). In Mann-Whitney tests, MKI67 was significantly different between all grades (p < 0.0001), while ESR1 (p = 0.0006) and ERBB2 (p = 0.027) were significantly different between G2 and G3. Higher expression of MKI67 (r = 0.49; p < 0.0001), ERBB2 (r = 0.22; p < 0.0001), and ESR1 (r = 0.18; p = 0.0009) mRNA was positively correlated with higher stage. MKI67 (p < 0.0001), ERBB2 (p = 0.0058), and PGR (p = 0.0007) were significantly different between pTa and pT1. In NMIBC expression of ESR1, ERBB2 and MKI67 are significantly different between stage and grade. This potentially provides objective parameters for pathological evaluation.

Effects of Repeated Intraperitoneal Injection of Pharmaceutical-grade and Nonpharmaceutical-grade Corn Oil in Female C57BL/6J Mice.

PubMed

Hubbard, Jennifer S; Chen, Patty H; Boyd, Kelli L

2017-11-01

Due to potential adverse effects on animal wellbeing, the use of nonpharmaceutical-grade substances in animal research must be scientifically justified in cases where a pharmaceutical-grade version of the substance exists. This requirement applies to all substances, including vehicles used to solubilize experimental drugs. To date, no studies have evaluated the direct effect of the pharmaceutical classification of a compound on animal wellbeing. In this study, we evaluated intraperitoneal administration of pharmaceutical-grade corn oil, nonpharmaceutical-grade corn oil, and saline in female C57BL/6J mice. Compounds were administered every 48 h for a total of 4 injections. Mice were evaluated clinically by using body weight, body condition score, visual assessment score, CBC, and serum chemistries. Animals were euthanized at 24 h and 14 d after the final injection. Inflammation of the peritoneal wall and mesenteric fat was assessed microscopically by using a semiquantitative scoring system. Saline-dosed groups had lower pathology scores at both time points. At day 21, pharmaceutical-grade corn oil had a significantly higher pathology score compared with nonpharmaceutical-grade corn oil. No other significant differences between the corn oil groups were observed. The use of nonpharmaceutical grade corn oil did not result in adverse clinical consequences and is presumed safe to use for intraperitoneal injection in mice. Differences in inflammation between the 2 groups suggest that the use of either pharmaceutical-grade or nonpharmaceutical-grade corn oil should be consistent within a study.

Immunohistochemical analysis of tenascin expression in different grades of oral submucous fibrosis.

PubMed

Tak, Jalaj; Rao, Nirmala N; Chandra, Akhilesh; Gupta, Neha

2015-01-01

Tenascin, a glycoprotein, is one of the major constituents of extracellular matrix, which may function in organizing the stroma in normal and pathological conditions. The study aimed to correlate the structural organization of tenascin with the pathological progression of disease from early, moderate and advanced changes in oral submucous fibrosis (OSMF). A retrospective cross-sectional immunohistochemical (IHC) analysis of OSMF cases was performed. Total 70 slide samples were prepared for the study from 35 formalin-fixed paraffin-embedded tissue blocks with 10 each from histologically proven and graded as early, moderate and advanced OSMF and 5 of normal oral mucosa. The IHC sections were analyzed for the intensity and pattern of tenascin expression at the junction of epithelium and connective tissue (ECJ) and deeper connective tissue (CT), as well as presence or absence of staining around inflammatory cells, fibroblast and endothelial cells using anti-human tenascin. Most of the OSMF cases showed retention of antigen at ECJ and in deeper CT. Its expression varied in different grades as well as around inflammatory cells, fibroblast and endothelial cells in same tissue section. Highly significant P values of 0.001 and 0.003 were obtained for tenascin intensity and pattern, respectively, at ECJ in different OSMF grades. In addition, for the expression of tenascin pattern in deeper CT among different OSMF grades, a significant P value of 0.018 was obtained. A differential expression of tenascin was observed with the progression of disease. The expression of tenascin as bright and continuous deposition at ECJ in early and moderate stages of OSMF signifies either proliferative organization within the overlying epithelium or an epithelial-mesenchymal interaction. However, a weak immunoreactivity of tenascin at ECJ was observed in advanced stage of OSMF.

Immunohistochemical analysis of tenascin expression in different grades of oral submucous fibrosis

PubMed Central

Tak, Jalaj; Rao, Nirmala N; Chandra, Akhilesh; Gupta, Neha

2015-01-01

Aim: Tenascin, a glycoprotein, is one of the major constituents of extracellular matrix, which may function in organizing the stroma in normal and pathological conditions. The study aimed to correlate the structural organization of tenascin with the pathological progression of disease from early, moderate and advanced changes in oral submucous fibrosis (OSMF). Study Design: A retrospective cross-sectional immunohistochemical (IHC) analysis of OSMF cases was performed. Total 70 slide samples were prepared for the study from 35 formalin-fixed paraffin-embedded tissue blocks with 10 each from histologically proven and graded as early, moderate and advanced OSMF and 5 of normal oral mucosa. The IHC sections were analyzed for the intensity and pattern of tenascin expression at the junction of epithelium and connective tissue (ECJ) and deeper connective tissue (CT), as well as presence or absence of staining around inflammatory cells, fibroblast and endothelial cells using anti-human tenascin. Result: Most of the OSMF cases showed retention of antigen at ECJ and in deeper CT. Its expression varied in different grades as well as around inflammatory cells, fibroblast and endothelial cells in same tissue section. Highly significant P values of 0.001 and 0.003 were obtained for tenascin intensity and pattern, respectively, at ECJ in different OSMF grades. In addition, for the expression of tenascin pattern in deeper CT among different OSMF grades, a significant P value of 0.018 was obtained. Conclusion: A differential expression of tenascin was observed with the progression of disease. The expression of tenascin as bright and continuous deposition at ECJ in early and moderate stages of OSMF signifies either proliferative organization within the overlying epithelium or an epithelial-mesenchymal interaction. However, a weak immunoreactivity of tenascin at ECJ was observed in advanced stage of OSMF. PMID:26980955

Thirty-five years of noninvasive bladder carcinoma: a plea for the use of papillary intraurothelial neoplasia as new terminology.

PubMed

Van der Kwast, Theodorus H; Zlotta, Alexandre R; Fleshner, Neil; Jewett, Michael; Lopez-Beltran, Antonio; Montironi, Roldolfo

2008-12-01

Since the introduction of the World Health Organization (WHO) 1973 terminology for bladder cancer, noninvasive epithelial bladder tumors have consistently been labeled bladder carcinomas. In the WHO 2004 classification the removal of the "carcinoma" label from a small subset of noninvasive bladder carcinomas with indolent behavior created the entity of papillary urothelial neoplasms of low malignant potential, but the remaining noninvasive carcinomas of the urothelial tract retained this label. In this overview, we analyze clinical, pathologic and molecular-genomic findings to support a more evidence-based nomenclature of papillary neoplastic lesions of the urinary tract. In line with the tendency during the last few decades to label flat precancerous lesions of various organs intraepithelial neoplasms, we may now also refer to dysplasia and carcinoma in situ of the urinary tract as low and high grade intraurothelial neoplasia, respectively. To harmonize nomenclature, we now propose that the terms low and high grade papillary urothelial carcinoma be replaced by low and high grade papillary intraurothelial neoplasiafor all noninvasive urothelial cancers.

Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder.

PubMed

Hodgson, Anjelica; Xu, Bin; Satkunasivam, Raj; Downes, Michelle R

2018-02-01

Inflammation and necrosis have been associated with prognosis in multiple epithelial malignancies. Our objective was to evaluate inflammation and necrosis in a cohort of patients with high-grade urothelial carcinomas of the bladder to determine their association with pathological parameters and their prognostic effect on relapse-free and disease-specific survival. A retrospective cohort that underwent radical cystectomy for urothelial carcinomas (n=235) was evaluated for invasive front and central inflammation using the Klintrup-Makinen assessment method. Necrosis was scored using a four-point scale. The relationship of inflammation and necrosis with stage, nodal status, carcinoma in situ, tumour size, margin status and vascular space invasion and the impact on relapse-free and disease-specific survival were calculated using appropriate statistical tests. On multivariate analysis, invasive front inflammation (p=0.003) and necrosis (p=0.000) were independent predictors of relapse-free survival. Both invasive front inflammation (p=0.009) and necrosis (p=0.002) again were independent predictors of disease-specific survival. For pathological features, low invasive front inflammation was associated with lymphovascular space invasion (p=0.008), a positive soft tissue margin (p=0.028) and carcinoma in situ (p=0.042). Necrosis was statistically associated with tumours >3 cm in size (p=0.013) and carcinoma in situ (p<0.001). Necrosis and invasive front inflammation are additional histological variables with independent prognostic relevance in high-grade urothelial carcinoma of the bladder. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mass spectrometric profiling reveals association of N-glycan patterns with epithelial ovarian cancer progression.

PubMed

Chen, Huanhuan; Deng, Zaian; Huang, Chuncui; Wu, Hongmei; Zhao, Xia; Li, Yan

2017-07-01

Aberrant changes of N-glycan modifications on proteins have been linked to various diseases including different cancers, suggesting possible avenue for exploring their etiologies based on N-glycomic analysis. Changes in N-glycan patterns during epithelial ovarian cancer development have so far been investigated mainly using serum, plasma, ascites, and cell lines. However, changes in patterns of N-glycans in tumor tissues during epithelial ovarian cancer progression have remained largely undefined. To investigate whether changes in N-glycan patterns correlate with oncogenesis and progression of epithelial ovarian cancer, we profiled N-glycans from formalin-fixed paraffin-embedded tissue slides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and quantitatively compared among different pathological grades of epithelial ovarian cancer and healthy controls. Our results show that among the 80 compositions of N-glycan detected, expression levels of high-mannose type were higher in epithelial ovarian cancer samples than that observed in healthy controls, accompanied by reduced levels of hybrid-type glycans. By applying receiver operating characteristic analysis, we show that a combined panel composed of four high-mannose and three fucosylated neutral complex N-glycans allows for good discrimination of epithelial ovarian cancer from healthy controls. Furthermore, using a statistical analysis of variance assay, we found that different N-glycan patterns, including 2 high-mannose-type, 2 fucosylated and sialylated complex structures, and 10 fucosylated neutral complex N-glycans, exhibited specific changes in N-glycan abundance across epithelial ovarian cancer grades. Together, our results provide strong evidence that N-glycomic changes are a strong indicator for epithelial ovarian cancer pathological grades and should provide avenues to identify novel biomarkers for epithelial ovarian cancer diagnosis and monitoring.

Site-specific tumor grading system in colorectal cancer: multicenter pathologic review of the value of quantifying poorly differentiated clusters.

PubMed

Ueno, Hideki; Hase, Kazuo; Hashiguchi, Yojiro; Shimazaki, Hideyuki; Tanaka, Masafumi; Miyake, Ohki; Masaki, Tadahiko; Shimada, Yoshifumi; Kinugasa, Yusuke; Mori, Yoshiyuki; Kishimoto, Mitsuo; Kameoka, Shingo; Sato, Yu; Matsuda, Keiji; Nakadoi, Koichi; Shinto, Eiji; Nakamura, Takahiro; Sugihara, Kenichi

2014-02-01

The study aimed to determine the value of a novel site-specific grading system based on quantifying poorly differentiated clusters (PDC; Grade(PDC)) in colorectal cancer (CRC). A multicenter pathologic review involving 12 institutions was performed on 3243 CRC cases (stage I, 583; II, 1331; III, 1329). Cancer clusters of ≥5 cancer cells and lacking a gland-like structure (PDCs) were counted under a ×20 objective lens in a field containing the maximum clusters. Tumors with <5, 5 to 9, and ≥10 PDCs were classified as grades G1, G2, and G3, respectively. According to Grade(PDC), 1594, 1005, and 644 tumors were classified as G1, G2, and G3 and had 5-year recurrence-free survival rates of 91.6%, 75.4%, and 59.6%, respectively (P<0.0001). Multivariate analysis showed that Grade exerted an influence on prognostic outcome independently of TNM staging; approximately 20% and 46% of stage I and II patients, respectively, were selected by Grade(PDC) as a population whose survival estimate was comparable to or even worse than that of stage III patients. Grade(PDC) surpassed TNM staging in the ability to stratify patients by recurrence-free survival (Akaike information criterion, 2915.6 vs. 2994.0) and had a higher prognostic value than American Joint Committee on Cancer (AJCC) grading (Grade(AJCC)) at all stages. Regarding judgment reproducibility of grading tumors, weighted κ among the 12 institutions was 0.40 for Grade(AJCC) and 0.52 for Grade(PDC). Grade(PDC) has a robust prognostic power and promises to be of sufficient clinical value to merit implementation as a site-specific grading system in CRC.

High rates of cervical cancer among HIV-infected women at a referral hospital in Malawi.

PubMed

Kohler, Racquel E; Tang, Jennifer; Gopal, Satish; Chinula, Lameck; Hosseinipour, Mina C; Liomba, N George; Chiudzu, Grace

2016-08-01

Cervical cancer is the most common cancer among women in Malawi. National guidelines recommend screening women aged 30-45 years every five years; however, no specific recommendations exist for women with HIV. We aimed to assess the frequency of high-grade dysplasia (CIN 2 or CIN3) and cervical cancer among women in central Malawi and to examine associations with CIN2+ (CIN2/3 or cancer). We extracted cervical Pap smear, biopsy, loop electrosurgical excision procedure and uterine specimen reports from a hospital pathology database from November 2012 to November 2013. We used logistic regression to estimate associations with CIN2+. We reviewed specimens from 824 women; we excluded 194 with unknown HIV status, leaving 630 in the analytic sample. Twelve percent had high-grade dysplasia and 109 women (17%) had cancer. Twenty-five percent of high-grade dysplasia cases and 35% of cancers occurred among women outside recommended screening ages. The odds of having CIN2+ were 6.55 times (95% CI 4.44-9.67) greater for HIV+ women. High-grade dysplasia and cervical cancer are very common among Malawian women, especially HIV+ women. HIV infection was strongly associated with CIN2+. Expanding screening to women not covered by current guidelines could avert a substantial proportion of cervical cancer cases in Malawi. © The Author(s) 2016.

Estimation of T2* Relaxation Time of Breast Cancer: Correlation with Clinical, Imaging and Pathological Features

PubMed Central

Seo, Mirinae; Jahng, Geon-Ho; Sohn, Yu-Mee; Rhee, Sun Jung; Oh, Jang-Hoon; Won, Kyu-Yeoun

2017-01-01

Objective The purpose of this study was to estimate the T2* relaxation time in breast cancer, and to evaluate the association between the T2* value with clinical-imaging-pathological features of breast cancer. Materials and Methods Between January 2011 and July 2013, 107 consecutive women with 107 breast cancers underwent multi-echo T2*-weighted imaging on a 3T clinical magnetic resonance imaging system. The Student's t test and one-way analysis of variance were used to compare the T2* values of cancer for different groups, based on the clinical-imaging-pathological features. In addition, multiple linear regression analysis was performed to find independent predictive factors associated with the T2* values. Results Of the 107 breast cancers, 92 were invasive and 15 were ductal carcinoma in situ (DCIS). The mean T2* value of invasive cancers was significantly longer than that of DCIS (p = 0.029). Signal intensity on T2-weighted imaging (T2WI) and histologic grade of invasive breast cancers showed significant correlation with T2* relaxation time in univariate and multivariate analysis. Breast cancer groups with higher signal intensity on T2WI showed longer T2* relaxation time (p = 0.005). Cancer groups with higher histologic grade showed longer T2* relaxation time (p = 0.017). Conclusion The T2* value is significantly longer in invasive cancer than in DCIS. In invasive cancers, T2* relaxation time is significantly longer in higher histologic grades and high signal intensity on T2WI. Based on these preliminary data, quantitative T2* mapping has the potential to be useful in the characterization of breast cancer. PMID:28096732

Seizure prognosis of patients with low-grade tumors.

PubMed

Kahlenberg, Cynthia A; Fadul, Camilo E; Roberts, David W; Thadani, Vijay M; Bujarski, Krzysztof A; Scott, Rod C; Jobst, Barbara C

2012-09-01

Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and radiation therapy have a favorable impact on seizure outcome. Additional epilepsy surgery is effective. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

African American men with low-grade prostate cancer have increased disease recurrence after prostatectomy compared with Caucasian men.

PubMed

Yamoah, Kosj; Deville, Curtiland; Vapiwala, Neha; Spangler, Elaine; Zeigler-Johnson, Charnita M; Malkowicz, Bruce; Lee, David I; Kattan, Michael; Dicker, Adam P; Rebbeck, Timothy R

2015-02-01

To explore whether disparities in outcomes exist between African American (AA) and Caucasian (CS) men with low-grade prostate cancer and similar cancer of the prostate risk assessment-postsurgery (CAPRA-S) features following prostatectomy (RP). The overall cohort consisted of 1,265 men (234 AA and 1,031 CS) who met the National comprehensive cancer network criteria for low- to intermediate-risk prostate cancer and underwent RP between 1990 and 2012. We first evaluated whether clinical factors were associated with adverse pathologic outcomes and freedom from biochemical failure (FFbF) using the entire cohort. Next, we studied a subset of 705 men (112 AA and 593 CS) who had pathologic Gleason score≤6 (low-grade disease). Using this cohort, we determined whether race affected FFbF in men with RP-proven low-grade disease and similar CAPRA-S scores. With a median follow-up time of 27 months, the overall 7-year FFbF rate was 86% vs. 79% in CS and AA men, respectively (P = 0.035). There was no significant difference in one or more adverse pathologic features between CS vs. AA men (27% vs. 31%; P = 0.35) or CAPRA-S score (P = 0.28). In the subset analysis of patients with low-grade disease, AA race was associated with worse FFbF outcomes (P = 0.002). Furthermore, AA race was a significant predictor of FFbF in men with low-grade disease (hazard ratio = 2.01, 95% CI: 1.08-3.72; P = 0.029). AA race is a predictor of worse FFbF outcomes in men with low-grade disease after RP. These results suggest that a subset of AA men with low-grade disease may benefit from more aggressive treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

The short-term outcomes of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy in patients with poor-risk locally advanced rectal cancer.

PubMed

Beppu, Naohito; Yoshie, Hidenori; Kimura, Fumihiko; Aihara, Tsukasa; Doi, Hiroshi; Kamikonya, Norihiko; Matsubara, Nagahide; Tomita, Naohiro; Yanagi, Hidenori; Yamanaka, Naoki

2016-10-01

To evaluate the safety and efficacy of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy and surgery in patients with poor-risk locally advanced rectal cancer. We enrolled eligible patients with poor-risk rectal cancer defined as T3 lower rectal cancer with mesorectal fascia involvement, T4a or T4b tumors or cases with lateral lymph node swelling. The primary endpoint was a pathological complete response (pCR), and the secondary endpoints were the objective response rate (ORR) and the pathological high response rate (Grade 2 plus 3). Twenty eligible patients were enrolled. The majority (75.0 %, 15/20) of the patients completed four cycles of induction chemotherapy, and all patients completed the radiotherapy (25 Gy/10 fractions/5 days). The global rate of Grade 3-4 toxicities was 30.0 % (6/20 patients). The ORRs were 85.0 % (17/20) and 95.0 % (19/20) in the patients who underwent R0 and R1 resection, respectively. The pathological high response rate was 70.0 % (14/20) and the pCR was 10.0 % (2/20). The regimen of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy is safe and is associated with good tumor regression in patients with poor-risk locally advanced rectal cancer.

The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors.

PubMed

Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias; Stummer, Walter

2016-03-01

Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. Age, tumor volume, and F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.

Comparative study of pulsed-continuous arterial spin labeling and dynamic susceptibility contrast imaging by histogram analysis in evaluation of glial tumors.

PubMed

Arisawa, Atsuko; Watanabe, Yoshiyuki; Tanaka, Hisashi; Takahashi, Hiroto; Matsuo, Chisato; Fujiwara, Takuya; Fujiwara, Masahiro; Fujimoto, Yasunori; Tomiyama, Noriyuki

2018-06-01

Arterial spin labeling (ASL) is a non-invasive perfusion technique that may be an alternative to dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) for assessment of brain tumors. To our knowledge, there have been no reports on histogram analysis of ASL. The purpose of this study was to determine whether ASL is comparable with DSC-MRI in terms of differentiating high-grade and low-grade gliomas by evaluating the histogram analysis of cerebral blood flow (CBF) in the entire tumor. Thirty-four patients with pathologically proven glioma underwent ASL and DSC-MRI. High-signal areas on contrast-enhanced T 1 -weighted images or high-intensity areas on fluid-attenuated inversion recovery images were designated as the volumes of interest (VOIs). ASL-CBF, DSC-CBF, and DSC-cerebral blood volume maps were constructed and co-registered to the VOI. Perfusion histogram analyses of the whole VOI and statistical analyses were performed to compare the ASL and DSC images. There was no significant difference in the mean values for any of the histogram metrics in both of the low-grade gliomas (n = 15) and the high-grade gliomas (n = 19). Strong correlations were seen in the 75th percentile, mean, median, and standard deviation values between the ASL and DSC images. The area under the curve values tended to be greater for the DSC images than for the ASL images. DSC-MRI is superior to ASL for distinguishing high-grade from low-grade glioma. ASL could be an alternative evaluation method when DSC-MRI cannot be used, e.g., in patients with renal failure, those in whom repeated examination is required, and in children.

Urine test for HPV genotypes as a predictor of precancerous cervical lesions and for cervical cancer screening.

PubMed

Maged, Ahmed M; Saad, Hany; Salah, Emad; Meshaal, Hadeer; AbdElbar, Mostafa; Omran, Eman; Eldaly, Ashraf

2018-06-01

To assess the sensitivity of a urine test for high-risk HPV DNA genotypes in the detection of high-grade squamous intra-epithelial lesion (HSIL) and its correlation with pathologic precancerous lesions. The present prospective cross-sectional study included women referred to Kasr AlAiny Medical School, Cairo, Egypt, for cervical smear anomalies, a history of cervical smear anomalies, or for suspicious cervix between May 1, 2015, and April 30, 2017. Paired urine tests and cervical smears were performed. HPV DNA was detected in urine using polymerase chain reaction and cervical smears were performed with a cervical spatula and a cytobrush. Agreement between urine test results and pathology was examined. In total, 1375 women were included. Urine test for high-risk HPV DNA demonstrated 97.8% (95% confidence interval [CI] 92.1%-99.7%) sensitivity and 100% (95% CI 99.7%-100.0%) specificity for HSIL. Overall, 87 women had a positive urine test for high-risk HPV; of these, 82 (94.3%, 95% CI 87.1%-98.1%) had pathologic findings of cervical intra-epithelial neoplasia 2 or 3 (CIN2/3). Similarly, 89 women had HSIL cytology; again, 82 had CIN2/3 (92.1%; 95% CI, 84.3%-96.4%). There was good agreement between a positive urine test for high-risk HPV DNA genotypes and pathologic findings of CIN2/3. © 2018 International Federation of Gynecology and Obstetrics.

Brain Tumor Segmentation Using Deep Belief Networks and Pathological Knowledge.

PubMed

Zhan, Tianming; Chen, Yi; Hong, Xunning; Lu, Zhenyu; Chen, Yunjie

2017-01-01

In this paper, we propose an automatic brain tumor segmentation method based on Deep Belief Networks (DBNs) and pathological knowledge. The proposed method is targeted against gliomas (both low and high grade) obtained in multi-sequence magnetic resonance images (MRIs). Firstly, a novel deep architecture is proposed to combine the multi-sequences intensities feature extraction with classification to get the classification probabilities of each voxel. Then, graph cut based optimization is executed on the classification probabilities to strengthen the spatial relationships of voxels. At last, pathological knowledge of gliomas is applied to remove some false positives. Our method was validated in the Brain Tumor Segmentation Challenge 2012 and 2013 databases (BRATS 2012, 2013). The performance of segmentation results demonstrates our proposal providing a competitive solution with stateof- the-art methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Reflex Human Papillomavirus Test Results as an Option for the Management of Korean Women With Atypical Squamous Cells Cannot Exclude High-Grade Squamous Intraepithelial Lesion

PubMed Central

Ryu, Ki-Jin; Lee, Sanghoon; Min, Kyung-Jin; Kim, Jae Won; Hong, Jin Hwa; Song, Jae Yun; Lee, Jae Kwan

2015-01-01

Background. Current guidelines recommend initial colposcopy with biopsy regardless of human papillomavirus (HPV) test results in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of this study was to evaluate the value of HPV testing in women with ASC-H based on colposcopic pathology results. Materials and Methods. A multicenter cross-sectional study was carried out at three academic hospitals and involved 40,847 Korean women who underwent cervical cancer screening with cytology and HPV tests with or without subsequent colposcopic biopsies between January 2007 and December 2013. Results. ASC-H was diagnosed in 276 women (0.7%). Only 6 of 68 (8.8%) women with ASC-H who were HPV negative had cervical intraepithelial neoplasia grade ≥2 (CIN ≥2) lesions, whereas 47.4% of the women with ASC-H who were HPV positive had CIN ≥2 lesions. No cases of invasive cervical cancer were diagnosed among women with ASC-H who were HPV negative. Logistic regression analysis was performed using the group with normal Papanicolaou test results and HPV-negative status as the reference group. Women with ASC-H who were HPV positive had a significantly increased risk of CIN ≥2 lesions, whereas no significant increase was observed in patients with ASC-H and HPV-negative status. Conclusion. If the result of the HPV test was negative, the risk of CIN ≥2 lesions in Korean women with ASC-H cytology was low. Reflex HPV testing should be an option for the management of women with cytology showing ASC-H to decrease unnecessary colposcopic biopsies, which are expensive and invasive. Implications for Practice: Current American Society for Colposcopy and Cervical Pathology guidelines recommend universal colposcopy for the management of women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on cytology, regardless of human papillomavirus (HPV) test results. The present study suggested that HPV cotesting in patients with ASC-H cytology can provide more detailed and useful information regarding the risk of high-grade cervical intraepithelial neoplasia (CIN) lesions and the need for further treatment. When the result of the HPV test was negative, the risk of CIN lesions of grade ≥2 in women with ASC-H cytology was low. Consequently, reflex HPV testing, rather than immediately performance of invasive and expensive colposcopy with biopsy, should be an option for the management of women with ASC-H. PMID:25964305

Validation of Greyscale-Based Quantitative Ultrasound in Manual Wheelchair Users

PubMed Central

Collinger, Jennifer L.; Fullerton, Bradley; Impink, Bradley G.; Koontz, Alicia M.; Boninger, Michael L.

2010-01-01

Objective The primary aim of this study is to establish the validity of greyscale-based quantitative ultrasound (QUS) measures of the biceps and supraspinatus tendons. Design Nine QUS measures of the biceps and supraspinatus tendons were computed from ultrasound images collected from sixty-seven manual wheelchair users. Shoulder pathology was measured using questionnaires, physical examination maneuvers, and a clinical ultrasound grading scale. Results Increased age, duration of wheelchair use, and body mass correlated with a darker, more homogenous tendon appearance. Subjects with pain during physical examination tests for biceps tenderness and acromioclavicular joint tenderness exhibited significantly different supraspinatus QUS values. Even when controlling for tendon depth, QUS measures of the biceps tendon differed significantly between subjects with healthy tendons, mild tendinosis, and severe tendinosis. Clinical grading of supraspinatus tendon health was correlated with QUS measures of the supraspinatus tendon. Conclusions Quantitative ultrasound is valid method to quantify tendinopathy and may allow for early detection of tendinosis. Manual wheelchair users are at a high risk for developing shoulder tendon pathology and may benefit from quantitative ultrasound-based research that focuses on identifying interventions designed to reduce this risk. PMID:20407304

Laser diagnostics of native cervix dabs with human papilloma virus in high carcinogenic risk

NASA Astrophysics Data System (ADS)

Peresunko, O. P.; Karpenko, Ju. G.; Burkovets, D. N.; Ivashko, P. V.; Nikorych, A. V.; Yermolenko, S. B.; Gruia, Ion; Gruia, M. J.

2015-11-01

The results of experimental studies of coordinate distributions of Mueller matrix elements of the following types of cervical scraping tissue are presented: rate- low-grade - highly differentiated dysplasia (CIN1-CIN3) - adenocarcinoma of high, medium and low levels of differentiation (G1-G3). The rationale for the choice of statistical points 1-4 orders polarized coherent radiation field, transformed as a result of interaction with the oncologic modified biological layers "epithelium-stroma" as a quantitative criterion of polarimetric optical differentiation state of human biological tissues are shown here. The analysis of the obtained Mueller matrix elements and statistical correlation methods, the systematized by types studied tissues is accomplished. The results of research images of Mueller matrix elements m34 for this type of pathology as low-grade dysplasia (CIN2), the results of its statistical and correlation analysis are presented.

Hemoglobin level and XRCC1 polymorphisms to select patients with locally advanced rectal cancer candidate for neoadjuvant chemoradiotherapy with concurrent capecitabine and a platinum salt.

PubMed

Formica, Vincenzo; Benassi, Michaela; Del Vecchio Blanco, Giovanna; Doldo, Elena; Martano, Laura; Portarena, Ilaria; Nardecchia, Antonella; Lucchetti, Jessica; Morelli, Cristina; Giudice, Emilia; Rossi, Piero; Anselmo, Alessandro; Sileri, Pierpaolo; Sica, Giuseppe; Orlandi, Augusto; Santoni, Riccardo; Roselli, Mario

2018-05-02

A platinum salt (oxaliplatin or cisplatin) is widely used to enhance chemoradation (CRT) response. The potential of cisplatin in neoadjuvant CRT for locally advanced rectal cancer (LARC) has not been fully investigated. Consecutive patients with histologically confirmed LARC were treated with standard pelvic radiotherapy and concurrent cisplatin plus capecitabine (CisCape CRT). Surgery and eight cycles of adjuvant FOLFOX4 were offered to all patients after CRT. Common biochemical variables and key germline genetic polymorphisms were analyzed as predictors of pathological complete response (pCR). Fifty-one patients were enrolled. pCR (regression AJCC grade 0) was documented in 7 patients (14%), nearly complete response (AJCC grade 1) in 10 pts. There was a strong association between disease-free survival and AJCC grade (p 0.0047). Grade 3-4 toxicities (mainly diarrhea) was observed in 41% of patients. Among all analyzed variables, baseline hemoglobin (Hb) was significantly associated with AJCC grade 0-1 response (p 0.027). As for the pharmacogenetic analysis, XRCC1 rs25487 polymorphism was significantly associated with AJCC grade 0-1, Odds Ratio 25.8, p 0.049. AJCC grade 0-1 response rate for patients with high Hb and/or XRCC1 rs25487 G/G genotype was as high as 57%. Baseline Hb and XRCC1 polymorphisms are valuable selection criteria for the CisCape CRT regimen, given its otherwise meaningful toxicity.

Evaluation of patellar chondromalacia with MR: comparison between T2-weighted FSE SPIR and GE MTC.

PubMed

Macarini, Luca; Perrone, Alessandra; Murrone, Mario; Marini, Stefania; Stefanelli, Michele

2004-09-01

To compare two different MR sequences to tissue signal suppression in the study of patellar cartilage abnormalities. We examined 26 patients with magnetic resonance (MR) imaging: sequences included spectral presaturation with inversion recovery (SPIR), with fat suppression and T2-weighted images, magnetization transfer contrast (MTC) sequences, T1-weighted and T2-weighted spin-echo sequences. All patients underwent conventional knee arthroscopy and in all patients a hyaline cartilage lesion was assessed in three articular zones: the patellar medial facet, the lateral facet and the patellar crista. Was assessed 78 articular facets. The lesions were classified using a standard arthroscopic grading system adapted to MR imaging: normal cartilage that corresponds to the grade 0 according to the Noyes grading system, low grade lesions that correspond to the grade I e IIa and high grade lesions that correspond to grades IIb and III. The arthroscopic results were compared with MR images. We assessed the MR diagnostic accuracy, sensitivity, specificity and MR positive predictive value and negative predictive value of the two sequences taking into consideration total lesions, and high-grade and low grade lesions separately. Twenty-four low grade lesions (16 grade I e 8 grade IIa) and 18 high grade lesions (10 grade IIb e 8 grade III) were diagnosed by arthroscopy. Regarding low grade and high-grade lesions together, the accuracy was 77% for MTC sequences and 90% for SPIR sequences. In identifying low-grade lesions, the sensitivity was 88% for SPIR sequence and 42% for MTC sequences. Specificity for the detection of all lesions was 89% for the SPIR sequences and 94% for the MTC sequences. The SPIR sequence visualised water content abnormalities in degenerating cartilage, which are representative of low-grade lesions. The sensitivity of the sequence enabled us to obtain improved contrast for detecting cartilage surface irregularities. The MTC sequences allowed us to grade high-grade lesions susceptible to surgery and small cartilage defects in the presence of joint fluid. The MTC sequences were insufficient in the diagnosis of early stages of chondromalacia because the suppression of the signal of bonded water reduced the contrast among areas of articular cartilage with different water content. For this reason cartilage oedema and early superficial fibrillation were not identified. In our experience the SPIR sequence proved superior to the MTC sequence in the identification of low grade lesions of the patellar cartilage. The overall value of such sequences in the study of articular pathology also needs to be assessed in the others sites where the articular cartilage is thinner and surfaces more curvilinear.

Prognostic indicators in ovarian serous borderline tumours.

PubMed

Malpica, Anais; Longacre, Teri A

2018-02-01

There have been great strides in our understanding of the serous group of borderline and malignant pelvic epithelial neoplasms in the past decade. While most serous borderline tumours have a favourable prognosis, recurrences and progression to carcinoma occur, often following a protracted clinical course. Clinical and pathological risk factors tend to co-vary, but the presence and type of extraovarian disease is the most important predictor for progression. Progression usually takes the form of low-grade serous carcinoma, although transformation to high-grade carcinoma is occasionally seen. A serous borderline - low-grade serous carcinoma pathway analogous to neoplastic transformation pathways seen in other organ systems has been proposed, based on global gene expression profiling, shared mutations in KRAS or BRAF, and in most cases, the presence of serous borderline tumour in de novo low-grade serous carcinoma. This discussion focuses on the key prognostic factors that predispose to disease progression and/or transformation to carcinoma in serous borderline tumours. Published by Elsevier B.V.

Urothelial cancer of bladder in young versus older adults: clinical and pathological characteristics and outcomes.

PubMed

Telli, Onur; Sarici, Hasmet; Ozgur, Berat Cem; Doluoglu, Omer Gokhan; Sunay, Mehmet Melih; Bozkurt, Selen; Eroglu, Muzaffer

2014-09-01

Bladder urothelial carcinoma is rare in young adults and occurs more commonly in older individuals. The aim of this study was to compare the clinical behavior, pathologic characteristics, and prognosis of urothelial carcinoma of urinary bladder in young versus older adults. A retrospective review of our records between 2007 and 2013 identified 56 patients (42 males and 14 females) with transitional cell carcinoma of the bladder who were less than 40 years old. Clinical and pathological parameters of patients who were less than 40 years of age were compared with those of a series of patients older than 40 years of age (the control group) during the same period. A survival analysis was performed using the Kaplan-Meier method and log-rank test, and Cox regression was performed to identify clinical parameters that affected the clinical outcomes. The mean age was 29.21 years (range, 5-40 years) for patients less than 40 years old and 61.66 years (range, 41-75) for those older than 40 years. The mean follow-up was 40.26 months (range, 12-65 months) for young patients and 42.57 months (range, 12-72 months) for the older patients. Young bladder cancer patients had smaller-sized tumors (less than 3 cm), less high-grade cancers, higher papillary urothelial neoplasms of low malignant potential, and low-grade tumors than patients older than 40 years. Multivariate logistic regression analysis predicted tumor recurrence in young patients with high-grade tumors [odds ratio (OR), 1.959; 95% confidence interval (CI), 1.235-2.965; p = 0.046] and tumors larger than 3 cm (OR, 1.772; 95% CI, 1.416-1.942; p = 0.032). The 5-year overall survival rate was 100% for young patients and 88.1% for older patients. No difference was observed in the recurrence-free (p = 0.321) and progression-free (p = 0.422) survival rates between the two groups. We concluded that although the clinical stage distribution, natural history, and outcomes of bladder urothelial cancer in young adults are similar to those in their older counterparts, clinicians must be aware that patients under 40 years of age presented with higher-grade and larger (>3 cm) tumors and are more likely to experience tumor recurrence. Copyright © 2014. Published by Elsevier B.V.

Multiparametric Quantitative Ultrasound Imaging in Assessment of Chronic Kidney Disease.

PubMed

Gao, Jing; Perlman, Alan; Kalache, Safa; Berman, Nathaniel; Seshan, Surya; Salvatore, Steven; Smith, Lindsey; Wehrli, Natasha; Waldron, Levi; Kodali, Hanish; Chevalier, James

2017-11-01

To evaluate the value of multiparametric quantitative ultrasound imaging in assessing chronic kidney disease (CKD) using kidney biopsy pathologic findings as reference standards. We prospectively measured multiparametric quantitative ultrasound markers with grayscale, spectral Doppler, and acoustic radiation force impulse imaging in 25 patients with CKD before kidney biopsy and 10 healthy volunteers. Based on all pathologic (glomerulosclerosis, interstitial fibrosis/tubular atrophy, arteriosclerosis, and edema) scores, the patients with CKD were classified into mild (no grade 3 and <2 of grade 2) and moderate to severe (at least 2 of grade 2 or 1 of grade 3) CKD groups. Multiparametric quantitative ultrasound parameters included kidney length, cortical thickness, pixel intensity, parenchymal shear wave velocity, intrarenal artery peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index. We tested the difference in quantitative ultrasound parameters among mild CKD, moderate to severe CKD, and healthy controls using analysis of variance, analyzed correlations of quantitative ultrasound parameters with pathologic scores and the estimated glomerular filtration rate (GFR) using Pearson correlation coefficients, and examined the diagnostic performance of quantitative ultrasound parameters in determining moderate CKD and an estimated GFR of less than 60 mL/min/1.73 m 2 using receiver operating characteristic curve analysis. There were significant differences in cortical thickness, pixel intensity, PSV, and EDV among the 3 groups (all P < .01). Among quantitative ultrasound parameters, the top areas under the receiver operating characteristic curves for PSV and EDV were 0.88 and 0.97, respectively, for determining pathologic moderate to severe CKD, and 0.76 and 0.86 for estimated GFR of less than 60 mL/min/1.73 m 2 . Moderate to good correlations were found for PSV, EDV, and pixel intensity with pathologic scores and estimated GFR. The PSV, EDV, and pixel intensity are valuable in determining moderate to severe CKD. The value of shear wave velocity in assessing CKD needs further investigation. © 2017 by the American Institute of Ultrasound in Medicine.

Accuracy of pre-operative hysteroscopic guided biopsy for predicting final pathology in uterine malignancies.

PubMed

Martinelli, Fabio; Ditto, Antonino; Bogani, Giorgio; Signorelli, Mauro; Chiappa, Valentina; Lorusso, Domenica; Haeusler, Edward; Raspagliesi, Francesco

2017-07-01

To evaluate concordance (C) between pre-operative hysteroscopic-directed sampling and final pathology in uterine cancers. A retrospective cross-sectional evaluation of prospectively collected data of women who underwent hysterectomy for uterine malignancies and a previous hysteroscopic-guided biopsy was performed. Diagnostic concordance between pre-operative (hysteroscopic biopsy) and postoperative (uterine specimen) histology was evaluated. In endometrioid-endometrial cancers cases Kappa (k) statistics was applied to evaluate agreement for grading (G) between the preoperative and final pathology. A total 101 hysterectomies for uterine malignancies were evaluated. There were 23 non-endometrioid cancers: 7 serous (C:5/7, 71.4%); 10 carcinosarcomas (C:7/10, 70%, remaining 3 cases only epithelial component diagnosed); 3 clear cell (C:3/3, 100%); 3 sarcomas (C:3/3, 100%). In 78 cases an endometrioid endometrial cancer was found. In 63 cases there was a histological C (63/78, 80.8%) between hysteroscopic-guided biopsy and final pathology, while in 15 cases (19.2%) only hyperplasia (with/without atypia) was found preoperatively. Overall accuracy to detect endometrial cancer was 80.2%. In 50 out of 63 endometrial cancers (79.4%) grading was concordant. The overall level of agreement between preoperative and postoperative grading was "substantial" according to Kappa (k) statistics (k 0.64; 95% CI: 0.449-0.83; p < 0.001), as well as for G1 (0.679; 95% CI: 0.432-0.926; p < 0.001) and G3 (0.774; 94% CI: 0.534-1; p < 0.001), while for G2 (0.531; 95% CI: 0.286-0.777; p < 0.001) it was moderate. In our series we found an 80% C between pre-operative hysteroscopic-guided biopsy and final pathology, in uterine malignancies. Moreover, hysteroscopic biopsy accurately predicted endometrial cancer in 80% of cases and "substantially" predicted histological grading. Hysteroscopic-guided uterine sampling could be a useful tool to tailor treatment in patients with uterine malignancies.

Novel Diffusion-Weighted MRI for High-Grade Prostate Cancer Detection

DTIC Science & Technology

2016-10-01

in image resolution and scale.This process is critical for evaluating new imaging modalities.Our initial findings illustrate the potential of the...eligible for analysis as determined by adequate pathologic processing and MR images deemed to be of adequate quality by the study team.  The...histology samples have been requested from the UIC biorepository for digitization  All MR images have been collected and prepared for image processing

Analysis of MYB oncogene in transformed adenoid cystic carcinomas reveals distinct pathways of tumor progression.

PubMed

Costa, Ana F; Altemani, Albina; García-Inclán, Cristina; Fresno, Florentino; Suárez, Carlos; Llorente, José L; Hermsen, Mario

2014-06-01

Adenoid cystic carcinomas can occasionally undergo dedifferentiation, a phenomenon also referred to as high-grade transformation. However, cases of adenoid cystic carcinomas have been described showing transformation to adenocarcinomas that are not poorly differentiated, indicating that high-grade transformation may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form, which may encompass a wide spectrum of carcinomas in terms of aggressiveness. The aim of this study was to gain more insight in the biology of this pathological phenomenon by means of genetic profiling of both histological components. Using microarray comparative genomic hybridization, we compared the genome-wide DNA copy-number changes of the conventional and transformed area of eight adenoid cystic carcinomas with high-grade transformation, comprising four with transformation into moderately differentiated adenocarcinomas and four into poorly differentiated carcinomas. In general, the poorly differentiated carcinoma cases showed a higher total number of copy-number changes than the moderately differentiated adenocarcinoma cases, and this correlated with a worse clinical course. Special attention was given to chromosomal translocation and protein expression of MYB, recently being considered to be an early and major oncogenic event in adenoid cystic carcinomas. Our data showed that the process of high-grade transformation is not always accompanied by an accumulation of genetic alterations; both conventional and transformed components harbored unique genetic alterations, which indicate a parallel progression. Our data further demonstrated that the MYB/NFIB translocation is not necessarily an early event or fundamental for the progression to adenoid cystic carcinoma with high-grade transformation.

Comparison between DICOM-calibrated and uncalibrated consumer grade and 6-MP displays under different lighting conditions in panoramic radiography

PubMed Central

Haapea, M; Liukkonen, E; Huumonen, S; Tervonen, O; Nieminen, M T

2015-01-01

Objectives: To compare observer performance in the detection of anatomical structures and pathology in panoramic radiographs using consumer grade with and without digital imaging and communication in medicine (DICOM)-calibration and 6-megapixel (6-MP) displays under different lighting conditions. Methods: 30 panoramic radiographs were randomly evaluated on three displays under bright (510 lx) and dim (16 lx) ambient lighting by two observers with different years of experience. Dentinoenamel junction, dentinal caries and periapical inflammatory lesions, visibility of cortical border of the floor and pathological lesions in maxillary sinus were evaluated. Consensus between the observers was considered as reference. Intraobserver agreement was determined. Proportion of equivalent ratings and weighted kappa were used to assess reliability. The level of significance was set to p < 0.05. Results: The proportion of equivalent ratings with consensus differed between uncalibrated and DICOM-calibrated consumer grade displays in dentinal caries in the lower molar in dim lighting (p = 0.021) and between DICOM-calibrated consumer grade and 6-MP display in bright lighting (p = 0.038) for an experienced observer. Significant differences were found between uncalibrated and DICOM-calibrated consumer grade displays in dentinal caries in bright lighting (p = 0.044) and periapical lesions in the upper molar in dim lighting (p = 0.008) for a less experienced observer. Intraobserver reliability was better at detecting dentinal caries than at detecting periapical and maxillary sinus pathology. Conclusions: DICOM calibration may improve observer performance in panoramic radiography in different lighting conditions. Therefore, a DICOM-calibrated consumer grade display can be used instead of a medical display in dental practice without compromising the diagnostic quality. PMID:25564888

Programmed Death-ligand 1 Expression in Upper Tract Urothelial Carcinoma.

PubMed

Skala, Stephanie L; Liu, Tzu-Ying; Udager, Aaron M; Weizer, Alon Z; Montgomery, Jeffrey S; Palapattu, Ganesh S; Siddiqui, Javed; Cao, Xuhong; Fields, Kristina; Abugharib, Ahmed E; Soliman, Moaaz; Hafez, Khaled S; Miller, David; Lee, Cheryl T; Alva, Ajjai; Chinnaiyan, Arul M; Morgan, Todd M; Spratt, Daniel E; Jiang, Hui; Mehra, Rohit

2017-10-01

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract. Upper tract (renal pelvis and ureter) urothelial carcinomas (UTUC) account for approximately 5% of UCs but a significant subset are invasive and associated with poor clinical outcomes. To evaluate programmed death-ligand 1 (PD-L1) expression in UTUC. UTUC cases from 1997-2016 were retrospectively identified from the surgical pathology database at a single large academic institution. The cohort included 149 cases: 27 low-grade and 24 high-grade pathologic T (pT)a, 29 pT1, 23 pT2, 38 pT3, and eight pT4. PD-L1 immunohistochemistry (IHC) was performed on representative whole tumor sections using anti-PD-L1 primary antibody clone 5H1. PD-L1 expression was evaluated using a previously established cut-off for positivity (≥ 5% membranous staining). Association between PD-L1 IHC expression and clinicopathologic parameters was examined with Fisher's exact test; the effect of PD-L1 expression on cancer-specific mortality was assessed using the Cox proportional hazard model. Approximately one-third (32.7%) of invasive primary UTUC and 23.5% of all primary UTUC (invasive and noninvasive tumors) demonstrated positive PD-L1 expression. Positive PD-L1 expression was associated with high histologic grade, high pathologic stage, and angiolymphatic invasion. Cancer-specific survival was not significantly associated with positive PD-L1 expression using a 5% cut-off. Study limitations include the retrospective nature and the fact that PD-L1 expression by IHC is an imperfect surrogate for response to therapy. Positive PD-L1 expression in approximately one-third of primary invasive UTUC and association with high-risk clinicopathologic features provide a rational basis for further investigation of PD-L1-based immunotherapeutics in these patients. Upper tract urothelial carcinoma is often associated with poor clinical outcome. While current treatment options for advanced upper tract urothelial carcinoma are limited, programmed death-ligand 1 positivity in approximately one-third of invasive tumors provides a rational basis for further investigation of programmed death-ligand 1-based immunotherapeutics in these patients. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Grading of Gliomas by Using Monoexponential, Biexponential, and Stretched Exponential Diffusion-weighted MR Imaging and Diffusion Kurtosis MR Imaging

PubMed Central

Bai, Yan; Lin, Yusong; Tian, Jie; Shi, Dapeng; Cheng, Jingliang; Haacke, E. Mark; Hong, Xiaohua; Ma, Bo; Zhou, Jinyuan

2016-01-01

Purpose To quantitatively compare the potential of various diffusion parameters obtained from monoexponential, biexponential, and stretched exponential diffusion-weighted imaging models and diffusion kurtosis imaging in the grading of gliomas. Materials and Methods This study was approved by the local ethics committee, and written informed consent was obtained from all subjects. Both diffusion-weighted imaging and diffusion kurtosis imaging were performed in 69 patients with pathologically proven gliomas by using a 3-T magnetic resonance (MR) imaging unit. An isotropic apparent diffusion coefficient (ADC), true ADC, pseudo-ADC, and perfusion fraction were calculated from diffusion-weighted images by using a biexponential model. A water molecular diffusion heterogeneity index and distributed diffusion coefficient were calculated from diffusion-weighted images by using a stretched exponential model. Mean diffusivity, fractional anisotropy, and mean kurtosis were calculated from diffusion kurtosis images. All values were compared between high-grade and low-grade gliomas by using a Mann-Whitney U test. Receiver operating characteristic and Spearman rank correlation analysis were used for statistical evaluations. Results ADC, true ADC, perfusion fraction, water molecular diffusion heterogeneity index, distributed diffusion coefficient, and mean diffusivity values were significantly lower in high-grade gliomas than in low-grade gliomas (U = 109, 56, 129, 6, 206, and 229, respectively; P < .05). Pseudo-ADC and mean kurtosis values were significantly higher in high-grade gliomas than in low-grade gliomas (U = 98 and 8, respectively; P < .05). Both water molecular diffusion heterogeneity index (area under the receiver operating characteristic curve [AUC] = 0.993) and mean kurtosis (AUC = 0.991) had significantly greater AUC values than ADC (AUC = 0.866), mean diffusivity (AUC = 0.722), and fractional anisotropy (AUC = 0.500) in the differentiation of low-grade and high-grade gliomas (P < .05). Conclusion Water molecular diffusion heterogeneity index and mean kurtosis values may provide additional information and improve the grading of gliomas compared with conventional diffusion parameters. © RSNA, 2015 Online supplemental material is available for this article. PMID:26230975

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

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

Effects of Repeated Intraperitoneal Injection of Pharmaceutical-grade and Nonpharmaceutical-grade Corn Oil in Female C57BL/6J Mice

PubMed Central

Hubbard, Jennifer S; Chen, Patty H; Boyd, Kelli L

2017-01-01

Due to potential adverse effects on animal wellbeing, the use of nonpharmaceutical-grade substances in animal research must be scientifically justified in cases where a pharmaceutical-grade version of the substance exists. This requirement applies to all substances, including vehicles used to solubilize experimental drugs. To date, no studies have evaluated the direct effect of the pharmaceutical classification of a compound on animal wellbeing. In this study, we evaluated intraperitoneal administration of pharmaceutical-grade corn oil, nonpharmaceutical-grade corn oil, and saline in female C57BL/6J mice. Compounds were administered every 48 h for a total of 4 injections. Mice were evaluated clinically by using body weight, body condition score, visual assessment score, CBC, and serum chemistries. Animals were euthanized at 24 h and 14 d after the final injection. Inflammation of the peritoneal wall and mesenteric fat was assessed microscopically by using a semiquantitative scoring system. Saline-dosed groups had lower pathology scores at both time points. At day 21, pharmaceutical-grade corn oil had a significantly higher pathology score compared with nonpharmaceutical-grade corn oil. No other significant differences between the corn oil groups were observed. The use of nonpharmaceutical grade corn oil did not result in adverse clinical consequences and is presumed safe to use for intraperitoneal injection in mice. Differences in inflammation between the 2 groups suggest that the use of either pharmaceutical-grade or nonpharmaceutical-grade corn oil should be consistent within a study. PMID:29256373

Spectral grading and Gleason grading of malignant prostate tissue using Stokes shift spectra

NASA Astrophysics Data System (ADS)

Al Salhi, M.; Masilamani, V.; Rabah, D.; Farhat, K.; Liu, C. H.; Pu, Y.; Alfano, R. R.

2012-01-01

Gleason score is the most common method of grading the virulence of prostate malignancy and is based on the pathological assessment of morphology of cellular matrix. Since this involves the excision of the tissue, we are working on a new, minimally invasive, non contact, procedure of spectral diagnosis of prostate malignancy. In this preliminary in vitro study reported here, we have analyzed 27 tissue samples (normal control =7: benign=8: malignant =12) by Stokes' shift spectra (SSS) to establish a one- to- one correlation between spectral grading and Gleason grading.

Preoperative easily misdiagnosed telangiectatic osteosarcoma: clinical–radiologic–pathologic correlations

PubMed Central

Gao, Zhen-Hua; Yin, Jun-Qiang; Liu, Da-Wei; Meng, Quan-Fei

2013-01-01

Abstract Purpose: To describe the clinical, imaging, and pathologic characteristics and diagnostic methods of telangiectatic osteosarcoma (TOS) for improving the diagnostic level. Materials and methods: The authors retrospectively reviewed patient demographics, serum alkaline phosphatase (AKP) levels, preoperative biopsy pathologic reports, pathologic materials, imaging findings, and treatment outcomes from 26 patients with TOS. Patient images from radiography (26 cases) and magnetic resonance (MR) imaging (22 cases) were evaluated by 3 authors in consensus for intrinsic characteristics. There were 15 male and 11 female patients in the study, with an age of 9–32 years (mean age 15.9 years). Results: Eighteen of 26 patients died of lung metastases within 5 years of follow-up. The distal femur was affected more commonly (14 cases, 53.8%). Regarding serum AKP, normal (8 cases) or mildly elevated (18 cases) levels were found before preoperative chemotherapy. Radiographs showed geographic bone lysis without sclerotic margin (26 cases), cortical destruction (26 cases), periosteal new bone formation (24 cases), soft-tissue mass (23 cases), and matrix mineralization (4 cases). The aggressive radiographic features of TOS simulated the appearance of conventional high-grade intramedullary osteosarcoma, though different from aneurysmal bone cyst. MR images demonstrated multiple big (16 cases) or small (6 cases) cystic spaces, fluid-fluid levels (14 cases), soft-tissue mass (22 cases), and thick peripheral and septal enhancement (22 cases). Nine of 26 cases were misdiagnosed as aneurysmal bone cysts by preoperative core-needle biopsy, owing to the absence of viable high-grade sarcomatous cells in the small tissue samples. Conclusion: The aggressive growth pattern with occasional matrix mineralization, and multiple big or small fluid-filled cavities with thick peripheral, septal, and nodular tissue surrounding the fluid-filled cavities are characteristic imaging features of TOS, and these features are helpful in making the correct preoperative diagnosis of TOS. PMID:24334494

MRI signal distribution within the intervertebral disc as a biomarker of adolescent idiopathic scoliosis and spondylolisthesis.

PubMed

Gervais, Julien; Périé, Delphine; Parent, Stefan; Labelle, Hubert; Aubin, Carl-Eric

2012-12-03

Early stages of scoliosis and spondylolisthesis entail changes in the intervertebral disc (IVD) structure and biochemistry. The current clinical use of MR T2-weighted images is limited to visual inspection. Our hypothesis is that the distribution of the MRI signal intensity within the IVD in T2-weighted images depends on the spinal pathology and on its severity. Therefore, this study aims to develop the AMRSID (analysis of MR signal intensity distribution) method to analyze the 3D distribution of the MR signal intensity within the IVD and to evaluate their sensitivity to scoliosis and spondylolisthesis and their severities. This study was realized on 79 adolescents who underwent a MRI acquisition (sagittal T2-weighted images) before their orthopedic or surgical treatment. Five groups were considered: low severity scoliosis (Cobb angle ≤50°), high severity scoliosis (Cobb angles >50°), low severity spondylolisthesis (Meyerding grades I and II), high severity spondylolisthesis (Meyerding grades III, IV and V) and control. The distribution of the MRI signal intensity within the IVD was analyzed using the descriptive statistics of histograms normalized by either cerebrospinal fluid or bone signal intensity, weighted centers and volume ratios. Differences between pathology and severity groups were assessed using one- and two-way ANOVAs. There were significant (p < 0.05) variations of indices between scoliosis, spondylolithesis and control groups and between low and high severity groups. The cerebrospinal fluid normalization was able to detect differences between healthy and pathologic IVDs whereas the bone normalization, which reflects both bone and IVD health, detected more differences between the severities of these pathologies. This study proves for the first time that changes in the intervertebral disc, non visible to the naked eye on sagittal T2-weighted MR images of the spine, can be detected from specific indices describing the distribution of the MR signal intensity. Moreover, these indices are able to discriminate between scoliosis and spondylolisthesis and their severities, and provide essential information on the composition and structure of the discs whatever the pathology considered. The AMRSID method may have the potential to complement the current diagnostic tools available in clinics to improve the diagnostic with earlier biomarkers, the prognosis of evolution and the treatment options of scoliosis and spondylolisthesis.

Mucoepidermoid carcinoma of the parotid gland treated by surgery and postoperative radiation therapy: clinicopathologic correlates of outcome.

PubMed

Chen, Allen M; Lau, Valerie H; Farwell, D Gregory; Luu, Quang; Donald, Paul J

2013-12-01

To determine clinical and pathological correlates of outcome among patients treated by surgery and postoperative radiation therapy for mucoepidermoid carcinoma of the parotid gland. Retrospective review. The medical records of 61 patients treated by surgery and postoperative radiation therapy for localized mucoepidermoid carcinoma of the parotid gland were retrospectively reviewed in an attempt to identify clinicopathologic correlates of overall survival. Secondary endpoints included local-regional control, distant metastasis-free survival, and complications. The 3- and 5-year estimates of overall survival were 85% and 79%, respectively. Multivariate analysis identified high tumor grade (hazard ratio [HR] = 7.92) and T4 disease (HR = 3.35) as independent predictors of decreased survival, with the former also predicting for distant metastasis and the latter predicting for local-regional recurrence. The 5-year estimate of overall survival was 83% for patients with non-high-grade tumors, compared to 52% for those with high-grade histology (P = 0.001). Late complications included trismus (2 patients), osteoradionecrosis (1 patient), and hearing loss (1 patient). Patients with high-grade tumors and T4 disease are at increased risk for treatment failure after surgery and postoperative radiation therapy for mucoepidermoid carcinoma of the parotid gland. Investigative strategies to improve outcome should be considered for these particular patients in the future. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

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

PubMed Central

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

2014-01-01

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

Indian Hedgehog signaling pathway members are associated with magnetic resonance imaging manifestations and pathological scores in lumbar facet joint osteoarthritis.

PubMed

Shuang, Feng; Zhou, Ying; Hou, Shu-Xun; Zhu, Jia-Liang; Liu, Yan; Zhang, Chun-Li; Tang, Jia-Guang

2015-05-20

Indian Hedgehog (HH) has been shown to be involved in osteoarthritis (OA) in articular joints, where there is evidence that Indian HH blockade could ameliorate OA. It seems to play a prominent role in development of the intervertebral disc (IVD) and in postnatal maintenance. There is little work on IHH in the IVD. Hence the aim of the current study was to investigate the role of Indian Hedgehog in the pathology of facet joint (FJ) OA. 24 patients diagnosed with lumbar intervertebral disk herniation or degenerative spinal stenosis were included. Preoperative magnetic resonance imaging (MRI) and Osteoarthritis Research Society International (OARSI) histopathology grading system was correlated to the mRNA levels of GLI1, PTCH1, and HHIP in the FJs. The Weishaupt grading and OARSI scores showed high positive correlation (r = 0.894) (P < 0.01). MRI Weishaupt grades showed positive correlation with GLI1 (r = 0.491), PTCH1 (r = 0.444), and HHIP (r = 0.654) mRNA levels (P < 0.05 in each case). OARSI scores were also positively correlated with GLI1 (r = 0. 646), PTCH1 (r = 0. 518), and HHIP (r = 0.762) mRNA levels (P < 0.01 in each case). Cumulatively our findings indicate that Indian HH signaling is increased in OA and is perhaps a key component in OA pathogenesis and progression.

Raman spectroscopy for grading of live osteosarcoma cells.

PubMed

Chiang, Yi-Hung; Wu, Stewart H; Kuo, Yi-Chun; Chen, How-Foo; Chiou, Arthur; Lee, Oscar K

2015-04-18

Osteosarcoma is the most common primary malignant bone tumor, and the grading of osteosarcoma cells relies on traditional histopathology and molecular biology methods, which require RNA extraction, protein isolation and immunohistological staining. All these methods require cell isolation, lysis or fixation, which is time-consuming and requires certain amount of tumor specimen. In this study, we report the use of Raman spectroscopy for grading of malignant osteosarcoma cells. We demonstrate that, based on the detection of differential production of mineral species, Raman spectroscopy can be used as a live cell analyzer to accurately assess the grades of osteosarcoma cells by evaluating their mineralization levels. Mineralization level was assessed by measuring amount of hydroxyapatite (HA), which is highly expressed in mature osteoblasts, but not in poorly differentiated osteosarcoma cell or mesenchymal stem cells, the putative cell-of-origin of osteosarcoma. We found that under Raman spectroscopy, the level of HA production was high in MG-63 cells, which are low-grade. Moreover, hydroxyapatite production was low in high-grade osteosarcoma cells such as 143B and SaOS2 cells (p < 0.05). Matrix metalloproteinase MMP2, MMP9 were highly expressed in SaOS2, 143B and MSCs and decreased in human fetal osteoblast (FOB) and MG-63 cells as expected (p < 0.05). These results may highlight the inverse correlation between HA level and prognosis of osteosarcoma. The use of Raman spectroscopy for the measurement of HA production by the protocol reported in this study may serve as a useful tool to rapidly and accurately assess the degree of malignancy in osteosarcoma cells in a label-free manner. Such application may shorten the period of pathological diagnosis and may benefit patients who are inflicted with osteosarcoma.

Mammography of ductal carcinoma in situ of the breast: review of 909 cases with radiographic-pathologic correlations.

PubMed

Barreau, Béatrice; de Mascarel, Isabelle; Feuga, Caroline; MacGrogan, Gaétan; Dilhuydy, Marie-Hélène; Picot, Véronique; Dilhuydy, Jean-Marie; de Lara, Christine Tunon; Bussières, Emmanuel; Schreer, I

2005-04-01

We retrospectively analysed mammographies of 909 ductal carcinoma in situ (DCIS) (1980-1999) and compared our results to those of literature. Microcalcifications were present in 75% of the cases, and soft-tissue abnormalities in 27% cases with association with calcifications in 14% of cases. Palpable masses were found in 12% of the cases and nipple discharge was present in 12% of the cases. The radiographic-pathologic correlation allowed to suspect the DCIS "aggressiveness" on radiologic signs. Granular, linear, branching and/or galactophoric topography of the microcalcifications were correlated with necrosis, grade 3, comedocarcinoma type. A number of microcalcifications higher than 20 was correlated with necrosis and grade 3. Mammographic size was correlated to histologic size. Masses were correlated with grade 1. A diagnosis strategy can be proposed with a multidisciplinar approach.

A new set of wavelet- and fractals-based features for Gleason grading of prostate cancer histopathology images

NASA Astrophysics Data System (ADS)

Mosquera Lopez, Clara; Agaian, Sos

2013-02-01

Prostate cancer detection and staging is an important step towards patient treatment selection. Advancements in digital pathology allow the application of new quantitative image analysis algorithms for computer-assisted diagnosis (CAD) on digitized histopathology images. In this paper, we introduce a new set of features to automatically grade pathological images using the well-known Gleason grading system. The goal of this study is to classify biopsy images belonging to Gleason patterns 3, 4, and 5 by using a combination of wavelet and fractal features. For image classification we use pairwise coupling Support Vector Machine (SVM) classifiers. The accuracy of the system, which is close to 97%, is estimated through three different cross-validation schemes. The proposed system offers the potential for automating classification of histological images and supporting prostate cancer diagnosis.

Neoadjuvant paclitaxel poliglumex, cisplatin, and radiation for esophageal cancer: a phase 2 trial.

PubMed

Dipetrillo, Thomas; Suntharalingam, Mohan; Ng, Thomas; Fontaine, Jacques; Horiba, Naomi; Oldenburg, Nicklas; Perez, Kimberly; Birnbaum, Ari; Battafarano, Richard; Burrows, Whitney; Safran, Howard

2012-02-01

To evaluate the pathologic complete response (CR) rate and safety of paclitaxel poliglumex (PPX), cisplatin, and concurrent radiation for patients with esophageal cancer. Patients with adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction with no evidence of distant metastasis received PPX (50 mg/m(2)/wk) and cisplatin (25 mg/m(2)/wk) for 6 weeks with 50.4 Gy concurrent radiation. Six to eight weeks after completion of chemoradiotherapy, patients underwent surgical resection. Forty patients were enrolled, 37 patients with adenocarcinoma and 3 patients with squamous cell cancer. The treatment-related grade 3 nonhematologic toxicities included esophagitis (7%), nausea (7%), and fatigue (5%). Three patients with clinical endoscopic CR (2 with squamous cell cancer) refused surgery. Twelve of the remaining 37 patients (32%) had a pathologic CR. The 12 patients with pathologic CR all had adenocarcinoma. PPX, cisplatin, and concurrent radiation are well tolerated, easily administered regimen for esophageal cancer with a low incidence of significant esophagitis and a high pathologic CR rate consistent with the preclinical data of PPX and radiation.

[MRI of the rotator cuff: evaluation of a new symptomatologic classification].

PubMed

Tavernier, T; Walch, G; Noël, E; Lapra, C; Bochu, M

1995-05-01

The different classifications use for the rotator cuff pathology seem to be incomplete. We propose a new classification with many advantages: 1) Differentiate the tendinopathy between less serious (grade 2A) and serious (grade 2B). 2) Recognize the intra-tendinous cleavage of the infra-spinatus associated with complete tear of the supra-spinatus. 3) Differentiate partial and complete tears of the supra-spinatus. We established this classification after a retrospective study of 42 patients operated on for a rotator cuff pathology. Every case had had a preoperative MRI. This classification is simple, reliable, especially for the associated intra tendinous cleavage.

An online readability analysis of pathology-related patient education articles: an opportunity for pathologists to educate patients.

PubMed

Prabhu, Arpan V; Kim, Christopher; Crihalmeanu, Tudor; Hansberry, David R; Agarwal, Nitin; DeFrances, Marie C; Trejo Bittar, Humberto E

2017-07-01

Information for patients regarding their clinical conditions and treatment options is widely available online. The American Medical Association and National Institutes of Health recommend that online patient-oriented materials be written at no higher than a seventh-grade reading level to ensure full comprehension by the average American. This study sought to determine whether online patient-oriented materials explaining common pathology procedures are written at appropriate reading levels. Ten pathology procedures that patients would likely research were queried into Google search, and plain text from the first 10 Web sites containing patient education materials for each procedure was analyzed using 10 validated readability scales. We determined mean reading levels of materials grouped by readability scale, procedure, and Web site domain, the overall average reading level of all resources, and popular Web site domains. One hundred Web sites were accessed; one was omitted for short length (<100 words). The average reading grade level of the 99 materials, none of which met national health literacy guidelines (range, 7.3-17.4), was 10.9. Twenty-nine articles (29%) required a high school education for full comprehension, and 4 (4%) required an undergraduate college education. Most frequently accessed Web site domains included medlineplus.gov, webmd.com (both accessed 7 times), and labtestsonline.org (accessed 6 times). Average reading levels of the 11 most commonly accessed Web sites ranged from 8.25 (patient.info) to 12.25 (mayoclinic.org). Readability levels of most online pathology-related patient education materials exceeded those recommended by national health literacy guidelines. These patient education materials should be revised to help patients fully understand them. Copyright © 2017 Elsevier Inc. All rights reserved.

[Multivariate analysis of the association between consumption of fried food and gastric cancer and precancerous lesions].

PubMed

Guo, L W; Liu, S Z; Zhang, M; Chen, Q; Zhang, S K; Sun, X B

2018-02-06

Objective: To investigate the effect of fried food intake on the pathogenesis of gastric cancer and precancerous lesions. Methods: From 2005 to 2013, the residents aged 40-69 years from 11 counties/cities where cancer screening of upper gastrointestinal cancer were conducted in rural areas of Henan province as the subjects (82 367 cases). The information such as demography and lifestyle was collected. The residents were screened with endoscopic examination. The biopsy sampleswere diagnosed pathologically, according to pathological diagnosis criteria, the subjects with high risk were divided into the groups with different pathological degrees. The multivariate ordinal logistic regression analysis was used to analyze the relationship between the frequency of fried food intake and gastric cancer and precancerous lesions. Results: The study coverd 46 425 males and 35 942 females, with a age of (53.46±8.07)years. The study collected 6 707 cases of normal stomach, 2 325 cases of low grade intraepithelial neoplasia, 226 cases of high grade intraepithelial neoplasia and 331 cases of gastric cancer. Multivariate logistic regression analysis showed that, compared with those whoeat fried food less than one time per week, fried foods intake (<2 times/week: OR= 1.89, 95 %CI: 1.57-2.28; ≥ 2 times/week: OR= 1.91, 95 %CI: 1.66-2.20) were a risk factor for gastric cancer and precancerous lesions after adjustment for age, sex, marital status, educational level, body mass index (BMI), smoking and drinking status. Conclusion: The intake of fried food is a risk factor for gastric cancer and precancerous lesions. Therefore, reducing the intake of fried food can prevent the occurrence of gastric carcinoma and precancerous lesions.

Identification of novel potential genetic predictors of urothelial bladder carcinoma susceptibility in Pakistani population.

PubMed

Ali, Syeda Hafiza Benish; Bangash, Kashif Sardar; Rauf, Abdur; Younis, Muhammad; Anwar, Khursheed; Khurram, Raja; Khawaja, Muhammad Athar; Azam, Maleeha; Qureshi, Abid Ali; Akhter, Saeed; Kiemeney, Lambertus A; Qamar, Raheel

2017-10-01

Urothelial bladder carcinoma (UBC) is the most common among urinary bladder neoplasms. We carried out a preliminary study to determine the genetic etiology of UBC in Pakistani population, for this 25 sequence variants from 17 candidate genes were studied in 400 individuals by using polymerase chain reaction-based techniques. Multivariate logistic regression analysis was performed for association analysis of the overall data as well as the data stratified by smoking status, tumor grade and tumor stage. Variants of GSTM1, IGFBP3, LEPR and ACE were found to be associated with altered UBC risk in the overall comparison. CYP1B1 and CDKN1A variants displayed a risk modulation among smokers; IGFBP3 and LEPR variants among non-smokers while GSTM1 polymorphism exhibited association with both. GSTM1 and LEPR variants conferred an altered susceptibility to low grade UBC; GSTT1, IGFBP3 and PPARG variants to high grade UBC while ACE polymorphism to both grades. GSTM1 and LEPR variants exhibited risk modulation for non-muscle-invasive bladder cancer (NMIBC); GSTT1 and PPARG variants for muscle-invasive bladder cancer (MIBC), and ACE variant for NMIBC as well as MIBC. In general, the susceptibility markers were common for low grade and NMIBC; and distinct from those for high grade and MIBC indicating the distinct pathologies of both groups. In brief, our results conform to reports of previously associated variants in addition to identifying novel potential genetic predictors of UBC susceptibility.

Molecular classification of endometrial carcinoma on diagnostic specimens is highly concordant with final hysterectomy: Earlier prognostic information to guide treatment.

PubMed

Talhouk, Aline; Hoang, Lien N; McConechy, Melissa K; Nakonechny, Quentin; Leo, Joyce; Cheng, Angela; Leung, Samuel; Yang, Winnie; Lum, Amy; Köbel, Martin; Lee, Cheng-Han; Soslow, Robert A; Huntsman, David G; Gilks, C Blake; McAlpine, Jessica N

2016-10-01

Categorization and risk stratification of endometrial carcinomas is inadequate; histomorphologic assessment shows considerable interobserver variability, and risk of metastases and recurrence can only be derived after surgical staging. We have developed a Proactive Molecular Risk classification tool for Endometrial cancers (ProMisE) that identifies four distinct prognostic subgroups. Our objective was to assess whether molecular classification could be performed on diagnostic endometrial specimens obtained prior to surgical staging and its concordance with molecular classification performed on the subsequent hysterectomy specimen. Sequencing of tumors for exonuclease domain mutations (EDMs) in POLE and immunohistochemistry for mismatch repair (MMR) proteins and p53 were applied to both pre- and post-staging archival specimens from 60 individuals to identify four molecular subgroups: MMR-D, POLE EDM, p53 wild type, p53 abn (abnormal). Three gynecologic subspecialty pathologists assigned histotype and grade to a subset of samples. Concordance of molecular and clinicopathologic subgroup assignments were determined, comparing biopsy/curetting to hysterectomy specimens. Complete molecular and pathologic categorization was achieved in 57 cases. Concordance metrics for pre- vs. post-staging endometrial samples categorized by ProMisE were highly favorable; average per ProMisE class sensitivity(0.9), specificity(0.96), PPV(0.9), NPV(0.96) and kappa statistic 0.86(95%CI, 0.72-0.93), indicating excellent agreement. We observed the highest level of concordance for 'p53 abn' tumors, the group associated with the worst prognosis. In contrast, grade and histotype assignment from original pathology reports pre- vs. post-staging showed only moderate levels of agreement (kappa=0.55 and 0.44 respectively); even with subspecialty pathology review only moderate levels of agreement were observed. Molecular classification can be achieved on diagnostic endometrial samples and accurately predicts the molecular features in the final hysterectomy specimens, demonstrating concordance superior to grade and histotype. This biologically relevant information, available at initial diagnosis, has the potential to inform management (surgery, adjuvant therapy) from the earliest time point in cancer care. Copyright © 2016 Elsevier Inc. All rights reserved.

MiR-18a regulates the proliferation, migration and invasion of human glioblastoma cell by targeting neogenin

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

Song, Yichen, E-mail: jeff200064017@163.com; Wang, Ping, E-mail: pingwang8000@163.com; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001

MiR-17-92 cluster has recently been reported as an oncogene in some tumors. However, the association of miR-18a, an important member of this cluster, with glioblastoma remains unknown. Therefore, this study aims to investigate the expression of miR-18a in glioblastoma and its role in biological behavior of U87 and U251 human glioblastoma cell lines. Quantitative RT-PCR results showed that miR-18a was highly expressed in glioblastoma tissues and U87 and U251 cell lines compared with that in human brain tissues and primary normal human astrocytes, and the expression levels were increased along with the rising pathological grades of glioblastoma. Neogenin was identifiedmore » as the target gene of miR-18a by dual-luciferase reporter assays. RT-PCR and western blot results showed that its expression levels were decreased along with the rising pathological grades of glioblastoma. Inhibition of miR-18a expression was established by transfecting exogenous miR-18a inhibitor into U87 and U251 cells, and its effects on the biological behavior of glioblastoma cells were studied using CCK-8 assay, transwell assay and flow cytometry. Inhibition of miR-18a expression in U87 and U251 cells significantly up-regulated neogenin, and dramatically suppressed the abilities of cell proliferation, migration and invasion, induced cell cycle arrest and promoted cellular apoptosis. Collectively, these results suggest that miR-18a may regulate biological behavior of human glioblastoma cells by targeting neogenin, and miR-18a can serve as a potential target in the treatment of glioblastoma. - Highlights: • MiR-18a was highly expressed in glioblastoma tissues and U87 and U251 cell lines. • Neogenin was identified as the target gene of miR-18a. • Neogenin expressions were decreased along with the rising pathological grades of glioblastoma. • Inhibition of miR-18a suppressed biological behavior of glioma cells by up-regulating neogenin.« less

Critical study of pathology theses supported at the medical university of Tunis (2000-2010).

PubMed

Mrabet, Ali; Chadli Debbiche, Aschraf; Abidi, Emna; Borsali Falfoul, Nabiha; Dziri, Chadli

2016-02-01

Medical writing is a coded language; its purpose is to convey a scientific message. In pathology, specialty involving the study of cell and tissue, quantitative and qualitative production of medical doctoral theses and their thematic focus has not been studied. The aim of this study was to analyze the pathology theses on the level of form, the background and methodology. Descriptive retrospective study of medical doctoral theses in the specialty "Pathology", listed in the catalog of theses of the library of the Faculty of Medicine of Tunis and supported between 2000 and 2010. Each thesis has been subject of a direct reading, systematic and thorough. The study involved 189 pathology theses. The average overall productivity per academic pathologist was 5.5 theses. Gastrointestinal pathology was the most studied theme (24.9%). Tumor pathology was addressed in 74.1% of the theses. The IMRAD structure was respected in 57.7% of theses; by assistant professor than by associate professor and professor (p = 0.005). The summary was structured in 88.3% of theses, comparably with the grade of the thesis director (p = 0.5) and with the grade of PhD student (p = 0.08). The transcript of references did not meet the recommendations of Vancouver in 87.8% of theses and irrespective of the rank of director of thesis (p = 0.2). The pathology theses presented some shortcomings, particularly in the quality of medical writing. To remedy this problem, our faculty should increase efforts to improve the quality of scientific work, in order to have a better view of medical research in Tunisia.

The impact of speech and language problems in kindergarten on academic learning and special education status in grade three.

PubMed

Janus, Magdalena; Labonté, Chantal; Kirkpatrick, Ryan; Davies, Scott; Duku, Eric

2017-11-24

This study addressed the implications of experiencing early speech-language pathologies (SLPs) in kindergarten on special education needs (SEN) and academic outcomes in grade three. Early Development Instrument (EDI) kindergarten data on development and the presence or absence of SLPs were matched with grade three school-system standardised tests of reading, writing and maths, and SEN classification in Ontario, Canada for 59 015 students. Children were classified as having a Persistent speech language pathology (SLP), Remittent SLP, Latent SEN or as a typically developing Control. Even though 72.3% of children's SLPs remitted by grade three, kindergarten SLPs conveyed higher likelihood of having an SEN, and of lower achievement levels in grade three. The degree of impact varied between Persistent and Remittent groups. Children in the Latent group had lower scores in kindergarten on all five EDI domains than Control children. These population level results provide strong evidence to indicate that all children who present with an SLP in kindergarten face further academic challenges, even if their SLP resolves over time. Findings have implications for early intervention and treatment for children with early SLPs.

Renal Histopathologic Findings Associated With Severity of Clinical Acute Kidney Injury.

PubMed

Kudose, Satoru; Hoshi, Masato; Jain, Sanjay; Gaut, Joseph P

2018-05-01

Acute kidney injury (AKI) is a significant cause of morbidity and mortality. Acute tubular injury is considered to be the early pathologic manifestation of AKI, however, the underlying pathology is complex, lacks standards for interpretation, and its relationship with AKI often is unclear or inconsistent. To clarify clinicopathologic correlations in AKI, we evaluated 32 histologic findings in 100 kidney biopsies from patients with AKI as a training set to correlate pathologic findings with clinical AKI grades. Kidney Injury Molecule-1 quantitative immunohistochemistry was performed to confirm tubular injury. A separate cohort of 50 biopsies were evaluated blinded to clinical information to validate the findings. Pathologic tubular injury correlated best with Kidney Disease Improving Global Outcomes criteria. Tubular epithelial simplification, tubular epithelial mitosis, and cell sloughing correlated well with clinically severe AKI and were used to construct a tubular injury classification scheme with sensitivity of 0.93 (0.85, 1), specificity of 0.95 (0.83, 1), and area under the receiver-operating characteristic curve of 0.98 (0.98, 1) for grades 2 to 3 AKI. Predictive ability of the model did not improve when Kidney Injury Molecule-1 immunostaining results were added. The results show a strong correlation between pathologic tubular injury and modern clinical definitions of AKI. The proposed classification scheme may aid in development of more precise and clinically meaningful interpretations of pathologic tubular injury in native kidney biopsies and provides simple pathologic criteria without special studies that can easily be adopted globally.

Oncogenic role of fibroblast growth factor receptor 3 in tumorigenesis of urinary bladder cancer.

PubMed

Pandith, Arshad A; Shah, Zafar A; Siddiqi, Mushtaq A

2013-05-01

Bladder cancer is the second most common genitourinary tumor and constitutes a very heterogeneous disease. Molecular and pathologic studies suggest that low-grade noninvasive and high-grade invasive urothelial cell carcinoma (UCC) arise via distinct pathways. Low-grade noninvasive UCC represent the majority of tumors at presentation. A high proportion of patients with low-grade UCC develop recurrences but usually with no progression to invasive disease. At presentation, a majority of the bladder tumors (70%-80%) are low-grade noninvasive (pTa). Several genetic changes may occur in bladder cancer, but activating mutations in the fibroblast growth factor receptor 3 (FGFR3) genes are the most common and most specific genetic abnormality in bladder cancer. Interestingly, these mutations are associated with bladder tumors of low stage and grade, which makes the FGFR3 mutation the first marker that can be used for diagnosis of noninvasive bladder tumors. Since the first report of FGFR3 involvement in bladder tumors, numerous studies have been conducted to understand its function and thereby confirm the oncogenic role of this receptor particularly in noninvasive groups. Efforts are on to exploit this receptor as a therapeutic target, which holds much promise in the treatment of bladder cancer, particularly low-grade noninvasive tumors. Further studies need to explore the potential use of FGFR3 mutations in bladder cancer diagnosis, prognosis, and in surveillance of patients with bladder cancer. This review focuses on the role of FGFR3 in bladder tumors in the backdrop of various studies published. Copyright © 2013 Elsevier Inc. All rights reserved.

[DAB2IP expression in bladder transitional cell carcinoma and its correlation with clinical outcome].

PubMed

Zhu, Jian-Ning; Wu, Kai-Jie; Guan, Zhen-Feng; Liu, Li-Xia; Ning, Zhong-Yun; Zhou, Jian-Cheng; Wang, Xin-Yang; Fan, Jin-Hai

2014-07-01

To investigate the expression of DAB2IP in bladder transitional cell carcinoma (BTCC) and its correlation with clinical characteristics and prognosis of BTCC patients. Immunohistochemical staining was applied to detect DAB2IP protein level in 79 cases of TCCB tissues and 11 cases of normal bladder tissues, and the relationships of the staining results with pathological grade, stage, lymph node metastasis, gender, age and the 3-year survival rate of the patients were analyzed. The expression of DAB2IP in BTCC tissues was significantly lower than that in normal bladder epithelium, and the expression score and rate of DAB2IP in the high-grade, invasive and metastatic BTCC were significantly lower than those in low-grade, superficial and non-metastatic BTCC (P < 0.05). The 3-year survival rate of the patients with high DAB2IP expression was significantly higher than that of the patients with low DAB2IP expression. DAB2IP may be one of the important inhibitory factors during the occurrence and progression of BTCC.

Quantitative diagnosis of bladder cancer by morphometric analysis of HE images

NASA Astrophysics Data System (ADS)

Wu, Binlin; Nebylitsa, Samantha V.; Mukherjee, Sushmita; Jain, Manu

2015-02-01

In clinical practice, histopathological analysis of biopsied tissue is the main method for bladder cancer diagnosis and prognosis. The diagnosis is performed by a pathologist based on the morphological features in the image of a hematoxylin and eosin (HE) stained tissue sample. This manuscript proposes algorithms to perform morphometric analysis on the HE images, quantify the features in the images, and discriminate bladder cancers with different grades, i.e. high grade and low grade. The nuclei are separated from the background and other types of cells such as red blood cells (RBCs) and immune cells using manual outlining, color deconvolution and image segmentation. A mask of nuclei is generated for each image for quantitative morphometric analysis. The features of the nuclei in the mask image including size, shape, orientation, and their spatial distributions are measured. To quantify local clustering and alignment of nuclei, we propose a 1-nearest-neighbor (1-NN) algorithm which measures nearest neighbor distance and nearest neighbor parallelism. The global distributions of the features are measured using statistics of the proposed parameters. A linear support vector machine (SVM) algorithm is used to classify the high grade and low grade bladder cancers. The results show using a particular group of nuclei such as large ones, and combining multiple parameters can achieve better discrimination. This study shows the proposed approach can potentially help expedite pathological diagnosis by triaging potentially suspicious biopsies.

Pathology Imagebase-a reference image database for standardization of pathology.

PubMed

Egevad, Lars; Cheville, John; Evans, Andrew J; Hörnblad, Jonas; Kench, James G; Kristiansen, Glen; Leite, Katia R M; Magi-Galluzzi, Cristina; Pan, Chin-Chen; Samaratunga, Hemamali; Srigley, John R; True, Lawrence; Zhou, Ming; Clements, Mark; Delahunt, Brett

2017-11-01

Despite efforts to standardize histopathology practice through the development of guidelines, the interpretation of morphology is still hampered by subjectivity. We here describe Pathology Imagebase, a novel mechanism for establishing an international standard for the interpretation of pathology specimens. The International Society of Urological Pathology (ISUP) established a reference image database through the input of experts in the field. Three panels were formed, one each for prostate, urinary bladder and renal pathology, consisting of 24 international experts. Each of the panel members uploaded microphotographs of cases into a non-public database. The remaining 23 experts were asked to vote from a multiple-choice menu. Prior to and while voting, panel members were unable to access the results of voting by the other experts. When a consensus level of at least two-thirds or 16 votes was reached, cases were automatically transferred to the main database. Consensus was reached in a total of 287 cases across five projects on the grading of prostate, bladder and renal cancer and the classification of renal tumours and flat lesions of the bladder. The full database is available to all ISUP members at www.isupweb.org. Non-members may access a selected number of cases. It is anticipated that the database will assist pathologists in calibrating their grading, and will also promote consistency in the diagnosis of difficult cases. © 2017 John Wiley & Sons Ltd.

Improving the prediction of pathologic outcomes in patients undergoing radical prostatectomy: the value of prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine.

PubMed

Ferro, Matteo; Lucarelli, Giuseppe; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Perruolo, Giuseppe; Marino, Ada; Cosimato, Vincenzo; Giorgio, Emilia; Tagliamonte, Virginia; Bottero, Danilo; De Cobelli, Ottavio; Terracciano, Daniela

2015-02-01

Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over-treatment. On this effort, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been presented as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume Institution. The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV)≥0.5 ml, pathologic Gleason sum (GS)≥7 and pT3 disease (all p-values≤0.01). ROC curve analysis showed that phi is an accurate predictor of high-stage (AUC 0.85 [0.77-0.93]), high-grade (AUC 0.83 [0.73-0.93]) and high-volume disease (AUC 0.94 [0.88-0.99]). Sarcosine showed a comparable AUC (0.85 [0.76-0.94]) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS). Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Detection of Human Brain Cancer Infiltration ex vivo and in vivo Using Quantitative Optical Coherence Tomography*

PubMed Central

Kut, Carmen; Chaichana, Kaisorn L.; Xi, Jiefeng; Raza, Shaan M.; Ye, Xiaobu; McVeigh, Elliot R.; Rodriguez, Fausto J.; Quinones-Hinojosa, Alfredo; Li, Xingde

2015-01-01

More complete brain cancer resection can prolong survival and delay recurrence. However, it is challenging to distinguish cancer from non-cancer tissues intraoperatively, especially at the transitional, infiltrative zones. This is especially critical in eloquent regions (e.g. speech and motor areas). This study tested the feasibility of label-free, quantitative optical coherence tomography (OCT) for differentiating cancer from non-cancer in human brain tissues. Fresh ex vivo human brain tissues were obtained from 32 patients with grades II-IV brain cancer and 5 patients with non-cancer brain pathologies. Based on volumetric OCT imaging data, pathologically confirmed brain cancer tissues (both high-grade and low-grade) had significantly lower optical attenuation values at both cancer core and infiltrated zones when compared with non-cancer white matter, and OCT achieved high sensitivity and specificity at an attenuation threshold of 5.5 mm-1 for brain cancer patients. We also used this attenuation threshold to confirm the intraoperative feasibility of performing in vivo OCT-guided surgery using a murine model harboring human brain cancer. Our OCT system was capable of processing and displaying a color-coded optical property map in real time at a rate of 110-215 frames per second, or 1.2-2.4 seconds for an 8-16 mm3 tissue volume, thus providing direct visual cues for cancer versus non-cancer areas. Our study demonstrates the translational and practical potential of OCT in differentiating cancer from non-cancer tissue. Its intraoperative use may facilitate safe and extensive resection of infiltrative brain cancers and consequently lead to improved outcomes when compared with current clinical standards. PMID:26084803

Glioma grading using cell nuclei morphologic features in digital pathology images

NASA Astrophysics Data System (ADS)

Reza, Syed M. S.; Iftekharuddin, Khan M.

2016-03-01

This work proposes a computationally efficient cell nuclei morphologic feature analysis technique to characterize the brain gliomas in tissue slide images. In this work, our contributions are two-fold: 1) obtain an optimized cell nuclei segmentation method based on the pros and cons of the existing techniques in literature, 2) extract representative features by k-mean clustering of nuclei morphologic features to include area, perimeter, eccentricity, and major axis length. This clustering based representative feature extraction avoids shortcomings of extensive tile [1] [2] and nuclear score [3] based methods for brain glioma grading in pathology images. Multilayer perceptron (MLP) is used to classify extracted features into two tumor types: glioblastoma multiforme (GBM) and low grade glioma (LGG). Quantitative scores such as precision, recall, and accuracy are obtained using 66 clinical patients' images from The Cancer Genome Atlas (TCGA) [4] dataset. On an average ~94% accuracy from 10 fold crossvalidation confirms the efficacy of the proposed method.

A Computer-Aided Distinction Method of Borderline Grades of Oral Cancer

NASA Astrophysics Data System (ADS)

Sami, Mustafa M.; Saito, Masahisa; Muramatsu, Shogo; Kikuchi, Hisakazu; Saku, Takashi

We have developed a new computer-aided diagnostic system for differentiating oral borderline malignancies in hematoxylin-eosin stained microscopic images. Epithelial dysplasia and carcinoma in-situ (CIS) of oral mucosa are two different borderline grades similar to each other, and it is difficult to distinguish between them. A new image processing and analysis method has been applied to a variety of histopathological features and shows the possibility for differentiating the oral cancer borderline grades automatically. The method is based on comparing the drop-shape similarity level in a particular manually selected pair of neighboring rete ridges. It was found that the considered similarity level in dysplasia was higher than those in epithelial CIS, of which pathological diagnoses were conventionally made by pathologists. The developed image processing method showed a good promise for the computer-aided pathological assessment of oral borderline malignancy differentiation in clinical practice.

GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression.

PubMed

Pinheiro, C; Sousa, B; Albergaria, A; Paredes, J; Dufloth, R; Vieira, D; Schmitt, F; Baltazar, F

2011-10-01

The goal of the present work was to evaluate the correlation of glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX) with the monocarboxylate transporters 1 (MCT1) and 4 (MCT4) and their chaperone, CD147, in breast cancer. The clinico-pathological value of GLUT1 and CAIX was also evaluated. For that, we analysed the immunohistochemical expression of GLUT1 and CAIX, in a large series of invasive breast carcinoma samples (n=124), previously characterized for MCT1, MCT4 and CD147 expression. GLUT1 expression was found in 46% of the cases (57/124), while CAIX was found in 18% of the cases (22/122). Importantly, both MCT1 and CD147, but not MCT4, were associated with GLUT1 and CAIX expression. Also, GLUT1 and CAIX correlated with each other. Concerning the clinico-pathological values, GLUT1 was associated with high grade tumours, basal-like subtype, absence of progesterone receptor, presence of vimentin and high proliferative index as measured by Ki-67. Additionally, CAIX was associated with large tumour size, high histological grade, basal-like subtype, absence of estrogen and progesterone receptors and presence of basal cytokeratins and vimentin expression. Finally, patients with CAIX positive tumours had a significantly shorter disease-free survival. The association between MCT1 and both GLUT1 and CAIX may result from hypoxia-mediated metabolic adaptations, which confer a glycolytic, acid-resistant and more aggressive phenotype to cancer cells.

Flexner 3.0-Democratization of Medical Knowledge for the 21st Century: Teaching Medical Science Using K-12 General Pathology as a Gateway Course.

PubMed

Weinstein, Ronald S; Krupinski, Elizabeth A; Weinstein, John B; Graham, Anna R; Barker, Gail P; Erps, Kristine A; Holtrust, Angelette L; Holcomb, Michael J

2016-01-01

A medical school general pathology course has been reformatted into a K-12 general pathology course. This new course has been implemented at a series of 7 to 12 grade levels and the student outcomes compared. Typically, topics covered mirrored those in a medical school general pathology course serving as an introduction to the mechanisms of diseases. Assessment of student performance was based on their score on a multiple-choice final examination modeled after an examination given to medical students. Two Tucson area schools, in a charter school network, participated in the study. Statistical analysis of examination performances showed that there were no significant differences as a function of school ( F = 0.258, P = .6128), with students at school A having an average test scores of 87.03 (standard deviation = 8.99) and school B 86.00 (standard deviation = 8.18; F = 0.258, P = .6128). Analysis of variance was also conducted on the test scores as a function of gender and class grade. There were no significant differences as a function of gender ( F = 0.608, P = .4382), with females having an average score of 87.18 (standard deviation = 7.24) and males 85.61 (standard deviation = 9.85). There were also no significant differences as a function of grade level ( F = 0.627, P = .6003), with 7th graders having an average of 85.10 (standard deviation = 8.90), 8th graders 86.00 (standard deviation = 9.95), 9th graders 89.67 (standard deviation = 5.52), and 12th graders 86.90 (standard deviation = 7.52). The results demonstrated that middle and upper school students performed equally well in K-12 general pathology. Student course evaluations showed that the course met the student's expectations. One class voted K-12 general pathology their "elective course-of-the-year."

Laparoscopic approach to colorectal procedures in the obese patient: risk factor or benefit?

PubMed

Scheidbach, Hubert; Benedix, Frank; Hügel, Omar; Kose, Daniela; Köckerling, Ferdinand; Lippert, Hans

2008-01-01

Obesity is a modern-day phenomenon that is increasing throughout the world. The aim of the present study was to provide data to establish whether the laparoscopic approach to colorectal surgery in the obese patient represents a risk or, rather, a benefit for the patient. The data presented in this paper were obtained within the framework of a prospective multicenter study initiated by the "Laparoscopic Colorectal Surgery Study Group (LCSSG)" and performed on 5,853 recruited patients. The perioperative course was compared between the three groups: nonobese, obesity grade I, and obesity grade II/III. Increasing body mass index correlated with a highly significant increase in the duration of the operation (nonobese 167 min, grade I 182 min, grade II/III 191 min; p < 0.001) and in the conversion rate (nonobese 5.5%, obesity grade I 7.9%, obesity grade II/III 13.1%; p < 0.001). The intraoperative complication rate also showed a tendency to increase (nonobese 5.0%, grade I 6.2%, grade II/III 7.1%; p = 0.219). In contrast, no significant differences were found between the groups with regard to the postoperative complication rate (nonobese 20.7%, grade I 21.0%, grade II/III 20.2%), the reoperation rate (nonobese 4.1%, grade I 3.9%, grade II/III 3.6%), and the postoperative mortality rate (nonobese 1.1%, grade I 1.9%, grade II/III 1.8%). Laparoscopic colorectal surgery is clearly more technically demanding in the obese patient. Apart from this, however, it is not associated with any increased risk of postoperative complications, and thus demonstrates that the pathologically overweight patient can benefit to a particular degree from the laparoscopic modality.

Sodium Fluorescein-Guided Resection under the YELLOW 560 nm Surgical Microscope Filter in Malignant Gliomas: Our First 38 Cases Experience.

PubMed

Zhang, Ningning; Tian, Hailong; Huang, Dezhang; Meng, Xianbing; Guo, Wenqiang; Wang, Chaochao; Yin, Xin; Zhang, Hongying; Jiang, Bin; He, Zheng; Wang, Zhigang

2017-01-01

Sodium fluorescein (FL) had been safely used in fluorescence-guided microsurgery for imaging various brain tumors. Under the YELLOW 560 nm surgical microscope filter, low-dose FL as a fluorescent dye helps in visualization. Our study investigated the safety and efficacy of this innovative technique in malignant glioma (MG) patients. 38 patients suffering from MGs confirmed by pathology underwent FL-guided resection under YELLOW 560 nm surgical microscope filter. We retrospectively analyzed the clinical characters, microsurgery procedure, extent of resection, pathology of MGs, progression-free survival (PFS), and overall survival (OS). Thirty-eight patients had MGs (10 WHO grade III, 28 WHO grade IV). With YELLOW 560 nm surgical microscope filter combined with neuronavigation, sodium fluorescein-guided gross total resection (GTR) was achieved in 35 (92.1%) patients and subtotal resection in 3 (7.69%). The sensitivity and specificity of FL were 94.4% and 88.6% regardless of radiographic localization. Intraoperatively, 10 biopsies (10/28 FL[+]) showed "low" or "high" fluorescence in non-contrast-enhancement region and are also confirmed by pathology. Our data showed 6-month PFS of 92.3% and median survival of 11 months. FL-guided resection of MGs under the YELLOW 560 nm surgical microscope filter combined with neuronavigation was safe and effective, especially in non-contrast-MRI regions. It is feasible for improving the extent of resection in MGs especially during emergency cases.

Neuroendocrine-type prostatic adenocarcinoma with microsatellite instability in a patient with lynch syndrome.

PubMed

Wagner, David G; Gatalica, Zoran; Lynch, Henry T; Kohl, Shane; Johansson, Sonny L; Lele, Subodh M

2010-12-01

Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified with microsatellite instability molecular tests or immunohistochemical stains on pathologic material from patients who meet the Amsterdam Criteria II. The development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC) of the prostate has not been previously reported in a patient with this syndrome. In this report, an 87-year-old White man with the Lynch syndrome had a prostate biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of the prostate with high-grade prostatic intraepithelial neoplasia of the small cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability and loss of MSH2 expression, a finding not previously published. These findings suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC can develop in a patient with the Lynch syndrome.

Endometrial cancer: correlation of apparent diffusion coefficient (ADC) with tumor cellularity and tumor grade.

PubMed

Kishimoto, Keiko; Tajima, Shinya; Maeda, Ichiro; Takagi, Masayuki; Ueno, Takahiko; Suzuki, Nao; Nakajima, Yasuo

2016-08-01

Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) are widely used for detecting uterine endometrial cancer. The relationships between ADC values and pathological features of endometrial cancer have not yet been established. To investigate whether ADC values of endometrial cancer vary according to histologic tumor cellularity and tumor grade. We retrospectively reviewed 30 pathologically confirmed endometrial cancers. All patients underwent conventional non-enhanced magnetic resonance imaging (MRI) and DWI procedures, and ADC values were calculated. Tumor cellularity was evaluated by counting cancer cells in three high-power ( × 400) fields. The correlation between ADC values and tumor cellularity was assessed using Pearson's correlation coefficient test for statistical analysis. The mean ± standard deviation (SD) ADC value ( ×10(-3) mm(2)/s) of endometrial cancer was 0.85 ± 0.22 (range, 0.55-1.71). The mean ± SD tumor cellularity was 528.36 ± 16.89 (range, 298.0-763.6). ADC values were significantly inversely correlated with tumor cellularity. No significant relationship was observed between ADC values and tumor grade (mean ADC values: G1, 0.88 ± 0.265 × 10(-3) mm(2)/s; G2, 0.80 ± 0.178 × 10(-3) mm(2)/s; G3, 0.81 ± 0.117 × 10(-3) mm(2)/s). There is a significant inverse relationship between ADC values and tumor cellularity in endometrial cancer. No significant differences in average ADC value were observed between G1, G2, and G3 tumors. However, the lower the tumor grade, the wider the SD. © The Foundation Acta Radiologica 2015.

Prognostic Evaluations Tailored to Specific Gastric Neuroendocrine Neoplasms: Analysis Of 200 Cases with Extended Follow-Up.

PubMed

Vanoli, Alessandro; La Rosa, Stefano; Miceli, Emanuela; Klersy, Catherine; Maragliano, Roberta; Capuano, Francesca; Persichella, Andrea; Martino, Michele; Inzani, Frediano; Luinetti, Ombretta; Di Sabatino, Antonio; Sessa, Fausto; Paulli, Marco; Corazza, Gino Roberto; Rindi, Guido; Bordi, Cesare; Capella, Carlo; Solcia, Enrico

2018-06-12

Gastric neuroendocrine neoplasms (NENs) are very heterogeneous, ranging from mostly indolent, atrophic gastritis-associated, type I neuroendocrine tumors (NETs), through highly malignant, poorly differentiated neuroendocrine carcinomas (pdNECs), to sporadic type III NETs with intermediate prognosis, and various rare tumor types. Histologic differentiation, proliferative grade, size, level of gastric wall invasion, and local or distant metastases are used as prognostic markers. However, their value remains to be tailored to specific gastric NENs. Series of type I NETs (n = 123 cases), type III NETs (n = 34 cases), and pdNECs (n = 43 cases) were retrospectively collected from four pathology centers specializing in endocrine pathology. All cases were characterized clinically and histopathologically. During follow-up (median 93 months) data were recorded to assess disease-specific patient survival. Type I NETs, type III NETs, and pdNECs differed markedly in terms of tumor size, grade, invasive and metastatic power, as well as patient outcome. Size was used to stratify type I NETs into subgroups with significantly different invasive and metastatic behavior. All 70 type I NETs < 0.5 cm (micro-NETs) were uneventful. Ki67-based grading proved efficient for the prognostic stratification of type III NETs; however, grade 2 (G2) was not associated with tumor behavior in type I NETs. Although G3 NETs (2 type I and 9 type III) had a very poor prognosis, it was found that patient survival was longer with type III G3 NETs compared to pdNECs. Given the marked, tumor type-related behavior differences, evaluation of gastric NEN prognostic parameters should be tailored to the type of neoplastic disease. © 2018 S. Karger AG, Basel.

Relationship of PCNA, C-erbB2 and CD44s expression with tumor grade and stage in urothelial carcinomas of the bladder

PubMed Central

Yıldırım, Ayhan; Kösem, Mustafa; Sayar, İlyas; Gelincik, İbrahim; Yavuz, Alparslan; Bozkurt, Aliseydi; Erkorkmaz, Ünal; Bayram, İrfan

2014-01-01

In the present study, the intention was to reveal the relationship of histological grade and stage with c-erbB2, CD44s, and PCNA immunoreactivity in bladder urothelial carcinomas (UC). In our study, we evaluated 46 items of transurethral resection material of patients submitted by YYU Faculty of Medicine, Main Department of Pathology, with a mass revealed in their bladder after clinical and radiological studies at our laboratories and who were diagnosed with urothelial carcinomas. PCNA, c-erbB2, and CD44s were applied in an immunohistochemical manner comprised from nine low-malignant potential papillary urothelial neoplasia, 23 low-grade papillary urothelial carcinoma, and 14 high-grade papillary urothelial carcinoma. Immunostaining was scored according to the percentage of positive cells. The immunohistochemical study demonstrated that the c-erbB2 and PCNA staining ratio increased when an increase occurred in stage and grade. The CD44s staining ratio decreased. C-erbB2, PCNA, and CD44s appear to be a useful marker in the assessment of the prognosis and treatment options in urothelial carcinomas. PMID:25035774

Pediatric Brain Tumors: Genomics and Epigenomics Pave the Way.

PubMed

Fontebasso, Adam M; Jabado, Nada

2015-01-01

Primary malignant brain tumors remain a disproportionate cause of morbidity and mortality in humans. A number of studies exploring the cancer genome of brain tumors across ages using integrated genetics and epigenetics and next-generation sequencing technologies have recently emerged. This has led to considerable advances in the understanding of the basic biology and pathogenesis of brain tumors, including the most malignant and common variants in children: gliomas and medulloblastoma. Notably, studies of pediatric brain tumors have identified unexpected oncogenic pathways implicated in tumorigenesis. These range from a single pathway/molecule defect such as abnormalities of the mitogen-activated protein kinase pathway, considered to be a hallmark of pilocytic astrocytomas, to alterations in the epigenome as a critical component altered in many subgroups of high-grade brain tumors. Importantly, the type, timing, and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective brain tumor they target and critical markers for therapy that will help refine pathological grading. We summarize these novel findings in pediatric brain tumors, which also are put in the context of the evolving notion of molecular pathology, now a mandated tool for proper classification and therapy assignment in the clinical setting.

MR imaging of post-traumatic articular cartilage injuries confined to the femoral trochlea. Arthroscopic correlation and clinical significance.

PubMed

Huegli, Rolf W; Moelleken, Sonja M C; Stork, Alexander; Bonel, Harald M; Bredella, Miriam A; Meckel, Stephan; Genant, Harry K; Tirman, Phillip F J

2005-01-01

To assess and describe post-traumatic articular cartilage injuries isolated to the trochlear groove and provide insight into potential mechanism of injury. We retrospectively evaluated MR imaging findings of all knee MRIs performed at our institution over the last 2 years (2450). Thirty patients met the criteria of a cartilage injury confined to the trochlear groove. In 15 cases, which were included in our study, arthroscopic correlation was available. Each plane was evaluated and graded for the presence and appearance of articular cartilage defects using a standard arthroscopic grading scheme adapted to MR imaging. Any additional pathological derangement was documented and information about the mechanism of injury was retrieved by chart review. In all cases the cartilaginous injury was well demonstrated on MRI. In 13 patients additional pathological findings could be observed. The most frequently associated injury was a meniscal tear in nine patients. In eight cases, the arthroscopic grading of the trochlear injury matched exactly with the MRI findings. In the remaining seven cases, the discrepancy between MRI and arthroscopy was never higher than one grade. In 13 out of 15 of patients trauma mechanism could be evaluated. Twelve patients suffered an indirect twisting injury and one suffered a direct trauma to their knee. The findings of this study demonstrate that MR imaging allows reliable grading of isolated injury to the trochlear groove cartilage and assists in directing surgical diagnosis and treatment. These injuries may be the only hyaline cartilage injury in the knee and meniscal tears are a frequently associated finding. Therefore, it is important to search specifically for cartilage injuries of the trochlear groove in patients with anterior knee pain, even if other coexistent pathology could potentially explain the patient's symptoms.

Chronic Lymphocytic Leukemia (CLL) as an Unusual Cause of Rapid Airway Compromise

DTIC Science & Technology

2017-04-15

into an aggressive, high-grade NHL is known as Richter syndrome and may occur in up to 10% of patients with CLL [6J. Although indolent in nature...racheostomy placement. The BOT mass was biopsied at the time of tracheostomy placement. The pathology specimen demonstrated squamous mucosa with acute ...clinicians and institutions and may involve single or multi-modality therapies [9] . The possibility of Richter syndrome with transformation of CLL into a

MR-monitored LITT as a palliative concept in patients with high grade gliomas: preliminary clinical experience.

PubMed

Reimer, P; Bremer, C; Horch, C; Morgenroth, C; Allkemper, T; Schuierer, G

1998-01-01

The purpose of this study was to evaluate the clinical utility of laser-induced thermotherapy (LITT) as a palliative treatment for patients with high-grade gliomas. Four consenting patients with recurrent high grade III/IV gliomas near the primary language or motor areas were palliatively treated with LITT (2-5 W, 3-13 minutes; Neodym YAG Laser, Dornier, Friedrichshafen, Germany). Temperature monitoring was performed by T1-weighted turbo-fast low-angle shot (FLASH) imaging at 1.5 T (Siemens Magnetom SP 4000, Siemens, Erlangen, Germany). MRI studies before LITT included contrast-enhanced conventional scans and functional activation studies to localize the primary motor cortex or language areas using an echo-planar imaging (EPI) spin-echo (SE) sequence. Follow-up studies consisted of contrast-enhanced conventional scans as well as diffusion studies (contrast-enhanced Fourier-acquired steady-state technique and EPI-SE) and perfusion studies (EPI-SE with .2 mmol of gadolinium (Gd)/kg body weight) to differentiate post-therapeutic effects from residual or recurrent tumor growth. Local tumor control was achieved in areas with laser energy deposition with clinically stable conditions > or = 6 months. Conventional contrast-enhanced scans demonstrated strong enhancement surrounding ablated tumor components, which showed a reduction in CBV/CBF. Perfusion studies were useful to discriminate granulomatous tissue enhancement from residual or recurrent tumor growth. Careful application of LITT may evolve as an alternative palliative concept for patients with end-stage high-grade cerebral gliomas reducing clinical symptoms from circumscribed areas of pathology.

'Telangiectatic' transformation in soft tissue sarcomas. a clinicopathology analysis of an aggressive feature of high-grade sarcomas.

PubMed

Sternheim, Amir; Jin, Xiaolong; Shmookler, Barry; Jelinek, James; Malawer, Martin M

2008-01-01

'Telangiectatic' change, which contains a large fluid hemorrhagic component, occurs in a variety of high-grade soft tissue sarcomas. In a retrospective database review, we identified 20 consecutive patients (3%) with 'telangiectatic' change in soft tissue sarcomas. Tumors were located in the thigh (55%), shoulder (15%), calf (15%), upper arm (10%), and buttock in one patient. All 20 tumors were high grade. Histological diagnoses were MFH (40%), leiomyosarcoma (15%), synovial sarcoma (10%), and one each of seven other sarcomas (35%). Tumor size was often large-more than 10 cm (35%), between 5 and 10 cm (60%), and less than 5 cm in one case. A history of contusion to the tumor site followed by swelling was recorded in 30% of patients and 80% presented with a painful mass. On MRI imaging, 60% of tumors appeared to contain more than 50% blood, 50% had a hemosiderin-laden rim, and 55% had well-defined tumor nodules within the wall of the hematoma. Limb-sparing surgery was carried out in 90% of patients, the other 10% underwent primary amputation. The 5-year, event-free survival rate was 30%. Of the patients, 15% presented initially with metastatic disease; in 53%, it developed within 2 years of diagnosis. The overall local recurrence rate was 30%. Telangiectatic transformation in soft tissue sarcomas is a rare feature of aggressive high-grade soft tissue sarcomas and is unique in its clinical presentation, MRI characteristics, pathological pattern, and a tendency for a worse-off prognosis.

Expression of Y-box-binding protein YB-1 allows stratification into long- and short-term survivors of head and neck cancer patients.

PubMed

Kolk, A; Jubitz, N; Mengele, K; Mantwill, K; Bissinger, O; Schmitt, M; Kremer, M; Holm, P S

2011-12-06

Histology-based classifications and clinical parameters of head and neck squamous cell carcinoma (HNSCC) are limited in their clinical capacity to provide information on prognosis and treatment choice of HNSCC. The primary aim of this study was to analyse Y-box-binding protein-1 (YB-1) protein expression in different grading groups of HNSCC patients, and to correlate these findings with the disease-specific survival (DSS). We investigated the expression and cellular localisation of the oncogenic transcription/translation factor YB-1 by immunohistochemistry on tissue micro arrays in a total of 365 HNSCC specimens and correlated expression data with clinico-pathological parameters including DSS. Compared with control tissue from healthy individuals, a significantly (P<0.01) increased YB-1 protein expression was observed in high-grade HNSCC patients. By univariate survival data analysis, HNSCC patients with elevated YB-1 protein expression had a significantly (P<0.01) decreased DSS. By multivariate Cox regression analysis, high YB-1 expression and nuclear localisation retained its significance as a statistically independent (P<0.002) prognostic marker for DSS. Within grade 2 group of HNSCC patients, a subgroup defined by high nuclear and cytoplasmic YB-1 levels (co-expression pattern) in the cells of the tumour invasion front had a significantly poorer 5-year DSS rate of only 38% compared with overall 55% for grade 2 patients. Vice versa, the DSS rate was markedly increased to 74% for grade 2 cancer patients with low YB-1 protein expression at the same localisation. Our findings point to the fact that YB-1 expression in combination with histological classification in a double stratification strategy is superior to classical grading in the prediction of tumour progression in HNSCC.

Expression of Y-box-binding protein YB-1 allows stratification into long- and short-term survivors of head and neck cancer patients

PubMed Central

Kolk, A; Jubitz, N; Mengele, K; Mantwill, K; Bissinger, O; Schmitt, M; Kremer, M; Holm, P S

2011-01-01

Background: Histology-based classifications and clinical parameters of head and neck squamous cell carcinoma (HNSCC) are limited in their clinical capacity to provide information on prognosis and treatment choice of HNSCC. The primary aim of this study was to analyse Y-box-binding protein-1 (YB-1) protein expression in different grading groups of HNSCC patients, and to correlate these findings with the disease-specific survival (DSS). Methods: We investigated the expression and cellular localisation of the oncogenic transcription/translation factor YB-1 by immunohistochemistry on tissue micro arrays in a total of 365 HNSCC specimens and correlated expression data with clinico-pathological parameters including DSS. Results: Compared with control tissue from healthy individuals, a significantly (P<0.01) increased YB-1 protein expression was observed in high-grade HNSCC patients. By univariate survival data analysis, HNSCC patients with elevated YB-1 protein expression had a significantly (P<0.01) decreased DSS. By multivariate Cox regression analysis, high YB-1 expression and nuclear localisation retained its significance as a statistically independent (P<0.002) prognostic marker for DSS. Within grade 2 group of HNSCC patients, a subgroup defined by high nuclear and cytoplasmic YB-1 levels (co-expression pattern) in the cells of the tumour invasion front had a significantly poorer 5-year DSS rate of only 38% compared with overall 55% for grade 2 patients. Vice versa, the DSS rate was markedly increased to 74% for grade 2 cancer patients with low YB-1 protein expression at the same localisation. Conclusion: Our findings point to the fact that YB-1 expression in combination with histological classification in a double stratification strategy is superior to classical grading in the prediction of tumour progression in HNSCC. PMID:22095225

[Clinical analysis of 19 pregnancies complicated listeriosis].

PubMed

Kuang, L H; Gong, Y H; Su, M; Jiang, Y M

2017-10-25

Objective: To analyze the clinical characteristics and perinatal outcomes of listeriosis during pregnancy. Methods: From July 2010 to April 2017, 70 131 women delivered in West China Second University Hospital. Nineteen cases were confirmed as listeriosis. The clinical symptoms, laboratory results, pathogens, placenta pathology and perinatal outcomes were analyzed retrospectively. Results: The median age of the 19 cases was 29.7 (19.0-42.0) years old. The median time before diagnosis was 4.8(0.5-19.0) days. The main clinical symptoms at first visits were high fever (17/19), increased white blood cells (18/19), abdominal pain (12/19). Listeria was found in samples of mother's blood (11/19), vaginal secretions (15/19), placenta (1/19), neonatal blood (4/19), neonatal phlegm (5/19) and neonatal ear secretions (1/19), respectively. Inflammation of placenta was identified in all 19 cases. Among the 19 cases, 1 was grade Ⅰ chorioamnionitis, 4 was grade Ⅱ, 5 was grade Ⅲ and 9 was grade Ⅵ. Only 4 newborn survived after therapy, and others suffered perinatal death, including 8 cases of intrauterine death, 3 cases of miscarriage and 6 cases of treatment failure. Conclusions: Listeriosis has characteristics of acute onset, quick development and high morbidity during pregnancy. The empiric use of antibiotics might not cover listeria. The understanding of listeriosis should be improved.

The Added Value of Pathology Review in Vulvar Cancer: Results From a Population-based Cohort Study.

PubMed

Barbera, Lisa; Gien, Lilian T; Sutradhar, Rinku; Thomas, Gillian; Covens, Al; Elit, Laurie; Fyles, Anthony; Rakovitch, Eileen; Liu, Ying; Khalifa, Mahmoud

2017-03-01

We conducted a population-based patterns of care study of vulvar carcinoma. This paper describes the changes in reporting based on pathology review. This is a retrospective population-based cohort study. We obtained all pathology records available from the provincial cancer registry for primary invasive squamous cell carcinoma of the vulva diagnosed between 1998 and 2007. Pathology reviews were conducted centrally by a group of gynecologic pathologists and were identified during abstraction. Corresponding original reports were matched to pathology review reports based on accession numbers. We compared the reported value for presence/absence of invasion, grade, depth, thickness, size, lymphovascular space invasion, peripheral margin status, and deep margin status in the original and review report. A total of 1011 vulvar resection reports were identified. From these, we identified 316 pairs of original/review reports. Missing data were common but improved in the reviews. In total, 55 (17%) reports had at least 1 change from the original to the review based on presence of invasion, depth, lymphovascular space invasion, or margin. When we included reports where a variable was missing in the original but then completed in the review, there were clinically relevant changes in 210 reports (66%). Vulvar carcinoma is a rare diagnosis and pathology reviews resulted in potentially important clinical changes in a significant proportion of cases. Referral pathologists play an important role in contributing to high-quality clinical decisions.

Outcome prediction of third ventriculostomy: a proposed hydrocephalus grading system.

PubMed

Kehler, U; Regelsberger, J; Gliemroth, J; Westphal, M

2006-08-01

An important factor in making a recommendation for different treatment modalities in hydrocephalus patients (VP shunt versus endoscopic third ventriculostomy) is the definition of the underlying pathology which determines the prognosis/outcome of the surgical procedure. Third ventriculostomies (3rd VS) are successful mainly in obstructive hydrocephalus but also in some subtypes of communicating hydrocephalus. A simple, easily applicable grading system that is designed to predict the outcome of 3rd VS is proposed. The hydrocephalus is graded on the basis of the extent of downward bulging of the floor of the third ventricle, which reflects the pressure gradient between the 3rd ventricle and the basal cisterns, presence of directly visualised CSF pathway obstruction in MRI, and the progression of the clinical symptoms resulting in five different grades. In this proposed grading system, grade 1 hydrocephalus subtype shows no downward bulged floor of the 3rd ventricle, no obstruction of the CSF pathway, and no progressive symptoms of hydrocephalus. There is no indication for 3rd VS. Grades 2 to 4 show different combinations of the described parameters. Grade 5 subtype shows a markedly downward bulged floor of the 3rd ventricle and direct detection of the CSF pathway obstruction (i.e., aqueductal stenosis) with progressive clinical deterioration. Retrospective application of this grading scheme to a series of 72 3rd VS has demonstrated a high correlation with the outcome: The success rate in grade 3 reached 40%, in grade 4: 58%, and in grade 5: 95%. This standardised grading system predicts the outcome of 3rd VS and helps in decision making for 3rd VS versus VP shunting.

Indian Hedgehog signaling pathway members are associated with magnetic resonance imaging manifestations and pathological scores in lumbar facet joint osteoarthritis

NASA Astrophysics Data System (ADS)

Shuang, Feng; Zhou, Ying; Hou, Shu-Xun; Zhu, Jia-Liang; Liu, Yan; Zhang, Chun-Li; Tang, Jia-Guang

2015-05-01

Indian Hedgehog (HH) has been shown to be involved in osteoarthritis (OA) in articular joints, where there is evidence that Indian HH blockade could ameliorate OA. It seems to play a prominent role in development of the intervertebral disc (IVD) and in postnatal maintenance. There is little work on IHH in the IVD. Hence the aim of the current study was to investigate the role of Indian Hedgehog in the pathology of facet joint (FJ) OA. 24 patients diagnosed with lumbar intervertebral disk herniation or degenerative spinal stenosis were included. Preoperative magnetic resonance imaging (MRI) and Osteoarthritis Research Society International (OARSI) histopathology grading system was correlated to the mRNA levels of GLI1, PTCH1, and HHIP in the FJs. The Weishaupt grading and OARSI scores showed high positive correlation (r = 0.894) (P < 0.01). MRI Weishaupt grades showed positive correlation with GLI1 (r = 0.491), PTCH1 (r = 0.444), and HHIP (r = 0.654) mRNA levels (P < 0.05 in each case). OARSI scores were also positively correlated with GLI1 (r = 0. 646), PTCH1 (r = 0. 518), and HHIP (r = 0.762) mRNA levels (P < 0.01 in each case). Cumulatively our findings indicate that Indian HH signaling is increased in OA and is perhaps a key component in OA pathogenesis and progression.

Effectiveness of Radiotherapy in Myxoid Sarcomas Is Associated With a Dense Vascular Pattern

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

Vreeze, Ronald S.A. de; Jong, Daphne de; Haas, Rick L.

2008-12-01

Purpose: Surgery and adjuvant radiotherapy (RT) have long been the standard treatment for most deep-seated sarcomas; however, since the randomized trial from the National Cancer Institute of Canada, which described similar local control for pre- vs. postoperative RT, both modalities are now widely accepted. As a group, sarcomas are classified as radiation resistant. The subgroup of myxoid liposarcoma (MLS), a sarcoma with a typical vascular crow's feet pattern, is highly radiosensitive, but a mechanism for this phenomenon is unknown. Here we describe our results with preoperative RT and propose a mechanism explaining the high sensitivity based on the distinctive vascularizationmore » pattern of MLS. Methods and Materials: Between 2002 and 2006, 31 sarcoma patients, including 10 with MLS, underwent preoperative RT at our institute. Resected specimens were histologically evaluated, focusing on classification, grade, and vascularization patterns. Results: Twenty sarcomas showed more than 80% pathologic response after preoperative RT. A pathologic complete response was found in all 'pure' MLS specimens after preoperative RT (n = 8). There were no pathologic complete responses in the remaining sarcoma patients (n = 23), although 12 showed 80% to 90% pathologic response. In contrast to the remaining RT-resistant sarcomas, the highly responding specimens contained branching vasculature, partial thrombus formation and inflammation of medium sized arterioles, similar to the vascular changes in MLS. Conclusions: Both MLS and sarcomas with MLS-like vasculature are highly radiosensitive. Radiation sensitivity may be explained by changes in medium-sized arterioles, obstructing the specific crow's feet vascularization and inducing hypoxia with secondary tumor cell death.« less

[Correlations between MRI apparent diffusion coefficient and histological grade and molecular biology of breast invasive ductal carcinoma].

PubMed

Yu, Xuejuan; Liu, Shangang; Chen, Zhaoqiu; Zhang, Pinliang; Zhang, Jianbo; Xu, Liang; Liu, Zengjun; Ren, Ruimei

2014-08-01

To study the correlation between the MRI apparent diffusion coefficient (ADC) value and histological grade and molecular biology of breast invasive ductal carcinoma (IDC). This retrospective study included 125 patients with IDC verified by pathology from February 2010 to February 2013. Conventional MRI and diffusion-weighted imaging (DWI) examination were performed using a 3.0T scanner with diffusion factor of 0 and 800 s/mm(2). The region of interest (ROI) was drawn on the largest lesion and/or its two adjacent slices. The ADC value of the whole tumor was calculated as the mean ADC value. The correlation between mean ADCs and histological grade and biological factors was analyzed. The mean ADC of pathological grade I, II and III IDC was (1.152 ± 0.072)×10(-3) mm(2)/s, (1.102 ± 0.101)×10(-3) mm(2)/s, and (1.035 ± 0.107)×10(-3) mm(2)/s, respectively. There was a statistically significant difference among them (P = 0.003). Statistically a significant difference was observed between grade III and I (P = 0.034), grade III and II (P = 0.006), but not between grade I and II (P = 0.741). A significant correlation was observed between ADC value and pathological grade (r = -0.342, P < 0.001). The median ADC values were significantly higher in the ER-negative than in the ER-positive cases [(1.130 ± 0.115)×10(-3) mm(2)/s vs. (1.060 ± 0.089) ×10(-3) mm(2)/s, P < 0.001)], in PR-negative than in PR-positive cases [(1.121 ± 0.106)×10(-3) mm(2)/s vs. (1.055 ± 0.096) ×10(-3) mm(2)/s, P < 0.001)], and in Ki-67-negative than in Ki-67-positive cases [(1.153 ± 0.090)×10(-3) mm(2)/s vs. (1.063 ± 0.101) ×10(-3) mm(2)/s, P < 0.001]. A statistically significant correlation was observed between ADC value and expressions of ER, PR, and Ki-67 (r = -0.311, r = -0.317, r = -0.414, P < 0.001). ADC value of breast invasive ductal carcinoma is correlated with histological grade, and expression of ER, PR and Ki-67.

Attention problems and pathological gaming: resolving the 'chicken and egg' in a prospective analysis.

PubMed

Ferguson, Christopher J; Ceranoglu, T Atilla

2014-03-01

Pathological gaming (PG) behaviors are behaviors which interfere with other life responsibilities. Continued debate exists regarding whether symptoms of PG behaviors are a unique phenomenon or arise from other mental health problems, including attention problems. Development of attention problems and occurrence of pathological gaming in 144 adolescents were followed during a 1-year prospective analysis. Teens and their parents reported on pathological gaming behaviors, attention problems, and current grade point average, as well as several social variables. Results were analyzed using regression and path analysis. Attention problems tended to precede pathological gaming behaviors, but the inverse was not true. Attention problems but not pathological gaming predicted lower GPA 1 year later. Current results suggest that pathological gaming arises from attention problems, but not the inverse. These results suggest that pathological gaming behaviors are symptomatic of underlying attention related mental health issues, rather than a unique phenomenon.

Endometrial stromal sarcoma diagnosed after uterine morcellation in laparoscopic supracervical hysterectomy.

PubMed

Della Badia, Carl; Karini, Homa

2010-01-01

Endometrial stromal sarcoma is a rare uterine cancer with no reliable method for preoperative diagnosis. A 30-year-old parous woman underwent laparoscopic supracervical hysterectomy because of a leiomyoma. The uterus was removed from the abdominal cavity with an electric morcellator with a spinning blade. The pathology report revealed low-grade endometrial stromal sarcoma. Two months after the initial surgery, a second laparoscopic procedure was performed. The final pathology report confirmed low-grade endometrial stromal sarcoma involving the ovary, fallopian tube, and ovarian artery. It was concluded that morcellation of leiomyomas at laparoscopic supracervical hysterectomy may potentially increase metastasis if the tumor is a sarcoma. Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.

Graft-versus-Host Disease of the Gut: A Histologic Activity Grading System and Validation.

PubMed

Myerson, David; Steinbach, Gideon; Gooley, Ted A; Shulman, Howard M

2017-09-01

The pathologic interpretation of gut biopsies in hematopoietic cell transplant recipients to assess graft-versus-host disease (GVHD) is well accepted and supplements clinical and endoscopic findings. However, the histologic activity grading of GVHD is controversial, with attempts to predict prognosis or response to treatment largely unsuccessful. GVHD is being diagnosed earlier in its course, raising the possibility that the pathologic grading system can be profitably modified. We developed a histologic activity grading system designed to replace the commonly used modified Lerner grading systems. Our system stratifies the low-level Lerner grade I category into 4 activity grade categories, based on the average frequency of apoptotic cells. The results are expressed as ordinal categories: GVHD of minimal, mild, moderate, severe histologic activity, or severe histologic activity with destruction (activity grades 1 to 5). In a retrospective study, we studied 87 consecutive cases with 201 post-transplantation specimens (median, 48 days; range, 18 to 1479 days) of stomach, duodenum, and colorectum, which had been activity graded at the time of the original diagnosis. Most of the biopsies diagnosed as GVHD were low grade-minimal (11%) or mild (71%) histologic activity. We hypothesized that the higher activity grades would be associated with more therapeutic intervention. The odds of increased therapy in the combined all-site specimens were increased as activity grade increased (odds ratio, 2.9 [95% confidence interval {CI}, 1.9 to 4.5]; P = < .0001). Thus, our grading system was validated. To investigate whether the activity grade was associated with therapy within the formerly undivided Lerner grade I category, the analysis was restricted to these 174 all-site specimens. The validation result was similar (odds ratio, 3.1 [95% CI, 1.3 to 7.2]; P = .009). This result interestingly suggests that there is useful information hidden in the Lerner grade I category, which could potentially guide immediately actionable treatment decisions. This histologic activity grade system has been in use at our institution for over 2 years with good acceptance. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Development and validation of a surgical-pathologic staging and scoring system for cervical cancer.

PubMed

Li, Shuang; Li, Xiong; Zhang, Yuan; Zhou, Hang; Tang, Fangxu; Jia, Yao; Hu, Ting; Sun, Haiying; Yang, Ru; Chen, Yile; Cheng, Xiaodong; Lv, Weiguo; Wu, Li; Zhou, Jin; Wang, Shaoshuai; Huang, Kecheng; Wang, Lin; Yao, Yuan; Yang, Qifeng; Yang, Xingsheng; Zhang, Qinghua; Han, Xiaobing; Lin, Zhongqiu; Xing, Hui; Qu, Pengpeng; Cai, Hongbing; Song, Xiaojie; Tian, Xiaoyu; Shen, Jian; Xi, Ling; Li, Kezhen; Deng, Dongrui; Wang, Hui; Wang, Changyu; Wu, Mingfu; Zhu, Tao; Chen, Gang; Gao, Qinglei; Wang, Shixuan; Hu, Junbo; Kong, Beihua; Xie, Xing; Ma, Ding

2016-04-12

Most cervical cancer patients worldwide receive surgical treatments, and yet the current International Federation of Gynecology and Obstetrics (FIGO) staging system do not consider surgical-pathologic data. We propose a more comprehensive and prognostically valuable surgical-pathologic staging and scoring system (SPSs). Records from 4,220 eligible cervical cancer cases (Cohort 1) were screened for surgical-pathologic risk factors. We constructed a surgical-pathologic staging and SPSs, which was subsequently validated in a prospective study of 1,104 cervical cancer patients (Cohort 2). In Cohort 1, seven independent risk factors were associated with patient outcome: lymph node metastasis (LNM), parametrial involvement, histological type, grade, tumor size, stromal invasion, and lymph-vascular space invasion (LVSI). The FIGO staging system was revised and expanded into a surgical-pathologic staging system by including additional criteria of LNM, stromal invasion, and LVSI. LNM was subdivided into three categories based on number and location of metastases. Inclusion of all seven prognostic risk factors improves practical applicability. Patients were stratified into three SPSs risk categories: zero-, low-, and high-score with scores of 0, 1 to 3, and ≥4 (P=1.08E-45; P=6.15E-55). In Cohort 2, 5-year overall survival (OS) and disease-free survival (DFS) outcomes decreased with increased SPSs scores (P=9.04E-15; P=3.23E-16), validating the approach. Surgical-pathologic staging and SPSs show greater homogeneity and discriminatory utility than FIGO staging. Surgical-pathologic staging and SPSs improve characterization of tumor severity and disease invasion, which may more accurately predict outcome and guide postoperative therapy.

Elastic Stable Intramedullary Nailing (ESIN), Orthoss® and Gravitational Platelet Separation - System (GPS®): An effective method of treatment for pathologic fractures of bone cysts in children

PubMed Central

2011-01-01

Background The different treatment strategies for bone cysts in children are often associated with persistence and high recurrence rates of the lesions. The safety and clinical outcomes of a combined mechanical and biological treatment with elastic intramedullary nailing, artificial bone substitute and autologous platelet rich plasma are evaluated. Methods From 02/07 to 01/09 we offered all children with bone cysts the treatment combination of elastic intramedullary nailing (ESIN), artificial bone substitute (Orthoss®) and autologous platelet rich plasma, concentrated by the Gravitational Platelet Separation (GPS®) - System. All patients were reviewed radiologically for one year following the removal of the intramedullary nailing, which was possible because of cyst obliteration. Results A cohort of 12 children (4 girls, 8 boys) was recruited. The mean patient age was 11.4 years (range 7-15 years). The bone defects (ten humeral, two femoral) included eight juvenile and four aneurysmal bone cysts. Five patients suffered from persistent cysts following earlier unsuccessful treatment of humeral bone cyst after pathologic fracture; the other seven presented with acute pathologic fractures. No peri- or postoperative complications occurred. The radiographic findings showed a total resolution of the cysts in ten cases (Capanna Grade 1); in two cases a small residual cyst remained (Capanna Grade 2). The intramedullary nails were removed six to twelve months (mean 7.7) after the operation; in one case, a fourteen year old boy (Capanna Grade 2), required a further application of GPS® and Orthoss® to reach a total resolution of the cyst. At follow-up (20-41 months, mean 31.8 months) all patients showed very good functional results and had returned to sporting activity. No refracture occurred, no further procedure was necessary. Conclusions The combination of elastic intramedullary nailing, artificial bone substitute and autologous platelet rich plasma (GPS®) enhances the treatment of bone cysts in children, with no resulting complications. PMID:21314981

A phase II study of preoperative chemoradiation with tegafur-uracil plus leucovorin for locally advanced rectal cancer with pharmacogenetic analysis.

PubMed

Kim, Sun Young; Baek, Ji Yeon; Oh, Jae Hwan; Park, Sung Chan; Sohn, Dae Kyung; Kim, Min Ju; Chang, Hee Jin; Kong, Sun-Young; Kim, Dae Yong

2017-03-27

This study aimed to evaluate the efficacy of a high dose of oral tegafur-uracil (400 mg/m 2 ) plus leucovorin with preoperative chemoradiation of locally advanced rectal cancer and to explore the impact of polymorphisms of cytochrome P 2A6 (CYP2A6), uridine monophosphate synthetase (UMPS), and ATP-binding cassette B1 (ABCB1) on clinical outcome. Patients with cT3 or cT4 rectal cancer were enrolled and were given tegafur-uracil 400 mg/m 2 /day and leucovorin 90 mg/m 2 /day for 7 days a week during preoperative chemoradiation (50.4 Gy/28 fractions) in this phase II trial. Primary endpoint was pathologic complete response rate, and the secondary endpoint was to explore the association between clinical outcomes and genetic polymorphisms CYP2A6 (*4, *7, *9 and *10), UMPS G638C, and three ABCB1 genotypes (C1236T, C3435T, and G2677T). Ninety-one patients were given study treatment, and 90 underwent surgery. Pathologic complete response was noted in 10 patients (11.1%). There was no grade 4 or 5 toxicity; 20 (22.0%) experienced grade 3 toxicities, including diarrhea (10, 11.0%), abdominal pain (2, 2.2%), and anemia (2, 2.2%). Relapse-free survival and overall survival at 5 years were 88.6% and 94.2%, respectively. Patients with the UMPS 638 CC genotype experienced significantly more frequent grade 2 or 3 diarrhea (p for trend = 0.018). Preoperative chemoradiation with tegafur-uracil 400 mg/m 2 /day with leucovorin was feasible, but did not meet the expected pathologic complete response rate. The UMPS 638 CC genotype might be a candidate biomarker predicting toxicity in patients receiving tegafur-uracil/leucovorin-based preoperative chemoradiation for locally advanced rectal cancer. ISRCTN11812525 , registered on 25 July 2016. Retrospectively registered.

Treatment of low-grade endometrial stromal sarcoma in a nulligravid woman.

PubMed

Michael Straughn, J; Boitano, Teresa; Smith, Haller J; Dilley, Sarah E; Liang, Margaret I; Novak, Lea

2018-06-07

A 32 year-old nulligravid woman with a uterine mass underwent exploratory laparotomy with myomectomy. Final pathology revealed a low-grade endometrial stromal sarcoma (ESS) with positive margins. She subsequently underwent definitive robotic hysterectomy and bilateral salpingectomy with ovarian preservation. She was diagnosed with a stage IB low-grade ESS. She is currently undergoing observation. Discussion of classification, surgical options, and adjuvant therapy is presented. Copyright © 2018 Elsevier Inc. All rights reserved.

Activation of Wnt signalling promotes development of dysplasia in Barrett's oesophagus.

PubMed

Moyes, Lisa H; McEwan, Hamish; Radulescu, Sorina; Pawlikowski, Jeff; Lamm, Catherine G; Nixon, Colin; Sansom, Owen J; Going, James J; Fullarton, Grant M; Adams, Peter D

2012-09-01

Barrett's oesophagus is a precursor of oesophageal adenocarcinoma, via intestinal metaplasia and dysplasia. Risk of cancer increases substantially with dysplasia, particularly high-grade dysplasia. Thus, there is a clinical need to identify and treat patients with early-stage disease (metaplasia and low-grade dysplasia) that are at high risk of cancer. Activated Wnt signalling is critical for normal intestinal development and homeostasis, but less so for oesophageal development. Therefore, we asked whether abnormally increased Wnt signalling contributes to the development of Barrett's oesophagus (intestinal metaplasia) and/or dysplasia. Forty patients with Barrett's metaplasia, dysplasia or adenocarcinoma underwent endoscopy and biopsy. Mice with tamoxifen- and β-naphthoflavone-induced expression of activated β-catenin were used to up-regulate Wnt signalling in mouse oesophagus. Immunohistochemistry of β-catenin, Ki67, a panel of Wnt target genes, and markers of intestinal metaplasia was performed on human and mouse tissues. In human tissues, expression of nuclear activated β-catenin was found in dysplasia, particularly high grade. Barrett's metaplasia did not show high levels of activated β-catenin. Up-regulation of Ki67 and Wnt target genes was also mostly associated with high-grade dysplasia. Aberrant activation of Wnt signalling in mouse oesophagus caused marked tissue disorganization with features of dysplasia, but only selected molecular indicators of metaplasia. Based on these results in human tissues and a mouse model, we conclude that abnormal activation of Wnt signalling likely plays only a minor role in initiation of Barrett's metaplasia but a more critical role in progression to dysplasia. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Are all grade group 4 prostate cancers created equal? Implications for the applicability of the novel grade grouping.

PubMed

Gandaglia, Giorgio; Karnes, R Jeffrey; Sivaraman, Arjun; Moschini, Marco; Fossati, Nicola; Zaffuto, Emanuele; DellʼOglio, Paolo; Cathelineau, Xavier; Montorsi, Francesco; Sanchez-Salas, Rafael; Briganti, Alberto

2017-07-01

According to the novel prostate cancer (PCa) grade grouping, men with Gleason score 8 should be included in the grade group 4 regardless of primary and secondary scores. We aimed at evaluating the effect of Gleason patterns on the risk of recurrence in men with grade group 4 PCa. Overall, 1,089 patients treated with radical prostatectomy with grade group 4 PCa at final pathology were identified. Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen values≥0.2ng/ml and rising. Clinical recurrence (CR) was defined as positive imaging after BCR. Kaplan-Meier analyses assessed time to BCR and CR. Multivariable Cox regression analyses assessed the impact of Gleason patterns on the risk of BCR and CR. Overall, 295 (27.1%), 651 (59.8%), and 143 (13.1%) patients had pathologic Gleason pattern 3+5, 4+4, and 5+3. Overall, 435 (39.9%) patients had positive margins and 439 (30.2%), 300 (27.5%), 350 (32.1%), and 216 (19.8%) had pT2, pT3a, pT3b/4, and pN1 disease. Median follow-up was 83 months. Overall, 536 and 221 patients experienced BCR and CR. The 10-year BCR- and CR-free survival rates were 42.9% and 67.5% vs. 38.3% and 59.7% vs. 40.6% and 50.4% for patients with pathologic Gleason pattern 3+5 vs. 4+4 vs. 5+3, respectively (all P≤0.005). In multivariable analyses, patients with Gleason pattern 3+5 were at lower risk of BCR compared to those with 4+4 (P = 0.002). Men with Gleason pattern 3+5 were at lower risk of CR compared to those with 4+4 and 5+3 (all P≤ 0.01). Patients with a primary Gleason score 3 are at reduced risk of recurrence as compared to their counterparts with 4 or 5. Primary and secondary Gleason scores should be considered to stratify the risk of recurrence after surgery in patients with grade group 4 PCa. Copyright © 2017 Elsevier Inc. All rights reserved.

Banff schema for grading pancreas allograft rejection: working proposal by a multi-disciplinary international consensus panel.

PubMed

Drachenberg, C B; Odorico, J; Demetris, A J; Arend, L; Bajema, I M; Bruijn, J A; Cantarovich, D; Cathro, H P; Chapman, J; Dimosthenous, K; Fyfe-Kirschner, B; Gaber, L; Gaber, O; Goldberg, J; Honsová, E; Iskandar, S S; Klassen, D K; Nankivell, B; Papadimitriou, J C; Racusen, L C; Randhawa, P; Reinholt, F P; Renaudin, K; Revelo, P P; Ruiz, P; Torrealba, J R; Vazquez-Martul, E; Voska, L; Stratta, R; Bartlett, S T; Sutherland, D E R

2008-06-01

Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined. The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.

Multiwavelet grading of prostate pathological images

NASA Astrophysics Data System (ADS)

Soltanian-Zadeh, Hamid; Jafari-Khouzani, Kourosh

2002-05-01

We have developed image analysis methods to automatically grade pathological images of prostate. The proposed method generates Gleason grades to images, where each image is assigned a grade between 1 and 5. This is done using features extracted from multiwavelet transformations. We extract energy and entropy features from submatrices obtained in the decomposition. Next, we apply a k-NN classifier to grade the image. To find optimal multiwavelet basis, preprocessing, and classifier, we use features extracted by different multiwavelets with either critically sampled preprocessing or repeated row preprocessing and different k-NN classifiers and compare their performances, evaluated by total misclassification rate (TMR). To evaluate sensitivity to noise, we add white Gaussian noise to images and compare the results (TMR's). We applied proposed methods to 100 images. We evaluated the first and second levels of decomposition using Geronimo, Hardin, and Massopust (GHM), Chui and Lian (CL), and Shen (SA4) multiwavelets. We also evaluated k-NN classifier for k=1,2,3,4,5. Experimental results illustrate that first level of decomposition is quite noisy. They also show that critically sampled preprocessing outperforms repeated row preprocessing and has less sensitivity to noise. Finally, comparison studies indicate that SA4 multiwavelet and k-NN classifier (k=1) generates optimal results (with smallest TMR of 3%).

Grading system for blood vessel tumor emboli of invasive ductal carcinoma of the breast.

PubMed

Sugiyama, Michiko; Hasebe, Takahiro; Shimada, Hiroko; Takeuchi, Hideki; Shimizu, Kyoko; Shimizu, Michio; Yasuda, Masanori; Ueda, Shigeto; Shigekawa, Takashi; Osaki, Akihiko; Saeki, Toshiaki

2015-06-01

We previously reported that the number of mitotic and apoptotic figures in tumor cells in blood vessel tumor emboli had the greatest significant power for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. The purpose of the present study was to devise a grading system for blood vessel tumor emboli based on the mitotic and apoptotic figures of tumor cells in blood vessel tumor emboli, enabling accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 263 invasive ductal carcinomas into the following 3 grades according to the numbers of mitotic and apoptotic figures in tumor cells located in blood vessels within 1 high-power field: grade 0, no blood vessel invasion; grade 1, absence of mitotic figures and presence of any number of apoptotic figures, or 1 mitotic figure and 0 to 2 apoptotic figures; and grade 2, 1 mitotic figure and 3 or more apoptotic figures, or 2 or more mitotic figures and 1 or more apoptotic figures. Multivariate analyses with well-known prognostic factors demonstrated that grade 2 blood vessel tumor emboli significantly increased the hazard ratios for tumor recurrence independent of the nodal status, pathological TNM stage, hormone receptor status, or HER2 status. The presently reported grading system for blood vessel tumor emboli is the strongest histologic factor for accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. Copyright © 2015 Elsevier Inc. All rights reserved.

Cranial Chordoma: A New Preoperative Grading System.

PubMed

Brito da Silva, Harley; Straus, David; Barber, Jason K; Rostomily, Robert C; Ferreira, Manuel; Sekhar, Laligam N

2017-11-03

Chordomas are rare but challenging neoplasms involving the skull base. A preoperative grading system will be useful to identify both areas for treatment and risk factors, and correlate to the degree of resection, complications, and recurrence. To propose a new grading system for cranial chordomas designed by the senior author. Its purpose is to enable comparison of different tumors with a similar pathology to clivus chordoma, and statistically correlate with postoperative outcomes. The numerical grading system included tumor size, site of the tumor, vascular encasement, intradural extension, brainstem invasion, and recurrence of the tumor either after surgery or radiotherapy with a range of 2 to 25 points; it was used in 42 patients with cranial chordoma. The grading system was correlated with number of operations for resection, degree of resection, number and type of complications, recurrence, and survival. We found 3 groups: low-risk 0 to 7 points, intermediate-risk 8 to 12 points, and high-risk ≥13 points in the grading system. The 3 groups were correlated with the following: extent of resection (partial, subtotal, or complete; P < .002); number of operative stages to achieve removal (P < .014); tumor recurrence (P = .03); postoperative Karnofsky Performance Status (P < .001); and with successful outcome (P = .005). The grading system itself correlated with the outcome (P = .005). The proposed chordoma grading system can help surgeons to predict the difficulty of the case and know which areas of the skull base will need attention to plan further therapy. © Congress of Neurological Surgeons 2017.

Thulium Laser Treatment of Upper Urinary Tract Carcinoma: A Multi-Institutional Analysis of Surgical and Oncological Outcomes.

PubMed

Musi, Gennaro; Mistretta, Francesco A; Marenghi, Carlo; Russo, Andrea; Catellani, Michele; Nazzani, Sebastiano; Conti, Andrea; Luzzago, Stefano; Ferro, Matteo; Matei, Deliu V; Carmignani, Luca; de Cobelli, Ottavio

2018-03-01

To evaluate the efficacy and safety of ureteroscopic thulium laser (TL) treatment of upper urinary tract carcinoma (UTUC). Forty-two consecutive patients underwent conservative TL treatment for UTUC at two referral institutions. All patients underwent preliminary biopsy and then laser vaporization. A 272 μm and 365 μm laser fibers were used with a flexible and semirigid scope, respectively. Ablation was carried out with a 10 to 20 W power. Mean age at surgery was 68 years (SD 10.7). Mean tumor size was 14.3 mm (range 2-30 mm). Preliminary biopsy revealed the presence of low-grade disease in 29 (69.1%) patients, high-grade disease in 4 (9.5%) and 1 carcinoma in situ 1 (2.4%), whereas it was not conclusive in 8 (19%) cases. Final stage was pTa and pTis in 41 (97.6%) and 1 (2.4%) patients, respectively. Thirty eight percent (16) experienced Clavien-Dindo grade I complication, 47.6% (20) grade II, and 2.4% (1) grade III. Five (12%) patients underwent a second-look procedure due to residual disease. Eight (19%) patients experienced clinical recurrence. The median estimated recurrence-free survival was 44 months (SE 3.68). Four patients (9.5%) underwent a nephroureterectomy. Final pathological stage was pTis, pT3 high grade, pTa low grade, and pT0. Median follow-up was 26.3 months (range 2-54 months), and no progression or upstaging of disease occurred. TL management of UTUC is a safe and efficacious conservative treatment. Our experience shows optimal vaporization and hemostatic control in the absence of major complications.

Non-small cell lung cancer: Whole-lesion histogram analysis of the apparent diffusion coefficient for assessment of tumor grade, lymphovascular invasion and pleural invasion.

PubMed

Tsuchiya, Naoko; Doai, Mariko; Usuda, Katsuo; Uramoto, Hidetaka; Tonami, Hisao

2017-01-01

Investigating the diagnostic accuracy of histogram analyses of apparent diffusion coefficient (ADC) values for determining non-small cell lung cancer (NSCLC) tumor grades, lymphovascular invasion, and pleural invasion. We studied 60 surgically diagnosed NSCLC patients. Diffusion-weighted imaging (DWI) was performed in the axial plane using a navigator-triggered single-shot, echo-planar imaging sequence with prospective acquisition correction. The ADC maps were generated, and we placed a volume-of-interest on the tumor to construct the whole-lesion histogram. Using the histogram, we calculated the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC, skewness, and kurtosis. Histogram parameters were correlated with tumor grade, lymphovascular invasion, and pleural invasion. We performed a receiver operating characteristics (ROC) analysis to assess the diagnostic performance of histogram parameters for distinguishing different pathologic features. The ADC mean, 10th, 25th, 50th, 75th, 90th, and 95th percentiles showed significant differences among the tumor grades. The ADC mean, 25th, 50th, 75th, 90th, and 95th percentiles were significant histogram parameters between high- and low-grade tumors. The ROC analysis between high- and low-grade tumors showed that the 95th percentile ADC achieved the highest area under curve (AUC) at 0.74. Lymphovascular invasion was associated with the ADC mean, 50th, 75th, 90th, and 95th percentiles, skewness, and kurtosis. Kurtosis achieved the highest AUC at 0.809. Pleural invasion was only associated with skewness, with the AUC of 0.648. ADC histogram analyses on the basis of the entire tumor volume are able to stratify NSCLCs' tumor grade, lymphovascular invasion and pleural invasion.

Pancreatic neuroendocrine tumors containing areas of iso- or hypoattenuation in dynamic contrast-enhanced computed tomography: Spectrum of imaging findings and pathological grading.

PubMed

Hyodo, Ryota; Suzuki, Kojiro; Ogawa, Hiroshi; Komada, Tomohiro; Naganawa, Shinji

2015-11-01

To evaluate dynamic contrast-enhanced computed tomography (CT) features of pancreatic neuroendocrine tumors (PNETs) containing areas of iso- or hypoattenuation and the relationship with pathological grading. Between June 2006 and March 2014, 61 PNETs in 58 consecutive patients (29 male, 29 female; median-age 55 years), which were surgically diagnosed, underwent preoperative dynamic contrast-enhanced CT. PNETs were classified based on contrast enhancement patterns in the pancreatic phase: iso/hypo-PNETs were defined as tumors containing areas of iso- or hypoattenuation except for cystic components, and hyper-PNETs were tumors showing hyperattenuation over the whole area. CT findings and contrast-enhancement patterns of the tumors were evaluated retrospectively by two radiologists and compared with the pathological grading. Iso/hypo-PNETs comprised 26 tumors, and hyper-PNETs comprised 35 tumors. Not only hyper-PNETs but also most iso/hypo-PNETs showed peak enhancement in the pancreatic phase and a washout from the portal venous phase to the delayed phase. Iso/hypo-PNETs showed larger tumor size than the hyper-PNETs (mean, 3.7 cm vs. 1.6 cm; P<0.001), and were significantly correlated with unclear tumor margins (n=4 vs. n=0; P=0.029), the existence of cystic components (n=10 vs. n=3; P=0.006), intratumoral blood vessels in the early arterial phase (n=13 vs. n=3; P<0.001), and a smooth rim enhancement in the delayed phase (n=12 vs. n=6; P=0.019). Iso/hypo-PNETs also showed significantly higher pathological grading (WHO 2010 classification; iso/hypo, G1=14, G2=11, G3=1; hyper, G1=34, G2=1; P<0.001). PNETs containing iso/hypo-areas showed a rapid enhancement pattern as well as hyper-PNETs, various radiological features and higher malignant potential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[CEA, CA-19-9 and il-8, sTNFRII and sil-2R in persons at high risk of colorectal cancer].

PubMed

Grotowski, Maciej; Wojtuń, Stanisław

2003-04-01

The aim of the study was to determine whether elevated concentrations of CEA, CA19-9, IL-8, sTNFRII and sIL-2R occur in persons at high risk of colorectal cancer. A group of 37 persons at high risk of colorectal cancer and 40 healthy subjects (control group) were included into this study. In both groups IL-8, sTNFRII and sIL-2R concentrations were measured by ELISA method (R&D Systems Minneapolis, USA). In the group of persons at high risk of colorectal cancer CEA and CA19-9 concentrations were determined using MEIA kits (Abbott Laboratories, USA). Using the 95th percentiles of the distribution in the control group the upper normal limits of IL-8, sTN-FRII and sIL-2R values were calculated. The cut-off value for CEA was 3 ng/ml and that for CA 19-9 was 37 U/ml. The incidence of elevated concentrations of the studied factors and concentrations of CEA and CA19-9 was compared. The association was assessed of elevated concentrations of the studied factors and CEA and CA19-9 with the results of histological examination of pathological changes in the colon and rectum. In the group of persons at high risk of colorectal cancer only CEA concentration was elevated in 2.7%. The percentages of persons with elevated concentrations of IL-8, sIL-2R and sTNFRII were 29.7, 8.1 and 18.9%, respectively. The percentage of persons with elevated concentrations of IL-8 and sTNFRII was higher in comparison with the percentage of persons with elevated concentrations of CEA and CA19-9 (p < 0.05). Pathological lesions in the colon and rectum were detected in 16 persons (43.2%). High-grade dysplasia was detected in 11 cases. Elevated concentration of IL-8 always accompanied high-grade dysplasia in ulcerative colitis. The concentrations of IL-8 were significantly higher in high-grade dysplasia (23.7 pg/ml, SD +/- 7.53) than in cases of its absence (18.9 pg/ml, SD +/- 3.53) (p < 0.05). The obtained results of preliminary studies with IL-8 in persons at high risk of colorectal cancer require a confirmation in population studies.

Closing the Personalized Medicine Information Gap: HER2 Test Documentation Practice

PubMed Central

Ferrusi, Ilia L.; Earle, Craig C.; Trudeau, Maureen; Leighl, Natasha B.; Pullenayegum, Eleanor; Khong, Hoa; Hoch, Jeffrey S.; Marshall, Deborah A.

2013-01-01

Background Uncertainty about human epidermal growth factor receptor-2 (HER2) testing practice in Canada continues to hinder efforts to improve personalized medicine. Pathologists routinely perform HER2 assessment for all tumors > 1 cm, and pathology is reported centrally to the provincial cancer registry. Objectives To understand patterns of HER2 test documentation for early-stage breast cancer (BC) patients in Ontario’s centralized pathology reporting system. Study Design Retrospective cohort study of central HER2 test documentation in early-stage BC patients diagnosed in 2006–2007. Methods Cohort and staging information was derived from cancer registry and admissions data. Linkage across administrative databases provided data on surgical and radiologic treatment, sociodemographic factors, diagnosis setting, and comorbidities. Pathology reports from the provincial cancer registry were reviewed for HER2 testing, hormone receptor, and grade. Unadjusted and adjusted odds ratios were calculated to determine factors related to HER2 documentation. Results A HER2 test was documented for 66% of 13,396 patients. HER2 documentation was associated with stage, hormone receptor, and tumor grade documentation. Higher stage and grade at diagnosis were also associated with HER2 documentation. All models suggested variable regional documentation patterns. Documentation did not differ by sociodemographic factors, presence of comorbidities, or surgical procedure. Conclusions Despite a universal testing policy, the rate of centralized HER2 test documentation was lower than expected and related to disease severity. Differences in regional reporting likely reflect ascertainment bias inherent to centralized pathology reporting rather than testing access. Improved HER2 reporting is encouraged for cancer registration, quality-of-care measurement, and program evaluation. PMID:23379747

[Clinical and pathological features of breast cancer in a population of Mexico].

PubMed

Maffuz-Aziz, Antonio; Labastida-Almendaro, Sonia; Espejo-Fonseca, Aura; Rodríguez-Cuevas, Sergio

Breast cancer is the most common among women in our country, and its treatment is based on prognostic factors to categorize patients into different risk groups. In this study, the clinical and pathological features that play a role as a prognostic factor in a representative population with breast cancer in México are described. A descriptive analysis of the clinical and pathological features of women diagnosed with breast cancer, in a period from June 2005 to May 2014; registered in a database and calculated by simple frequencies. A total of 4,411 patients were included, the average age at diagnosis was 53 years, 19.7% were diagnosed by mammography screening program and 80.3% derived from any signs or symptoms. Regarding the stages at diagnosis, 6.8% were carcinoma in situ, 36% at early stages (I and IIA), 45% locally advanced (IIB to IIIC), 7.7% metastatic and 3.9% unclassifiable. A 79% were ductal histology, lobular 7.8% and the rest, other types. Of ductal carcinomas, 9.1% were grade I, 54.1% grade II, and 34.6% grade III. Regarding the biological subtypes, 65.7% were luminal, 10.9% luminal Her positive, 8.7% pure Her 2 positive and 14.6% triple negative. In the present study, we described the clinical and pathologic features of a group of Mexican women with breast cancer that might reflect a national landscape, and represent the prognostic factors to determine groups of risk and treatment decisions. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Prognostic Value of the New Prostate Cancer International Society of Urological Pathology Grade Groups.

PubMed

Offermann, Anne; Hohensteiner, Silke; Kuempers, Christiane; Ribbat-Idel, Julika; Schneider, Felix; Becker, Finn; Hupe, Marie Christine; Duensing, Stefan; Merseburger, Axel S; Kirfel, Jutta; Reischl, Markus; Lubczyk, Verena; Kuefer, Rainer; Perner, Sven

2017-01-01

Gleason grading is the best independent predictor for prostate cancer (PCa) progression. Recently, a new PCa grading system has been introduced by the International Society of Urological Pathology (ISUP) and is recommended by the World Health Organization (WHO). Following studies observed more accurate and simplified grade stratification of the new system. Aim of this study was to compare the prognostic value of the new grade groups compared to the former Gleason Grading and to determine whether re-definition of Gleason Pattern 4 might reduce upgrading from prostate biopsy to radical prostatectomy (RP) specimen. A cohort of men undergoing RP from 2002 to 2015 at the Hospital of Goeppingen (Goeppingen, Germany) was used for this study. In total, 339 pre-operative prostatic biopsies and corresponding RP specimens, as well as additional 203 RP specimens were re-reviewed for Grade Groups according to the ISUP. Biochemical recurrence-free survival (BFS) after surgery was used as endpoint to analyze prognostic significance. Other clinicopathological data included TNM-stage and pre-operative PSA level. Kaplan-Meier analysis revealed risk stratification of patients based on both former Gleason Grading and ISUP Grade Groups, and was statistically significant using the log-rank test ( p  < 0.001). Both grading systems significantly correlated with TNM-stage and pre-operative PSA level ( p  < 0.001). Higher tumor grade in RP specimen compared to corresponding pre-operative biopsy was observed in 44 and 34.5% of cases considering former Gleason Grading and ISUP Grade Groups, respectively. Both, former Gleason Grading and ISUP Grade Groups predict survival when applied on tumors in prostatic biopsies as well as RP specimens. This is the first validation study on a large representative German community-based cohort to compare the former Gleason Grading with the recently introduced ISUP Grade Groups. Our data indicate that the ISUP Grade Groups do not improve predictive value of PCa grading and might be less sensitive in deciphering tumors with 3 + 4 and 4 + 3 pattern on RP specimen. However, the Grade Group system results less frequently in an upgrading from biopsy to the corresponding RP specimens, indicating a lower risk to miss potentially aggressive tumors not represented on biopsies.

Histogram and gray level co-occurrence matrix on gray-scale ultrasound images for diagnosing lymphocytic thyroiditis.

PubMed

Shin, Young Gyung; Yoo, Jaeheung; Kwon, Hyeong Ju; Hong, Jung Hwa; Lee, Hye Sun; Yoon, Jung Hyun; Kim, Eun-Kyung; Moon, Hee Jung; Han, Kyunghwa; Kwak, Jin Young

2016-08-01

The objective of the study was to evaluate whether texture analysis using histogram and gray level co-occurrence matrix (GLCM) parameters can help clinicians diagnose lymphocytic thyroiditis (LT) and differentiate LT according to pathologic grade. The background thyroid pathology of 441 patients was classified into no evidence of LT, chronic LT (CLT), and Hashimoto's thyroiditis (HT). Histogram and GLCM parameters were extracted from the regions of interest on ultrasound. The diagnostic performances of the parameters for diagnosing and differentiating LT were calculated. Of the histogram and GLCM parameters, the mean on histogram had the highest Az (0.63) and VUS (0.303). As the degrees of LT increased, the mean decreased and the standard deviation and entropy increased. The mean on histogram from gray-scale ultrasound showed the best diagnostic performance as a single parameter in differentiating LT according to pathologic grade as well as in diagnosing LT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recommendations for the reporting of surgically resected specimens of renal cell carcinoma: the Association of Directors of Anatomic and Surgical Pathology.

PubMed

Higgins, John P; McKenney, Jesse K; Brooks, James D; Argani, Pedram; Epstein, Jonathan I

2009-04-01

A checklist based approach to reporting the relevant pathologic details of renal cell carcinoma resection specimens improves the completeness of the report. Karyotypic evaluation of renal neoplasms has refined but also complicated their classification. The number of diagnostic possibilities has increased and the importance of distinguishing different tumor types has been underscored by dramatic variation in prognosis and the development of targeted therapies for specific subtypes. The increasing number of recognized renal neoplasms has implications for handling renal resection specimens. Furthermore, the prognostic significance of other features of renal neoplasms related to grade and stage has been demonstrated. This guideline for the handling of renal resection specimens will focus on problem areas in the evolving practice of diagnosis, grading, and staging of renal neoplasms. The accompanying checklist will serve to ensure that all necessary details of the renal resection specimen are included in the surgical pathology report.

[Joint endoprosthesis pathology. Histopathological diagnostics and classification].

PubMed

Krenn, V; Morawietz, L; Jakobs, M; Kienapfel, H; Ascherl, R; Bause, L; Kuhn, H; Matziolis, G; Skutek, M; Gehrke, T

2011-05-01

Prosthesis durability has steadily increased with high 10-year rates of 88-95%. However, four pathogenetic groups of diseases can decrease prosthesis durability: (1) periprosthetic wear particle disease (aseptic loosening) (2) bacterial infection (septic loosening) (3) periprosthetic ossification, and (4) arthrofibrosis. The histopathological "extended consensus classification of periprosthetic membranes" includes four types of membranes, arthrofibrosis, and osseous diseases of endoprosthetics: The four types of neosynovia are: wear particle-induced type (type I), mean prosthesis durability (MPD) in years 12.0; infectious type (type II), MPD 2.5; combined type (type III) MPD 4.2; and indeterminate type (type IV), MPD 5.5. Arthrofibrosis can be determined in three grades: grade 1 needs clinical information to be differentiated from a type IV membrane, and grades 2 & 3 can be diagnosed histopathologically. Periprosthetic ossification, osteopenia-induced fractures, and aseptic osteonecrosis can be histopathologically diagnosed safely with clinical information. The extended consensus classification of periprosthetic membranes may be a diagnostic groundwork for a future national endoprosthesis register.

Diagnostic accuracy of dynamic contrast-enhanced MR imaging using a phase-derived vascular input function in the preoperative grading of gliomas.

PubMed

Nguyen, T B; Cron, G O; Mercier, J F; Foottit, C; Torres, C H; Chakraborty, S; Woulfe, J; Jansen, G H; Caudrelier, J M; Sinclair, J; Hogan, M J; Thornhill, R E; Cameron, I G

2012-09-01

The accuracy of tumor plasma volume and K(trans) estimates obtained with DCE MR imaging may have inaccuracies introduced by a poor estimation of the VIF. In this study, we evaluated the diagnostic accuracy of a novel technique by using a phase-derived VIF and "bookend" T1 measurements in the preoperative grading of patients with suspected gliomas. This prospective study included 46 patients with a new pathologically confirmed diagnosis of glioma. Both magnitude and phase images were acquired during DCE MR imaging for estimates of K(trans)_φ and V(p_)φ (calculated from a phase-derived VIF and bookend T1 measurements) as well as K(trans)_SI and V(p_)SI (calculated from a magnitude-derived VIF without T1 measurements). Median K(trans)_φ values were 0.0041 minutes(-1) (95 CI, 0.00062-0.033), 0.031 minutes(-1) (0.011-0.150), and 0.088 minutes(-1) (0.069-0.110) for grade II, III, and IV gliomas, respectively (P ≤ .05 for each). Median V(p_)φ values were 0.64 mL/100 g (0.06-1.40), 0.98 mL/100 g (0.34-2.20), and 2.16 mL/100 g (1.8-3.1) with P = .15 between grade II and III gliomas and P = .015 between grade III and IV gliomas. In differentiating low-grade from high-grade gliomas, AUCs for K(trans)_φ, V(p_φ), K(trans)_SI, and V(p_)SI were 0.87 (0.73-1), 0.84 (0.69-0.98), 0.81 (0.59-1), and 0.84 (0.66-0.91). The differences between the AUCs were not statistically significant. K(trans)_φ and V(p_)φ are parameters that can help in differentiating low-grade from high-grade gliomas.

Antisense oligonucleotides as innovative therapeutic strategy in the treatment of high-grade gliomas.

PubMed

Caruso, Gerardo; Caffo, Mariella; Raudino, Giuseppe; Alafaci, Concetta; Salpietro, Francesco M; Tomasello, Francesco

2010-01-01

Despite the intensive recent research in cancer therapy, the prognosis in patients affected by high-grade gliomas is still very unfavorable. The efficacy of classical anti-cancer strategies is seriously limited by lack of specific therapies against malignant cells. The extracellular matrix plays a pivotal role in processes such as differentiation, apoptosis, and migration in both the normal and the pathologic nervous system. Glial tumors seem to be able to create a favorable environment for the invasion of glioma cells in cerebral parenchyma when they combine with the extracellular matrix via cell surface receptors. Glioma cells synthesize matrix proteins, such as tenascin, laminin, fibronectin that facilitate the tumor cell's motility. New treatments have shown to hit the acting molecules in the tumor growth and to increase the efficacy and minimize the toxicity. Antisense oligonucleotides are synthetic stretches of DNA which hybridize with specific mRNA strands. The specificity of hybridization makes antisense method an interesting strategy to selectively modulate the expression of genes involved in tumorigenesis. In this review we will focus on the mechanisms of action of antisense oligonucleotides and report clinical and experimental studies on the treatment of high-grade gliomas. We will also report the patents of preclinical and/or clinical studies that adopt the antisense oligonucleotide therapy list in cerebral gliomas.

The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors

PubMed Central

Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias

2015-01-01

BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined. ABBREVIATIONS: 5-ALA, 5-aminolevulinic acid CRT, classification and regression tree 18F-FET PET, 18F-fluoroethyl tyrosine positron emission tomography FLAIR, fluid-attenuated inversion recovery GBM, glioblastoma multiforme O6-MGMT, methylguanine DNA methyltransferase ROC, receiver-operating characteristic SUV, standardized uptake value WHO, World Health Organization PMID:26366972

Expression of Voltage-Gated Sodium Channel Nav1.8 in Human Prostate Cancer is Associated with High Histological Grade

PubMed Central

Suy, Simeng; Hansen, Todd P.; Auto, Heather D.; Kallakury, Bhaskar V.S.; Dailey, Vernon; Danner, Malika; MacArthur, Linda; Zhang, Ying; Miessau, Matthew J.; Collins, Sean P.; Brown, Milton L.

2013-01-01

Voltage-gated sodium (Nav) channels are required for impulse conductance in excitable tissues. Navs have been linked to human cancers, including prostate. The expression and distribution of Nav isoforms (Nav1.1-Nav1.9) in human prostate cancer are not well established. Here, we evaluated the expression of these isoforms and investigated the expression of Nav1.8 in human prostate cancer tissues. Nav1.8 was highly expressed in all examined cells. Expression of Nav1.1, Nav1.2, and Nav1.9 were high in DU-145, PC-3 and PC-3M cells compared to LNCaP (hormone-dependent), C4-2, C4-2B, and CWR22Rv-1 cells. Nav1.5 and Nav1.6 were expressed in all cells examined. Nav1.7 expression was absent in PC-3M and CWR22Rv-1, but expressed in the other cells examined. Immunohistochemistry revealed intensive Nav1.8 staining correlated with more advanced pathologic stage of disease. Increased intensity of nuclear Nav1.8 correlated with increased Gleason grade. Our results revealed that Nav1.8 is universally expressed in human prostate cancer cells. Nav1.8 expression statistically correlated with pathologic stage (P=0.04) and Gleason score (P=0.01) of human prostate tissue specimens. The aberrant nuclear localization of Nav1.8 with advanced prostate cancer tissues warrant further investigation into use of Nav1.8 as a potential biomarker to differentiate between early and advanced disease. PMID:24163825

Discordance in pathology report after central pathology review: Implications for breast cancer adjuvant treatment.

PubMed

Orlando, Laura; Viale, Giuseppe; Bria, Emilio; Lutrino, Eufemia Stefania; Sperduti, Isabella; Carbognin, Luisa; Schiavone, Paola; Quaranta, Annamaria; Fedele, Palma; Caliolo, Chiara; Calvani, Nicola; Criscuolo, Mario; Cinieri, Saverio

2016-12-01

Pathological predictive factors are the most important markers when selecting early breast cancer adjuvant therapy. In randomized clinical trials the variability in pathology report after central pathology review is noteworthy. We evaluated the discordance rate (DR) and inter-rater agreement between local and central histopathological report and the clinical implication on treatment decision. A retrospective analysis was conducted in a series of consecutive early breast cancer tumors diagnosed by local pathologists and subsequently reviewed at the Pathology Division of European Institute of Oncology. The inter-rater agreement (k) between local and central pathology was calculated for Ki-67, grading, hormone receptors (ER/PgR) and HER2/neu. The Bland-Altman plots were derived to determine discrepancies in Ki-67, ER and PgR. DR was calculated for ER/PgR and HER2. From 2007 to 2013, 187 pathology specimens from 10 Cancer Centers were reviewed. Substantial agreement was observed for ER (k0.612; 95% CI, 0538-0.686), PgR (k0.659; 95% CI, 0580-0.737), Ki-67 (k0.609; 95% CI, 0.534-0.684) and grading (k0.669; 95% CI, 0.569-0.769). Moderate agreement was found for HER2 (k0.546; 95% CI, 0444-0.649). DR was 9.5% (negativity to positivity) and 31.7% (positivity to negativity) for HER2 and 26.2% (negativity to positivity) and 12.5% (positivity to negativity) for ER/PgR. According to changes in Her2 and ER/PgR status, 23 (12.2%) and 33 (17.6%) systemic prescription were respectively modified. In our retrospective analysis, central pathological review has a significant impact in the decision-making process in early breast cancer, as shown in clinical trials. Further studies are warranted to confirm these provocative results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dedifferentiated chondrosarcoma: Radiological features, prognostic factors and survival statistics in 23 patients

PubMed Central

Liu, Chenglei; Xi, Yan; Li, Mei; Jiao, Qiong; Zhang, Huizhen; Yang, Qingcheng; Yao, Weiwu

2017-01-01

Background Dedifferentiated chondrosarcoma is a rare, highly malignant tumor with a poor survival. There are many confusing issues concerning the imaging feature that can facilitate early diagnosis and the factors that might be related to outcomes. Methods Twenty-three patients with dedifferentiated chondrosarcoma confirmed by pathology were retrospectively reviewed from 2008 to 2015. The patients’ clinical information, images from radiographs (n = 17), CT (n = 19), and MRI (n = 17), histological features, treatment and prognosis were analyzed. Results There were 12 males and 11 females, and the mean age was 50.39 years old. Fourteen cases affected the axial bone (pelvis, spine), and 9 cases involved the appendicular bone. Seven (41.17%), 9 (47.36), and 12 (66.66%) lesions showed a biphasic nature on radiograph, CT and MRI, respectively. Of the lesions, 17.39% (4/23) were accompanied by pathological fractures. Histologically, the cartilage component was considered histological Grade1 in 12 patients and Grade 2 in 11 patients. The dedifferentiated component showed features of osteosarcoma in 8 cases, malignant fibrous histiocytoma in3 cases, myofibroblastic sarcoma in 1 case and spindle cell sarcoma in 11cases. Twenty-two cases were treated with surgical resection, and 17 cases achieved adequate (wide or radical) surgical margin. In 8 cases, surgery was combined with adjuvant chemotherapy. The overall median survival time was nine months; 17.4% of patients survived to five years. Conclusion Axial bone location, lung metastasis at diagnosis, inadequate surgical margin, incorrect diagnosis before surgery and pathological fractures was related to poorer outcome. Pre- or postoperative chemotherapy had no definitively effect on improved survival. PMID:28301537

Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group.

PubMed

Roman, S; Gyawali, C P; Savarino, E; Yadlapati, R; Zerbib, F; Wu, J; Vela, M; Tutuian, R; Tatum, R; Sifrim, D; Keller, J; Fox, M; Pandolfino, J E; Bredenoord, A J

2017-10-01

An international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro-esophageal reflux disease (GERD). Literature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed during several structured meetings. Reflux testing should be performed after cessation of acid suppressive medication in patients with a low likelihood of GERD. In this setting, testing can be either catheter-based or wireless pH-monitoring or pH-impedance monitoring. In patients with a high probability of GERD (esophagitis grade C and D, histology proven Barrett's mucosa >1 cm, peptic stricture, previous positive pH monitoring) and persistent symptoms, pH-impedance monitoring should be performed on treatment. Recommendations are provided for data acquisition and analysis. Esophageal acid exposure is considered as pathological if acid exposure time (AET) is greater than 6% on pH testing. Number of reflux episodes and baseline impedance are exploratory metrics that may complement AET. Positive symptom reflux association is defined as symptom index (SI) >50% or symptom association probability (SAP) >95%. A positive symptom-reflux association in the absence of pathological AET defines hypersensitivity to reflux. The consensus group determined that grade C or D esophagitis, peptic stricture, histology proven Barrett's mucosa >1 cm, and esophageal acid exposure greater >6% are sufficient to define pathological GERD. Further testing should be considered when none of these criteria are fulfilled. © 2017 John Wiley & Sons Ltd.

Endometrial cancers in mutation carriers from hereditary breast ovarian cancer syndrome kindreds: report from the Creighton University Hereditary Cancer Registry with review of the implications.

PubMed

Casey, Murray Joseph; Bewtra, Chhanda; Lynch, Henry T; Snyder, Carrie L; Stacey, Mark

2015-05-01

The aim of this study was to categorize and report endometrial cancers in mutation carriers from hereditary breast ovarian cancer families. Our Hereditary Cancer Registry was searched for gynecologic and peritoneal cancers linked to mutations in BRCA1 or BRCA2. Invasive cancers were registered in 101 mutation carriers with complete pathology reports. Efforts were made to secure diagnostic surgical pathology tissues for review. All records and available diagnostic slides were meticulously studied, and primary cancers were classified. Eight malignancies were classified as primary endometrial cancers. Five of these were low- or intermediate-grade endometrioid carcinomas, and 3 were pure serous carcinomas or contained serous carcinoma elements mixed with high-grade endometrioid carcinoma. Breast cancers were diagnosed in 5 patients before and in 1 patient after endometrial carcinoma. Three endometrioid carcinomas were preceded by estrogen treatment, 2 for many years and the other for only 2 months, and 2 of the patients with serous carcinoma had been treated with tamoxifen. The finding that 8 of gynecologic and peritoneal cancers in 101 mutation carriers were endometrial cancers with a smaller proportion of endometrioid carcinomas than reported in general populations is added to the current controversial literature on endometrial cancer, particularly regarding serous carcinomas, in hereditary breast ovarian cancer syndrome. Well-designed prospective programs for standardized surgical and pathologic handling, processing, and reporting are essential for working out the pathogenesis, true risks, and best management of this disease in carriers of deleterious BRCA1 and BRCA2 germline mutations.

Multimodal fiber-probe spectroscopy for the diagnostics and classification of bladder tumors

NASA Astrophysics Data System (ADS)

Anand, Suresh; Cicchi, Riccardo; Fantechi, Riccardo; Gacci, Mauro; Nesi, Gabriella; Carini, Marco; Pavone, Francesco S.

2017-02-01

The gold standard for the detection of bladder cancer is white light cystoscopy, followed by an invasive biopsy and pathological examination. Tissue pathology is time consuming and often prone to sampling errors. Recently, optical spectroscopy techniques have evolved as promising techniques for the detection of neoplasia. The specific goal of this study is to evaluate the application of combined auto-fluorescence (excited using 378 nm and 445 nm wavelengths) and diffuse reflectance spectroscopy to discriminate normal bladder tissue from tumor at different grades. The fluorescence spectrum at both excitation wavelengths showed an increased spectral intensity in tumors with respect to normal tissues. Reflectance data indicated an increased reflectance in the wavelength range 610 nm - 700 nm for different grades of tumors, compared to normal tissues. The spectral data were further analyzed using principal component analysis for evaluating the sensitivity and specificity for diagnosing tumor. The spectral differences observed between various grades of tumors provides a strong genesis for the future evaluation on a larger patient population to achieve statistical significance. This study indicates that a combined spectroscopic strategy, incorporating fluorescence and reflectance spectroscopy, could improve the capability for diagnosing bladder tumor as well as for differentiating tumors in different grades.

Long Noncoding RNA H19 in Digestive System Cancers: A Meta-Analysis of Its Association with Pathological Features.

PubMed

Lin, Yang; Xu, Lijian; Wei, Wei; Zhang, Xiaohui; Ying, Rongchao

2016-01-01

Long noncoding RNA (lncRNA) H19 has been reported to be upregulated in malignant digestive tumors, but its clinical relevance is not yet established. The meta-analysis was to investigate the association between H19 expression and pathological features of digestive system cancers. The databases of PubMed, EMBase, Web of Science, CNKI, and WanFang were searched for the related studies. A total of 478 patients from 6 studies were finally included. The meta-analysis showed that the patient group of high H19 expression had a higher risk of poorly differentiated grade, deep tumor invasion (T2 stage or more), lymph node metastasis, and advanced TNM stage than the group of low H19 expression, although there was no difference between them in terms of distant metastasis. Therefore, the high expression of lncRNA H19 might predict poor oncological outcomes of patients with digestive system cancers.

Wide-field computational imaging of pathology slides using lens-free on-chip microscopy.

PubMed

Greenbaum, Alon; Zhang, Yibo; Feizi, Alborz; Chung, Ping-Luen; Luo, Wei; Kandukuri, Shivani R; Ozcan, Aydogan

2014-12-17

Optical examination of microscale features in pathology slides is one of the gold standards to diagnose disease. However, the use of conventional light microscopes is partially limited owing to their relatively high cost, bulkiness of lens-based optics, small field of view (FOV), and requirements for lateral scanning and three-dimensional (3D) focus adjustment. We illustrate the performance of a computational lens-free, holographic on-chip microscope that uses the transport-of-intensity equation, multi-height iterative phase retrieval, and rotational field transformations to perform wide-FOV imaging of pathology samples with comparable image quality to a traditional transmission lens-based microscope. The holographically reconstructed image can be digitally focused at any depth within the object FOV (after image capture) without the need for mechanical focus adjustment and is also digitally corrected for artifacts arising from uncontrolled tilting and height variations between the sample and sensor planes. Using this lens-free on-chip microscope, we successfully imaged invasive carcinoma cells within human breast sections, Papanicolaou smears revealing a high-grade squamous intraepithelial lesion, and sickle cell anemia blood smears over a FOV of 20.5 mm(2). The resulting wide-field lens-free images had sufficient image resolution and contrast for clinical evaluation, as demonstrated by a pathologist's blinded diagnosis of breast cancer tissue samples, achieving an overall accuracy of ~99%. By providing high-resolution images of large-area pathology samples with 3D digital focus adjustment, lens-free on-chip microscopy can be useful in resource-limited and point-of-care settings. Copyright © 2014, American Association for the Advancement of Science.

Correlation of 6-18F-fluoro-L-dopa PET uptake with proliferation and tumor grade in newly diagnosed and recurrent gliomas.

PubMed

Fueger, Barbara J; Czernin, Johannes; Cloughesy, Timothy; Silverman, Daniel H; Geist, Cheri L; Walter, Martin A; Schiepers, Christiaan; Nghiemphu, Phioanh; Lai, Albert; Phelps, Michael E; Chen, Wei

2010-10-01

6-(18)F-fluoro-l-dopa ((18)F-FDOPA) measured with PET as a biomarker of amino acid uptake has been investigated in brain tumor imaging. The aims of the current study were to determine whether the degree of (18)F-FDOPA uptake in brain tumors predicted tumor grade and was associated with tumor proliferative activity in newly diagnosed and recurrent gliomas. Fifty-nine patients (40 men, 19 women; mean age ± SD, 44.4 ± 12.3 y) with newly diagnosed (n = 22) or recurrent (n = 37) gliomas underwent (18)F-FDOPA PET perioperatively. Tumor tissue was obtained by resection or biopsy in all patients. The tumor grade and Ki-67 proliferation index were obtained by standard pathology assays. Tumor (18)F-FDOPA uptake was quantified by determining various standardized uptake value (SUV) parameters (mean SUV, maximum SUV [SUVmax], mean values of voxels with top 20% SUVs, and tumor-to-normal-brain tissue ratios) that were then correlated with histopathologic grade and Ki-67 proliferation index. Fifty-nine lesions in 59 patients were analyzed. (18)F-FDOPA uptake was significantly higher in high-grade than in low-grade tumors for newly diagnosed tumors (SUVmax, 4.22 ± 1.30 vs. 2.34 ± 1.35, P = 0.005) but not for recurrent tumors that had gone through treatment previously (SUVmax, 3.36 ± 1.26 vs. 2.67 ± 1.18, P = 0.22). An SUVmax threshold of 2.72 differentiated low-grade from high-grade tumors, with a sensitivity and specificity of 85% and 89%, respectively, using receiver-operating-characteristic curve analysis (area under the curve, 0.86). (18)F-FDOPA PET uptake correlated significantly with Ki-67 tumor proliferation index in newly diagnosed tumors (r = 0.66, P = 0.001) but not in recurrent tumors (r = 0.14, P = 0.41). (18)F-FDOPA uptake is significantly higher in high-grade than in low-grade tumors in newly diagnosed but not recurrent tumors that had been treated previously. A significant correlation between (18)F-FDOPA uptake and tumor proliferation in newly diagnosed tumors was observed, whereas this correlation was not identified for recurrent tumors. Thus, (18)F-FDOPA PET might serve as a noninvasive marker of tumor grading and might provide a useful surrogate of tumor proliferative activity in newly diagnosed gliomas.

Development and validation of a surgical-pathologic staging and scoring system for cervical cancer

PubMed Central

Zhou, Hang; Tang, Fangxu; Jia, Yao; Hu, Ting; Sun, Haiying; Yang, Ru; Chen, Yile; Cheng, Xiaodong; Lv, Weiguo; Wu, Li; Zhou, Jin; Wang, Shaoshuai; Huang, Kecheng; Wang, Lin; Yao, Yuan; Yang, Qifeng; Yang, Xingsheng; Zhang, Qinghua; Han, Xiaobing; Lin, Zhongqiu; Xing, Hui; Qu, Pengpeng; Cai, Hongbing; Song, Xiaojie; Tian, Xiaoyu; Shen, Jian; Xi, Ling; Li, Kezhen; Deng, Dongrui; Wang, Hui; Wang, Changyu; Wu, Mingfu; Zhu, Tao; Chen, Gang; Gao, Qinglei; Wang, Shixuan; Hu, Junbo; Kong, Beihua; Xie, Xing; Ma, Ding

2016-01-01

Background Most cervical cancer patients worldwide receive surgical treatments, and yet the current International Federation of Gynecology and Obstetrics (FIGO) staging system do not consider surgical-pathologic data. We propose a more comprehensive and prognostically valuable surgical-pathologic staging and scoring system (SPSs). Methods Records from 4,220 eligible cervical cancer cases (Cohort 1) were screened for surgical-pathologic risk factors. We constructed a surgical-pathologic staging and SPSs, which was subsequently validated in a prospective study of 1,104 cervical cancer patients (Cohort 2). Results In Cohort 1, seven independent risk factors were associated with patient outcome: lymph node metastasis (LNM), parametrial involvement, histological type, grade, tumor size, stromal invasion, and lymph-vascular space invasion (LVSI). The FIGO staging system was revised and expanded into a surgical-pathologic staging system by including additional criteria of LNM, stromal invasion, and LVSI. LNM was subdivided into three categories based on number and location of metastases. Inclusion of all seven prognostic risk factors improves practical applicability. Patients were stratified into three SPSs risk categories: zero-, low-, and high-score with scores of 0, 1 to 3, and ≥4 (P=1.08E-45; P=6.15E-55). In Cohort 2, 5-year overall survival (OS) and disease-free survival (DFS) outcomes decreased with increased SPSs scores (P=9.04E-15; P=3.23E-16), validating the approach. Surgical-pathologic staging and SPSs show greater homogeneity and discriminatory utility than FIGO staging. Conclusions Surgical-pathologic staging and SPSs improve characterization of tumor severity and disease invasion, which may more accurately predict outcome and guide postoperative therapy. PMID:27014971

Flexner 3.0—Democratization of Medical Knowledge for the 21st Century

PubMed Central

Krupinski, Elizabeth A.; Weinstein, John B.; Graham, Anna R.; Barker, Gail P.; Erps, Kristine A.; Holtrust, Angelette L.; Holcomb, Michael J.

2016-01-01

A medical school general pathology course has been reformatted into a K-12 general pathology course. This new course has been implemented at a series of 7 to 12 grade levels and the student outcomes compared. Typically, topics covered mirrored those in a medical school general pathology course serving as an introduction to the mechanisms of diseases. Assessment of student performance was based on their score on a multiple-choice final examination modeled after an examination given to medical students. Two Tucson area schools, in a charter school network, participated in the study. Statistical analysis of examination performances showed that there were no significant differences as a function of school (F = 0.258, P = .6128), with students at school A having an average test scores of 87.03 (standard deviation = 8.99) and school B 86.00 (standard deviation = 8.18; F = 0.258, P = .6128). Analysis of variance was also conducted on the test scores as a function of gender and class grade. There were no significant differences as a function of gender (F = 0.608, P = .4382), with females having an average score of 87.18 (standard deviation = 7.24) and males 85.61 (standard deviation = 9.85). There were also no significant differences as a function of grade level (F = 0.627, P = .6003), with 7th graders having an average of 85.10 (standard deviation = 8.90), 8th graders 86.00 (standard deviation = 9.95), 9th graders 89.67 (standard deviation = 5.52), and 12th graders 86.90 (standard deviation = 7.52). The results demonstrated that middle and upper school students performed equally well in K-12 general pathology. Student course evaluations showed that the course met the student’s expectations. One class voted K-12 general pathology their “elective course-of-the-year.” PMID:28725762

Reduced glucocorticoid receptor expression predicts bladder tumor recurrence and progression.

PubMed

Ishiguro, Hitoshi; Kawahara, Takashi; Zheng, Yichun; Netto, George J; Miyamoto, Hiroshi

2014-08-01

To assess the levels of glucocorticoid receptor (GR) expression in bladder tumors because the status and its prognostic value remain largely unknown. We immunohistochemically stained for GR in bladder tumor and matched non-neoplastic bladder tissue specimens. Overall, GR was positive in 129 (87%) of 149 urothelial tumors, which was significantly (P=.026) lower than in non-neoplastic urothelium (90 [96%] of 94). Forty-two (79%) of 53 low-grade tumors vs 45 (47%) of 96 high-grade carcinomas (P<.001) and 61 (73%) of 84 non-muscle-invasive (NMI) tumors vs 26 (40%) of 65 muscle-invasive (MI) carcinomas (P<.001) were moderately to strongly immunoreactive for GR. Kaplan-Meier and log-rank tests revealed that loss or weak positivity of GR significantly or marginally correlated with recurrence of NMI tumors (P=.025), progression of MI tumors (P=.082), and cancer-specific survival of MI tumors (P=.067). Multivariate analysis identified low GR expression as a strong predictor for recurrence of NMI tumors (P=.034). GR expression was downregulated in bladder tumors compared with nonneoplastic bladder tumors and in high-grade/MI tumors compared with low-grade/NMI tumors. Decreased expression of GR, as an independent prognosticator, predicted recurrence of NMI tumors. These results support experimental evidence suggesting an inhibitory role of GR signals in bladder cancer outgrowth. Copyright© by the American Society for Clinical Pathology.

Predicting features of breast cancer with gene expression patterns.

PubMed

Lu, Xuesong; Lu, Xin; Wang, Zhigang C; Iglehart, J Dirk; Zhang, Xuegong; Richardson, Andrea L

2008-03-01

Data from gene expression arrays hold an enormous amount of biological information. We sought to determine if global gene expression in primary breast cancers contained information about biologic, histologic, and anatomic features of the disease in individual patients. Microarray data from the tumors of 129 patients were analyzed for the ability to predict biomarkers [estrogen receptor (ER) and HER2], histologic features [grade and lymphatic-vascular invasion (LVI)], and stage parameters (tumor size and lymph node metastasis). Multiple statistical predictors were used and the prediction accuracy was determined by cross-validation error rate; multidimensional scaling (MDS) allowed visualization of the predicted states under study. Models built from gene expression data accurately predict ER and HER2 status, and divide tumor grade into high-grade and low-grade clusters; intermediate-grade tumors are not a unique group. In contrast, gene expression data is inaccurate at predicting tumor size, lymph node status or LVI. The best model for prediction of nodal status included tumor size, LVI status and pathologically defined tumor subtype (based on combinations of ER, HER2, and grade); the addition of microarray-based prediction to this model failed to improve the prediction accuracy. Global gene expression supports a binary division of ER, HER2, and grade, clearly separating tumors into two categories; intermediate values for these bio-indicators do not define intermediate tumor subsets. Results are consistent with a model of regional metastasis that depends on inherent biologic differences in metastatic propensity between breast cancer subtypes, upon which time and chance then operate.

Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.

PubMed

Tothill, Richard W; Tinker, Anna V; George, Joshy; Brown, Robert; Fox, Stephen B; Lade, Stephen; Johnson, Daryl S; Trivett, Melanie K; Etemadmoghadam, Dariush; Locandro, Bianca; Traficante, Nadia; Fereday, Sian; Hung, Jillian A; Chiew, Yoke-Eng; Haviv, Izhak; Gertig, Dorota; DeFazio, Anna; Bowtell, David D L

2008-08-15

The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features. Microarray gene expression profiling was done on 285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results. Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends. Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance.

Quantitative nuclear histomorphometry predicts oncotype DX risk categories for early stage ER+ breast cancer.

PubMed

Whitney, Jon; Corredor, German; Janowczyk, Andrew; Ganesan, Shridar; Doyle, Scott; Tomaszewski, John; Feldman, Michael; Gilmore, Hannah; Madabhushi, Anant

2018-05-30

Gene-expression companion diagnostic tests, such as the Oncotype DX test, assess the risk of early stage Estrogen receptor (ER) positive (+) breast cancers, and guide clinicians in the decision of whether or not to use chemotherapy. However, these tests are typically expensive, time consuming, and tissue-destructive. In this paper, we evaluate the ability of computer-extracted nuclear morphology features from routine hematoxylin and eosin (H&E) stained images of 178 early stage ER+ breast cancer patients to predict corresponding risk categories derived using the Oncotype DX test. A total of 216 features corresponding to the nuclear shape and architecture categories from each of the pathologic images were extracted and four feature selection schemes: Ranksum, Principal Component Analysis with Variable Importance on Projection (PCA-VIP), Maximum-Relevance, Minimum Redundancy Mutual Information Difference (MRMR MID), and Maximum-Relevance, Minimum Redundancy - Mutual Information Quotient (MRMR MIQ), were employed to identify the most discriminating features. These features were employed to train 4 machine learning classifiers: Random Forest, Neural Network, Support Vector Machine, and Linear Discriminant Analysis, via 3-fold cross validation. The four sets of risk categories, and the top Area Under the receiver operating characteristic Curve (AUC) machine classifier performances were: 1) Low ODx and Low mBR grade vs. High ODx and High mBR grade (Low-Low vs. High-High) (AUC = 0.83), 2) Low ODx vs. High ODx (AUC = 0.72), 3) Low ODx vs. Intermediate and High ODx (AUC = 0.58), and 4) Low and Intermediate ODx vs. High ODx (AUC = 0.65). Trained models were tested independent validation set of 53 cases which comprised of Low and High ODx risk, and demonstrated per-patient accuracies ranging from 75 to 86%. Our results suggest that computerized image analysis of digitized H&E pathology images of early stage ER+ breast cancer might be able predict the corresponding Oncotype DX risk categories.

Prognostic value of the new Grade Groups in Prostate Cancer: a multi-institutional European validation study.

PubMed

Mathieu, R; Moschini, M; Beyer, B; Gust, K M; Seisen, T; Briganti, A; Karakiewicz, P; Seitz, C; Salomon, L; de la Taille, A; Rouprêt, M; Graefen, M; Shariat, S F

2017-06-01

We aimed to assess the prognostic relevance of the new Grade Groups in Prostate Cancer (PCa) within a large cohort of European men treated with radical prostatectomy (RP). Data from 27 122 patients treated with RP at seven European centers were analyzed. We investigated the prognostic performance of the new Grade Groups (based on Gleason score 3+3, 3+4, 4+3, 8 and 9-10) on biopsy and RP specimen, adjusted for established clinical and pathological characteristics. Multivariable Cox proportional hazards regression models assessed the association of new Grade Groups with biochemical recurrence (BCR). Prognostic accuracies of the models were assessed using Harrell's C-index. Median follow-up was 29 months (interquartile range, 13-54). The 4-year estimated BCR-free survival (bRFS) for biopsy Grade Groups 1-5 were 91.3, 81.6, 69.8, 60.3 and 44.4%, respectively. The 4-year estimated bRFS for RP Grade Groups 1-5 were 96.1%, 86.7%, 67.0%, 63.1% and 41.0%, respectively. Compared with Grade Group 1, all other Grade Groups based both on biopsy and RP specimen were independently associated with a lower bRFS (all P<0.01). Adjusted pairwise comparisons revealed statistically differences between all Grade Groups, except for group 3 and 4 on RP specimen (P=0.10). The discriminations of the multivariable base prognostic models based on the current three-tier and the new five-tier systems were not clinically different (0.3 and 0.9% increase in discrimination for clinical and pathological model). We validated the independent prognostic value of the new Grade Groups on biopsy and RP specimen from European PCa men. However, it does not improve the accuracies of prognostic models by a clinically significant margin. Nevertheless, this new classification may help physicians and patients estimate disease aggressiveness with a user-friendly, clinically relevant and reproducible method.

Grading of Total Mesorectal Excision Specimens: Assessment of Interrater Agreement.

PubMed

Goebel, Emily A; Stegmaier, Melissa; Gorassini, Donald R; Kubica, Matthew; Parfitt, Jeremy R; Driman, David K

2018-06-01

Total mesorectal excision is the standard of care for patients with rectal cancer. Pathological evaluation of the quality of the total mesorectal excision specimen is an important prognostic factor that correlates with local recurrence, but is potentially subjective. This study aimed to determine the degree of variation in grading, both between assessors and between fresh and formalin-fixed specimens. Raters included surgeons, pathologists, pathology residents, pathologists' assistants, and pathologists' assistant trainees. Specimens were assessed by up to 6 raters in the fresh state and by 2 raters postfixation. Four parameters were evaluated: mesorectal bulk, surface regularity, defects, and coning. Interrater agreement was measured using ordinal α-values. The study was conducted at a single academic center. The primary outcome was agreement between individuals when grading total mesorectal excision specimens. A total of 37 total mesorectal excision specimens were assessed. Reliability between all raters for fresh specimens for mesorectal bulk, surface regularity, defects, coning, and overall grade were 0.85, 0.85, 0.92, 0.84, and 0.91. When compared with all raters, pathologists and residents had higher agreement and pathologists and surgeons had lower agreement. Ordinal α-values comparing pathologist and pathologist's assistant agreement for overall grade were similar pre- and postfixation (0.78 vs 0.80), but agreement for assessing defects decreased postfixation. Among pathologists' assistants, agreement was higher when grading specimens postfixation than when grading fresh specimens. Assessment bias may have occurred because of the greater number of pathologists' assistants participating than the number of residents and pathologists. The results indicate good interrater agreement for the assessment of overall grade, with defects showing the best interrater agreement in fresh specimens. Although total mesorectal excision specimens may be consistently graded postfixation, the assessment of defects postfixation may be less reliable. This study highlights the need for additional knowledge-transfer activities to ensure consistency and accurate grading of total mesorectal excision specimens. See Video Abstract at http://links.lww.com/DCR/A497.

Evaluation of a modified knee rotation angle in MRI scans with and without trochlear dysplasia: a parameter independent of knee size and trochlear morphology.

PubMed

Dornacher, Daniel; Trubrich, Angela; Guelke, Joachim; Reichel, Heiko; Kappe, Thomas

2017-08-01

Regarding TT-TG in knee realignment surgery, two aspects have to be considered: first, there might be flaws in using absolute values for TT-TG, ignoring the knee size of the individual. Second, in high-grade trochlear dysplasia with a dome-shaped trochlea, measurement of TT-TG has proven to lack precision and reliability. The purpose of this examination was to establish a knee rotation angle, independent of the size of the individual knee and unaffected by a dysplastic trochlea. A total of 114 consecutive MRI scans of knee joints were analysed by two observers, retrospectively. Of these, 59 were obtained from patients with trochlear dysplasia, and another 55 were obtained from patients presenting with a different pathology of the knee joint. Trochlear dysplasia was classified into low grade and high grade. TT-TG was measured according to the method described by Schoettle et al. In addition, a modified knee rotation angle was assessed. Interobserver reliability of the knee rotation angle and its correlation with TT-TG was calculated. The knee rotation angle showed good correlation with TT-TG in the readings of observer 1 and observer 2. Interobserver correlation of the parameter showed excellent values for the scans with normal trochlea, low-grade and high-grade trochlear dysplasia, respectively. All calculations were statistically significant (p < 0.05). The knee rotation angle might meet the requirements for precise diagnostics in knee realignment surgery. Unlike TT-TG, this parameter seems not to be affected by a dysplastic trochlea. In addition, the dimensionless parameter is independent of the knee size of the individual. II.

[Arthur Vick Prize 2017 of the German Society of Orthopaedic Rheumatology].

PubMed

Bause, L; Niemeier, A; Krenn, V

2018-03-01

The German Society of Orthopaedic Rheumatology (DGORh) honored Prof. Dr. med. Veit Krenn (MVZ-ZHZMD-Trier) with the Arthur Vick Prize 2017. With this award, scientific results with high impact on the diagnosis, therapy and pathogenetic understanding of rheumatic diseases are honored. In cooperation with pathologists and colleagues from various clinical disciplines Prof. Dr. med. Veit Krenn developed several histopathologic scoring systems which contribute to the diagnosis and pathogenetic understanding of degenerative and rheumatic diseases. These scores include the synovitis score, the meniscal degeneration score, the classification of periprosthetic tissues (SLIM classification), the arthrofibrosis score, the particle score and the CD15 focus score. Of highest relevance for orthopedic rheumatology is the synovitis score which is a semiquantitative score for evaluating immunological and inflammatory changes of synovitis in a graded manner. Based on this score, it is possible to divide results into low-grade synovitis and high-grade synovitis: a synovitis score of 1-4 is called low-grade synovitis and occurs for example in association with osteoarthritis (OA), post-trauma, with meniscal lesions and hemochromatosis. A synovitis score of 5-9 is called high-grade synovitis, e.g. rheumatoid arthritis, psoriatic arthritis, Lyme arthritis, postinfection and reactive arthritis as well as peripheral arthritis with Bechterew's disease (sensitivity 61.7%, specificity 96.1%). The first publication (2002) and an associated subsequent publication (2006) of the synovitis score has led to national and international acceptance of this score as the standard for histopathological assessment of synovitis. The synovitis score provides a diagnostic, standardized and reproducible histopathological evaluation method for joint diseases, particularly when this score is applied in the context with the joint pathology algorithm.

Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival.

PubMed

Viganò, Luca; Capussotti, Lorenzo; De Rosa, Giovanni; De Saussure, Wassila Oulhaci; Mentha, Gilles; Rubbia-Brandt, Laura

2013-11-01

We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy. CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear. Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases. A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%.The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032).After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival rate of 23.3% vs 45.7% if absent, P = 0.017; 0% vs 42.3%, P = 0.032, respectively). TRG was confirmed to be a crucial prognostic determinant. CALI do not negatively impact long-term prognosis, but the tumor response is reduced in patients with grade 2-3 SOS. Steatosis was found to have a protective effect on survival. Micrometastases significantly impacted prognosis assessment.

A Survey of FDG- and Amyloid-PET Imaging in Dementia and GRADE Analysis

PubMed Central

Daniela, Perani; Orazio, Schillaci; Alessandro, Padovani; Mariano, Nobili Flavio; Leonardo, Iaccarino; Pasquale Anthony, Della Rosa; Giovanni, Frisoni; Carlo, Caltagirone

2014-01-01

PET based tools can improve the early diagnosis of Alzheimer's disease (AD) and differential diagnosis of dementia. The importance of identifying individuals at risk of developing dementia among people with subjective cognitive complaints or mild cognitive impairment has clinical, social, and therapeutic implications. Within the two major classes of AD biomarkers currently identified, that is, markers of pathology and neurodegeneration, amyloid- and FDG-PET imaging represent decisive tools for their measurement. As a consequence, the PET tools have been recognized to be of crucial value in the recent guidelines for the early diagnosis of AD and other dementia conditions. The references based recommendations, however, include large PET imaging literature based on visual methods that greatly reduces sensitivity and specificity and lacks a clear cut-off between normal and pathological findings. PET imaging can be assessed using parametric or voxel-wise analyses by comparing the subject's scan with a normative data set, significantly increasing the diagnostic accuracy. This paper is a survey of the relevant literature on FDG and amyloid-PET imaging aimed at providing the value of quantification for the early and differential diagnosis of AD. This allowed a meta-analysis and GRADE analysis revealing high values for PET imaging that might be useful in considering recommendations. PMID:24772437

Proposed Terminology for Anal Squamous Lesions: Its Application and Interobserver Agreement Among Pathologists in Academic and Community Hospitals.

PubMed

Roma, Andres A; Liu, Xiuli; Patil, Deepa T; Xie, Hao; Allende, Daniela

2017-07-01

To analyze interobserver reproducibility and compare practice patterns between academic and community settings of Lower Anogenital Squamous Terminology (LAST). In total, 132 anal biopsy slides were revised as well as p16 immunostains. LAST was used in 49% of cases (academic center, 68%; satellite hospitals [community practice setting], 32%). After pathology review and consensus interpretation, 23 (17%) case diagnoses were reclassified: eight (34.8%) cases (benign or low-grade squamous intraepithelial lesion [LSIL]) were upgraded to high-grade squamous intraepithelial lesion (HSIL) (p16 confirmed ordered during review); four (17.4%) cases originally classified as HSIL were downgraded to LSIL (p16 originally ordered in one case). There was no significant difference in discrepancies between original and consensus diagnosis in the community vs academic setting or by subspecialty (gynecological vs gastrointestinal). Overall interobserver agreement among reviewers was substantial (κ = 0.63) and improved with the use of p16 immunostain in challenging cases (κ = 0.71; P < .001). This new terminology is not yet uniformly used by pathologists in anal/perianal biopsy specimens; this two-tier system has a good interobserver agreement and is further improved with p16 use in appropriate cases. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

[Clinical characteristics of Henoch-Schönlein purpura in children].

PubMed

Liu, Li-Jun; Yu, Jing; Li, Yu-Ning

2015-10-01

To explore the clinical characteristics of Henoch-Schönlein purpura (HSP) in children. The clinical data of 325 hospitalized children who were diagnosed with HSP between June 2012 and June 2014 were analyzed retrospectively. In the 325 children with HSP, the incidence of HSP was higher in winter and spring, with 33.9% and 27.4%, respectively. Infection was the major factor to induce HSP (57.2%). The incidence of renal damage in children with purpura accompanied by abdominal symptoms and children with purpura accompanied by abdominal and joint symptoms was 60.3% and 48.9%, respectively, with statistically significant differences compared with children with purpura alone (P<0.05). In 32 children with purpura nephritis, the pathological grades of IIIa and IIIb were more common, accounting for 28% and 31%, respectively. In 325 children, an increased serum D-dimer level was observed in 260 children (80.0%), an increased peripheral IgA content in 101 children (46.3%), and a decreased CD4+ cell percentage in 62 children (56.4%). A high incidence of HSP is often seen in spring and winter. HSP is often induced by upper respiratory tract infection. Renal damage is more likely to occur in children with digestive tract symptoms, with IIIa and IIIb as the common pathological grades of renal damage.

Metabolomic analysis reveals altered metabolic pathways in a rat model of gastric carcinogenesis.

PubMed

Gu, Jinping; Hu, Xiaomin; Shao, Wei; Ji, Tianhai; Yang, Wensheng; Zhuo, Huiqin; Jin, Zeyu; Huang, Huiying; Chen, Jiacheng; Huang, Caihua; Lin, Donghai

2016-09-13

Gastric cancer (GC) is one of the most malignant tumors with a poor prognosis. Alterations in metabolic pathways are inextricably linked to GC progression. However, the underlying molecular mechanisms remain elusive. We performed NMR-based metabolomic analysis of sera derived from a rat model of gastric carcinogenesis, revealed significantly altered metabolic pathways correlated with the progression of gastric carcinogenesis. Rats were histologically classified into four pathological groups (gastritis, GS; low-grade gastric dysplasia, LGD; high-grade gastric dysplasia, HGD; GC) and the normal control group (CON). The metabolic profiles of the five groups were clearly distinguished from each other. Furthermore, significant inter-metabolite correlations were extracted and used to reconstruct perturbed metabolic networks associated with the four pathological stages compared with the normal stage. Then, significantly altered metabolic pathways were identified by pathway analysis. Our results showed that oxidative stress-related metabolic pathways, choline phosphorylation and fatty acid degradation were continually disturbed during gastric carcinogenesis. Moreover, amino acid metabolism was perturbed dramatically in gastric dysplasia and GC. The GC stage showed more changed metabolite levels and more altered metabolic pathways. Two activated pathways (glycolysis; glycine, serine and threonine metabolism) substantially contributed to the metabolic alterations in GC. These results lay the basis for addressing the molecular mechanisms underlying gastric carcinogenesis and extend our understanding of GC progression.

Endoscopic screening for synchronous esophageal neoplasia among patients with incident head and neck cancer: Prevalence, risk factors, and outcomes.

PubMed

Wang, Yao-Kuang; Chuang, Yun-Shiuan; Wu, Tzung-Shiun; Lee, Ka-Wo; Wu, Che-Wei; Wang, Hsiang-Chen; Kuo, Chie-Tong; Lee, Chien-Hung; Kuo, Wen-Rei; Chen, Chung-Ho; Wu, Deng-Chyang; Wu, I-Chen

2017-11-15

Esophageal squamous-cell neoplasia (ESCN) is a common second primary neoplasia found in patients with head-and-neck squamous-cell carcinoma (HNSCC). This study sought to identify the risk factors for synchronous ESCN and how they influence survival in HNSCC patient. Eight hundred and fifteen incident HNSCC patients were prospectively recruited for endoscopy screening for ESCN using white-light imaging, narrow-band imaging, Lugol chromoendoscopy, and pathological confirmation. Associated lifestyle and clinicopathological data were collected. The interquartile follow-up period cutoffs were 11.3, 20.5 and 34.9 months. 124 patients (15.2%) were diagnosed as having synchronous ESCN (66 low-grade dysplasia, 29 high-grade dysplasia, and 29 esophageal squamous-cell carcinoma). Consumption of alcohol, but not betel nut or cigarette, was significantly associated with the presence of synchronous ESCN (adjusted odds ratio [aOR] = 7.1 and 10.9 for former and current drinkers, respectively). There was an interaction between cumulative dose of alcohol consumption and alcohol flushing response on the development of ESCN. High-dose drinkers with flush response were 16.9 times more likely to have esophageal high-grade dysplasia/SCC than non-drinkers. Compared with oral cavity cancer patients, those with hypopharyngeal, laryngeal and oropharyngeal cancer were 6.8, 4.6 and 2.8 times more likely to have esophageal high-grade dysplasia/SCC. HNSCC patients with synchronous ESCN had lower overall survival than those without (p < 0.0001). In conclusion, surveillance of ESCN is strongly recommended for the high-risk subpopulation of HNSCC patients, especially drinkers who have a flush response to alcohol, and those with distant metastasis of index cancer and cancers in hypopharynx, oropharynx and larynx. © 2017 UICC.

Trypanosoma cruzi persistence in the native heart is associated with high-grade myocarditis, but not with Chagas' disease reactivation after heart transplantation.

PubMed

Benvenuti, Luiz A; Roggério, Alessandra; Nishiya, Anna S; Campos, Silvia V; Fiorelli, Alfredo I; Levi, José E

2014-07-01

Chagas' disease reactivation (CDR) after heart transplantation (HTx) is characterized by relapse of the infectious disease, with direct detection of Trypanosoma cruzi parasites in blood, cerebrospinal fluid, or tissues. We investigated whether a detailed pathologic examination of the explanted heart at HTx with evaluation of myocarditis and parasitic persistence or load in the myocardium could be useful to identify patients at high risk of CDR. The native hearts of 18 chagasic patients who presented CDR after HTx (CDR+ group) were compared with the native hearts of 16 chagasic patients who never presented CDR in a follow-up of at least 18 months after HTx (CDR- group). The intensity of myocarditis was evaluated semiquantitatively. Parasite persistence/load in the myocardium was investigated through immunohistochemistry for T cruzi antigens and by qualitative and quantitative real-time PCR for T cruzi DNA. The rate of high-grade myocarditis, parasite persistence, and the median of parasitic load and parasitic load/10(6) cells in the CDR+ group were 83.3%, 77.8%, 8.43 × 10(-3), and 9.890, respectively, whereas in the CDR- group the values were 87.5%, 50%, 7.49×10(-3), and 17.800. There was no statistical difference between the groups. High-grade myocarditis was present in all 22 samples (100%) with parasite persistence and in 7 of 12 samples (58.3%) with no parasite persistence (p = 0.003). Although associated with high-grade myocarditis, T cruzi parasite persistence in the myocardium of the native heart is not associated with the occurrence of CDR after HTx. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

IMPACT OF STAGE MIGRATION AND PRACTICE CHANGES ON HIGH RISK PROSTATE CANCER: RESULTS FROM PATIENTS TREATED WITH RADICAL PROSTATECTOMY OVER THE LAST TWO DECADES

PubMed Central

Fossati, N.; Passoni, N. M.; Moschini, M.; Gandaglia, G.; Larcher, A.; Freschi, M.; Guazzoni, G.; Sjoberg, D. D.; Vickers, A. J.; Montorsi, F.; Briganti, A.

2016-01-01

Background Phenotype of prostate cancer at diagnosis has changed through the years. We aim to evaluate the impact of year of surgery on clinical, pathologic and oncologic outcomes of high-risk prostate cancer patients. Patients and methods We evaluated 1,033 clinically high-risk patients, defined as the presence of at least one of the following risk factors: pre-operative prostate specific antigen (PSA) level >20 ng/ml, and/or clinical stage ≥T3, and/or biopsy Gleason score ≥8. Patients were treated between 1990 and 2013 at a single Institution. Year-per-year trends of clinical and pathologic characteristics were examined. Multivariable Cox regression analysis was used to test the relationship between year of surgery and oncologic outcomes. Results We observed a decrease over time in the proportion of high-risk patients with a pre-operative PSA level >20 ng/ml or clinical stage cT3. An opposite trend was seen for biopsy Gleason score ≥8. We observed a considerable increase in the median number of lymph nodes removed that was associated with an increased rate of LNI. At multivariable Cox regression analysis, year of surgery was associated with a reduced risk of biochemical recurrence (HR per 5-year: 0.90; 95% CI: 0.84–0.96; p=0.01) and distant metastasis (HR per 5-year: 0.91; 95% CI: 0.83–0.99; p=0.039), after adjusting for age, pre-operative PSA, pathologic stage, lymph node invasion, surgical margin status, and pathological Gleason score. Conclusions In this single center study, an increased diagnosis of localized and less extensive high-grade prostate cancer was observed over the last two decades. High-risk patients selected for radical prostatectomy showed better cancer control over time. Better definitions of what constitutes high-risk prostate cancer among contemporary patients are needed. PMID:25787671

Boron neutron capture therapy for recurrent high-grade meningiomas.

PubMed

Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Ono, Koji; Miyatake, Shin-Ichi

2013-10-01

Similar to glioblastomas, high-grade meningiomas are difficult pathologies to control. In this study, the authors used boron neutron capture therapy (BNCT), a tumor-selective intensive particle radiation modality, to treat high-grade meningioma. From June 2005 to September 2011, BNCT was applied 28 times in 20 cases of recurrent high-grade meningioma. All patients had previously undergone intensive treatments such as repetitive surgeries and multiple sessions of radiation therapy. Fluorine-18-labeled boronophenylalanine ((18)F-BPA) PET was performed before BNCT in 19 of the 20 cases; BPA is itself a therapeutic compound. Compound uptake, tumor shrinkage, long-term control rate including survival time, and failure pattern of the treated patients were all evaluated. Eighteen of 19 cases studied using (18)F-BPA PET showed good BPA uptake, with ratios of tumor to normal brain greater than 2.7. These ratios indicated the likely effects of BNCT prior to neutron irradiation. The original tumor sizes were between 4.3 cm(3) and 109 cm(3). A mean tumor volume reduction of 64.5% was obtained after BNCT within just 2 months. The median follow-up duration was 13 months. Six patients are still alive; at present, the median survival times after BNCT and diagnosis are 14.1 months (95% CI 8.6-40.4 months) and 45.7 months (95% CI 32.4-70.7 months), respectively. Clinical symptoms before BNCT, such as hemiparesis and facial pain, were improved after BNCT in symptomatic cases. Systemic metastasis, intracranial distant recurrence outside the radiation field, CSF dissemination, and local tumor progression were observed in 6, 7, 3, and 3 cases, respectively, during the clinical course. Apparent pseudoprogression was observed in at least 3 cases. Symptomatic radiation injuries occurred in 6 cases, and were controllable in all but 1 case. Boron neutron capture therapy may be especially effective in cases of high-grade meningioma.

Bowel sonography in sepsis with pathological correlation: an experimental study.

PubMed

Kim, Hwa-Young; Kim, In-One; Kim, Woo Sun; Kang, Gyeong Hoon

2011-02-01

Sepsis predisposes full-term infants to necrotizing enterocolitis (NEC). As such, experimental induction of NEC was applied to a sepsis model to evaluate the potential role of US in the early diagnosis of NEC in full-term infants. To evaluate the resistive index (RI) of the superior mesenteric artery (SMA) on Doppler sonography in experimentally induced sepsis and correlate it with the pathological findings. Fifteen 1-week-old New Zealand white rabbits (control group n = 3, sepsis group n = 12) were used in this study. We injected 1 mg/kg of E. coli O55-B5 lipopolysaccharide (LPS) into 12 rabbits to induce sepsis. Then we conducted grayscale evaluation of the caliber of the abdominal aorta as well as bowel wall thickness and echogenicity. In addition, we measured peak systolic and end-diastolic velocities and SMA RI on Doppler sonography. Pathological findings were analyzed and correlated with RI readings. Peak systolic and end-diastolic velocities and SMA RI values were analyzed statistically at each hour using the Wilcoxon rank sum test; the control and sepsis groups were compared using the Mann-Whitney test. The bowel wall thickness in the sepsis group was significantly increased after LPS injection. The caliber of the abdominal aorta in the sepsis group was significantly decreased after LPS injection. There were echogenic foci (<10 in axial plane) in the bowel wall after LPS injection. Peak systolic velocity in the sepsis group was not significantly changed, but end-diastolic velocity was decreased. SMA RIs in the sepsis group were significantly increased post-LPS injection from baseline. In the control group there were no significant changes in bowel wall thickness, abdominal aorta caliber, bowel wall echogenicity or peak systolic and end-diastolic velocities and RIs. Pathologically, eight of the 12 rabbits in the sepsis group showed grade 1 intestinal injury, three showed grade 2 injury and one showed grade 3 injury. SMA RIs were higher in grades 2 and 3 than in grade 1 when measured at 2 h and 4 h. Sepsis caused necrotic injury in the animal models, and these findings were accompanied by significant changes on Doppler US. These findings could facilitate early detection of intestinal injury in septic infants with NEC.

T1 mapping combined with Gd-EOB-DTPA-enhanced magnetic resonance imaging in predicting the pathologic grading of hepatocellular carcinoma.

PubMed

Chen, C Y; Chen, J; Xia, C C; Huang, Z X; Song, B

2017-01-01

The aim of this study was to investigate the value of Gd-EOB-DTPA-enhanced MRI on hepatobiliary phase (HBP) imaging and T1 mapping sequence in the differentiation of hepatocellular carcinoma (HCC). A total of 45 patients with HCC who were to undergo a resection were enrolled in this study. Gd-EOB-DTPA-enhanced magnetic resonance examination was performed prior to resection. T1 mapping was performed before and 20 min after injection of Gd-EOB-DTPA. T1 values of the lesions were measured on pre-contrast (T1p) and during HBP (T1-HBP) on T1 maps. The signal intensity, the diameter and the margin of HCC lesions on HBP images were analyzed. The reduction in T1 value (T1d) and the reduction rate (ΔT1%) of T1 mapping between pre-contrast and HBP were calculated. The Edmondson-Steiner classification of each lesion was made after surgery. The SPSS software package was used for statistical analysis and the analysis of receiver operator characteristic (ROC) curve and area under the curve (AUC) were carried out by using MedCalc software package. Mean values of T1p and T1-HBP were 1935.4±730.8 ms and 1257.1±529.1 ms, respectively. T1p accuracy (AUC = 0.685, p = 0.037) in predicting pathological grading was similar to that of T1-HBP (AUC = 0.751, p = 0.005). A T1p of 1648.2 ms or greater had a sensitivity and specificity of 85.19% and 61.11%, respectively. A T1-HBP of 1006 ms or greater had a sensitivity and specificity of 81.84% and 61.11%, respectively. The number of HCCs with a non-smooth tumor margin was 20 (44.4%), and a non-smooth tumor margin correlated moderately with the Edmondson-Steiner grade (Spearman r = 0.491, p = 0.041). There was no significant correlation between T1d, ΔT1%, HCC signal intensity on HBP image and lesion diameter with pathologic grading. T1 mapping in pre-contrast and HBP of Gd-EOB-DTPA-enhanced MRI, a non-smooth tumor margin in the HBP of Gd-EOB-DTPA-enhanced MRI, are useful in predicting the pathologic grading of HCC.

Incidence and correlates of Internet usage among adolescents in North Cyprus.

PubMed

Bayraktar, Fatih; Gün, Zübeyit

2007-04-01

The purpose of this study was to investigate the role of Internet usage among adolescents in Northern Cyprus. A total of 686 adolescents (mean age of 14.4 years, range of 12-17 years) were recruited from elementary and high schools. Results showed that the Internet was used primarily by male students. Adolescents used the Internet generally for entertainment and communication. The quality of chat on the Internet was studied, and it was found that adolescents generally introduce themselves differently while chatting. Also, the type of games on the Internet and the correlation between playing these games and aggression was studied in this research. It was found that mostly violent games were played on the Internet and playing these games were related to anti-social aggression and aggression toward the self. Research findings indicated that 1.1% of the students who used the Internet were pathological Internet users. These pathological Internet users visited significantly more chat sites, mp3 sites, pornographic sites, and shopping sites than other users. Also, it was found that students' grade point average (GPA) decreased when pathological Internet usage increased.

SUS users' perception: a speech-language pathology approach based on health promotion.

PubMed

Cunha, Jenane Topanotti da; Massi, Giselle; Guarinello, Ana Cristina; Pereira, Francine Martins

2016-01-01

This study aimed to analyze the perceptions of users of the Brazilian Unified Health System (SUS) about the treatment Center where they were assisted, as well as about the speech-language pathology services rendered by this Center. This is a transversal study composed of an interview with 26 open questions and 14 closed questions applied to 111 individuals who were assisted at the SUS Center in August 2013. The quantitative content analysis was conducted through the use of the GraphPadPrisma 5.1, Statistic Package for Social Sciences (SPSS) 15.0 software and the application of the D'agostino & Person, F-test and chi-squared test. Most participants reported a positive perception about the facilities and staff of the treatment center. They were also positive about the waiting time and the speech-language pathologists' explanations and conduct, especially in the audiology department. Most responses from participants were short and did not present an argumentative context. The treatment center received a high approval rating by most users. The audiology department had better grades than the clinical services related to language and oral motor pathologies.

Wide field of view CT and acromioclavicular joint instability: A technical innovation.

PubMed

Dyer, David R; Troupis, John M; Kamali Moaveni, Afshin

2015-06-01

A 21-year-old female with a traumatic shoulder injury is investigated and managed for symptoms relating to this injury. Pathology at the acromioclavicular joint is detected clinically; however, clinical examination and multiple imaging modalities do not reach a unified diagnosis on the grading of this acromioclavicular joint injury. When management appropriate to that suggested injury grading fail to help the patient's symptoms, further investigation methods were utilised. Wide field of view, dynamic CT (4D CT) is conducted on the patient's affected shoulder using a 320 × 0.5 mm detector multislice CT. Scans were conducted with a static table as the patient completed three movements of the affected shoulder. Capturing multiple data sets per second over a z-axis of 16 cm, measurements of the acromioclavicular joint were made, to show dynamic changes at the joint. Acromioclavicular (AC) joint translations were witnessed in three planes (a previously unrecognised pathology in the grading of acromioclavicular joint injuries). Translation in multiple planes was also not evident on careful clinical examination of this patient. AC joint width, anterior-posterior translation, superior-inferior translation and coracoclavicular width were measured with planar reconstructions while volume-rendered images and dynamic sequences aiding visual understanding of the pathology. Wide field of view dynamic CT (4D CT) is an accurate and quick modality to diagnose complex acromioclavicular joint injury. It provides dynamic information that no other modality can; 4D CT shows future benefits for clinical approach to diagnosis and management of acromioclavicular joint injury, and other musculoskeletal pathologies. © 2015 The Royal Australian and New Zealand College of Radiologists.

Determining the relationship between "microvessel density" and different grades of astrocytoma based on immunohistochemistry for "factor VIII-related antigen" (von Willebrand factor) expression in tumor microvessels.

PubMed

Mahzouni, Parvin; Mohammadizadeh, Fereshteh; Mougouei, Kourosh; Moghaddam, Noushin Afshar; Chehrei, Ali; Mesbah, Alireza

2010-01-01

Astrocytic brain tumors are the most common primary central nervous system tumors, which are classified into four grades. One of the most important pathologic criteria for the diagnosis of higher-grade astrocytomas (especially glioblastoma multiforme) is microvessel proliferation, particularly in the form of glomeruloid complex. Because tumor angiogenesis is a necessary factor for growth and invasiveness of malignancies, microvessel density (MVD) and intensity of angiogenesis may be used to determine the grade of astrocytomas and plan therapy accordingly. We have planned this study to evaluate the relationship between vwf expression in microvessels and different grades of astrocytoma. Sixty-four formalin-fixed and paraffin-embedded blocks of surgical specimens with diagnosis of astrocytoma (grades I to IV, each of them 16 blocks) were selected in a simple-nonrandom sampling. Thin sections of tissue blocks underwent immunohistochemical staining for vwf. The stained slides were examined using a light microscope at low (100) and high (400) magnifications. MVD was estimated by calculating the mean number of stained microvessels in three areas of highest vascularization in the high-power field (400). The intensity of staining was determined based on a 3 scale model, in which scores 0, 1, 2, and 3 mean no detectable stain, trace staining, moderate amount of diffuse stain, and strong diffuse staining, respectively. Thirty-six (56%) patients were male and 28 (44%) were female. Scores 0 and 1 of microvessel staining intensity were not observed in any grades studied, but severe staining intensity (score 3) was observed in 18.8%, 37.5%, 56.3%, and 87.5% of grades I, II, III, and IV astrocytomas, respectively. "Vwf vessel index" (MVD staining intensity of microvessels) was 23.84, 25.62, 31.62, and 62.43 in grades I, II, III, and IV astrocytomas, respectively. We found a significant relationship between staining intensity of vwf in microvessels and different grades of astrocytomas. The intensity of microvessel stain increases in parallel with increasing tumor grade. Regarding "microvessel density" and "vwf vessel index," the difference is predominantly between grade IV and all other grades. However, there is no other statistically meaningful difference between grades I, II and III.

Spontaneous complete regression of a brain stem glioma pathologically diagnosed as a high-grade glioma.

PubMed

Ishihara, Masahiro; Yamamoto, Kazumi; Miwa, Hideaki; Nishi, Masaya

2017-12-01

Spontaneous regressions of brain stem gliomas are extremely rare. Only six cases have been reported in the literature. We describe the case of a patient who was diagnosed with a pontomedullary dorsal brain stem glioma at the age of 15 years. An open biopsy showed the presence of an anaplastic glioma. Because the patient and her parents refused conventional therapies, including radiation and chemotherapy, we followed up the patient by performing magnetic resonance imaging scans on her every 3 months. At 3 months after biopsy, we observed the radiological disappearance of her tumor. One year after biopsy, the tumor retained the spontaneous complete regression observed earlier. In this case report, we present the first report of the spontaneous complete regression of a brain stem glioma that was histologically proven to be a high-grade glioma and we believe that this regression was the natural progression of this case, as may be the scenario in a few other cases of brain stem gliomas.

Conducting Molecular Epidemiological Research in the Age of HIPAA: A Multi-Institutional Case-Control Study of Breast Cancer in African-American and European-American Women

PubMed Central

Ambrosone, Christine B.; Ciupak, Gregory L.; Bandera, Elisa V.; Jandorf, Lina; Bovbjerg, Dana H.; Zirpoli, Gary; Pawlish, Karen; Godbold, James; Furberg, Helena; Fatone, Anne; Valdimarsdottir, Heiddis; Yao, Song; Li, Yulin; Hwang, Helena; Davis, Warren; Roberts, Michelle; Sucheston, Lara; Demissie, Kitaw; Amend, Kandace L.; Tartter, Paul; Reilly, James; Pace, Benjamin W.; Rohan, Thomas; Sparano, Joseph; Raptis, George; Castaldi, Maria; Estabrook, Alison; Feldman, Sheldon; Weltz, Christina; Kemeny, Margaret

2009-01-01

Breast cancer in African-American (AA) women occurs at an earlier age than in European-American (EA) women and is more likely to have aggressive features associated with poorer prognosis, such as high-grade and negative estrogen receptor (ER) status. The mechanisms underlying these differences are unknown. To address this, we conducted a case-control study to evaluate risk factors for high-grade ER- disease in both AA and EA women. With the onset of the Health Insurance Portability and Accountability Act of 1996, creative measures were needed to adapt case ascertainment and contact procedures to this new environment of patient privacy. In this paper, we report on our approach to establishing a multicenter study of breast cancer in New York and New Jersey, provide preliminary distributions of demographic and pathologic characteristics among case and control participants by race, and contrast participation rates by approaches to case ascertainment, with discussion of strengths and weaknesses. PMID:19865486

Small Bowel Gastrointestinal Stromal Tumors: Multidetector Computed Tomography Enhancement Pattern and Risk of Progression.

PubMed

Verde, Franco; Hruban, Ralph H; Fishman, Elliot K

Small bowel gastrointestinal stromal tumors (SB-GISTs) are rare lesions with a variable appearance on computed tomography (CT). This case series analyzes the CT enhancement pattern with the histologic risk assessment of tumor progression. Local institutional pathology database was searched for SB-GISTs from 2000 to 2015. Pathology reports and clinical notes were reviewed. Imaging was qualitatively reviewed for pattern of enhancement categorized into homogeneous or heterogeneous groups. Nonparametric statistical analysis was performed comparing enhancement to segment of bowel involved, presence of necrosis, tumor size, histologic grade (ie, G1 or G2), and histologic risk of progression (ie low, moderate, high). For simplicity, risk of progression was binned into low-risk or non-low-risk groups. Twenty-six pathology-proven, first presentation, nonmetastatic SB-GISTs were included into study. Seventeen were located in duodenum, 7 in jejunum, and 2 within the ileum. Dual phase (arterial and venous) CT imaging was available for 22 cases. Four cases did not have dual phase (three venous phase and one arterial phase only). Seventeen cases demonstrated heterogeneous enhancement and 9 cases homogeneous enhancement. Statistically significant difference was found between size versus enhancement groups (3.1 cm for homogeneous versus 6.8 cm for heterogeneous) (Mann-Whitney U test, n = 26, P = 0.002). Presence of necrosis versus enhancement group was statistically significant (Pearson χ, P = 0.001). Low-risk and non-low-risk groups versus enhancement groups was very significant (P = 0.001). Bowel segment involvement and histologic grading versus enhancement group did not reach statistical significance (P = 0.174 and P = 0.07, respectively). This case series reveals an important significant association between heterogeneous enhancement and non-low risk (ie, moderate/high) SB-GISTs. Beyond just describing the tumor, using enhancing pattern, the interpreting radiologist can preoperatively suggest additional prognostic information, potentially helpful for surgical planning.

Hypoxic cell waves around necrotic cores in glioblastoma: a biomathematical model and its therapeutic implications.

PubMed

Martínez-González, Alicia; Calvo, Gabriel F; Pérez Romasanta, Luis A; Pérez-García, Víctor M

2012-12-01

Glioblastoma is a rapidly evolving high-grade astrocytoma that is distinguished pathologically from lower grade gliomas by the presence of necrosis and microvascular hyperplasia. Necrotic areas are typically surrounded by hypercellular regions known as "pseudopalisades" originated by local tumor vessel occlusions that induce collective cellular migration events. This leads to the formation of waves of tumor cells actively migrating away from central hypoxia. We present a mathematical model that incorporates the interplay among two tumor cell phenotypes, a necrotic core and the oxygen distribution. Our simulations reveal the formation of a traveling wave of tumor cells that reproduces the observed histologic patterns of pseudopalisades. Additional simulations of the model equations show that preventing the collapse of tumor microvessels leads to slower glioma invasion, a fact that might be exploited for therapeutic purposes.

Clinicopathologic Characteristics and Treatment Outcomes of Penile Cancer

PubMed Central

Nam, Jong Kil; Lee, Dong Hoon; Park, Sung Woo; Kam, Sung Chul; Lee, Ki Soo; Kim, Tae Hyo; Kim, Taek Sang; Oh, Cheol Kyu; Park, Hyun Jun

2017-01-01

Purpose The aim of this study was to assess the clinicopathologic characteristics of penile cancer, including patterns of therapy, oncologic results, and survival. Materials and Methods Between January 2005 and July 2015, 71 patients at 6 institutions who had undergone penectomy or penile biopsy were enrolled. Their medical records were reviewed to identify the mode of therapy, pathology reports, and cancer-specific survival (CSS) rate. Results Clinicopathologic and outcome information was available for 52 male patients (mean age, 64.3 years; mean follow-up, 61.4 months). At presentation, 17 patients were node-positive, and 4 had metastatic disease. Management was partial penectomy in 34 patients, total penectomy in 12 patients, and chemotherapy or radiotherapy in 6 patients. The pathology reports were squamous cell carcinoma in 50 patients and other types of carcinoma in the remaining 2 patients. Kaplan-Meier survival analysis showed a 5-year CSS rate of 84.0%. In univariate and multivariate analyses, the American Joint Committee on Cancer (AJCC) stage and pathologic grade were associated with survival. Conclusions Partial penectomy was the most common treatment of penile lesions. The oncologic outcomes were good, with a 5-year CSS of 84.0%. The AJCC stage and pathologic grade were independent prognostic factors for survival. PMID:28459145

[Study of susceptibility weighted imaging on MR and pathologic findings to distinguish benign or malignant soft tissue tumor].

PubMed

Liu, J; Chen, Y; Bao, X M; Ling, X L; Ding, J P; Zhang, Z K

2017-05-23

Objective: To explore the diagnostic performance of susceptibility weighted imaging (SWI)in distinguishing benign or malignant soft tissue tumor, and to study pathological observation. Methods: Sixty-eight patients with soft tissue tumor, who received no previous treatment or invasive examination, received routine preoperative MRI examination and SWI scanning. The graduation and distribution of intratumoral susceptibility signal intensity(ITSS) and proportion of tumor volume were observed.The pathological results were also included for comparative analysis. Results: Fourty of 68 patients were benign and 28 were malignant. 72.5% (29/40) patients with benign soft tissue tumors were ITSS grade 1 and ITSS grade 3 (hemangioma). 89.3%(25/28) patients with malignant soft tissue tumors were ITSS grade 2 and ITSS grade 3. The difference was statistically significant ( P <0.01). The distribution of ITSS in patients with benign soft tissue tumors was dominated by peripheral distribution and diffuse distribution (hemangioma), accounting for 90.0% (36/40). The distribution of ITSS in patients with malignant soft tissue tumors mainly distributed in the central region, accounting for 78.6% (22 /28). The difference was statistically significant ( P <0.01). The proportion of tumor volume occupied by ITSS in benign soft tissue tumors was <1/3 and> 2/3 (hemangioma), accounting for 90.0% (36/40). The volume of malignant soft tissue tumors were predominantly <1/3 , accounting for 82.1% (23/28). The difference was statistically significant ( P <0.01). Conclusion: SWI is sensitive in displaying the vein and blood metabolites in soft tissue lesions, which is helpful for the differential diagnosis of benign and malignant tumors in soft tissue.

Decreased expression of glutathione S-transferase pi correlates with poorly differentiated grade in patients with oral squamous cell carcinoma.

PubMed

Ma, Hai-long; Yu, Cong; Liu, Ying; Tan, Yi-ran; Qiao, Jin-ke; Yang, Xi; Wang, Li-zhen; Li, Jiang; Chen, Qiong; Chen, Fu-xiang; Zhang, Zhi-yuan; Zhong, Lai-ping

2015-03-01

Glutathione S transferase pi (GSTP1) is a member of phase II detoxification enzymes as a major regulator of cell signaling in response to stress, hypoxia, growth factors, and other stimuli. The clinical role of GSTP1 in cancer is still unclear. The aim of this study was to investigate the serum GSTP1 level in patients with oral squamous cell carcinoma (OSCC) and the GSTP1 expression in tissue samples from patients with OSCC and OSCC lines. One hundred and sixty-six patients with OSCC and 120 normal persons were used to screen potential serum peptide biomarkers using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Serum GSTP1 concentration was detected in 18 patients with OSCC and 18 normal persons using ELISA. Immunohistochemistry was used to detect GSTP1 expression in tissue samples from twenty-eight OSCC patients. Western blot and real-time PCR were used to detect GSTP1 expression in nine OSCC lines. Decreased GSTP1 concentration was found in the patients with OSCC compared with the normal persons by MALDI-TOF-MS, which was then confirmed by ELISA (P = 0.019). Decreased GSTP1 mRNA level and protein expression were also found in the OSCC lines. Decreased GSTP1 expression was found correlating with pathological differentiation grade in the tissue samples from OSCC patients, a lower GSTP1 expression indicating a poorer pathological differentiation grade (P = 0.041). These results suggest that decreased GSTP1 expression in patients with OSCC and a lower GSTP1 expression indicating a poorer pathological differentiation grade in OSCC tissue samples. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Histopathologic grading of medulloblastomas: a Pediatric Oncology Group study.

PubMed

Eberhart, Charles G; Kepner, James L; Goldthwaite, Patricia T; Kun, Larry E; Duffner, Patricia K; Friedman, Henry S; Strother, Douglas R; Burger, Peter C

2002-01-15

Medulloblastomas are small cell embryonal tumors of the cerebellum found predominantly in children, only slightly more than half of whom survive. Predicting favorable outcome has been difficult, and improved stratification clearly is required to avoid both undertreatment and overtreatment. Patients currently are staged clinically, but no pathologic staging system is in use. Two rare subtypes at extreme ends of the histologic spectrum, i.e., medulloblastomas with extensive nodularity and large cell/anaplastic medulloblastomas, are associated with better and worse clinical outcomes, respectively. However, there is little data about correlations between histologic features and clinical outcome for most patients with medulloblastomas that fall between these histologic extremes of nodularity and anaplasia. Therefore, the authors evaluated the clinical effects of increasing anaplasia and nodularity in a large group of children with medulloblastomas, hypothesizing that increasing nodularity would predict better clinical outcomes and that increasing anaplasia would presage less favorable results. Medulloblastomas from 330 Pediatric Oncology Group patients were evaluated histologically with respect to extent of nodularity, presence of desmoplasia, grade of anaplasia, and extent of anaplasia. Pathologic and clinical data were then compared using Kaplan-Meier and log-rank analyses. Increasing grade of anaplasia and extent of anaplasia were associated strongly with progressively worse clinical outcomes (P < 0.0001 for both). Significant anaplasia (moderate or severe) was identified in 24% of medulloblastoma specimens. Neither increasing degrees of nodularity nor desmoplasia were associated significantly with longer survival. Moderate anaplasia and severe anaplasia were associated with aggressive clinical behavior in patients with medulloblastomas and were detected in a significant number of specimens (24%). Pathologic grading of medulloblastomas with respect to anaplasia may be of clinical utility.

Pathological examination of radical prostatectomy specimens in men with very low risk disease at biopsy reveals distinct zonal distribution of cancer in black American men.

PubMed

Sundi, Debasish; Kryvenko, Oleksandr N; Carter, H Ballentine; Ross, Ashley E; Epstein, Jonathan I; Schaeffer, Edward M

2014-01-01

Of men with very low risk prostate cancer at biopsy recent evidence shows that black American men are at greater risk for adverse oncologic outcomes after radical prostatectomy. We studied radical prostatectomy specimens from black and white men at very low risk to determine whether there are systematic pathological differences. Radical prostatectomy specimens were evaluated in men with National Comprehensive Cancer Network® (NCCN) very low risk prostate cancer. At diagnosis all men underwent extended biopsy sampling (10 or more cores) and were treated in the modern Gleason grade era. We analyzed tumor volume, grade and location in 87 black and 89 white men. For each specimen the dominant nodule was defined as the largest tumor with the highest grade. Compared to white men, black men were more likely to have significant prostate cancer (61% vs 29%), Gleason 7 or greater (37% vs 11%, each p <0.001) and a volume of greater than 0.5 cm(3) (45% vs 21%, p = 0.001). Dominant nodules in black men were larger (median 0.28 vs 0.13 cm(3), p = 0.002) and more often anterior (51% vs 29%, p = 0.003). In men who underwent pathological upgrading the dominant nodule was also more frequently anterior in black than in white men (59% vs 0%, p = 0.001). Black men with very low risk prostate cancer at diagnosis have a significantly higher prevalence of anterior cancer foci that are of higher grade and larger volume. Enhanced imaging or anterior zone sampling may detect these significant anterior tumors, improving the outcome in black men considering active surveillance. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Radiomics Evaluation of Histological Heterogeneity Using Multiscale Textures Derived From 3D Wavelet Transformation of Multispectral Images.

PubMed

Chaddad, Ahmad; Daniel, Paul; Niazi, Tamim

2018-01-01

Colorectal cancer (CRC) is markedly heterogeneous and develops progressively toward malignancy through several stages which include stroma (ST), benign hyperplasia (BH), intraepithelial neoplasia (IN) or precursor cancerous lesion, and carcinoma (CA). Identification of the malignancy stage of CRC pathology tissues (PT) allows the most appropriate therapeutic intervention. This study investigates multiscale texture features extracted from CRC pathology sections using 3D wavelet transform (3D-WT) filter. Multiscale features were extracted from digital whole slide images of 39 patients that were segmented in a pre-processing step using an active contour model. The capacity for multiscale texture to compare and classify between PTs was investigated using ANOVA significance test and random forest classifier models, respectively. 12 significant features derived from the multiscale texture (i.e., variance, entropy, and energy) were found to discriminate between CRC grades at a significance value of p  < 0.01 after correction. Combining multiscale texture features lead to a better predictive capacity compared to prediction models based on individual scale features with an average (±SD) classification accuracy of 93.33 (±3.52)%, sensitivity of 88.33 (± 4.12)%, and specificity of 96.89 (± 3.88)%. Entropy was found to be the best classifier feature across all the PT grades with an average of the area under the curve (AUC) value of 91.17, 94.21, 97.70, 100% for ST, BH, IN, and CA, respectively. Our results suggest that multiscale texture features based on 3D-WT are sensitive enough to discriminate between CRC grades with the entropy feature, the best predictor of pathology grade.

Apparent diffusion coefficient value as a biomarker reflecting morphological and biological features of prostate cancer.

PubMed

Bae, Hyeyeol; Yoshida, Soichiro; Matsuoka, Yoh; Nakajima, Hiroshi; Ito, Eisaku; Tanaka, Hiroshi; Oya, Miyako; Nakayama, Takayuki; Takeshita, Hideki; Kijima, Toshiki; Ishioka, Junichiro; Numao, Noboru; Koga, Fumitaka; Saito, Kazutaka; Akashi, Takumi; Fujii, Yasuhisa; Kihara, Kazunori

2014-03-01

To assess whether there is an association between the apparent diffusion coefficient (ADC) value and the pathological characteristics of prostate cancer. The study cohort consisted of 29 consecutive patients with prostate cancer treated with radical prostatectomy. All patients underwent diffusion-weighted MRI before the prostate biopsy. In 42 tumor foci, the associations of the ADC values with the clinicopathological characteristics and Ki-67 labeling index (LI) were analyzed. High-grade cancers (Gleason score [GS] ≥ 4 + 3), larger cancers (maximum diameter (MD) ≥ 16 mm), and highly proliferating cancers (Ki-67 LI ≥ 4.43 %) had significantly lower ADC values, respectively (P < .001, P = .008, and P = .044, respectively). There was no significant difference in ADC value according to age, prostate-specific antigen, presence of extra-prostatic extension, and intra-tumoral stroma proportion. Multivariate analysis showed that GS, Ki-67 LI, and MD had independent and significant correlations with ADC value (P < .001, P = .006, and P = .002, respectively). Low ADC tumors (<0.52 × 10(-3) mm(2)/s) are likely to be high-grade cancer foci compared with high ADC tumors (relative risk: 65.2). The sensitivity and specificity of the ADC value to predict high-grade cancer foci are 81.8 and 93.5 %, respectively. A low ADC value reflects the morphological and biological features of prostate cancer. Analyzing the ADC value may make it possible to more precisely predict the cancer aggressiveness of each focus before treatment.

Head and Neck Sarcomas: The UCLA Experience

PubMed Central

Tajudeen, Bobby A.; Fuller, Jennifer; Lai, Chi; Grogan, Tristan; Elashoff, David; Abemayor, Elliot; St. John, Maie

2014-01-01

Purpose To profile the clinical presentation, subtype distribution, and treatment results of sarcomas of the head and neck at a single tertiary academic center over an 11-year period. Materials and Methods A retrospective review was performed by examining the records and reviewing the pathology of 186 patients with head and neck sarcomas treated at UCLA Medical Center from 2000 to 2011. Results The mean age of the study population was 49 +/− 22 years. 58% of the patients were male and 42% were female. Median duration of follow-up for the entire group was 18.5 months. The most common presenting symptom was a mass lesion in 59.9% of patients. The nasal cavity/sinus was the most common presenting site seen in 22% of patients. Solitary fibrous tumor/hemangiopericytoma was the most common subtype. 15% of patients had evidence of prior radiation exposure. 26.3% of tumors were greater than 5cm and 35.5% were high-grade. Margins were positive in 31.2% of patients. Lymph node metastasis was rare at 6.5%. Perineural invasion was identified in 6.5%. Among all subtypes, 5-yr recurrence-free survival and overall survival were 50% and 49%, respectively. Multivariate analysis demonstrated that grade and margin status were predictors of recurrence-free survival while grade and age affected overall survival. Conclusions Head and neck sarcomas are a rare entity frequently presenting as a mass lesion. In our series, lesions tended to be high-grade with a significant portion of surgical specimens having positive margins. Grade and margin status were the most important predictors of survival. PMID:24721744

A Unique Four-Hub Protein Cluster Associates to Glioblastoma Progression

PubMed Central

Simeone, Pasquale; Trerotola, Marco; Urbanella, Andrea; Lattanzio, Rossano; Ciavardelli, Domenico; Di Giuseppe, Fabrizio; Eleuterio, Enrica; Sulpizio, Marilisa; Eusebi, Vincenzo; Pession, Annalisa; Piantelli, Mauro; Alberti, Saverio

2014-01-01

Gliomas are the most frequent brain tumors. Among them, glioblastomas are malignant and largely resistant to available treatments. Histopathology is the gold standard for classification and grading of brain tumors. However, brain tumor heterogeneity is remarkable and histopathology procedures for glioma classification remain unsatisfactory for predicting disease course as well as response to treatment. Proteins that tightly associate with cancer differentiation and progression, can bear important prognostic information. Here, we describe the identification of protein clusters differentially expressed in high-grade versus low-grade gliomas. Tissue samples from 25 high-grade tumors, 10 low-grade tumors and 5 normal brain cortices were analyzed by 2D-PAGE and proteomic profiling by mass spectrometry. This led to identify 48 differentially expressed protein markers between tumors and normal samples. Protein clustering by multivariate analyses (PCA and PLS-DA) provided discrimination between pathological samples to an unprecedented extent, and revealed a unique network of deranged proteins. We discovered a novel glioblastoma control module centered on four major network hubs: Huntingtin, HNF4α, c-Myc and 14-3-3ζ. Immunohistochemistry, western blotting and unbiased proteome-wide meta-analysis revealed altered expression of this glioblastoma control module in human glioma samples as compared with normal controls. Moreover, the four-hub network was found to cross-talk with both p53 and EGFR pathways. In summary, the findings of this study indicate the existence of a unifying signaling module controlling glioblastoma pathogenesis and malignant progression, and suggest novel targets for development of diagnostic and therapeutic procedures. PMID:25050814

[Age characteristics of the cardiovascular system, depending on the thyroid function in type 2 diabetes mellitus].

PubMed

Ignateva, P A; Ballyuzek, M F; Shpakov, A O

To study the features of cardiovascular system in patients with diabetes mellitus type 2 considering the thyroid pathology and age, 264 patients were examined. They were divided into three groups: 1st - patients with diffuse-nodular changes in the thyroid gland, 2nd - patients with autoimmune thyroid disease, 3rd - a control group of patients without thyroid disease. The patients of different ages were examined in each of these groups. All patients were in euthyroid state. It was established that identified in diabetes mellitus type 2 thyroid pathology and the thyroid disease contribute special features to the clinical picture for combined diabetic and cardiovascular pathology even in a euthyroid state including the age features. The laboratory and instrumental researches showed that the patients with combined diabetes and thyroid pathology have a higher incidence of atrial fibrillation, ischemic heart disease, and ventricular arrhythmias of high grades. They also were noticed to have a more adverse form of the left ventricle remodeling, also the combination of diastolic and systolic dysfunctions were found to be more frequent. It was concluded about the necessity of early diagnosis and correction of the cardiovascular disorders and thyroid systems in type 2 diabetes mellitus patients, including euthyroid patients.

Detection of tuberculosis patterns in digital photographs of chest X-ray images using Deep Learning: feasibility study.

PubMed

Becker, A S; Blüthgen, C; Phi van, V D; Sekaggya-Wiltshire, C; Castelnuovo, B; Kambugu, A; Fehr, J; Frauenfelder, T

2018-03-01

To evaluate the feasibility of Deep Learning-based detection and classification of pathological patterns in a set of digital photographs of chest X-ray (CXR) images of tuberculosis (TB) patients. In this prospective, observational study, patients with previously diagnosed TB were enrolled. Photographs of their CXRs were taken using a consumer-grade digital still camera. The images were stratified by pathological patterns into classes: cavity, consolidation, effusion, interstitial changes, miliary pattern or normal examination. Image analysis was performed with commercially available Deep Learning software in two steps. Pathological areas were first localised; detected areas were then classified. Detection was assessed using receiver operating characteristics (ROC) analysis, and classification using a confusion matrix. The study cohort was 138 patients with human immunodeficiency virus (HIV) and TB co-infection (median age 34 years, IQR 28-40); 54 patients were female. Localisation of pathological areas was excellent (area under the ROC curve 0.82). The software could perfectly distinguish pleural effusions from intraparenchymal changes. The most frequent misclassifications were consolidations as cavitations, and miliary patterns as interstitial patterns (and vice versa). Deep Learning analysis of CXR photographs is a promising tool. Further efforts are needed to build larger, high-quality data sets to achieve better diagnostic performance.

The changing role of the pathologist in the management of Barrett's oesophagus.

PubMed

Hopcroft, Suzanne A; Shepherd, Neil A

2014-10-01

Pathological specimens from columnar-lined oesophagus (CLO) comprise a considerable proportion of the workload of gastrointestinal pathologists in Western countries. There remain controversies concerning the diagnostic role of pathology. More recently, in the UK at least, the diagnosis has been regarded as primarily an endoscopic endeavour, with pathology being corroborative and only diagnostic when endoscopic features are equivocal or when there are additional features that make the endoscopic diagnosis unclear. There is also recognition that demonstration of intestinalisation or 'goblet cells' is not paramount, and should not be required for the diagnosis. There have been notable changes in the management of CLO neoplasia: pathologists are centrally involved in its management. Pathological assessment of endoscopic mucosal resection (EMR) specimens provides the most useful means of determining the management of early neoplasia and of determining indications for surgery. This represents an extraordinarily rapid change in management, in that, <10 years ago, laborious Seattle-type biopsy protocols were recommended, and high grade dysplasia was an indication for resectional surgery. Now, individual patient management is paramount: multi-professional meetings determine management after biopsy and EMR assessment. One significant change is that major resections are undertaken less often, in Western countries, for CLO neoplasia. © 2014 John Wiley & Sons Ltd.

Automated detection of diagnostically relevant regions in H&E stained digital pathology slides

NASA Astrophysics Data System (ADS)

Bahlmann, Claus; Patel, Amar; Johnson, Jeffrey; Ni, Jie; Chekkoury, Andrei; Khurd, Parmeshwar; Kamen, Ali; Grady, Leo; Krupinski, Elizabeth; Graham, Anna; Weinstein, Ronald

2012-03-01

We present a computationally efficient method for analyzing H&E stained digital pathology slides with the objective of discriminating diagnostically relevant vs. irrelevant regions. Such technology is useful for several applications: (1) It can speed up computer aided diagnosis (CAD) for histopathology based cancer detection and grading by an order of magnitude through a triage-like preprocessing and pruning. (2) It can improve the response time for an interactive digital pathology workstation (which is usually dealing with several GByte digital pathology slides), e.g., through controlling adaptive compression or prioritization algorithms. (3) It can support the detection and grading workflow for expert pathologists in a semi-automated diagnosis, hereby increasing throughput and accuracy. At the core of the presented method is the statistical characterization of tissue components that are indicative for the pathologist's decision about malignancy vs. benignity, such as, nuclei, tubules, cytoplasm, etc. In order to allow for effective yet computationally efficient processing, we propose visual descriptors that capture the distribution of color intensities observed for nuclei and cytoplasm. Discrimination between statistics of relevant vs. irrelevant regions is learned from annotated data, and inference is performed via linear classification. We validate the proposed method both qualitatively and quantitatively. Experiments show a cross validation error rate of 1.4%. We further show that the proposed method can prune ~90% of the area of pathological slides while maintaining 100% of all relevant information, which allows for a speedup of a factor of 10 for CAD systems.

Femoral metastases from ovarian serous/endometroid adenocarcinoma

PubMed Central

Beresford–Cleary, NJA; Mehdi, SA; Magowan, B

2012-01-01

Bony metastases from ovarian cancer are rare, tend to affect the axial skeleton and are associated with abdomino-pelvic disease. The median time interval between diagnosis of ovarian carcinoma and presentation of bony metastases is 44 months (1). We describe a rare case of high grade left ovarian serous / endometrioid adenocarcinoma presenting with a pathological right femoral fracture 4 weeks following diagnosis and optimal debulking of the ovarian tumour. Orthopaedic surgeons must be vigilant when planning treatment of fractures presenting in patients with a history of ovarian cancer. PMID:24960734

What Is Cancer?

MedlinePlus

... myeloid). Our page on leukemia has more information. Lymphoma Lymphoma is cancer that begins in lymphocytes (T ... tumors has more information. Related Resources Tumor Grade Pathology Reports Metastatic Cancer Common Cancer Myths and Misconceptions ...

Opportunities for Improvement in Pathology Reporting of Childhood Nonrhabdomyosarcoma Soft Tissue Sarcomas:  A Report From Children's Oncology Group (COG) Study ARST0332.

PubMed

Black, Jennifer O; Coffin, Cheryl M; Parham, David M; Hawkins, Douglas S; Speights, Rose A; Spunt, Sheri L

2016-09-01

Treatment of soft tissue tumors in young patients relies on the diagnostic information conveyed in the pathology report. We examined pathology reports from Children's Oncology Group ARST0332 for inclusion of data elements required in published guidelines. Pathology reports for 551 eligible patients were examined for required data elements defined by the College of American Pathologists, including tissue type, procedure, tumor site, tumor maximum diameter, macroscopic extent of tumor, histologic type, mitotic rate, extent of necrosis, tumor grade, margin status, use of ancillary studies, and pathologic stage. Only 65 (12%) of 551 reports included all required data elements. Of reports containing synoptic templates, 57% were complete. This study reveals significant opportunity to improve the quality of pathology reports in young patients with soft tissue tumors. Use of templates or checklists improves completeness of reports. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Differentiating the grades of thymic epithelial tumor malignancy using textural features of intratumoral heterogeneity via (18)F-FDG PET/CT.

PubMed

Lee, Hyo Sang; Oh, Jungsu S; Park, Young Soo; Jang, Se Jin; Choi, Ik Soo; Ryu, Jin-Sook

2016-05-01

We aimed to explore the ability of textural heterogeneity indices determined by (18)F-FDG PET/CT for grading the malignancy of thymic epithelial tumors (TETs). We retrospectively enrolled 47 patients with pathologically proven TETs who underwent pre-treatment (18)F-FDG PET/CT. TETs were classified by pathological results into three subgroups with increasing grades of malignancy: low-risk thymoma (LRT; WHO classification A, AB and B1), high-risk thymoma (B2 and B3), and thymic carcinoma (TC). Using (18)F-FDG PET/CT, we obtained conventional imaging indices including SUVmax and 20 intratumoral heterogeneity indices: i.e., four local-scale indices derived from the neighborhood gray-tone difference matrix (NGTDM), eight regional-scale indices from the gray-level run-length matrix (GLRLM), and eight regional-scale indices from the gray-level size zone matrix (GLSZM). Area under the receiver operating characteristic curve (AUC) was used to demonstrate the abilities of the imaging indices for differentiating subgroups. Multivariable logistic regression analysis was performed to show the independent significance of the textural indices. Combined criteria using optimal cutoff values of the SUVmax and a best-performing heterogeneity index were applied to investigate whether they improved differentiation between the subgroups. Most of the GLRLM and GLSZM indices and the SUVmax showed good or fair discrimination (AUC >0.7) with best performance for some of the GLRLM indices and the SUVmax, whereas the NGTDM indices showed relatively inferior performance. The discriminative ability of some of the GLSZM indices was independent from that of SUVmax in multivariate analysis. Combined use of the SUVmax and a GLSZM index improved positive predictive values for LRT and TC. Texture analysis of (18)F-FDG PET/CT scans has the potential to differentiate between TET tumor grades; regional-scale indices from GLRLM and GLSZM perform better than local-scale indices from the NGTDM. The SUVmax and heterogeneity indices may have complementary value in differentiating TET subgroups.

[Plasmablastic lymphoma].

PubMed

Fernández-Álvarez, Rubén; Sancho, Juan-Manuel; Ribera, Josep-María

2016-11-04

Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin lymphoma that commonly occurs in human immunodeficiency virus (HIV)-positive individuals, and affects oral sites. Occasionally, it has been described in HIV-negative patients and involving non-oral sites. Pathologically, PBL is a high-grade B-cell lymphoma that displays the immunophenotype of a terminally differentiated B-lymphocyte with loss of B-cell markers (CD20) and expression of plasma-cell antigens. Epstein-Barr virus infection and MYC rearrangements are frequently observed. Treatment of PBL is challenging because of the lack of established treatment and poor outcomes, with median survival times shorter than one year. In this review, we discuss the clinical and epidemiologic spectrum of PBL as well as its distinct pathological features. Finally, we summarize the currently available approaches for the treatment of patients with PBL. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Impact of sarcopenia on outcomes of locally advanced esophageal cancer patients treated with neoadjuvant chemoradiation followed by surgery

PubMed Central

Venkat, Puja S.; Jin, William; Leuthold, Susan; Latifi, Kujtim; Almhanna, Khaldoun; Pimiento, Jose M.; Fontaine, Jacques-Pierre; Hoffe, Sarah E.; Frakes, Jessica M.

2017-01-01

Background Sarcopenia is an independent predictor of clinical outcomes in multiple gastrointestinal cancers. Total psoas area (TPA), as measured on a single cross-sectional CT image at the L4 vertebral body level, has been correlated with sarcopenia. We sought to evaluate whether TPA was predictive of acute grade ≥3 toxicity, pathologic response, and overall survival in patients with locally advanced esophageal cancer receiving tri-modality therapy. Methods An institutional database of esophageal cancer patients treated with neoadjuvant chemoradiation followed by surgery was queried. Of 77 patients treated from 2008 to 2012 with intensity modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT), 56 patients were eligible based on having CT imaging that included the L4 vertebral body. The L4 vertebra was identified on axial CT and the psoas muscle was manually contoured bilaterally to determine the skeletal muscle index. Sarcopenia was defined by the presence of the psoas area less than the median of the cohort. Acute toxicity was defined as within 3 months of radiotherapy based on Common Terminology Criteria for Adverse Events. ROC curve, logistic regression, and Kaplan Meier estimates were used when appropriate. Results Sarcopenia was associated with increased acute grade ≥3 toxicity from chemoradiation by ROC analysis using a cut off of 841.5 mm2/m2 (P=0.003, AUC 0.709, sensitivity 60.9%, specificity 78.8%) and logistic regression (P=0.002). Patients with TPA <841.5 mm2/m2 were 5.78 times more likely to develop grade 3 or higher toxicity (P=0.004). Sarcopenia did not predict a difference in overall survival (P=0.217) and was not significant for pathologic complete response or favorable pathologic response (TRG 0/1). Conclusions In our cohort of patients, sarcopenia was associated with a significant increase in acute grade ≥3 toxicity with chemoradiation, suggesting a potential role for neoadjuvant patient selection strategies. There was no difference in pathologic response or overall survival. PMID:29184684

Polyp on ultrasound: now what? The association between gallbladder polyps and cancer.

PubMed

Donald, Graham; Sunjaya, Dharma; Donahue, Timothy; Hines, O Joe

2013-10-01

The association between gallbladder polyps (GBP) and gallbladder cancer (GBC) is unclear. We sought to determine the association between preoperative diagnosis of GBP on imaging and GBC. A retrospective review of patients over 9 years was conducted using International Classification of Diseases, 9th Revision codes for GBP and GBC who underwent cholecystectomy at our institution. Demographics, imaging findings, and pathology results were recorded. A total of 2416 patients underwent cholecystectomy during the study period. Twenty-seven had an operation for GBP either as a result of concern for size or symptoms. Polyp sizes were categorized as less than 1 cm, 1 to 2 cm, or 2 cm or greater. Twenty-four patients in this group (88.9%) had no evidence of high-grade dysplasia or cancer and all of these benign polyps were 2 cm or less on imaging. One patient with a 2.4-cm polyp had high-grade dysplasia, and two patients with polyps over 3 cm had adenocarcinoma. During the same period, 20 patients had an operation for GBC with two patients common to the polyp group. The group of patients with noncancerous polyps was significantly younger than the cancer group (polyps and no polyps). The cancer group was more likely to be symptomatic. Therefore, polyps over 2 cm should be removed given the risk of high-grade dysplasia and cancer above this size. Polyps less than 2 cm were not associated with high-grade dysplasia or cancer and thus surgery may not be required. Intermediate- and small-sized polyps can be monitored with serial ultrasound, especially in younger, asymptomatic patients in whom the risk of malignancy is low.

The effectiveness of conization treatment for post-menopausal women with high-grade cervical intraepithelial neoplasia

PubMed Central

CHENG, XIAODONG; FENG, YAN; WANG, XINYU; WAN, XIAOYUN; XIE, XING; LU, WEIGUO

2013-01-01

The aim of this study was to evaluate the effectiveness of conization in the diagnosis and treatment of high-grade cervical intraepithelial neoplasia (CIN) in post-menopausal women. A total of 101 post-menopausal patients who were diagnosed with high-grade lesion CIN by biopsy and in whom conization was used as the primary treatment were examined and 202 pre-menopausal patients were studied as the controls. Clinical and pathological data including symptoms, cytological examination and HPV DNA test results before and after conization treatment were analyzed. Both the cytological abnormalities (57.9 vs. 58.5%, P=0.260) and the positive rate of the HPV DNA test (89.5 vs. 86.4%, P=0.812) did not show a significant difference between the post- and pre-menopausal group. The rate of satisfactory colposcopy was significantly lower in post-menopausal patients compared with pre-menosausal patients (23.2 vs. 68.9%, P<0.001). Post-menopausal patients presented a significantly lower diagnostic consistency between colpscopy-directed biopsy and conization (46.4 vs. 68.9%, P=0.004), and a significantly higher positive margin rate of conization (20.8 vs. 10.9%, P=0.020). A total of 10 of the 101 post-menopausal and 2 of the 202 pre-menopausal women were diagnosed with invasive cancer by conization and underwent further treatment. In conclusion, these data suggest that conization, as a conservative primary treatment, is not suitable for post-menopausal women with high-grade lesion CIN due to the lower rate of satisfactory colposcopy, lower consistency of diagnosis between colposcopy-directed biopsy and conization, and a higher positive margin of conization. PMID:23251264

Germline PMS2 and somatic POLE exonuclease mutations cause hypermutability of the leading DNA strand in biallelic mismatch repair deficiency syndrome brain tumours.

PubMed

Andrianova, Maria A; Chetan, Ghati Kasturirangan; Sibin, Madathan Kandi; Mckee, Thomas; Merkler, Doron; Narasinga, Rao Kvl; Ribaux, Pascale; Blouin, Jean-Louis; Makrythanasis, Periklis; Seplyarskiy, Vladimir B; Antonarakis, Stylianos E; Nikolaev, Sergey I

2017-11-01

Biallelic mismatch repair deficiency (bMMRD) in tumours is frequently associated with somatic mutations in the exonuclease domains of DNA polymerases POLE or POLD1, and results in a characteristic mutational profile. In this article, we describe the genetic basis of ultramutated high-grade brain tumours in the context of bMMRD. We performed exome sequencing of two second-cousin patients from a large consanguineous family of Indian origin with early onset of high-grade glioblastoma and astrocytoma. We identified a germline homozygous nonsense variant, p.R802*, in the PMS2 gene. Additionally, by genome sequencing of these tumours, we found extremely high somatic mutation rates (237/Mb and 123/Mb), as well as somatic mutations in the proofreading domain of POLE polymerase (p.P436H and p.L424V), which replicates the leading DNA strand. Most interestingly, we found, in both cancers, that the vast majority of mutations were consistent with the signature of POLE exo - , i.e. an abundance of C>A and C>T mutations, particularly in special contexts, on the leading strand. We showed that the fraction of mutations under positive selection among mutations in tumour suppressor genes is more than two-fold lower in ultramutated tumours than in other glioblastomas. Genetic analyses enabled the diagnosis of the two consanguineous childhood brain tumours as being due to a combination of PMS2 germline and POLE somatic variants, and confirmed them as bMMRD/POLE exo - disorders. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Inter-observer variability in the classification of ovarian cancer cell type using microscopy: a pilot study

NASA Astrophysics Data System (ADS)

Gavrielides, Marios A.; Ronnett, Brigitte M.; Vang, Russell; Seidman, Jeffrey D.

2015-03-01

Studies have shown that different cell types of ovarian carcinoma have different molecular profiles, exhibit different behavior, and that patients could benefit from typespecific treatment. Different cell types display different histopathology features, and different criteria are used for each cell type classification. Inter-observer variability for the task of classifying ovarian cancer cell types is an under-examined area of research. This study served as a pilot study to quantify observer variability related to the classification of ovarian cancer cell types and to extract valuable data for designing a validation study of digital pathology (DP) for this task. Three observers with expertise in gynecologic pathology reviewed 114 cases of ovarian cancer with optical microscopy, with specific guidelines for classifications into distinct cell types. For 93 cases all 3 pathologists agreed on the same cell type, for 18 cases 2 out of 3 agreed, and for 3 cases there was no agreement. Across cell types with a minimum sample size of 10 cases, agreement between all three observers was {91.1%, 80.0%, 90.0%, 78.6%, 100.0%, 61.5%} for the high grade serous carcinoma, low grade serous carcinoma, endometrioid, mucinous, clear cell, and carcinosarcoma cell types respectively. These results indicate that unanimous agreement varied over a fairly wide range. However, additional research is needed to determine the importance of these differences in comparison studies. These results will be used to aid in the design and sizing of such a study comparing optical and digital pathology. In addition, the results will help in understanding the potential role computer-aided diagnosis has in helping to improve the agreement of pathologists for this task.

Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria.

PubMed

Vargo, John A; Boisen, Michelle M; Comerci, John T; Kim, Hayeon; Houser, Christopher J; Sukumvanich, Paniti; Olawaiye, Alexander B; Kelley, Joseph L; Edwards, Robert P; Huang, Marilyn; Courtney-Brooks, Madeleine; Beriwal, Sushil

2014-11-01

For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45-50.4Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5Gy times 3-4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy. All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity. Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5Gy times 3-4 fractions, for a cumulative EQD2 of 60-70Gy, is well tolerated with high rates of clinical and pathological response. Copyright © 2014 Elsevier Inc. All rights reserved.

Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

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

Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge

Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performedmore » 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.« less

MRI-Derived Cellularity Index as a Potential Noninvasive Imaging Biomarker of Prostate Cancer

DTIC Science & Technology

2016-12-01

whole mount pathology sections. Analysis of these UCLA data resulted in four published manuscripts (White et al, Cancer Research 2014; Rakow-Penner...Yamin et al., Clinical Cancer Research , 2016) RSI-MRI mean z-score grouped by pathologic Gleason grade. Mean RSI-MRI cellularity index represented as...Figure 2). A quantitative validation of this approach is now provided in this study. Specifically, in a group of patients with known PCa, ROC

Pathological response after neoadjuvant bevacizumab- or cetuximab-based chemotherapy in resected colorectal cancer liver metastases.

PubMed

Pietrantonio, Filippo; Mazzaferro, Vincenzo; Miceli, Rosalba; Cotsoglou, Christian; Melotti, Flavia; Fanetti, Giuseppe; Perrone, Federica; Biondani, Pamela; Muscarà, Cecilia; Di Bartolomeo, Maria; Coppa, Jorgelina; Maggi, Claudia; Milione, Massimo; Tamborini, Elena; de Braud, Filippo

2015-07-01

Neoadjuvant chemotherapy (NACT) prior to liver resection is advantageous for patients with colorectal cancer liver metastases (CLM). Bevacizumab- or cetuximab-based NACT may affect patient outcome and curative resection rate, but comparative studies on differential tumour regression grade (TRG) associated with distinct antibodies-associated regimens are lacking. Ninety-three consecutive patients received NACT plus bevacizumab (n = 46) or cetuximab (n = 47) followed by CLM resection. Pathological response was determined in each resected metastasis as TRG rated from 1 (complete) to 5 (no response). Except for KRAS mutations prevailing in bevacizumab versus cetuximab (57 vs. 21 %, p = 0.001), patients characteristics were well balanced. Median follow-up was 31 months (IQR 17-48). Bevacizumab induced significantly better pathological response rates (TRG1-3: 78 vs. 34 %, p < 0.001) as well as complete responses (TRG1: 13 vs. 0 %, p = 0.012) with respect to cetuximab. Three-year progression-free survival (PFS) and overall survival (OS) were not significantly different in the two cohorts. At multivariable analysis, significant association with pathological response was found for number of resected metastases (p = 0.015) and bevacizumab allocation (p < 0.001), while KRAS mutation showed only a trend. Significant association with poorer PFS and OS was found for low grades of pathological response (p = 0.009 and p < 0.001, respectively), R2 resection or presence of extrahepatic disease (both p < 0.001) and presence of KRAS mutation (p = 0.007 and p < 0.001, respectively). Bevacizumab-based regimens, although influenced by the number of metastases and KRAS status, improve significantly pathological response if compared to cetuximab-based NACT. Possible differential impact among regimens on patient outcome has still to be elucidated.

How to define pathologic pelvic floor descent in MR defecography during defecation?

PubMed

Schawkat, Khoschy; Heinrich, Henriette; Parker, Helen L; Barth, Borna K; Mathew, Rishi P; Weishaupt, Dominik; Fox, Mark; Reiner, Caecilia S

2018-06-01

To assess the extents of pelvic floor descent both during the maximal straining phase and the defecation phase in healthy volunteers and in patients with pelvic floor disorders, studied with MR defecography (MRD), and to define specific threshold values for pelvic floor descent during the defecation phase. Twenty-two patients (mean age 51 ± 19.4) with obstructed defecation and 20 healthy volunteers (mean age 33.4 ± 11.5) underwent 3.0T MRD in supine position using midsagittal T2-weighted images. Two radiologists performed measurements in reference to PCL-lines in straining and during defecation. In order to identify cutoff values of pelvic floor measurements for diagnosis of pathologic pelvic floor descent [anterior, middle, and posterior compartments (AC, MC, PC)], receiver-operating characteristic (ROC) curves were plotted. Pelvic floor descent of all three compartments was significantly larger during defecation than at straining in patients and healthy volunteers (p < 0.002). When grading pelvic floor descent in the straining phase, only two healthy volunteers showed moderate PC descent (10%), which is considered pathologic. However, when applying the grading system during defecation, PC descent was overestimated with 50% of the healthy volunteers (10 of 20) showing moderate PC descent. The AUC for PC measurements during defecation was 0.77 (p = 0.003) and suggests a cutoff value of 45 mm below the PCL to identify patients with pathologic PC descent. With the adapted cutoff, only 15% of healthy volunteers show pathologic PC descent during defecation. MRD measurements during straining and defecation can be used to differentiate patients with pelvic floor dysfunction from healthy volunteers. However, different cutoff values should be used during straining and during defecation to define normal or pathologic PC descent.

The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System.

PubMed

Epstein, Jonathan I; Egevad, Lars; Amin, Mahul B; Delahunt, Brett; Srigley, John R; Humphrey, Peter A

2016-02-01

In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out of 10, it implies that their prognosis is intermediate and contributes to their fear of having a more aggressive cancer. Also, in the literature and for therapeutic purposes, various scores have been incorrectly grouped together with the assumption that they have a similar prognosis. For example, many classification systems consider Gleason score 7 as a single score without distinguishing 3+4 versus 4+3, despite studies showing significantly worse prognosis for the latter. The basis for a new grading system was proposed in 2013 by one of the authors (J.I.E.) based on data from Johns Hopkins Hospital resulting in 5 prognostically distinct Grade Groups. This new system was validated in a multi-institutional study of over 20,000 radical prostatectomy specimens, over 16,000 needle biopsy specimens, and over 5,000 biopsies followed by radiation therapy. There was broad (90%) consensus for the adoption of this new prostate cancer Grading system in the 2014 consensus conference based on: (1) the new classification provided more accurate stratification of tumors than the current system; (2) the classification simplified the number of grading categories from Gleason scores 2 to 10, with even more permutations based on different pattern combinations, to Grade Groups 1 to 5; (3) the lowest grade is 1 not 6 as in Gleason, with the potential to reduce overtreatment of indolent cancer; and (4) the current modified Gleason grading, which forms the basis for the new grade groups, bears little resemblance to the original Gleason system. The new grades would, for the foreseeable future, be used in conjunction with the Gleason system [ie. Gleason score 3+3=6 (Grade Group 1)]. The new grading system and the terminology Grade Groups 1-5 have also been accepted by the World Health Organization for the 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs.

Blood-Brain Barrier Disruption, Sodium Fluorescein, And Fluorescence-Guided Surgery Of Gliomas.

PubMed

Xiang, Yan; Zhu, Xiao-Peng; Zhao, Jian-Nong; Huang, Guo-Hao; Tang, Jun-Hai; Chen, Huan-Ran; Du, Lei; Zhang, Dong; Tang, Xue-Feng; Yang, Hui; Lv, Sheng-Qing

2018-01-22

Sodium fluorescein (SF) is an ideal dye for intraoperative guided-resection of high-grade gliomas (HGGs). However, it is not well understood whether the SF-guided technique is suitable for different grades of gliomas, and the correlation between fluorescence and pathology is also not yet clear. In this study, we investigated 28 patients, including 23 patients with HGG and 5 patients with low-grade glioma (LGG). All patients were treated using the SF-guided technique on a Pentero 900 microscope (Carl Zeiss, Oberkochen, Germany). Claudin-5 immunohistochemical (IHC) staining for the tumours and peritumour tissues was analyzed. Intraoperative yellow fluorescence was noted in all the HGGs but not in the LGGs. Claudin-5 expression in the blood brain barrier endothelial cells was downregulated and disconnected in the HGGs (p < 0.05), but had no difference or slightly decreased in the LGGs (p > 0.05). The SF-guided technique is suitable for HGG surgery but not for LGG surgery. Downregulation of claudin-5 expression may contribute to the presence of yellow fluorescence in the glioma in SF-guided surgery.

Decreased expression of Toll-like receptor 4 and 5 during progression of prostate transformation in transgenic adenocarcinoma of mouse prostate mice.

PubMed

Han, Ju-Hee; Park, Jong-Hwan; Kim, Bo-Yeon; Chang, Seo-Na; Kim, Tae-Hyoun; Park, Jae-Hak; Kim, Dong-Jae

2015-01-01

Chronic inflammation has been considered an important risk factor for development of prostate cancer. Toll-like receptors (TLRs) recognize microbial moieties or endogenous molecules and play an important role in the triggering and promotion of inflammation. In this study, we examined whether expression of TLR4 and TLR5 was associated with progression of prostate transformation in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. The expression of TLR4 and TLR5 was evaluated by immunohistochemisty in formalin-fixed paraffin-embedded prostate tissue from wild-type (WT) and TRAMP mice. Normal prostate tissue from WT mice showed strong expression of TLR4 and TLR5. However, TLR4 expression in the prostate tissue from TRAMP mice gradually decreased as pathologic grade became more aggressive. TLR5 expression in the prostate tissue from TRAMP mice also decreased in low-grade prostate intraepithelial neoplasia (PIN), high-grade PIN and poorly differentiated adenocarcinoma. Overall, our results suggest that decreased expression of TLR4 and TLR5 may contribute to prostate tumorigenesis.

Gain of GRHL2 is associated with early recurrence of hepatocellular carcinoma.

PubMed

Tanaka, Yasuo; Kanai, Fumihiko; Tada, Motohisa; Tateishi, Ryosuke; Sanada, Masashi; Nannya, Yasuhito; Ohta, Miki; Asaoka, Yoshinari; Seto, Motoko; Shiina, Shuichiro; Yoshida, Haruhiko; Kawabe, Takao; Yokosuka, Osamu; Ogawa, Seishi; Omata, Masao

2008-11-01

The aim of this study is to identify genomic changes that might be implicated in hepatocellular carcinoma (HCC) progression, and evaluate the associations with clinico-pathological features. The genomic DNA of 17 hepatoma cell lines was analyzed using Affymetrix GeneChip Human Mapping 50K high-density oligonucleotide arrays. We selected representative genes from recurrent amplified regions and measured the copy number of these genes in 70 HCC clinical samples. We found 10 recurrent high-grade gain regions spanning less than 3 Mb in at least two hepatoma cell lines, and selected 10 representative genes. The copy number was almost normal in non-cancerous tissue and frequently amplified in Edmondson grade II or III HCC compared to Edmondson grade I HCC. Gain of TAX1BP1 in 7p15.2-1 was associated with larger tumor size and positivity of HCV antibody, and gain of CCND1 in 11q13.2-3 was associated with larger tumor size by multivariate analysis. Furthermore, a gain of GRHL2 in 8q22.3 was associated with early recurrence of HCC, controlling for clinical parameters. Decreased GRHL2 expression by RNA interference inhibits the growth of hepatoma cells, suggesting its association with cell proliferation. A gain of GRHL2 might be a predictive marker for HCC recurrence.

Non-small cell lung cancer: Whole-lesion histogram analysis of the apparent diffusion coefficient for assessment of tumor grade, lymphovascular invasion and pleural invasion

PubMed Central

Tsuchiya, Naoko; Doai, Mariko; Usuda, Katsuo; Uramoto, Hidetaka

2017-01-01

Purpose Investigating the diagnostic accuracy of histogram analyses of apparent diffusion coefficient (ADC) values for determining non-small cell lung cancer (NSCLC) tumor grades, lymphovascular invasion, and pleural invasion. Materials and methods We studied 60 surgically diagnosed NSCLC patients. Diffusion-weighted imaging (DWI) was performed in the axial plane using a navigator-triggered single-shot, echo-planar imaging sequence with prospective acquisition correction. The ADC maps were generated, and we placed a volume-of-interest on the tumor to construct the whole-lesion histogram. Using the histogram, we calculated the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC, skewness, and kurtosis. Histogram parameters were correlated with tumor grade, lymphovascular invasion, and pleural invasion. We performed a receiver operating characteristics (ROC) analysis to assess the diagnostic performance of histogram parameters for distinguishing different pathologic features. Results The ADC mean, 10th, 25th, 50th, 75th, 90th, and 95th percentiles showed significant differences among the tumor grades. The ADC mean, 25th, 50th, 75th, 90th, and 95th percentiles were significant histogram parameters between high- and low-grade tumors. The ROC analysis between high- and low-grade tumors showed that the 95th percentile ADC achieved the highest area under curve (AUC) at 0.74. Lymphovascular invasion was associated with the ADC mean, 50th, 75th, 90th, and 95th percentiles, skewness, and kurtosis. Kurtosis achieved the highest AUC at 0.809. Pleural invasion was only associated with skewness, with the AUC of 0.648. Conclusions ADC histogram analyses on the basis of the entire tumor volume are able to stratify NSCLCs' tumor grade, lymphovascular invasion and pleural invasion. PMID:28207858

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

Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena

Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical datamore » have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.« less

Smoking increased the risk of prostate cancer with grade group ≥ 4 and intraductal carcinoma in a prospective biopsy cohort.

PubMed

Tang, Bo; Han, Cheng-Tao; Gan, Hua-Lei; Zhang, Gui-Ming; Zhang, Cui-Zhu; Yang, Wei-Yi; Shen, Ying; Zhu, Yao; Ye, Ding-Wei

2017-06-01

To investigate the association between smoking and different prostate cancer (PCa) pathological subtypes incidence in Chinese men. We prospectively included 1795 patients who underwent prostate biopsies in one tertiary center between March 2013 and April 2016. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the association between cigarette smoking and PCa incidence. A total of 737 men, 480 men and 58 men were diagnosed with PCa, high-grade PCa (HGPCa, grade group ≥ 4 as accepted by the 2014 ISUP) and intraductal carcinoma of the prostate (IDC-P), respectively. Current smokers had a significantly higher risk of HGPCa than never smokers (OR = 1.89, 95%CI: 1.44-2.48). No such association was observed for low-grade disease and cigarette smoking (OR = 0.84, 95%CI: 0.61-1.16). In a sub-analysis, men who had smoked longer than 30 years had a higher risk of HGPCa, compared with men who had smoked fewer than 30 years (OR = 1.50, 95%CI: 1.09-2.06). Current smokers were more likely to develop IDC-P than never smokers (OR = 2.29, 95%CI: 1.14-4.59). Among men in this Chinese biopsy cohort, current smoking was associated with highly malignant PCa incidence, such as HGPCa and IDC-P. The duration of smoking may be associated with HGPCa. © 2017 Wiley Periodicals, Inc.

Xp11.2 translocation renal cell carcinomas in young adults.

PubMed

Xu, Linfeng; Yang, Rong; Gan, Weidong; Chen, Xiancheng; Qiu, Xuefeng; Fu, Kai; Huang, Jin; Zhu, Guancheng; Guo, Hongqian

2015-07-01

Little is known about the biological behavior of Xp11.2 translocation renal cell carcinomas (RCCs) as few clinical studies have been performed using a large sample size. This study included 103 consecutive young adult patients (age ≤ 45 years) with RCC who underwent partial or radical nephrectomy at our institution from 2008 to 2013. Five patients without complete clinical data were excluded. Of the 98 remaining patients, 16 and 82 patients were included in the Xp11.2 translocation and non-Xp11.2 translocation groups, respectively. Clinicopathologic data were collected, including age, gender, tumor size, laterality, symptoms at diagnosis, surgical procedure, pathologic stage, tumor grade, time of recurrence and death. Xp11.2 translocation RCCs were associated with higher tumor grade and pathologic stage (P < 0.05, Fisher's exact test). During the median follow-up of 36 months (range: 3-71 months), the number of cancer-related deaths was 4 (4.9%) and 3 (18.7%) in the non-Xp11.2 translocation and Xp11.2 translocation groups, respectively. The Kaplan-Meier cancer specific survival curves revealed a significant difference between non-Xp11.2 translocation RCCs and Xp11.2 translocation RCCs in young adults (P = 0.042). Compared with non-Xp11.2 translocation RCCs, the Xp11.2 translocation RCCs seemingly showed a higher tumor grade and pathologic stage and have similar recurrence-free survival rates but poorer cancer-specific survival rates in young adults.

Enhanced expression of peroxisome proliferator-activated receptor gamma in epithelial ovarian carcinoma.

PubMed

Zhang, G Y; Ahmed, N; Riley, C; Oliva, K; Barker, G; Quinn, M A; Rice, G E

2005-01-17

The peroxisome proliferator-activated receptors (PPARs) belong to a subclass of nuclear hormone receptor that executes important cellular transcriptional functions. Previous studies have demonstrated the expression of PPARgamma in several tumours including colon, breast, bladder, prostate, lung and stomach. This study demonstrates the relative expression of PPARgamma in normal ovaries and different pathological grades of ovarian tumours of serous, mucinous, endometrioid, clear cell and mixed subtypes. A total of 56 ovarian specimens including 10 normal, eight benign, 10 borderline, seven grade 1, nine grade 2 and 12 grade 3 were analysed using immunohistochemistry. Immunoreactive PPARgamma was not expressed in normal ovaries. Out of eight benign and 10 borderline tumours, only one tumour in each group showed weak cytoplasmic PPARgamma expression. In contrast, 26 out of 28 carcinomas studied were positive for PPARgamma expression with staining confined to cytoplasmic and nuclear regions. An altered staining pattern of PPARgamma was observed in high-grade ovarian tumours with PPARgamma being mostly localized in the nuclei with little cytoplasmic immunoreactivity. On the other hand, predominant cytoplasmic staining was observed in lower-grade tumours. Significantly increased PPARgamma immunoreactivity was observed in malignant ovarian tumours (grade 1, 2 and 3) compared to benign and borderline tumours (chi2 = 48.80, P < 0.001). Western blot analyses showed significant elevation in the expression of immunoreactive PPARgamma in grade 3 ovarian tumours compared with that of normal ovaries and benign ovarian tumours (P < 0.01). These findings suggest an involvement of PPARgamma in the onset and development of ovarian carcinoma and provide an insight into the regulation of this molecule in the progression of the disease.

British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus.

PubMed

Fitzgerald, Rebecca C; di Pietro, Massimiliano; Ragunath, Krish; Ang, Yeng; Kang, Jin-Yong; Watson, Peter; Trudgill, Nigel; Patel, Praful; Kaye, Philip V; Sanders, Scott; O'Donovan, Maria; Bird-Lieberman, Elizabeth; Bhandari, Pradeep; Jankowski, Janusz A; Attwood, Stephen; Parsons, Simon L; Loft, Duncan; Lagergren, Jesper; Moayyedi, Paul; Lyratzopoulos, Georgios; de Caestecker, John

2014-01-01

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett's oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett's oesophagus and related neoplasia.

Pancreatic neuroendocrine neoplasms: a current summary of diagnostic, prognostic, and differential diagnostic information.

PubMed

Wick, M R; Graeme-Cook, F M

2001-06-01

Pancreatic endocrine tumors (PETs) continue to be challenging diagnostic and prognostic lesions in surgical pathology and clinical medicine. These neoplasms can be graded into 1 of 3 tiers, based on histologic characteristics in likeness to epithelial neuroendocrine tumors in other anatomic sites. However, grade 1 tumors are by far the most common and are the most difficult to prognosticate. The most helpful features by which to gauge the behavior of such lesions include size (3 cm or larger); mitotic activity (2 or more mitoses per 10 high-power [x400] microscopic fields); marked nuclear atypia, especially with atypical mitoticfigures; predominant tumor synthesis of gastrin, vasoactive intestinal polypeptide, somatostatin, glucagon, calcitonin, or adrenocorticotropic hormone; complete nonfunctionality of the tumor at an immunohistochemical level; or invasion of blood vessels, nerves, or adjacent organs by the neoplasm. Differential diagnosis of PETs includes lesions such as solid-pseudopapillary neoplasms, acinar carcinomas, metastatic neuroendocrine tumors, and plasmacytomas.

[Grading of tumors in the tubular digestive tract : Esophagus, stomach, colon and rectum].

PubMed

Bläker, H

2016-07-01

Grading of tumors located in the tubular digestive tract is an integral component of pathology assessment reports but is subordinate to the histological typing of tumors with respect to the prognostic significance. Tumor grading has not been shown to be an independent prognostic marker for most tumor entities in the gastrointestinal tract; however, it may be relevant for further routine treatment decision making in early Union Internationale Contre le Cancer (UICC) stage cancers in which the prognosis for patients is less dominated by advanced tumor spread. Owing to the more favorable prognosis of microsatellite instability in colorectal cancer, the World Health Organization (WHO) has recommended that poorly differentiated tumors should be tested and graded as low grade (G1/G2) when microsatellite instability is detected. This recommendation has been integrated into the German S3 guidelines for colorectal cancers. Accordingly, microsatellite instability testing for grading purposes should become routine practice.

Electron microscopic examination of the myelinated axons of corpus callosum in perfused young and old rats.

PubMed

Sargon, Mustafa F; Denk, C Cem; Celik, H Hamdi; Surucu, H Selcuk; Aldur, M Mustafa

2007-07-01

In this study, the myelinated axons of parts of the corpus callosums of young and old rats were examined under the electron microscope and a grading system was performed for quantitating the ultrastructural pathological changes of these axons. Except the old splenium group, the only ultrastructural pathological change, observed in the myelinated axons was the separation in myelin configuration. In addition to this finding, in the old splenium group, in some of the myelinated axons, an interruption was observed in the myelin configuration. Additionally, these ultrastructural pathological findings were present in the larger sized myelinated axons of the corpus callosum.

Pathway modulations and epigenetic alterations in ovarian tumorbiogenesis

PubMed Central

Saldanha, Sabita N.; Tollefsbol, Trygve O.

2013-01-01

Cellular pathways are numerous and are highly integrated in function in the control of cellular systems. They collectively regulate cell division, proliferation, survival and apoptosis of cells and mutagenesis of key genes that control these pathways can initiate neoplastic transformations. Understanding these pathways is crucial to future therapeutic and preventive strategies of the disease. Ovarian cancers are of three major types; epithelial, germ-cell and stromal. However, ovarian cancers of epithelial origin, arising from the mesothelium, are the predominant form. Of the subtypes of ovarian cancer, the high-grade serous tumors are fatal, with low survival rate due to late detection and poor response to treatments. Close examination of preserved ovarian tissues and in vitro studies have provided insights into the mechanistic changes occurring in cells mediated by a few key genes. This review will focus on pathways and key genes of the pathways that are mutated or have aberrant functions in the pathology of ovarian cancer. Non-genetic mechanisms that are gaining prominence in the pathology of ovarian cancer, miRNAs and epigenetics, will also be discussed in the review. PMID:24105793

Cellular autofluorescence imaging for early diagnosis of cancers

NASA Astrophysics Data System (ADS)

Steenkeste, Karine; Deniset, Ariane; Lecart, Sandrine; Leveque-Fort, Sandrine; Fontaine-Aupart, Marie-Pierre; Ferlicot, Sophie; Eschwege, Pascal

2005-08-01

Urinary cytology is employed in diagnostic guidelines of bladder cancer in anatomo-pathological laboratories mostly for its ability to diagnose non detectable cancers using cystoscopy, but also because it is a non-invasive and non-constraining technique for a regular follow-up of the more exposed populations. The impossibility to detect such cancers is mainly due to their localization either in the bladder or in the upper urinary tract and the prostate. However, urinary cytology lacks sensitivity, especially for the detection of low grade low stage tumors due to inherent limitation of morphological criteria to distinguish low grade tumor cells from normal urothelial cells. For this purpose, we developed, in addition to urinary cytology, an original screening of these cytological slides by using spectrally-resolved and time-resolved fluorescence as a contrast factor, without changing any parameters in the cytological slide preparation. This method takes advantage of a femtosecond Ti:sapphire laser, continuously tunable in the spectral range 700-950 nm allowing the observation of most endogenous cellular chromophores by biphotonic excitation. A commercial confocal microscope was also used in the measurements allowing an excitation of the samples between 458 nm and 633 nm. We observed that the fluorescence emission is differentially distributed in normal and pathological urothelial cells. Spectral- and time-resolved measurements attested this difference over about one hundred cases which have been tested to confirm the high accuracy of this non-invasive technique.

Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants.

PubMed

Yoshida, S; Haque, A; Mizobuchi, T; Iwata, T; Chiyo, M; Webb, T J; Baldridge, L A; Heidler, K M; Cummings, O W; Fujisawa, T; Blum, J S; Brand, D D; Wilkes, D S

2006-04-01

Immunity to collagen V [col(V)] contributes to lung 'rejection.' We hypothesized that ischemia reperfusion injury (IRI) associated with lung transplantation unmasks antigenic col(V) such that fresh and well-healed lung grafts have differential susceptibility to anti-col(V)-mediated injury; and expression of the autoimmune cytokines, IL-17 and IL-23, are associated with this process. Adoptive transfer of col(V)-reactive lymphocytes to WKY rats induced grade 2 rejection in fresh isografts, but induced worse pathology (grade 3) when transferred to isograft recipients 30 days post-transplantation. Immunhistochemistry detected col(V) in fresh and well-healed isografts but not native lungs. Hen egg lysozyme-reactive lymphocytes (HEL, control) did not induce lung disease in any group. Col(V), but not HEL, immunization induced transcripts for IL-17 and IL-23 (p19) in the cells utilized for adoptive transfer. Transcripts for IL-17 were upregulated in fresh, but not well-healed isografts after transfer of col(V)-reactive cells. These data show that IRI predisposes to anti-col(V)-mediated pathology; col(V)-reactive lymphocytes express IL-17 and IL-23; and anti-col(V)-mediated lung disease is associated with local expression of IL-17. Finally, because of similar histologic patterns, the pathology of clinical rejection may reflect the activity of autoimmunity to col(V) and/or alloimmunity.

Observations on the function of the female urethra: II: Relation between maximum urethral closure pressure at rest and the degree of urethral incompetence.

PubMed

Schick, Erik; Bertrand, Pierre E; Jolivet-Tremblay, Martine; Dupont, Charles; Tessier, Jocelyne

2004-01-01

To study the relation between maximum urethral closure pressure (MUCP) at rest and the degree of urethral incompetence in the female. Two hundred fifty five patients aged 20 years or older, with stable bladders on multichannel urodynamics, without known neurological pathology, and with no previous history of pelvic or anti-incontinence surgery were included in the study. Resting urethral pressure profile (UPP) and the grade of urethral incompetence was registered. Mean age of the group was 45.6+/-12.7 years; mean MUCP was 62.7+/-28.5 cm of water. There was a statistically significant difference in the MUCP when the different grades of urethral incompetence were compared to each other, the higher grades being associated with a lower maximal closure pressure. This study demonstrates that there is a highly significant relationship between MUCP and between all grades of urethral incompetence. This supports previous observations that MUCP decreases when abdominal leak point pressure (ALPP) is low and that this might be secondary to some mechanical failure in the pressure transmission from the abdominal cavity to the urethra. Studies should never compare continent to incontinent cohorts without considering their ALPP because in doing so they are comparing groups that are functionally heterogeneous. Copyright 2003 Wiley-Liss, Inc.

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)

Diagnostic performance of HPV E6/E7 mRNA assay for detection of cervical high-grade intraepithelial neoplasia and cancer among women with ASCUS Papanicolaou smears.

PubMed

Ren, Chenchen; Zhu, Yuanhang; Yang, Li; Zhang, Xiaoan; Liu, Ling; Ren, Chunying

2018-02-01

The aim of this study was to investigate the clinical performance of high risk (HR) HPV E6/E7 mRNA assay in detecting cervical high-grade intraepithelial neoplasia and cancer among women with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou (Pap) smears. A total of 160 patients with ASCUS who underwent HR-HPV DNA assay, HR-HPV E6/E7 mRNA assay and colposcopy biopsy at Third Affiliated Hospital of Zhengzhou University, China, from December 2015 to March 2017, were enrolled. Logistic regression analysis was used to evaluate the relationship between pathological results with clinical biologic factors. Univariate analysis showed that the qualitative results of HR-HPV DNA, qualitative results of HR-HPV E6/E7 mRNA and expression levels of HR-HPV E6/E7 mRNA were risk factors of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer (all P < 0.05). Multivariable analysis found that only the expression levels of HR-HPV E6/E7 mRNA was associated with high-grade CIN and cervical cancer (OR = 8.971, 95% CI = 2.572-31.289, P = 0.001). An optimal cut-off value of ≥ 558.26 copies/ml was determined using receiver operating characteristic curve, and specificity of cut-off value were higher than E6/E7 mRNA qualitative assay and DNA qualitative assay. HPV E6/E7 mRNA quantitative assay may be a valuable tool in triage of ASCUS pap smears. A high specificity of E6/E7 mRNA quantitative assay as a triage test in women with ASCUS can be translated into a low referral for colposcopy.

Pathological, Oncologic and Functional Outcomes of a Prospective Registry of Salvage High Intensity Focused Ultrasound Ablation for Radiorecurrent Prostate Cancer.

PubMed

Siddiqui, Khurram M; Billia, Michele; Arifin, Andrew; Li, Fan; Violette, Philippe; Chin, Joseph L

2017-01-01

In this prospective registry we prospectively assessed the oncologic, functional and safety outcomes of salvage high intensity focused ultrasound for radiorecurrent prostate cancer. A total of 81 men were prospectively recruited and evaluated at regular scheduled study visits to 6 months after high intensity focused ultrasound and thereafter as per standard of care. Transrectal ultrasound guided biopsy was performed at 6 months. The primary end point was absence or histological persistence of disease at 6-month biopsy. Secondary end points included quality of life, biochemical recurrence-free survival, overall survival, cancer specific survival and progression to androgen deprivation therapy. Survival analysis was performed according to the Kaplan-Meier method and multivariate analysis was performed using the log rank (Mantel-Cox) test. Mean ± SD prostate specific antigen before high intensity focused ultrasound was 4.06 ± 2.88 ng/ml. At 6 months 63 men underwent biopsy, of whom 22 (35%) had residual disease. At a mean followup of 53.5 ± 31.6 months median biochemical recurrence-free survival was 63 months. The 5-year overall and cancer specific survival rates were 88% and 94.4%, respectively. Nadir prostate specific antigen less than 0.5 ng/ml was a significant predictor of biochemical recurrence-free survival (p=0.014, 95% CI 1.22-5.87). I-PSS significantly increased (p <0.001) while IIEF-5 scores decreased and the SF-36 score did not change significantly. The rate of rectal fistulization and severe incontinence was 3.7% each. A total of 223 complications were recorded in the 180 days after high intensity focused ultrasound (Clavien-Dindo grade 1-195, grade II-20, grade III-7, grade IVa-1). Salvage high intensity focused ultrasound appears to be a viable treatment option for radiorecurrent prostate cancer, with acceptable morbidity. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Human herpesvirus multiplex ddPCR detection in brain tissue from low- and high-grade astrocytoma cases and controls.

PubMed

Lin, Cheng-Te Major; Leibovitch, Emily C; Almira-Suarez, M Isabel; Jacobson, Steven

2016-01-01

Glioblastoma (GBM) is a fatal CNS malignancy, representing 50 % of all gliomas with approximately 12-18 months survival time after initial diagnosis. Recently, the human herpesvirus cytomegalovirus (CMV) has been suggested to have an oncogenic role, yet this association remains controversial. In addition, human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have also been associated with low-grade gliomas, but few studies have examined HHV-6 and EBV in glioblastomas. Droplet digital PCR (ddPCR) is a highly precise diagnostic tool that enables the absolute quantification of target DNA. This study examines the association between multiple human herpesviruses and astrocytomas. This study analyzed 112 brain tissue specimens, including 45 glioblastoma, 12 astrocytoma grade III, 2 astrocytoma grade II, 4 astrocytoma grade I, and 49 controls. All brain tissue samples were de-identified and pathologically confirmed. Each tissue block was sectioned for DNA extraction and CMV, EBV, HHV-6A and HHV-6B, and a cellular housekeeping gene were amplified by ddPCR. Neither CMV nor HHV-6A were detected in any of the astrocytoma samples. However, HHV-6B (p = 0.147) and EBV (p = 0.049) had a higher positivity frequency in the GBM compared to the controls. The undetectable CMV DNA in the astrocytoma cohort does not support the observation of an increased prevalence of CMV DNA in GBM, as reported in other studies. EBV has a significantly higher positivity in the GBM cohort compared to the controls, while HHV-6B has a higher but not statistically significant positivity in the case cohort. Whether these viruses play an oncogenic role in GBM remains to be further investigated.

MR elastography of the liver at 3.0 T in diagnosing liver fibrosis grades; preliminary clinical experience.

PubMed

Yoshimitsu, Kengo; Mitsufuji, Toshimichi; Shinagawa, Yoshinobu; Fujimitsu, Ritsuko; Morita, Ayako; Urakawa, Hiroshi; Hayashi, Hiroyuki; Takano, Koichi

2016-03-01

To clarify the usefulness of 3.0-T MR elastography (MRE) in diagnosing the histological grades of liver fibrosis using preliminary clinical data. Between November 2012 and March 2014, MRE was applied to all patients who underwent liver MR study at a 3.0-T clinical unit. Among them, those who had pathological evaluation of liver tissue within 3 months from MR examinations were retrospectively recruited, and the liver stiffness measured by MRE was correlated with histological results. Institutional review board approved this study, waiving informed consent. There were 70 patients who met the inclusion criteria. Liver stiffness showed significant correlation with the pathological grades of liver fibrosis (rho = 0.89, p < 0.0001, Spearman's rank correlation). Areas under the receiver operating characteristic curve were 0.93, 0.95, 0.99 and 0.95 for fibrosis score greater than or equal to F1, F2, F3 and F4, with cut-off values of 3.13, 3.85, 4.28 and 5.38 kPa, respectively. Multivariate analysis suggested that grades of necroinflammation also affected liver stiffness, but to a significantly lesser degree as compared to fibrosis. 3.0-T clinical MRE was suggested to be sufficiently useful in assessing the grades of liver fibrosis. MR elastography may help clinicians assess patients with chronic liver diseases. Usefulness of 3.0-T MR elastography has rarely been reported. Measured liver stiffness correlated well with the histological grades of liver fibrosis. Measured liver stiffness was also affected by necroinflammation, but to a lesser degree. 3.0-T MRE could be a non-invasive alternative to liver biopsy.

Chromosome 3 allelic losses and microsatellite alterations in transitional cell carcinoma of the urinary bladder.

PubMed Central

Li, M.; Zhang, Z. F.; Reuter, V. E.; Cordon-Cardo, C.

1996-01-01

A deletion analysis of chromosome 3 was conducted in 72 cases of transitional cell carcinoma of the urinary bladder using seven microsatellites spanning the 3p arm and two additional microsatellites in 3q. Results showed that 19 of 72 (26.4%) cases had deletions in one or more 3p regions. Two regions of frequent deletion were identified: 3p12-14 and 3p21-23. Less frequent deletions at 3p24.2-25 were also observed. Deletions at 3p were weakly correlated with tumor grade, but strongly with pathological stage. Among 70 cases with histological grade available, 4 of 29 (13.8%) grade 1 and 2 tumors, and 15 of 41 (36.6%) grade 3 tumors showed allelic losses in one or more of the 3p regions studied (P = 0.055). Among 69 cases with pathological stage available, none of 27 superficial carcinomas (pTa, pTis, and pT1) showed 3p deletions, whereas 18 of 42 (42.9%) muscle invasive lesions (pT2, pT3, and pT4) displayed allelic losses at 3p (P < 0.001). In addition, 12 cases showed microsatellite instability, but there was no correlation between abnormalities and tumor grade or stage. No correlation was found between deletions at 3p21-23 and microsatellite instability. In conclusion, deletions at three discrete regions of 3p were identified in bladder carcinoma, suggesting the involvement of candidate tumor suppressor genes residing in these regions. Moreover, detection of allelic losses in these regions was associated with higher tumor grade and more advanced stage, suggesting their potential involvement in bladder tumor progression. Images Figure 1 Figure 3 PMID:8686747

Gleason grade remains an important prognostic predictor in men diagnosed with prostate cancer while on finasteride therapy

PubMed Central

CARVER, BRETT S.; KATTAN, MICHAEL W.; SCARDINO, PETER T.; EASTHAM, JAMES A.

2007-01-01

OBJECTIVE To evaluate men treated with finasteride for lower urinary tract symptoms, who subsequently were diagnosed with prostate cancer and had a radical prostatectomy (RP) at our institution, to determine if finasteride therapy prevented accurate Gleason grade assignment and prediction of biochemical recurrence. PATIENTS AND METHODS Between May 1996 and July 2003, 45 men were identified who had RP and had previously been treated with finasteride for ≥6 months before the diagnosis of prostate cancer. Clinical and pathological information was gathered from a RP database. Serum prostate-specific antigen (PSA) level, duration of finasteride therapy, biopsy Gleason grade, clinical stage, RP Gleason grade and pathological stage were reviewed. Freedom from recurrence was predicted using validated nomograms before and after RP, and compared against actuarial 5-year freedom from recurrence using the Kaplan-Meier method. RESULTS The mean duration of finasteride therapy before diagnosis was 23.6 months, the mean serum PSA (doubled to account for finasteride use) 11.02 ng/mL and mean biopsy Gleason score 6. When comparing the biopsy and RP specimen Gleason score, it was downgraded by 1 point in six men, upgraded by 1 point in eight, and upgraded by 2 points in one. The Gleason score was constant in 30 patients. The nomograms predicted freedom from recurrence in 83% and 85%, respectively; the 5-year actuarial freedom from recurrence was 86%. CONCLUSION Finasteride does not appear to compromise the assignment of Gleason grade for use in prediction tools before or after RP in men undergoing prostate biopsy or RP. The actuarial 5-year freedom from recurrence was similar to that predicted by the validated nomograms. Gleason grade remains an important prognostic predictor in men treated with finasteride and undergoing RP for clinically localized prostate cancer. PMID:15705069

Hyperplasia of Pericytes Is One of the Main Characteristics of Microvascular Architecture in Malignant Glioma

PubMed Central

Sun, Huiqin; Guo, Deyu; Su, Yongping; Yu, Dongmei; Wang, Qingliang; Wang, Tao; Zhou, Qing; Ran, Xinze; Zou, Zhongmin

2014-01-01

Objectives To investigate the role of pericytes in constructing the malformed microvessels (MVs) and participating microvascular architecture heterogeneity of glioma. Methods Forty human glioma tissue samples (WHO grade II-IV) were included in present study. Observation of blood vessel patterns, quantitative analysis of endothelial cells (ECs)- and pericyte-labeled MVs and comparison between malignant grades based on single- or double-immunohistochemical staining. The MV number density (MVND), microvascular pericyte number density (MPND), and microvascular pericyte area density (MPAD) were calculated. The expression of PDGFβ was also scored after immunostaining. Results In grade II glioma, most of tumor MVs were the thin-wall CD34+ vessels with near normal morphology. In addition to thin-wall CD34+ MVs, more thick-wall MVs were found in grade III glioma, which often showed α-SMA positive. Most of MVs in grade IV glioma were in the form of plexus, curled cell cords and glomeruloid microvascular proliferation while the α-SMA+ cells were the main components. The MVs usually showed disordered arrangement, loose connection and active cell proliferation as shown by Ki67 and α-SMA coexpression. With the increase of glioma grades, the α-SMA+ MVND, CD34+ MVND and MPND were significantly augmented although the increase of CD34+ MVND but not MPAD was statistically insignificant between grade III and IV. It was interesting that some vessel-like structures only consist of α-SMA+ cells, assuming the guiding role of pericytes in angiogenesis. The expression level of PDGFβ was upregulated and directly correlated with the MPND in different glioma grades. Conclusion Hyperplasia of pericytes was one of the significant characteristics of malignant glioma and locally proliferated pericytes were the main constituent of MVs in high grade glioma. The pathological characteristics of pericytes could be used as indexes of malignant grades of glioma. PMID:25478951

Morphologic three-dimensional scanning of fallopian tubes to assist ovarian cancer diagnosis

NASA Astrophysics Data System (ADS)

Madore, Wendy-Julie; De Montigny, Etienne; Deschênes, Andréanne; Benboujja, Fouzi; Leduc, Mikaël; Mes-Masson, Anne-Marie; Provencher, Diane M.; Rahimi, Kurosh; Boudoux, Caroline; Godbout, Nicolas

2017-07-01

The majority of high-grade serous ovarian cancers is now believed to originate in the fallopian tubes. Therefore, current practices include the pathological examination of excised fallopian tubes. Detection of tumors in the fallopian tubes using current clinical approaches remains difficult but is of critical importance to achieve accurate staging and diagnosis. Here, we present an intraoperative imaging system for the detection of human fallopian tube lesions. The system is based on optical coherence tomography (OCT) to access subepithelial tissue architecture. To demonstrate that OCT could identify lesions, we analyzed 180 OCT volumes taken from five different ovarian lesions and from healthy fallopian tubes, and compared them to standard pathological review. We demonstrated that qualitative features could be matched to pathological conditions. We then determined the feasibility of intraluminal imaging of intact human fallopian tubes by building a dedicated endoscopic single-fiber OCT probe to access the mucosal layer inside freshly excised specimens from five patients undergoing prophylactic surgeries. The probe insertion into the lumen acquired images over the entire length of the tubes without damaging the mucosa, providing the first OCT images of intact human fallopian tubes.

Dedifferentiated Chondrosarcoma of the Larynx.

PubMed

Fidai, Shiraz S; Ginat, Daniel T; Langerman, Alexander J; Cipriani, Nicole A

2016-09-01

Primary dedifferentiated chondrosarcoma occurring in the larynx is a rare head and neck malignancy. The cases reported in the literature suggest male gender predilection and variable clinical outcomes ranging from disease-free survival to disease-related death. Although a calcified matrix is suggestive of chondrosarcoma, the dedifferentiated component is not readily appreciated on conventional imaging modalities and thorough tissue sampling is necessary for confirming the diagnosis. Histologically, there is an abrupt transition from a well-differentiated chondrosarcoma to a high-grade spindle cell component, which can show focal heterologous differentiation. These features are exemplified in this sine qua non radiology-pathology correlation article.

A False-Negative Case of Primary Central Nervous System Lymphoma on 11C-Methionine PET and Intense 18F-FDG Uptake.

PubMed

García-Garzon, J R; Villasboas-Rosciolesi, Diego; Baquero, Miguel; Bassa, Pere; Soler, Marina; Riera, Eduard

2016-08-01

We report a case of a 44-year-old man with neurological symptoms and MRI findings, which were unable to differentiate between glioma and lymphoma. Metabolic characterization by means of PET imaging with F-FDG and C-methionine is proposed to determine the benign or tumor (high- and low-grade) origin of brain lesions. In this case, the MRI lesion corresponded with an inconclusive metabolic pattern of intense F-FDG uptake and no significant C-methionine uptake. Pathological study revealed a false-negative case of C-methionine due to lymphoma.

An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: Interim results.

PubMed

Packiam, Vignesh T; Lamm, Donald L; Barocas, Daniel A; Trainer, Andrew; Fand, Benjamin; Davis, Ronald L; Clark, William; Kroeger, Michael; Dumbadze, Igor; Chamie, Karim; Kader, A Karim; Curran, Dominic; Gutheil, John; Kuan, Arthur; Yeung, Alex W; Steinberg, Gary D

2017-07-26

CG0070 is a replication-competent oncolytic adenovirus that targets bladder tumor cells through their defective retinoblastoma pathway. Prior reports of intravesical CG0070 have shown promising activity in patients with high-grade non-muscle invasive bladder cancer (NMIBC) who previously did not respond to bacillus Calmette-Guérin (BCG). However, limited accrual has hindered analysis of efficacy, particularly for pathologic subsets. We evaluated interim results of a phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy. At interim analysis (April 2017), 45 patients with residual high-grade Ta, T1, or carcinoma-in-situ (CIS) ± Ta/T1 had evaluable 6-month follow-up in this phase II single-arm multicenter trial (NCT02365818). All patients received at least 2 prior courses of intravesical therapy for CIS, with at least 1 being a course of BCG. Patients had either failed BCG induction therapy within 6 months or had been successfully treated with BCG with subsequent recurrence. Complete response (CR) at 6 months was defined as absence of disease on cytology, cystoscopy, and random biopsies. Of 45 patients, there were 24 pure CIS, 8 CIS + Ta, 4 CIS + T1, 6 Ta, 3 T1. Overall 6-month CR (95% CI) was 47% (32%-62%). Considering 6-month CR for pathologic subsets, pure CIS was 58% (37%-78%), CIS ± Ta/T1 50% (33%-67%), and pure Ta/T1 33% (8%-70%). At 6 months, the single patient that progressed to muscle-invasive disease had Ta and T1 tumors at baseline. No patients with pure T1 had 6-month CR. Treatment-related adverse events (AEs) at 6 months were most commonly urinary bladder spasms (36%), hematuria (28%), dysuria (25%), and urgency (22%). Immunologic treatment-related AEs included flu-like symptoms (12%) and fatigue (6%). Grade III treatment-related AEs included dysuria (3%) and hypotension (1.5%). There were no Grade IV/V treatment-related AEs. This phase II study demonstrates that intravesical CG0070 yielded an overall 47% CR rate at 6 months for all patients and 50% for patients with CIS, with an acceptable level of toxicity for patients with high-risk BCG-unresponsive NMIBC. There is a particularly strong response and limited progression in patients with pure CIS. Copyright © 2017 Elsevier Inc. All rights reserved.

A prognostic index for predicting lymph node metastasis in minor salivary gland cancer.

PubMed

Lloyd, Shane; Yu, James B; Ross, Douglas A; Wilson, Lynn D; Decker, Roy H

2010-01-01

Large studies examining the clinical and pathological factors associated with nodal metastasis in minor salivary gland cancer are lacking in the literature. Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 2,667 minor salivary gland cancers with known lymph node status from 1988 to 2004. Univariate and multivariate analyses were conducted to identify factors associated with the use of neck dissection, the use of external beam radiation therapy, and the presence of cervical lymph node metastases. Four hundred twenty-six (16.0%) patients had neck nodal involvement. Factors associated with neck nodal involvement on univariate analysis included increasing age, male sex, increasing tumor size, high tumor grade, T3-T4 stage, adenocarcinoma or mucoepidermoid carcinomas, and pharyngeal site of primary malignancy. On multivariate analysis, four statistically significant factors were identified, including male sex, T3-T4 stage, pharyngeal site of primary malignancy, and high-grade adenocarcinoma or high-grade mucoepidermoid carcinomas. The proportions (and 95% confidence intervals) of patients with lymph node involvement for those with 0, 1, 2, 3, and 4 of these prognostic factors were 0.02 (0.01-0.03), 0.09 (0.07-0.11), 0.17 (0.14-0.21), 0.41 (0.33-0.49), and 0.70 (0.54-0.85), respectively. Grade was a significant predictor of metastasis for adenocarcinoma and mucoepidermoid carcinoma but not for adenoid cystic carcinoma. A prognostic index using the four clinicopathological factors listed here can effectively differentiate patients into risk groups of nodal metastasis. The precision of this index is subject to the limitations of SEER data and should be validated in further clinical studies.

Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis.

PubMed

Bregar, Amy J; Alejandro Rauh-Hain, J; Spencer, Ryan; Clemmer, Joel T; Schorge, John O; Rice, Laurel W; Del Carmen, Marcela G

2017-04-01

To examine patterns of care and survival for Hispanic women compared to white and African American women with high-grade endometrial cancer. We utilized the National Cancer Data Base (NCDB) to identify women diagnosed with uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear cell carcinoma and papillary serous carcinoma between 2003 and 2011. The effect of treatment on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. 43,950 women were eligible. African American and Hispanic women had higher rates of stage III and IV disease compared to white women (36.5% vs. 36% vs. 33.5%, p<0.001). African American women were less likely to undergo surgical treatment for their cancer (85.2% vs. 89.8% vs. 87.5%, p<0.001) and were more likely to receive chemotherapy (36.8% vs. 32.4% vs. 32%, p<0.001) compared to white and Hispanic women. Over the entire study period, after adjusting for age, time period of diagnosis, region of the country, urban or rural setting, treating facility type, socioeconomic status, education, insurance, comorbidity index, pathologic stage, histology, lymphadenectomy and adjuvant treatment, African American women had lower overall survival compared to white women (Hazard Ratio 1.21, 95% CI 1.16-1.26). Conversely, Hispanic women had improved overall survival compared to white women after controlling for the aforementioned factors (HR 0.87, 95% CI 0.80-0.93). Among women with high-grade endometrial cancer, African American women have lower all-cause survival while Hispanic women have higher all-cause survival compared to white women after controlling for treatment, sociodemographic, comorbidity and histopathologic variables. Copyright © 2017 Elsevier Inc. All rights reserved.

Prevalence of amblyopia and strabismus in a population of 7th-grade junior high school students in Central China: the Anyang Childhood Eye Study (ACES).

PubMed

Fu, Jing; Li, Shi Ming; Liu, Luo Ru; Li, Jin Ling; Li, Si Yuan; Zhu, Bi Dan; Li, He; Yang, Zhou; Li, Lei; Wang, Ning Li

2014-06-01

To determine the prevalence of amblyopia and strabismus in 7th-grade junior high school students in central China. Using stratified cluster sampling, 2363 7th-grade students were recruited from four junior high schools in Anyang city into the cross-sectional Anyang Childhood Eye Study (ACES). All students underwent visual acuity (VA), cycloplegic autorefraction, cover test, and ocular movement examinations. Uncorrected VA and best-corrected VA (BCVA) were measured with a logarithm of the minimum angle of resolution (logMAR) chart. Cycloplegic autorefraction was performed after administration of 1.0% cyclopentolate and Mydrin-P. Strabismus was defined as heterotropia at near or distance fixation. Amblyopia was defined as BCVA ≤ 0.1 logMAR units in one or both eyes, without ocular pathology in either eye. Of the 2363 eligible students, 2260 (95.6%) completed all examinations. The mean age of the students was 12.4 ± 0.6 years. Amblyopia was present in 52 students (2.5%), of whom 33 (63.5%) had unilateral and 19 (36.6%) had bilateral amblyopia. Of those with unilateral amblyopia, 18 (54.5 %) had anisometropia and 7 (21.2%) had strabismus. Of those with bilateral amblyopia, 6 (31.6%) had significant refractive error. Strabismus was present in 108 students (5.0%), of whom 2 (1.9%) had esotropia, 102 (94.4%) had exotropia, 3 (2.8%) had vertical strabismus, and 1 (0.9%) had microstrabismus. Of the 108 students with strabismus, 9 (8.3%) had amblyopia. The cross-sectional ACES which examined the prevalence of amblyopia and strabismus in 7th-grade students in central China revealed the prevalence of strabismus, particularly the proportion of exotropia, to be higher than previously reported.

A Prognostic Index for Predicting Lymph Node Metastasis in Minor Salivary Gland Cancer

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

Lloyd, Shane; Yu, James B.; Ross, Douglas A.

2010-01-15

Purpose: Large studies examining the clinical and pathological factors associated with nodal metastasis in minor salivary gland cancer are lacking in the literature. Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 2,667 minor salivary gland cancers with known lymph node status from 1988 to 2004. Univariate and multivariate analyses were conducted to identify factors associated with the use of neck dissection, the use of external beam radiation therapy, and the presence of cervical lymph node metastases. Results: Four hundred twenty-six (16.0%) patients had neck nodal involvement. Factors associated with neck nodal involvement on univariatemore » analysis included increasing age, male sex, increasing tumor size, high tumor grade, T3-T4 stage, adenocarcinoma or mucoepidermoid carcinomas, and pharyngeal site of primary malignancy. On multivariate analysis, four statistically significant factors were identified, including male sex, T3-T4 stage, pharyngeal site of primary malignancy, and high-grade adenocarcinoma or high-grade mucoepidermoid carcinomas. The proportions (and 95% confidence intervals) of patients with lymph node involvement for those with 0, 1, 2, 3, and 4 of these prognostic factors were 0.02 (0.01-0.03), 0.09 (0.07-0.11), 0.17 (0.14-0.21), 0.41 (0.33-0.49), and 0.70 (0.54-0.85), respectively. Grade was a significant predictor of metastasis for adenocarcinoma and mucoepidermoid carcinoma but not for adenoid cystic carcinoma. Conclusions: A prognostic index using the four clinicopathological factors listed here can effectively differentiate patients into risk groups of nodal metastasis. The precision of this index is subject to the limitations of SEER data and should be validated in further clinical studies.« less

Macroscopic and pathological assessment of methylene blue and normal saline on postoperative adhesion formation in a rat cecum model.

PubMed

Panahi, Farzad; Sadraie, Seyed Homayoon; Khoshmohabat, Hadi; Shahram, Elias; Kaka, Gholamreza; Hosseinalipour, Mohammad

2012-01-01

Adhesion formation after abdominal surgery is a major cause of postoperative bowel obstruction, infertility, and chronic abdominal pain. In this study, we evaluated the effect of normal saline and methylene blue (MB) on postoperative adhesion formation in a rat cecum model. A total of 30 Wistar female rats in 2 treatment and 1 control groups underwent midline laparotomy and standardized abrasion of the visceral peritoneum. Normal saline and methylene blue were administrated intraperitoneally at the end of the surgical procedure in 2 treatment groups. Fourteen days after surgery, a re-laparotomy was performed for macroscopic and pathological assessment. The adhesion grade and extent of the normal saline group was lower than control and MB groups in macroscopic assessment (P<0.05 for both). A comparison of adhesion stages in pathological assessment showed increment in abdominal adhesion by usage methylene blue 1% and demonstrated significant difference between MB and 2 other groups (P<0.05). Administrated normal saline individually reduce the adhesion grade near cecum. Conversely, usage of methylene blue 1% may unpredictably increase risk of adhesion formation. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Non‐Hodgkin's Lymphomas in Turkey: Eighteen Years’Experience at the Hacettepe University

PubMed Central

Barista, Ibrahim; Tekuzman, Gülten; Firat, Dinçer; Baltali, Esmen; Kansu, Emin; Kars, Ayse; Özisik, Yavuz; Ruacan, Sevket; Uzunalimoglu, Bedri; Karaagaoglu, Ergun

1994-01-01

In this retrospective study, 470 patients with non‐Hodgkin's lymphoma (NHL) who had been followed in the Hacettepe University Medical Oncology Department between 1973 and 1990, were evaluated to establish their epidemiologic, clinical and therapeutic characteristics. Out of 470 patients, 302 (62.2%) were male and 168 (37.8%) were female. The ages ranged from 16 to 85, with a median of 44 years. Constitutional symptoms were present in 46.4% of the patients. According to the Working Formulation, low, intermediate, and high‐grade lymphomas comprised 33.4%, 54.9%, and 12.7%, respectively. The most common extranodal presentation was gastrointestinal. The chemotherapy regimens most commonly used were CVP (cyclophosphamide, vincristine, prednisone), BCNOP (bleomycin, cyclophosphamide, mitoxantrone, vincristine, prednisone), CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and CHOP‐Bleo (cyclophosphamide, doxorubicin, vincristine, prednisone, bleomycin). The response rates and the survival figures attained with these regimens were not statistically significantly different (P > 0.05). In the Cox multivariate model, pathologic grade, leukopenia, responsiveness to chemotherapy, bone marrow involvement and age were the important factors influencing the disease‐free survival, while responsiveness to chemotherapy, age, presence of constitutional symptoms, pathologic grade, extranodal presentation and stage were the important factors influencing the overall survival. The distribution of NHL according to grade and stage was similar to that in western societies, while constitutional symptoms and lymphomas of the small intestine including immunoproliferative small intestinal disease were more common in Turkey. PMID:7531679

Expression of p27 and its ubiquitin ligase subunit Skp2 in upper urinary tract transitional cell carcinoma.

PubMed

Langner, Cord; von Wasielewski, Reinhard; Ratschek, Manfred; Rehak, Peter; Zigeuner, Richard

2004-09-01

To analyze p27 and S-phase kinase-associated protein 2 (Skp2) expression in upper urinary tract transitional cell carcinoma (TCC) with respect to biologic significance. p27 (p27/kip1) is involved in cell cycle control, and loss of p27 protein expression may result in tumor development and/or progression. The association of p27 with the ubiquitin ligase subunit Skp2 targets p27 for degradation. A total of 53 upper urinary tract TCC specimens were investigated immunohistochemically using a tissue microarray technique. The immunoreactivity of p27 and Skp2 was analyzed with respect to associations with pT stage, grade, and prognosis. Non-neoplastic renal tissue showed p27 immunoreactivity in tubule epithelium and pelvic urothelium, but lacked immunoreactivity for Skp2. In the TCC specimens, p27 immunoreactivity was noted in 47 (89%) of 53 cases. High p27 expression (50% or greater of tumor cell nuclei) tended to decrease with rising tumor stage (14 [45%] of 31 with pT1-pT2 versus 4 [18%] of 22 with pT3; P = 0.076), but was independent of tumor grade (11 [39%] of 28 grade 2 versus 7 [28%] of 25 grade 3-4; P = 0.56). Skp2 immunoreactivity was noted in 32 (60%) of 53 tumors. Skp2 expression increased with rising tumor stage (9 [41%] of 22 pT1 versus 23 [74%] of 31 pT2-pT3; P = 0.023) and tumor grade (12 [43%] of 28 grade 2 versus 20 [80%] of 25 grade 3; P = 0.043) and was associated with angioinvasion (P = 0.017). In multivariate analysis, tumor stage proved to be the only independent prognostic factor regarding disease-free survival. p27 and Skp2 are additional biomarkers in urogenital pathologic findings. The statistically significant association of Skp2 expression with high-grade TCC, as well as the lack of expression in non-neoplastic tissue, suggests that Skp2 could be a promising target for future cancer therapy strategies.

Pathological video game use among youths: a two-year longitudinal study.

PubMed

Gentile, Douglas A; Choo, Hyekyung; Liau, Albert; Sim, Timothy; Li, Dongdong; Fung, Daniel; Khoo, Angeline

2011-02-01

We aimed to measure the prevalence and length of the problem of pathological video gaming or Internet use, to identify risk and protective factors, to determine whether pathological gaming is a primary or secondary problem, and to identify outcomes for individuals who become or stop being pathological gamers. A 2-year, longitudinal, panel study was performed with a general elementary and secondary school population in Singapore, including 3034 children in grades 3 (N = 743), 4 (N = 711), 7 (N = 916), and 8 (N = 664). Several hypothesized risk and protective factors for developing or overcoming pathological gaming were measured, including weekly amount of game play, impulsivity, social competence, depression, social phobia, anxiety, and school performance. The prevalence of pathological gaming was similar to that in other countries (∼9%). Greater amounts of gaming, lower social competence, and greater impulsivity seemed to act as risk factors for becoming pathological gamers, whereas depression, anxiety, social phobias, and lower school performance seemed to act as outcomes of pathological gaming. This study adds important information to the discussion about whether video game "addiction" is similar to other addictive behaviors, demonstrating that it can last for years and is not solely a symptom of comorbid disorders.

Chemotherapy and target therapy in the management of adult high- grade gliomas.

PubMed

Spinelli, Gian Paolo; Miele, Evelina; Lo Russo, Giuseppe; Miscusi, Massimo; Codacci-Pisanelli, Giovanni; Petrozza, Vincenzo; Papa, Anselmo; Frati, Luigi; Della Rocca, Carlo; Gulino, Alberto; Tomao, Silverio

2012-10-01

Adult high grade gliomas (HGG) are the most frequent and fatal primary central nervous system (CNS) tumors. Despite recent advances in the knowledge of the pathology and the molecular features of this neoplasm, its prognosis remains poor. In the last years temozolomide (TMZ) has dramatically changed the life expectancy of these patients: the association of this drug with radiotherapy (RT), followed by TMZ alone, is the current standard of care. However, malignant gliomas often remain resistant to chemotherapy (CHT). Therefore, preclinical and clinical research efforts have been directed on identifying and understanding the different mechanisms of chemo-resistance operating in this subset of tumors,in order to develop effective strategies to overcome resistance. Moreover, the evidence of alterations in signal transduction pathways underlying tumor progression, has increased the number of trials investigating molecular target agents, such as anti-epidermal growth factor receptor (EGFR) and anti- vascular endothelial growth factor (VEGF) signaling. The purpose of this review is to point out the current standard of treatment and to explore new available target therapies in HGG.

International Image Concordance Study to Compare a Point of Care Tampon Colposcope to a Standard-of-Care Colposcope

PubMed Central

Mueller, Jenna L.; Asma, Elizabeth; Lam, Christopher T.; Krieger, Marlee S.; Gallagher, Jennifer E.; Erkanli, Alaattin; Hariprasad, Roopa; Malliga, J.S.; Muasher, Lisa C.; Mchome, Bariki; Oneko, Olola; Taylor, Peyton; Venegas, Gino; Wanyoro, Anthony; Mehrotra, Ravi; Schmitt, John W.; Ramanujam, Nimmi

2017-01-01

Objective Barriers to cervical cancer screening in low resource settings include lack of accessible high quality services, high cost, and the need for multiple visits. To address these challenges, we developed a low cost intra-vaginal optical cervical imaging device, the Point of Care Tampon (POCkeT) colposcope, and evaluated whether its performance is comparable to a standard-of-care colposcope. Methods There were two protocols, which included 44 and 18 patients respectively. For the first protocol, white light cervical images were collected in vivo, blinded by device, and sent electronically to 8 physicians from high, middle and low income countries. For the second protocol, green light images were also collected and sent electronically to the highest performing physician from the first protocol who has experience in both a high and low income country. For each image, physicians completed a survey assessing cervix characteristics and severity of precancerous lesions. Corresponding pathology was obtained for all image pairs. Results For the first protocol, average percent agreement between devices was 70% across all physicians. POCkeT and standard-of-care colposcope images had 37% and 51% percent agreement respectively with pathology for high-grade squamous intraepithelial lesions (HSILs). Investigation of HSIL POCkeT images revealed decreased visibility of vascularization and lack of contrast in lesion margins. After changes were made for the second protocol, the two devices achieved similar agreement to pathology for HSIL lesions (55%). Conclusions Based on the exploratory study, physician interpretation of cervix images acquired using a portable, low cost, POCkeT colposcope was comparable to a standard-of-care colposcope. PMID:28263237

Presence of koilocytosis in low-grade smears of high-risk HPV-positive women is a negative predictor for cervical intraepithelial neoplasia grade 3 or more.

PubMed

Siebers, A G; van der Linden, H; Vedder, J E M; Bekkers, R L M; Melchers, W L G; Bulten, J

2018-03-25

The Netherlands converted to high-risk (hr)HPV-based screening in 2017. An increase in referral of hrHPV-positive women with low risk for cervical intraepithelial neoplasia grade 3 or more (CIN3+) is anticipated and reduction of unjustified referrals will have priority. The relevance of koilocytosis in relation to the underlying risk of high-grade CIN in a primary HPV screening setting is unclear. The aim was to investigate whether the risk for CIN3+ differs between hrHPV-positive atypical squamous cells of undetermined significance (ASC-US)/low-grade squamous intraepithelial lesion (LSIL) with or without koilocytosis. Retrospective cohort study, using data from the Dutch national pathology database (PALGA). The population was 1201 hrHPV-positive women with cytological diagnosis of ASC-US/LSIL. Reporting of koilocytosis was assessed as well as detection rates of CIN1 or less, CIN2 and CIN3+ for ASC-US/LSIL cytology stratified by presence or absence of koilocytosis. Crude and adjusted odds ratios were determined. Koilocytosis was present in 40.1% of ASC-US and 45.9% of LSIL cases. CIN3+ is significantly less often found when koilocytosis is present (7.8% for hrHPV-positive ASC-US with- vs 15.8% without koilocytosis). For hrHPV-positive LSIL this was 11.7% vs 20.2%. The crude and adjusted odds ratios for CIN3+ was 0.45 for hrHPV-positive ASC-US and 0.52 for hrHPV-positive LSIL. The presence of koilocytosis is a negative predictor of CIN3+. The risk of hrHPV-positive ASC-US with koilocytosis is in the same range as hrHPV-positive/cytology negative cases and in a setting of primary hrHPV screening these cases could be followed conservatively by repeat cytology. The results should be confirmed by the first data from the Dutch HPV-based screening programme. © 2018 John Wiley & Sons Ltd.

MR imaging of intracranial hemangiopericytomas.

PubMed

Mama, N; Ben Abdallah, A; Hasni, I; Kadri, K; Arifa, N; Ladib, M; Tlili-Graiess, K

2014-12-01

To describe the MR features of primary intracranial hemangiopericytomas (HPCs) on conventional imaging, diffusion and MR spectroscopy and aim to determinate distinguishing features from meningiomas. From 2006 to 2012, seven patients with pathologically confirmed primary intracranial HPCs were included. The clinical data, conventional MR findings (n=7), DWI features (n=7) and MR spectroscopy (n=5) were retrospectively analyzed. ADC values of the HPCs (n=7) were measured on ADC map and were compared with that of contralateral normal white matter. Of the seven HPCs, four were anaplastic HPCs (WHO grade III) and three were HPCs (WHO grade II). MR pattern consisted in lobulated or irregular margin tumors in all cases with cross-leaf growth on both side of the falx in two cases. The lesions showed mainly iso signal (n=4) on T1 WI and heterogeneous high signal (n=5) on T2 WI. Heterogenity was mainly related to intra tumoral hemorrhage (n=4), and proeminent intratumoral flow voids (n=3). Marked heterogeneous enhancement (n=5) with dural tail (n=4) was noted. All tumours showed significant peritumoral edema. ADC values of the tumor tissue component range between 0.638 and 1.50×10(-3)mm/s(2) (average = 1,02). Three grade II HPCs showed higher values compared to normal parenchyma ADC (range between 0.772 and 0.930×10(-3)mm/s(2) with average of 0.830), whereas grade III HPCs showed either equal (three cases) or decreased ADC values (one case). MRS showed in all cases markedly increased Cho with lip/lac peak, decreased Cr and almost absent NAA. High mI peak with large glutamine/glutamate were noted in the three grade II HPCs. Conventional MR pattern when combined with DWI and MRS findings are highly suggestive of HPC and appear valuable data to differentiate HPCs from meningiomas. Copyright © 2014. Published by Elsevier Masson SAS.

Quality of life measures in glioma patients with different grades: A preliminary study.

PubMed

Mahalakshmi, P; Vanisree, A J

2015-01-01

Plethora of information exists in the literature on pathology of the glioma while prevailing research data on quality-of-life (QOL) of glioma patients marks dearth thus demanding more studies. In this study, we examined the QOL of different grades of glioma patients among the Chennai population in India. A total of 162 patients with different grades of glioma enrolled from August 2007 to February 2011, at their first contact to Department of Neurology and Neurosurgery, Government General Hospital, Chennai, India were included and their QOL was assessed by European Organization for Research and Treatment of Cancer Core QOL questionnaire (EORTC QLQc-30), EORTC brain cancer module (QLQ BN-20). Both low and high grade glioma (LGG and HGG) patients had poor mean scores in social functioning (87.0), physical functioning (82.0) and emotional functioning (75.2) and role functioning (58.9). The mean scores on cognitive functioning (61.9) and global QOL (60.3) were better. Age, Karnofsky performance status, World Health Organization grades showed significant associations with all functional scales. The percentage values were higher for symptoms of fatigue (76.9%), pain (71.5%), financial difficulties (77.6%) and appetite loss (38.46%) in both LGG and HGG. Similarly, with respect to QLQ-BN20 domains, HGG patients showed more symptoms than low grade with a significant correlation in communication deficit problems (P = 0.02), headache (P = 0.04), seizures (P < 0.01), hair loss (P < 0.05) than the other symptoms. This initial assessment suggests that an increasing burden of symptoms exists, with poor QOL and survival, which has become a major concern in different grades of glioma patients.

Frozen tissue preparation for high-resolution multiplex histological analyses of human brain specimens.

PubMed

Shao, Fangjie; Jiang, Wenhong; Gao, Qingqing; Li, Baizhou; Sun, Chongran; Wang, Qiyuan; Chen, Qin; Sun, Bing; Shen, Hong; Zhu, Keqing; Zhang, Jianmin; Liu, Chong

2017-10-01

The availability of a comprehensive tissue library is essential for elucidating the function and pathology of human brains. Considering the irreplaceable status of the formalin-fixation-paraffin-embedding (FFPE) preparation in routine pathology and the advantage of ultra-low temperature to preserve nucleic acids and proteins for multi-omics studies, these methods have become major modalities for the construction of brain tissue libraries. Nevertheless, the use of FFPE and snap-frozen samples is limited in high-resolution histological analyses because the preparation destroys tissue integrity and/or many important cellular markers. To overcome these limitations, we detailed a protocol to prepare and analyze frozen human brain samples that is particularly suitable for high-resolution multiplex immunohistological studies. As an alternative, we offered an optimized procedure to rescue snap-frozen tissues for the same purpose. Importantly, we provided a guideline to construct libraries of frozen tissue with minimal effort, cost and space. Taking advantage of this new tissue preparation modality to nicely preserve the cellular information that was otherwise damaged using conventional methods and to effectively remove tissue autofluorescence, we described the high-resolution landscape of the cellular composition in both lower-grade gliomas and glioblastoma multiforme samples. Our work showcases the great value of fixed frozen tissue in understanding the cellular mechanisms of CNS functions and abnormalities.

Expression analysis of URI/RMP gene in endometrioid adenocarcinoma by tissue microarray immunohistochemistry.

PubMed

Gu, Junxia; Liang, Yuting; Qiao, Longwei; Li, Xiaoyun; Li, Xingang; Lu, Yaojuan; Zheng, Qiping

2013-01-01

Multiple studies have recently demonstrated the oncogenic property of URI (or RMP, a member of the prefoldin family of molecular chaperones) during progression of hepatocellular carcinoma, ovarian cancer, and possibly prostate cancer. Most recently, we have shown that URI/RMP is up-regulated in cervical cancer, another reproductive system tumor beside ovarian and prostate cancers. To investigate if URI/RMP also plays a role in other reproductive system tumors, especially in endometrioid adenocarcinoma, we analyzed URI/RMP expression in a TMA (tissue microarray) containing tissues from 30 cases of endometrioid adenocarcinoma (which covers tumor tissues from Grade I through Grade III) and adjacent endometrium by immunohistochemistry (IHC) and densitometry analysis using image-pro plus 6.0 software. Our results showed that the mean density of URI/RMP expression in cancerous tissue is slightly higher than that of the adjacent endometrial tissue, though not statistically significant (p>0.05). There is no significant difference either between the mean density of Grade III cancerous tissue and that of Grade I and II cancers. Notably, we detected significantly higher signal intensity in cancerous tissue of all 7 Grade III cases than that of their adjacent endometrial tissue (p<0.05), suggesting a correlation of URI/RMP expression with the differentiation and pathological classification of endometrioid adenocarcinoma. Together, our results demonstrate the heterogeneous expression of URI/RMP in endometrioid adenocarcinoma. The higher level of URI/RMP expression in high-grade endometrioid adenocarcinomas compared to tissues of adjacent endometrium or gland suggests a diagnostic and possibly, a prognostic value of URI/RMP in endometrioid adenocarcinoma.

Expression analysis of URI/RMP gene in endometrioid adenocarcinoma by tissue microarray immunohistochemistry

PubMed Central

Gu, Junxia; Liang, Yuting; Qiao, Longwei; Li, Xiaoyun; Li, Xingang; Lu, Yaojuan; Zheng, Qiping

2013-01-01

Multiple studies have recently demonstrated the oncogenic property of URI (or RMP, a member of the prefoldin family of molecular chaperones) during progression of hepatocellular carcinoma, ovarian cancer, and possibly prostate cancer. Most recently, we have shown that URI/RMP is up-regulated in cervical cancer, another reproductive system tumor beside ovarian and prostate cancers. To investigate if URI/RMP also plays a role in other reproductive system tumors, especially in endometrioid adenocarcinoma, we analyzed URI/RMP expression in a TMA (tissue microarray) containing tissues from 30 cases of endometrioid adenocarcinoma (which covers tumor tissues from Grade I through Grade III) and adjacent endometrium by immunohistochemistry (IHC) and densitometry analysis using image-pro plus 6.0 software. Our results showed that the mean density of URI/RMP expression in cancerous tissue is slightly higher than that of the adjacent endometrial tissue, though not statistically significant (p>0.05). There is no significant difference either between the mean density of Grade III cancerous tissue and that of Grade I and II cancers. Notably, we detected significantly higher signal intensity in cancerous tissue of all 7 Grade III cases than that of their adjacent endometrial tissue (p<0.05), suggesting a correlation of URI/RMP expression with the differentiation and pathological classification of endometrioid adenocarcinoma. Together, our results demonstrate the heterogeneous expression of URI/RMP in endometrioid adenocarcinoma. The higher level of URI/RMP expression in high-grade endometrioid adenocarcinomas compared to tissues of adjacent endometrium or gland suggests a diagnostic and possibly, a prognostic value of URI/RMP in endometrioid adenocarcinoma. PMID:24228101

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

PubMed

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

2017-02-01

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

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma

PubMed Central

Barth, Rolf F.; Miyatake, Shin-Ichi; Kawabata, Shinji; Suzuki, Minoru; Ono, Koji

2017-01-01

We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1R132H, were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1R132H-positive and 1 control IDH1R132H-negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients’ tumors were IDH1R132H-negative small cell GBMs. The remaining patients had tumors consisting of other IDH1R132H-negative GBM variants, an IDH1R132H-positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1R132H-negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event. PMID:28534152

Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma.

PubMed

Kondo, Natsuko; Barth, Rolf F; Miyatake, Shin-Ichi; Kawabata, Shinji; Suzuki, Minoru; Ono, Koji; Lehman, Norman L

2017-05-01

We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1 R132H , were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1 R132H -positive and 1 control IDH1 R132H -negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients' tumors were IDH1 R132H -negative small cell GBMs. The remaining patients had tumors consisting of other IDH1 R132H -negative GBM variants, an IDH1 R132H -positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1 R132H -negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event.

An online app platform enhances collaborative medical student group learning and classroom management.

PubMed

Peacock, Justin G; Grande, Joseph P

2016-01-01

The authors presented their results in effectively using a free and widely-accessible online app platform to manage and teach a first-year pathology course at Mayo Medical School. The authors utilized the Google "Blogger", "Forms", "Flubaroo", "Sheets", "Docs", and "Slides" apps to effectively build a collaborative classroom teaching and management system. Students were surveyed on the use of the app platform in the classroom, and 44 (94%) students responded. Thirty-two (73%) of the students reported that "Blogger" was an effective place for online discussion of pathology topics and questions. 43 (98%) of the students reported that the "Forms/Flubaroo" grade-reporting system was helpful. 40 (91%) of the students used the remote, collaborative features of "Slides" to create team-based learning presentations, and 39 (89%) of the students found those collaborative features helpful. "Docs" helped teaching assistants to collaboratively create study guides or grading rubrics. Overall, 41 (93%) of the students found that the app platform was helpful in establishing a collaborative, online classroom environment. The online app platform allowed faculty to build an efficient and effective classroom teaching and management system. The ease of accessibility and opportunity for collaboration allowed for collaborative learning, grading, and teaching.

Non-Gaussian diffusion MR imaging of glioma: comparisons of multiple diffusion parameters and correlation with histologic grade and MIB-1 (Ki-67 labeling) index.

PubMed

Yan, Ren; Haopeng, Pang; Xiaoyuan, Feng; Jinsong, Wu; Jiawen, Zhang; Chengjun, Yao; Tianming, Qiu; Ji, Xiong; Mao, Sheng; Yueyue, Ding; Yong, Zhang; Jianfeng, Luo; Zhenwei, Yao

2016-02-01

This study was conducted to compare the association of Gaussian and non-Gaussian magnetic resonance imaging (MRI)-derived parameters with histologic grade and MIB-1 (Ki-67 labeling) index (MI) in brain glioma. Sixty-five patients with pathologically confirmed glioma, who underwent diffusion-weighted MRI with 2 b values (0, 1000 s/mm(2)) and 22 b values (≤5000 s/mm(2)), respectively, were divided into three groups of grade II (n = 35), grade III (n = 8), and grade IV (n = 22). Comparisons by two groups were made for apparent diffusion coefficient (ADC), slow diffusion coefficient (Dslow), distributed diffusion coefficient (DDC), and heterogeneity index α. Analyses of receiver operating characteristic (ROC) curve were performed to maximize the area under the curve (AUC) for differentiating grade III + IV (high-grade glioma, HGG) from grade II (low-grade glioma, LGG) and grade IV (glioblastoma multiforme, GBM) from grade II + III (other grade glioma, OGG). Correlations with MI were analyzed for the MRI parameters. On tumor regions, the values of ADC, Dslow, DDC, and α were significantly higher in grade II [(1.37 ± 0.29, 0.70 ± 0.11, 1.39 ± 0.34) (×10(-3) mm(2)/s) and 0.88 ± 0.05, respectively] than in grade III [(0.99 ± 0.13, 0.55 ± 0.07, 1.04 ± 0.20) (×10(-3) mm(2)/s) and 0.80 ± 0.03, respectively] and grade IV [(1.03 ± 0.14, 0.50 ± 0.05, 1.02 ± 0.16) (×10(-3) mm(2)/s) and 0.76 ± 0.04, respectively] (all P < 0.001). The parameter α showed the highest AUCs of 0.950 and 0.922 in discriminating HGG from LGG and GBM from OGG, respectively. Significant correlations with histologic grade and MI were observed for the MRI parameters. The non-Gaussian MRI-derived parameters α and Dslow are superior to ADC in glioma grading, which are comparable with ADC as reliable biomarkers in noninvasively predicting the proliferation level of glioma malignancy.

Ultrasound-guided core biopsy in the diagnosis of lymphoma of the head and neck. A 9 year experience

PubMed Central

Burke, C; Thomas, R; Inglis, C; Baldwin, A; Ramesar, K; Grace, R; Howlett, D C

2011-01-01

Objectives This retrospective study aimed to evaluate the diagnostic utility of ultrasound-guided core biopsy (USCB) in lymphoma of the head and neck, in particular whether core biopsy can provide sufficient diagnostic information for definitive treatment. Methods All lymphomas diagnosed in the head and neck at Eastbourne General Hospital between January 2000 and June 2009 were identified. Radiology and pathology reports were reviewed and the diagnostic techniques recorded. The type of biopsy (fine needle aspiration, needle core, surgical excision biopsy) used to establish a diagnosis sufficient to allow treatment, i.e. the "index" diagnostic technique, was identified. Previous inconclusive or inadequate biopsies were noted. Pathology reports based on USCB were graded 0–3 according to diagnostic completeness and ability to provide treatment information. Results Of 691 overall cases of lymphoma diagnosed over the 9 year period, 171 different patients presented with lymphoma in the head and neck. Of these 171, 83 had USCB biopsy during diagnostic work up. 60 were regarded as grade 3 where a confident diagnosis of lymphoma was made. In seven patients, clinical management proceeded on the basis of a suggestive (grade 2) pathology report without surgical excision, and these were therefore also included as "index" biopsies. Overall therefore, 67/83 core biopsies (81%) provided adequate information to allow treatment. Surgical excision biopsy was the index modality in 104 cases. Conclusion In the majority of cases USCB is adequate for confident histopathological diagnosis avoiding the need for surgical excision biopsy in cases of suspected head and neck lymphoma. PMID:21427181

Intra-articular pathology associated with isolated posterior cruciate ligament injury on MRI.

PubMed

Ringler, Michael D; Shotts, Ezekiel E; Collins, Mark S; Howe, B Matthew

2016-12-01

Unlike with anterior cruciate ligament injury, little is known about the prevalence of intra-articular pathology associated with isolated posterior cruciate ligament (PCL) injury in the knee. The objectives of this study were to characterize and identify the frequency of meniscal tears and osteochondral injuries in these patients, and to see if management might be affected. Altogether, 48 knee MRI exams with isolated PCL tears were evaluated for the presence of: grade and location of PCL tear, meniscal tear, articular chondral lesion, bone bruise, and fracture. Comparisons between PCL tear grade and location, as well as mechanism of injury when known, with the presence of various intra-articular pathologies, were made using the chi-square or Fisher's exact test as appropriate. In all, 69 % of isolated PCL tears occur in the midsubstance, 27 % proximally. Meniscal tears were seen in 25 % of knees, involving all segments of both menisci, except for the anterior horn medial meniscus. Altogether, 23 % had focal cartilage lesions, usually affecting the central third medial femoral condyle and medial trochlea, while 12.5 % of knees had fractures, and 48 % demonstrated bone bruises, usually involving the central to anterior tibiofemoral joint. The presence of a fracture (p = 0.0123) and proximal location of PCL tear (p = 0.0016) were both associated with the hyperextension mechanism of injury. There were no statistically significant associations between PCL tear grade and presence of intra-articular abnormality. Potentially treatable meniscal tears and osteochondral injuries are relatively prevalent, and demonstrable on MRI in patients with isolated acute PCL injury of the knee.

Physician satisfaction with surgical pathology reports: a 2-year College of American Pathologists Q-Tracks Study.

PubMed

Nakhleh, Raouf E; Souers, Rhona; Ruby, Stephen G

2008-11-01

There are multiple elements that can be measured to assess the quality of a surgical pathology laboratory. Overall customer satisfaction is an excellent "global" measure, because it highlights the unique insight of laboratory performance from the users' perspective. To measure customer satisfaction with surgical pathology reports. This study was based on a subscription Q-Tracks study. Voluntary participants were asked to distribute and collect a minimum of 25 surveys per quarter from their clients. Four parameters were graded, which included overall satisfaction, report turnaround time (TAT), completeness, and style on a scale of 1 (poor) to 5 (excellent). Each laboratory submitted quarterly data to the College of American Pathologists, where the data were tabulated and analyzed. Each laboratory could compare their performance in all 4 measures against the entire cohort or a selected subgroup of laboratories. Overall customer satisfaction with surgical pathology reports and 3 subcategories of report TAT, completeness, and style were the main outcome measures. This study ran during 2004 and 2005, with 41 and 33 participant laboratories, respectively. The median score for overall satisfaction, TAT, completeness, and style were 4.57, 4.31, 4.62, and 4.64 in 2004, and 4.64, 4.56, 4.65, and 4.68 in 2005, respectively. Most laboratories reported results for 4 quarters or fewer. There was no statistically significant change in overall satisfaction over time. Overall satisfaction scores for surgical pathology reports as well as satisfaction with report TAT, completeness, and style were high. Report TAT received the lowest scores of all parameters.

Risk factors for under-diagnosis of gastric intraepithelial neoplasia and early gastric carcinoma in endoscopic forceps biopsy in comparison with endoscopic submucosal dissection in Chinese patients.

PubMed

Xu, Guifang; Zhang, Weijie; Lv, Ying; Zhang, Bin; Sun, Qi; Ling, Tingsheng; Zhang, Xiaoqi; Zhou, Zhihua; Wang, Lei; Huang, Qin; Zou, Xiaoping

2016-07-01

Differences in pathologic diagnosis between endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) for gastric intraepithelial neoplasia (GIN) and early gastric carcinoma (EGC) in Chinese patients remain unknown. The aim of the study was to investigate risk factors for under-diagnosed pathology in initial EFB, compared to final ESD. We reviewed endoscopic and histopathologic findings for tumor location, size, macroscopic pattern, nodularity, erythema, erosion, GIN (low and high grade), and EGC diagnosed with the WHO criteria. Differences in those features between EFB and ESD were compared and risk factors for under-diagnosis by EFB were analyzed. Although concordant in most (74.9 %) cases between EFBs and ESDs, pathological diagnoses in 57 (25.1 %) cases were upgraded in ESDs. Compared to the concordant group, the lesion size ≥2 cm, and depressed and excavated patterns were significantly more frequent in the upgraded group. Further multivariate regression analysis demonstrated the depressed pattern and lesion size ≥2 cm as independent risk factors for upgraded pathology with the odds ratio of 5.778 (95 % confidence interval 2.893-11.542) and 2.535 (95 % confidence interval 1.257-5.111), respectively. Lesion size ≥2.0 cm and the depressed pattern at initial EFB were independent risk factors for pathologic upgrade to advanced diseases in ESD. Therefore, these endoscopic characteristics should be considered together with the initial EFB diagnosis to guide the optimal clinical management of patients with GIN and EGC.

Gallium scintigraphic pattern in lung CMV infections

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

Ganz, W.I.; Cohen, D.; Mallin, W.

1994-05-01

Due to extensive use of prophylactic therapy for Pneumonitis Carinii Pneumonia (PCP), Cytomegalic Viral (CMV) infection may now be the most common lung infection in AIDS patients. This study was performed to determine Gallium-67 patterns in AIDS patients with CMV. Pathology reports were reviewed in AIDS patients who had a dose of 5 to 10 mCi of Gallium-67 citrate. Analysis of images were obtained 48-72 hours later of the entire body was performed. Gallium-67 scans in 14 AIDS patients with biopsy proven CMV, were evaluated for eye, colon, adrenal, lung and renal uptake. These were compared to 40 AIDS patientsmore » without CMV. These controls had infections including PCP, Mycobacterial infections, and lymphocytic interstitial pneumonitis. 100% of CMV patients had bowel uptake greater than or equal to liver. Similar bowel activity was seen in 50% of AIDS patients without CMV. 71% had intense eye uptake which was seen in only 10% of patients without CMV. 50% of CMV patients had renal uptake compared to 5% of non-CMV cases. Adrenal uptake was suggested in 50%, however, SPECT imaging is needed for confirmation. 85% had low grade lung uptake. The low grade lung had perihilar prominence. The remaining 15% had high grade lung uptake (greater than sternum) due to superimposed PCP infection. Colon uptake is very sensitive indicator for CMV infection. However, observing eye, renal, and or adrenal uptake improved the diagnostic specificity. SPECT imaging is needed to confirm renal or adrenal abnormalities due to intense bowel activity present in 100% of cases. When high grade lung uptake is seen superimposed PCP is suggested.« less

Lung Metastasis in a Case of Recurrent Poorly Differentiated Leiomyosarcoma of the Bartholin Gland: A Case Report and Review of the Literature

PubMed Central

Alfieri, Joanne

2016-01-01

Vulvar neoplasms represent four percent of all gynecological cancers. While most cases of vulvar neoplasms are benign, two percent of patients present with malignant disease. We present the case of a 37-year-old premenopausal female who presented to an outside institution with a lump in her left vulva, which had progressively enlarged to the size of an egg. A wide local excision of the left vulva was performed, and the pathology revealed a high-grade sarcoma, not otherwise specified (NOS), with negative margins. Imaging showed enlarged bilateral external iliac lymph nodes, likely metastatic. After discussion at a multidisciplinary gynecology oncology tumor board, she was treated with gemcitabine/docetaxel chemotherapy, followed by a left inguinal lymph node dissection and a left radical vulvectomy after being referred to our centre. The final pathology at that time showed a residual sarcoma of 3.5 mm in the left vulva with no lympho-vascular invasion (LVI) and negative margins, with the closest, laterally, at 2 mm. A total of three lymph nodes were negative. She received additional chemotherapy postoperatively. Approximately one year later, she returned to her gynecologist with a 1 cm mass on the left vulva. She underwent a left hemi-vulvectomy and lymph node dissection, and pathology confirmed the presence of a high-grade sarcoma with close margins. She received adjuvant radiotherapy. Three months later, she presented with persistent cough and pneumonia. Imaging revealed a 10 cm lung mass, which was believed to be metastasis from the vulva. This was confirmed with biopsy and was completely resected. Any mass in the Bartholin gland area should be investigated carefully. Poorly differentiated vulvar leiomyosarcoma in the Bartholin gland can recur locally but may also lead to distant metastasis. Despite surgical and systemic treatment, as well as adjuvant radiation, the tumor recurred. Due to the rarity of this condition, there are no clear recommendations for treatment of this disease. To our knowledge, this is the first report of vulvar leiomyosarcoma of the Bartholin gland with metastasis to the lung. PMID:27158579

Detection of human papillomavirus in intraepithelial lesions and carcinoma of the cervix uteri in southern Thai women.

PubMed

Tungsinmunkong, Kobkul; Suwiwat, Supaporn; Sriplung, Hutcha

2006-01-01

To evaluate the prevalence of high-risk type human papillomavirus (HR-HPV) in preneoplastic lesions and invasive squamous cell carcinoma (SCC) of the cervix uteri in southern Thai women. A total of 148 formalin-fixed, paraffin-embedded blocks of cervix tissue were retrieved from the files of the Department of Pathology, Prince of Songkla University Hospital. They were classified as negative for intraepithelial lesion (NIL) in 37 cases, low grade lesion (LGL) in 58 cases, high grade lesion (HGL) in 39 cases and SCC in 14 cases. HR-HPV DNA was tested with an Amplicor HPV (Roche Diagnostics) detection kit. Of the 111 cases, 42 of 58 LGLs (72.4%), 34 of 39 HGLs (87.2%) and 13 of 14 SCCs (92.9%) were positive for HR-HPV DNA. In 37 cases of histologically normal cervix, there were 15 cases that showed the presence of HR-HPV DNA. Applying the HR-HPV results for NILs to the general population, the age standardized incidence rate of HR-HPV infection in the normal Thai population was 12.8%. HR-HPV DNA can be found in all grades of intraepithelial lesions and carcinoma of the cervix uteri, even in the histologically "normal" looking cervix. These results provide strong evidence for a role in carcinogenesis of the cervix uteri and the existence of a non-productive or latent period of HPV infection.

Redefining the Ki-67 Index Stratification for Low-Grade Pancreatic Neuroendocrine Tumors: Improving Its Prognostic Value for Recurrence of Disease.

PubMed

Lopez-Aguiar, Alexandra G; Ethun, Cecilia G; Postlewait, Lauren M; Zhelnin, Kristen; Krasinskas, Alyssa; El-Rayes, Bassel F; Russell, Maria C; Sarmiento, Juan M; Kooby, David A; Staley, Charles A; Maithel, Shishir K; Cardona, Kenneth

2018-01-01

The Ki-67 index is an established prognostic marker for recurrence after resection of pancreatic neuroendocrine tumors (PanNETs) that groups tumors into three categories: low grade (< 3%), intermediate grade (3-20%), and high grade (> 20%). Given that the majority of resected PanNETs have a Ki-67 less than 3%, this study aimed to stratify this group further to predict disease recurrence more accurately. The Ki-67 index was pathologically re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables using tissue microarray blocks made in triplicate. All patients who underwent curative-intent resection of non-metastatic PanNETs at a single institution from 2000 to 2013 were included in the study. The primary outcome was recurrence-free survival (RFS). Of 113 patients with well-differentiated PanNETs resected, 83 had tissue available for pathologic re-review. The Ki-67 index was lower than 3% for 72 tumors (87%) and between 3 and 20% for 11 tumors (13%). Considering only Ki-67 less than 3%, the tumors were further stratified by Ki-67 into three groups: group A (< 1%, n = 43), group B (1-1.99%, n = 23), and group C (2-2.99%, n = 6). Compared with group A, groups B and C more frequently had advanced T stage (T3: 44% and 67% vs 12%; p = 0.003) and lymphovascular invasion (50% and 83% vs 23%; p = 0.007). Groups B and C had similar 1- and 3-year RFS, both less than group A. After combining groups B and C, a Ki-67 of 1-2.99% was associated with decreased RFS compared with group A (< 1%). This persisted in the multivariable analysis (hazard ratio [HR] 8.6; 95% confidence interval [CI] 1.0-70.7; p = 0.045), with control used for tumor size, margin-positivity, lymph node involvement, and advanced T stage. PanNETs with a Ki-67 of 1-2.99% exhibit distinct biologic behavior and earlier disease recurrence than those with a Ki-67 lower than 1%. This new stratification scheme, if externally validated, should be incorporated into future grading systems to guide both surveillance protocols and treatment strategies.

Genetic analyses of isolated high-grade pancreatic intraepithelial neoplasia (HG-PanIN) reveal paucity of alterations in TP53 and SMAD4.

PubMed

Hosoda, Waki; Chianchiano, Peter; Griffin, James F; Pittman, Meredith E; Brosens, Lodewijk Aa; Noë, Michaël; Yu, Jun; Shindo, Koji; Suenaga, Masaya; Rezaee, Neda; Yonescu, Raluca; Ning, Yi; Albores-Saavedra, Jorge; Yoshizawa, Naohiko; Harada, Kenichi; Yoshizawa, Akihiko; Hanada, Keiji; Yonehara, Shuji; Shimizu, Michio; Uehara, Takeshi; Samra, Jaswinder S; Gill, Anthony J; Wolfgang, Christopher L; Goggins, Michael G; Hruban, Ralph H; Wood, Laura D

2017-05-01

High-grade pancreatic intraepithelial neoplasia (HG-PanIN) is the major precursor of pancreatic ductal adenocarcinoma (PDAC) and is an ideal target for early detection. To characterize pure HG-PanIN, we analysed 23 isolated HG-PanIN lesions occurring in the absence of PDAC. Whole-exome sequencing of five of these HG-PanIN lesions revealed a median of 33 somatic mutations per lesion, with a total of 318 mutated genes. Targeted next-generation sequencing of 17 HG-PanIN lesions identified KRAS mutations in 94% of the lesions. CDKN2A alterations occurred in six HG-PanIN lesions, and RNF43 alterations in five. Mutations in TP53, GNAS, ARID1A, PIK3CA, and TGFBR2 were limited to one or two HG-PanINs. No non-synonymous mutations in SMAD4 were detected. Immunohistochemistry for p53 and SMAD4 proteins in 18 HG-PanINs confirmed the paucity of alterations in these genes, with aberrant p53 labelling noted only in three lesions, two of which were found to be wild type in sequencing analyses. Sixteen adjacent LG-PanIN lesions from ten patients were also sequenced using targeted sequencing. LG-PanIN harboured KRAS mutations in 94% of the lesions; mutations in CDKN2A, TP53, and SMAD4 were not identified. These results suggest that inactivation of TP53 and SMAD4 are late genetic alterations, predominantly occurring in invasive PDAC. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: Implications for adjuvant therapy

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

Chen, Allen M.; Granchi, Phillip J.; Garcia, Joaquin

2007-03-15

Purpose: To determine factors predictive of local-regional recurrence (LRR) after surgery alone for carcinomas of the major salivary glands in an attempt to evaluate the potential role of postoperative radiation therapy. Methods and Materials: Between 1960 and 2004, 207 patients with carcinomas of the major salivary glands were treated with definitive surgery without postoperative radiation therapy. Histology was: 67 mucoepidermoid (32%), 50 adenoid cystic (24%), 34 acinic cell (16%), 23 malignant mixed (11%), 16 adenocarcinoma (8%), 6 oncocytic (3%), 6 myoepithelial (3%), and 5 other (2%). Distribution of pathologic T-stage was: 54 T1 (26%), 83 T2 (40%), 46 T3 (22%),more » and 24 T4 (12%). Sixty patients (29%) had microscopically positive margins. Median follow-up was 6.1 years (range, 0.5-18.7 years). Results: The 5-year and 10-year estimates of local-regional control were 86% and 74%, respectively. A Cox proportional hazard model identified pathologic lymph node metastasis (hazard ratio [HR], 4.8; p = 0.001), high histologic grade (HR, 4.2; p = 0.003), positive margins (HR, 2.6; p = 0.03), and T3-4 disease (HR, 2.0; p = 0.04) as independent predictors of LRR. The presence of any one of these factors was associated with 10-year local-regional control rates of 37% to 63%. Conclusion: Lymph node metastasis, high tumor grade, positive margins, and T3-4 stage predict for significant rates of LRR after surgery for carcinomas of the major salivary glands. Postoperative radiation therapy should be considered for patients with these disease characteristics.« less

Standardizing of Pathology in Patients Receiving Neoadjuvant Chemotherapy.

PubMed

Bossuyt, Veerle; Symmans, W Fraser

2016-10-01

The use of neoadjuvant systemic therapy for the treatment of breast cancer patients is increasing. Pathologic response in the form of pathologic complete response (pCR) and grading systems of partial response, such as the residual cancer burden (RCB) system, gives valuable prognostic information for patients and is used as a primary endpoint in clinical trials. The breast cancer and pathology communities are responding with efforts to standardize pathology in patients receiving neoadjuvant chemotherapy. In this review, we summarize the challenges that postneoadjuvant systemic therapy surgical specimens pose and how pathologists and the multidisciplinary team can work together to optimize handling of these specimens. Multidisciplinary communication is essential. A single, standardized approach to macroscopic and microscopic pathologic examination makes it possible to provide reliable response information. This approach employs a map of tissue sections to correlate clinical, gross, microscopic, and imaging findings in order to report the presence of pCR (ypT0 ypN0 and ypT0/is ypN0) versus residual disease, the ypT and ypN stage using the current AJCC/UICC staging system, and the RCB.

[Observation on twins of cosmic radiation influence as a risk factor].

PubMed

Vişănescu, Magdalena

2009-01-01

During flight, cosmic radiation is capable to penetrate the walls of airplanes and produce mutations in human chromosomes. To evaluate the correlations between cosmic radiation and the pathology of flying personnel. Two twin patients, one with 15 years work as a flight crew member, and the other with regular work on the ground. The patients were examined clinically, biochemically and with imaging methods. The genetic and environmental contribution to their pathology was noted. The patient, working in flight, received additional genetic tests to refute or to confirm the presence of chromosome alterations induced by the cosmic radiation. The patient, member of the flight crew, presented hypercholesterolemia, more evident structure modifications of the mammary gland, but chromosome alterations were not present. Having a first grade relative with dyslipidemia and uterine cancer, the structural or blood homeostasis modifications of the flight crew member can be either due to a high, genetically transmitted, susceptibility to the effects of the plane's microclimate and possibly to effects of lifestyle.

What drives osteoarthritis?-synovial versus subchondral bone pathology.

PubMed

Hügle, Thomas; Geurts, Jeroen

2017-09-01

Subchondral bone and the synovium play an important role in the initiation and progression of OA. MRI often permits an early detection of synovial hypertrophy and bone marrow lesions, both of which can precede cartilage damage. Newer imaging modalities including CT osteoabsorptiometry and hybrid SPECT-CT have underlined the importance of bone in OA pathogenesis. The subchondral bone in OA undergoes an uncoupled remodelling process, which is notably characterized by macrophage infiltration and osteoclast formation. Concomitant increased osteoblast activity leads to spatial remineralization and osteosclerosis in end-stage disease. A plethora of metabolic and mechanical factors can lead to synovitis in OA. Synovial tissue is highly vascularized and thus exposed to systemic influences such as hypercholesterolaemia or low grade inflammation. This review aims to describe the current understanding of synovitis and subchondral bone pathology and their connection in OA. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

In vivo light scattering for the detection of cancerous and precancerous lesions of the cervix

PubMed Central

Mourant, Judith R.; Powers, Tamara M.; Bocklage, Thérese J.; Greene, Heather M.; Dorin, Maxine H.; Waxman, Alan G.; Zsemlye, Meggan M.; Smith, Harriet O.

2009-01-01

A non-invasive optical diagnostic system for detection of cancerous and precancerous lesions of the cervix was evaluated, in vivo. The optical system included a fiber optic probe designed to measure polarized and unpolarized light transport properties of a small volume of tissue. An algorithm for diagnosing tissue based on the optical measurements was developed which used four optical properties, three of which were related to light scattering properties and the fourth of which was related to hemoglobin concentration. A sensitivity of ∼77% and specificities in the mid 60's were obtained for separating high grade squamous intraepithelial lesions and cancer from other pathologies and normal tissue. The use of different cross-validation methods in algorithm development is analyzed and the relative difficulties of diagnosing certain pathologies is assessed. Furthermore, the robustness of the optical system for use by different doctors and to changes in fiber optic probe were also assessed and potential improvements in the optical system are discussed. PMID:19340117

Gut microbiota: A player in aging and a target for anti-aging intervention.

PubMed

Vaiserman, Alexander M; Koliada, Alexander K; Marotta, Francesco

2017-05-01

Aging-associated alterations in composition, diversity and functional features of intestinal microbiota are well-described in the modern literature. They are suggested to be caused by an age-related decline in immune system functioning (immunosenescence) and a low-grade chronic inflammation (inflammaging), which accompany many aging-associated pathologies. The microbiota-targeted dietary and probiotic interventions have been shown to favorably affect the host health and aging by an enhancement of antioxidant activity, improving immune homeostasis, suppression of chronic inflammation, regulation of fat deposition and metabolism and prevention of insulin resistance. Recently, a high effectiveness and safety of novel therapeutic application such as fecal microbiota transplantation in the prevention and treatment of age-related pathological conditions including atherosclerosis, type 2 diabetes and Parkinson's disease has been demonstrated. In this review, recent research findings are summarized on the role of gut micribiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in anti-aging medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

Examination of concomitant glenohumeral pathologies in patients treated arthroscopically for calcific tendinitis of the shoulder and implications for routine diagnostic joint exploration.

PubMed

Lang, Gernot; Izadpanah, Kaywan; Kubosch, Eva Johanna; Maier, Dirk; Südkamp, Norbert; Ogon, Peter

2017-11-21

Glenohumeral exploration is routinely performed during arthroscopic removal of rotator cuff calcifications in patients with calcific tendinitis of the shoulder (CTS). However, evidence on the prevalence of intraarticular co-pathologies is lacking and the benefit of glenohumeral exploration remains elusive. The aim of the present study was to assess and quantify intraoperative pathologies during arthroscopic removal of rotator cuff calcifications in order to determine whether standardized diagnostic glenohumeral exploration appears justified in CTS patients. One hundred forty five patients undergoing arthroscopic removal of calcific depots (CD) that failed conservative treatment were included in a retrospective cohort study. Radiographic parameters including number/localization of calcifications and acromial types, intraoperative arthroscopic findings such as configuration of glenohumeral ligaments, articular cartilage injuries, and characteristics of calcifications and sonographic parameters (characteristics/localization of calcification) were recorded. One hundred forty five patients were analyzed. All CDs were removed by elimination with a blunt hook probe via "squeeze-and-stir-technique" assessed postoperatively via conventional X-rays. Neither subacromial decompression nor refixation of the rotator cuff were performed in any patient. Prevalence of glenohumeral co-pathologies, such as partial tears of the proximal biceps tendon (2.1%), superior labral tears from anterior to posterior (SLAP) lesions (1.4%), and/or partial rotator cuff tears (0.7%) was low. Most frequently, glenohumeral articular cartilage was either entirely intact (ICRS grade 0 (humeral head/glenoid): 46%/48%) or showed very mild degenerative changes (ICRS grade 1: 30%/26%). Two patients (1.3%) required intraarticular surgical treatment due to a SLAP lesion type III (n = 1) and an intraarticular rupture of CD (n = 1). Routine diagnostic glenohumeral exploration does not appear beneficial in arthroscopic treatment of CTS due to the low prevalence of intraarticular pathologies which most frequently do not require surgical treatment. Exploration of the glenohumeral joint in arthroscopic removal of CD should only be performed in case of founded suspicion of relevant concomitant intraarticular pathologies.

Nomograms for Prediction of Outcome With or Without Adjuvant Radiation Therapy for Patients With Endometrial Cancer: A Pooled Analysis of PORTEC-1 and PORTEC-2 Trials

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

Creutzberg, Carien L., E-mail: c.l.creutzberg@lumc.nl; Stiphout, Ruud G.P.M. van; Nout, Remi A.

Background: Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required. Methods and Materials: Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240). For most patients (86%) pathology review data were available; otherwise original pathology data were used. Trial variablesmore » which were clinically relevant and eligible according to data constraints were age, stage, given treatment (pelvic external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), or no adjuvant treatment, FIGO histological grade, depth of invasion, and lymph-vascular invasion (LVSI). Multivariate analyses were based on Cox proportional hazards regression model. Predictors were selected based on a backward elimination scheme. Model results were expressed by the c-index (0.5-1.0; random to perfect prediction). Two validation sets (n=244 and 291 patients) were used. Results: Accuracy of the developed models was good, with training accuracies between 0.71 and 0.78. The nomograms validated well for DR (0.73), DFS (0.69), and OS (0.70), but validation was only fair for LRR (0.59). Ranking of variables as to their predictive power showed that age, tumor grade, and LVSI were highly predictive for all outcomes, and given treatment for LRR and DFS. The nomograms were able to significantly distinguish low- from high-probability patients for these outcomes. Conclusions: The nomograms are internally validated and able to accurately predict long-term outcome for endometrial cancer patients with observation, pelvic EBRT, or VBT after surgery. These models facilitate decision support in daily clinical practice and can be used for patient counseling and shared decision making, selecting patients who benefit most from adjuvant treatment, and generating new hypotheses.« less

Chromosome 3 Anomalies Investigated by Genome Wide SNP Analysis of Benign, Low Malignant Potential and Low Grade Ovarian Serous Tumours

PubMed Central

Birch, Ashley H.; Arcand, Suzanna L.; Oros, Kathleen K.; Rahimi, Kurosh; Watters, A. Kevin; Provencher, Diane; Greenwood, Celia M.; Mes-Masson, Anne-Marie; Tonin, Patricia N.

2011-01-01

Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive from LMP tumours. PMID:22163003

Chromosome 3 anomalies investigated by genome wide SNP analysis of benign, low malignant potential and low grade ovarian serous tumours.

PubMed

Birch, Ashley H; Arcand, Suzanna L; Oros, Kathleen K; Rahimi, Kurosh; Watters, A Kevin; Provencher, Diane; Greenwood, Celia M; Mes-Masson, Anne-Marie; Tonin, Patricia N

2011-01-01

Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive from LMP tumours.

Use of mutation profiles to refine the classification of endometrial carcinomas.

PubMed

McConechy, Melissa K; Ding, Jiarui; Cheang, Maggie Cu; Wiegand, Kimberly; Senz, Janine; Tone, Alicia; Yang, Winnie; Prentice, Leah; Tse, Kane; Zeng, Thomas; McDonald, Helen; Schmidt, Amy P; Mutch, David G; McAlpine, Jessica N; Hirst, Martin; Shah, Sohrab P; Lee, Cheng-Han; Goodfellow, Paul J; Gilks, C Blake; Huntsman, David G

2012-09-01

The classification of endometrial carcinomas is based on pathological assessment of tumour cell type; the different cell types (endometrioid, serous, carcinosarcoma, mixed, undifferentiated, and clear cell) are associated with distinct molecular alterations. This current classification system for high-grade subtypes, in particular the distinction between high-grade endometrioid (EEC-3) and serous carcinomas (ESC), is limited in its reproducibility and prognostic abilities. Therefore, a search for specific molecular classifiers to improve endometrial carcinoma subclassification is warranted. We performed target enrichment sequencing on 393 endometrial carcinomas from two large cohorts, sequencing exons from the following nine genes: ARID1A, PPP2R1A, PTEN, PIK3CA, KRAS, CTNNB1, TP53, BRAF, and PPP2R5C. Based on this gene panel, each endometrial carcinoma subtype shows a distinct mutation profile. EEC-3s have significantly different frequencies of PTEN and TP53 mutations when compared to low-grade endometrioid carcinomas. ESCs and EEC-3s are distinct subtypes with significantly different frequencies of mutations in PTEN, ARID1A, PPP2R1A, TP53, and CTNNB1. From the mutation profiles, we were able to identify subtype outliers, ie cases diagnosed morphologically as one subtype but with a mutation profile suggestive of a different subtype. Careful review of these diagnostically challenging cases suggested that the original morphological classification was incorrect in most instances. The molecular profile of carcinosarcomas suggests two distinct mutation profiles for these tumours: endometrioid-type (PTEN, PIK3CA, ARID1A, KRAS mutations) and serous-type (TP53 and PPP2R1A mutations). While this nine-gene panel does not allow for a purely molecularly based classification of endometrial carcinoma, it may prove useful as an adjunct to morphological classification and serve as an aid in the classification of problematic cases. If used in practice, it may lead to improved diagnostic reproducibility and may also serve to stratify patients for targeted therapeutics. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Experimental Actinobacillus pleuropneumoniae challenge in swine: Comparison of computed tomographic and radiographic findings during disease

PubMed Central

2012-01-01

Background In pigs, diseases of the respiratory tract like pleuropneumonia due to Actinobacillus pleuropneumoniae (App) infection have led to high economic losses for decades. Further research on disease pathogenesis, pathogen-host-interactions and new prophylactic and therapeutic approaches are needed. In most studies, a large number of experimental animals are required to assess lung alterations at different stages of the disease. In order to reduce the required number of animals but nevertheless gather information on the nature and extent of lung alterations in living pigs, a computed tomographic scoring system for quantifying gross pathological findings was developed. In this study, five healthy pigs served as control animals while 24 pigs were infected with App, the causative agent of pleuropneumonia in pigs, in an established model for respiratory tract disease. Results Computed tomographic (CT) findings during the course of App challenge were verified by radiological imaging, clinical, serological, gross pathology and histological examinations. Findings from clinical examinations and both CT and radiological imaging, were recorded on day 7 and day 21 after challenge. Clinical signs after experimental App challenge were indicative of acute to chronic disease. Lung CT findings of infected pigs comprised ground-glass opacities and consolidation. On day 7 and 21 the clinical scores significantly correlated with the scores of both imaging techniques. At day 21, significant correlations were found between clinical scores, CT scores and lung lesion scores. In 19 out of 22 challenged pigs the determined disease grades (not affected, slightly affected, moderately affected, severely affected) from CT and gross pathological examination were in accordance. Disease classification by radiography and gross pathology agreed in 11 out of 24 pigs. Conclusions High-resolution, high-contrast CT examination with no overlapping of organs is superior to radiography in the assessment of pneumonic lung lesions after App challenge. The new CT scoring system allows for quantification of gross pathological lung alterations in living pigs. However, computed tomographic findings are not informative of the etiology of respiratory disease. PMID:22546414

High-Dose Ursodeoxycholic Acid Is Associated With the Development of Colorectal Neoplasia in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

PubMed Central

Eaton, John E.; Silveira, Marina G.; Pardi, Darrell S.; Sinakos, Emmanouil; Kowdley, Kris V.; Luketic, Velimir A.C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Lindor, Keith D.

2011-01-01

OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28–30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30–20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC. PMID:21556038

A pragmatic clinicopathobiological grouping/staging system for gliomas: proposal of the Indian TNM subcommittee on brain tumors.

PubMed

Gupta, Tejpal; Sarin, Rajiv; Jalali, Rakesh; Sharma, Suash; Kurkure, Purna; Goel, Atul

2009-01-01

There is no universally accepted staging system for primary brain tumors wherein prognostication is mainly based on complex composite indices. To develop a simple, pragmatic, and widely applicable grouping/staging system for gliomas, the most common primary brain tumor. An expert neurooncology panel with representation from radiation oncology, neurosurgery, pathology, radiology, and medical oncology had several rounds of discussion on issues pertinent to brain tumor staging. The trade off was between the accuracy of prognostic categorization and a pragmatic, widely applicable approach. The Tumor-Node-Metastasis staging was considered irrelevant for gliomas that seldom metastasize to lymphatics or outside the neuraxis. Instead, a 4-point staging/grouping system is proposed, using histological grade as the main prognostic variable and at least one stage migration based on other unfavorable features such as tumor location (brainstem); age (<5 years for all grades, >50 years for high-grade, and >40 years for low-grade gliomas); poor neurological performance status (NPS 2-4); multicentricity and/or gliomatosis; and adverse biological parameters (proliferative index, angiogenesis markers, apoptotic index, cytogenetic abnormalities, and molecular markers). In absence of a grouping/staging system for primary brain tumors, prognostification is mostly based on complex composite indices. The proposed clinicopathobiological grouping/staging system for gliomas is a simple, pragmatic, and user-friendly tool with a potential to fulfill the objectives of staging classification.

Analysis of E2 gene integrity in HPV16 and HPV58 viruses isolated from women with cervical pathology

PubMed Central

González-Losa, María del R; Puerto-Solis, Marylin; Tenorio Ruiz, Juan; Rosado-López, Ariel I; Hau-Aviles, Oscar; Ayora-Talavera, Guadalupe; Cisneros-Cutz, Isidro; Conde-Ferráez, Laura

2016-01-01

Integration of human papillomavirus (HPV) DNA into human cells accompanied by the disruption of the viral genome has been described as a prerequisite for cancer development. This study aimed to investigate E2 gene integrity of HPV16 and HPV58 viruses isolated from infected women with cervical lesions. Forty-two HPV16- and 31 HPV58-positive samples were analysed. E2 integrity was assumed when all fragments covering the E2 gene were amplified with specific polymerase chain reaction primers. Overall, in 59% of the samples, at least one fragment was not amplified in HPV16- (57%) and HPV58-positive samples (61%). Samples from high-grade squamous intraepithelial lesions had the highest frequency of E2 gene disruptions (73%), followed by samples from low-grade squamous intraepithelial lesions (63%) and, finally, samples from invasive cervical cancer (35%). Association between the integrity status of the E2 gene, and lesion grade was assessed by the chi-squared test applied to the combined set of viruses (p = 0.6555) or to populations of the same virus type (HPV58, p = 0.3101; HPV16, p = 0.3024). In conclusion, in this study, no association was found between the presence of E2 gene disruptions and the grade of cervical lesions caused by HPV16 and HPV58. PMID:27812600

Regular transition zone biopsy during active surveillance for prostate cancer may improve detection of pathological progression.

PubMed

Wong, Lih-Ming; Toi, Ants; Van der Kwast, Theodorus; Trottier, Greg; Alibhai, Shabbir M H; Timilshina, Narhari; Evans, Andrew; Zlotta, Alexandre; Fleshner, Neil; Finelli, Antonio

2014-10-01

We investigated the frequency of cancer and pathological progression in transition zone biopsies in men undergoing multiple rebiopsies while on active surveillance. Eligibility criteria of the active surveillance prostate cancer database (1997 to 2012) at our tertiary center includes prostate specific antigen 10 ng/ml or less, cT2 or less, no Gleason grade 4 or 5, 3 or fewer positive cores, no core with greater than 50% involvement, patient age 75 years or less and 1 or more biopsies after initial diagnostic biopsy. We excluded from analysis men with fewer than 10 cores at diagnostic biopsy and/or confirmatory biopsy greater than 24 months after diagnostic biopsy. Multiparametric magnetic resonance imaging was performed selectively to investigate incongruity between prostate specific antigen and biopsy findings. Pathological progression was defined by grade and/or volume (greater than 50% of core involved). Transition zone progression was subdivided into exclusively transition zone and combined transition zone (transition and peripheral zones). A multivariate Cox proportional hazards model was used to determine predictors of transition zone progression. A total of 392 men were considered in analysis. Median followup was 45.5 months. At each biopsy during active surveillance (confirmatory biopsy to biopsy 5+) there were transition zone positive cores in 18.6% to 26.7% of cases, all transition zone progression in 5.9% to 11.1% and exclusively transition zone progression in 2.7% to 6.7%. Volume related progression was noted more frequently than grade related progression (24 vs 9 cases). Predictors of only transition zone progression were the maximum percent in a single core (HR 1.99, 95% CI 1.30-3.04, p = 0.002) and cancer on magnetic resonance imaging (HR 3.19, 95% CI 1.23-8.27, p = 0.02). Across multiple active surveillance biopsies 2.7% to 6.7% of men had only transition zone progression. We recommend that transition zone biopsy be considered in all men at confirmatory biopsy. Positive magnetic resonance imaging findings or a high percent of core involvement may subsequently be useful to identify patients at risk. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of the Diagnostic Accuracy of DSC- and Dynamic Contrast-Enhanced MRI in the Preoperative Grading of Astrocytomas.

PubMed

Nguyen, T B; Cron, G O; Perdrizet, K; Bezzina, K; Torres, C H; Chakraborty, S; Woulfe, J; Jansen, G H; Sinclair, J; Thornhill, R E; Foottit, C; Zanette, B; Cameron, I G

2015-11-01

Dynamic contrast-enhanced MR imaging parameters can be biased by poor measurement of the vascular input function. We have compared the diagnostic accuracy of dynamic contrast-enhanced MR imaging by using a phase-derived vascular input function and "bookend" T1 measurements with DSC MR imaging for preoperative grading of astrocytomas. This prospective study included 48 patients with a new pathologic diagnosis of an astrocytoma. Preoperative MR imaging was performed at 3T, which included 2 injections of 5-mL gadobutrol for dynamic contrast-enhanced and DSC MR imaging. During dynamic contrast-enhanced MR imaging, both magnitude and phase images were acquired to estimate plasma volume obtained from phase-derived vascular input function (Vp_Φ) and volume transfer constant obtained from phase-derived vascular input function (K(trans)_Φ) as well as plasma volume obtained from magnitude-derived vascular input function (Vp_SI) and volume transfer constant obtained from magnitude-derived vascular input function (K(trans)_SI). From DSC MR imaging, corrected relative CBV was computed. Four ROIs were placed over the solid part of the tumor, and the highest value among the ROIs was recorded. A Mann-Whitney U test was used to test for difference between grades. Diagnostic accuracy was assessed by using receiver operating characteristic analysis. Vp_ Φ and K(trans)_Φ values were lower for grade II compared with grade III astrocytomas (P < .05). Vp_SI and K(trans)_SI were not significantly different between grade II and grade III astrocytomas (P = .08-0.15). Relative CBV and dynamic contrast-enhanced MR imaging parameters except for K(trans)_SI were lower for grade III compared with grade IV (P ≤ .05). In differentiating low- and high-grade astrocytomas, we found no statistically significant difference in diagnostic accuracy between relative CBV and dynamic contrast-enhanced MR imaging parameters. In the preoperative grading of astrocytomas, the diagnostic accuracy of dynamic contrast-enhanced MR imaging parameters is similar to that of relative CBV. © 2015 by American Journal of Neuroradiology.

Classification and grading of muscle injuries: a narrative review

PubMed Central

Hamilton, Bruce; Valle, Xavier; Rodas, Gil; Til, Luis; Grive, Ricard Pruna; Rincon, Josep Antoni Gutierrez; Tol, Johannes L

2015-01-01

A limitation to the accurate study of muscle injuries and their management has been the lack of a uniform approach to the categorisation and grading of muscle injuries. The goal of this narrative review was to provide a framework from which to understand the historical progression of the classification and grading of muscle injuries. We reviewed the classification and grading of muscle injuries in the literature to critically illustrate the strengths, weaknesses, contradictions or controversies. A retrospective, citation-based methodology was applied to search for English language literature which evaluated or utilised a novel muscle classification or grading system. While there is an abundance of literature classifying and grading muscle injuries, it is predominantly expert opinion, and there remains little evidence relating any of the clinical or radiological features to an established pathology or clinical outcome. While the categorical grading of injury severity may have been a reasonable solution to a clinical challenge identified in the middle of the 20th century, it is time to recognise the complexity of the injury, cease trying to oversimplify it and to develop appropriately powered research projects to answer important questions. PMID:25394420

[Expression of ATAD2 in different liver lesions and its clinical significance].

PubMed

Liu, F; Zhou, X; Ji, H H; Li, H; Xiang, F G

2017-05-20

Objective: To examine the expression of ATAD2 in different liver lesions and its clinical significance. Methods: ATAD2 expression in 60 hepatocellular carcinoma (HCC) surgical specimens (49 of which have concurrent liver cirrhosis), 43 HCC biopsy specimens, 2 high-grade liver dysplastic nodule specimens, 3 low-grade liver dysplastic nodule specimens, 50 liver cirrhosis tissue samples, and 20 normal liver tissue samples were measured using immunohistochemistry. The F-test, q-test, t-test, and chi-square test were used for statistical analysis of data. Results: ATAD2 was expressed in 56 HCC surgical specimens (93.33%), 35 HCC biopsy specimens (81.40%), and 2 high-grade liver dysplastic nodule specimens (2/2), but not in the low-grade liver dysplastic nodule, liver cirrhosis tissue, and normal liver tissue samples. The mean expression of ATAD2 was significantly higher in HCC tissues than in high-grade and low-grade liver dysplastic nodule tissues, liver cirrhosis tissue, and normal liver tissue ( F = 22.96, q = 3.138, 3.972, 12.272, and 9.101, respectively, all P < 0.01). There were no significant differences in the mean expression and positive expression rate of ATAD2 between HCC surgical and biopsy specimens ( t = 1.40, P > 0.05; χ ² = 3.47, P >0.05). Of the 35 HCC biopsy specimens that expressed ATAD2, the mean ATAD2 expression was ≥1% in 35 specimens (100%), ≥3% in 27 specimens (77.14%), and ≥5 % in 23 specimens (65.71%). In addition, among the pathological grade I-II HCC biopsy specimens, the mean ATAD2 expression was ≥1% in 28 specimens (100%), ≥3% in 22 specimens (62.86%), and ≥5% in 19 specimens (54.29%). Moreover, ATAD2 expression in HCC was associated with serum alpha-fetoprotein level, presence of hepatitis B virus surface antigen (HBsAg), and presence of concurrent liver cirrhosis ( t = 2.09, 2.30, and 2.18, respectively, all P < 0.05). Conclusion: ATAD2 may play an important role in HCC tumorigenesis, and may be involved in malignant transformation of cells. ATAD2 expression can be a valuable marker for differentiating the nature of lesions in liver biopsy tissues during clinical practice.

Application of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2): Interobserver Agreement and Positive Predictive Value for Localization of Intermediate- and High-Grade Prostate Cancers on Multiparametric Magnetic Resonance Imaging.

PubMed

Chen, Frank; Cen, Steven; Palmer, Suzanne

2017-09-01

To evaluate interobserver agreement with the use of and the positive predictive value (PPV) of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) for the localization of intermediate- and high-grade prostate cancers on multiparametric magnetic resonance imaging (mpMRI). In this retrospective, institutional review board-approved study, 131 consecutive patients who had mpMRI followed by transrectal ultrasound-MR imaging fusion-guided biopsy of the prostate were included. Two readers who were blinded to initial mpMRI reports, clinical data, and pathologic outcomes reviewed the MR images, identified all prostate lesions, and scored each lesion based on the PI-RADS v2. Interobserver agreement was assessed by intraclass correlation coefficient (ICC), and PPV was calculated for each PI-RADS category. PI-RADS v2 was found to have a moderate level of interobserver agreement between two readers of varying experience, with ICC of 0.74, 0.72, and 0.67 for all lesions, peripheral zone lesions, and transitional zone lesions, respectively. Despite only moderate interobserver agreement, the calculated PPV in the detection of intermediate- and high-grade prostate cancers for each PI-RADS category was very similar between the two readers, with approximate PPV of 0%, 12%, 64%, and 87% for PI-RADS categories 2, 3, 4, and 5, respectively. In our study, PI-RADS v2 has only moderate interobserver agreement, a similar finding in studies of the original PI-RADS and in initial studies of PI-RADS v2. Despite this, PI-RADS v2 appears to be a useful system to predict significant prostate cancer, with PI-RADS scores correlating well with the likelihood of intermediate- and high-grade cancers. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

ART and uterine pathology: how relevant is the maternal side for implantation?

PubMed

Galliano, Daniela; Bellver, José; Díaz-García, César; Simón, Carlos; Pellicer, Antonio

2015-01-01

Assisted reproduction technology (ART) has become a standard treatment for infertile couples. Increased success rates obtained over the years have resulted primarily from improved embryo quality, but implantation rates still remain lower than expected. The uterus, an important player in implantation, has been frequently neglected. While a number of uterine pathologies have been associated with decreased natural fertility, less information exists regarding the impact of these pathologies in ART. This report reviews the evidence to help clinicians advise ART patients. An electronic search of PubMed and EMBASE was performed to identify articles in the English, French or Spanish language published until May 2014 which addressed uterine pathology and ART. Data from natural conception were used only in the absence of data from ART. Studies were classified in decreasing categories: RCTs, prospective controlled trials, prospective non-controlled trials, retrospective studies and experimental studies. Studies included in lower categories were only used if insufficient evidence was available. Pooled data were obtained from systematic reviews with meta-analyses when available. The summary of the evidence for the different outcomes and the degree of the recommendation for interventions were based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) statement recommendations. There is strong evidence that surrogacy is effective for uterine agenesia. For the remaining pathologies, however, there is very little evidence that the established treatments improve outcomes, or that these pathologies have a negative effect on ART. In the presence of an apparently normal uterus, assessing endometrial receptivity (ER) is the goal; however diagnostic tests are still under development. The real effect of different uterine/endometrial integrity pathologies on ART is not known. Moreover, currently proposed treatments are not based on solid evidence, and little can be done to assess ER in normal or abnormal conditions. No strong recommendations can be given based on the published experience, bringing an urgent need for well-designed studies. In this context, we propose algorithms to study the uterus in ART. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bone Sarcoma Pathology: Diagnostic Approach for Optimal Therapy.

PubMed

Rosenberg, Andrew E

2017-01-01

The pathologic interpretation of malignant bone tumors is one of the more challenging areas in surgical pathology. This is based on the reality that primary bone sarcomas are uncommon, demonstrate significant morphologic heterogeneity, and have a broad spectrum of biology. Accordingly, it is difficult for pathologists to acquire the necessary experience to confidently and accurately diagnose bone sarcomas. The task is further complicated by the fact that it requires the integration of clinical and radiologic information into the diagnostic process. Lastly, molecular aberrations in sarcomas are being newly discovered and their identification is often critical to make specific diagnoses. The pathologist's role in guiding optimal treatment in biopsy specimens is to make an accurate diagnosis and provide the grade and molecular aberrations when appropriate. The pathology report of resected tumors must confirm this information and assess the surgical resection margins and the percentage of necrosis if the sarcoma has been treated with neoadjuvant systemic therapy.

Dynamic prognostication using conditional survival analysis for patients with operable lung adenocarcinoma

PubMed Central

Kim, Wooil; Lee, Ho Yun; Jung, Sin-Ho; Woo, Min-Ah; Kim, Hong Kwan; Choi, Yong Soo; Kim, Jhingook; Zo, Jae Ill; Shim, Young Mog; Han, Joungho; Jeong, Ji Yun; Choi, Joon Young; Lee, Kyung Soo

2017-01-01

Purpose To evaluate conditional survival among patients with surgically resected stage I-IIIa lung adenocarcinoma and identify changes in prognostic contributions for various prognostic factors over time. Patients and Methods We performed conditional survival analysis at each t0 (=0, 1, 2, 3, 4, 5 years) for 723 consecutive patients who underwent surgical resection for lung adenocarcinoma, stratified by various clinico-demographic features, as well as pathologic and imaging (tumor-shadow disappearance ratio [TDR] on CT and maximum standardized uptake value [SUVmax] on PET) characteristics. Uni- and multivariableCox regression analyses were performed to evaluate relationships between those variables and conditional survival. Results Three-year conditional overall survival (OS) and disease-free survival (DFS) were 92.12% and 75.51% at baseline, but improved steadily up to 98.33% and 95.95% at 5 years after surgery. In contrast to demographic factors, pathologic (stage, subtype, pathologic grade and differentiation) and radiologic factors (TDR and SUVmax) maintained a statistically significant association with subseqeunt 3-year OS until 3 years after surgery. According to the multivariableanalysis, high SUVmax and low TDR value were independent predictors of subsequent 3-year OS and DFS at baseline, 1 and 2 years after surgery, respectively. Conclusion Our findings based on CS provide theoretical background for clinicians to plan longer period of surveillance following lung adenocarcinoma resection in survivors with preoperatively high SUVmax and low TDR on PET-CT and chest CT, respectively. PMID:27793026

HGNET-BCOR Tumors of the Cerebellum: Clinicopathologic and Molecular Characterization of 3 Cases.

PubMed

Appay, Romain; Macagno, Nicolas; Padovani, Laetitia; Korshunov, Andrey; Kool, Marcel; André, Nicolas; Scavarda, Didier; Pietsch, Torsten; Figarella-Branger, Dominique

2017-09-01

The central nervous system (CNS) high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR) is a recently described molecular entity. We report 3 new CNS HGNET-BCOR cases sharing common clinical presentation and pathologic features. The 3 cases concerned children aged 3 to 7 years who presented with a voluminous mass of the cerebellum. Pathologic features included proliferation of uniform spindle to ovoid cells with fine chromatin associated with a rich arborizing capillary network. Methylation profiling classified these cases as CNS HGNET-BCOR tumors. Polymerase chain reaction analysis confirmed the presence of internal tandem duplications in the C-terminus of BCOR (BCOR-ITD), a characteristic of these tumors, in all 3 cases. Immunohistochemistry showed a strong nuclear BCOR expression. In 2 cases, local recurrence occurred within 6 months. The third case, a patient who received a craniospinal irradiation after total surgical removal followed by a metronomics maintenance with irinotecan, temozolomide, and itraconazole, is still free of disease 14 months after diagnosis. In summary, CNS HGNET-BCOR represents a rare tumor occurring in young patients with dismal prognosis. BCOR nuclear immunoreactivity is highly suggestive of a BCOR-ITD. Whether CNS HGNET-BCOR should be classified among the category of "embryonal tumors" or within the category of "mesenchymal, nonmeningothelial tumors" remains to be clarified. Because CNS HGNET-BCOR share pathologic features and characteristic BCOR-ITD with clear cell sarcoma of the kidney, these tumors may represent local variants of the same entity.

PRP For the Treatment of Cartilage Pathology

PubMed Central

Kon, Elizaveta; Filardo, Giuseppe; Di Matteo, Berardo; Marcacci, Maurilio

2013-01-01

In recent years biological strategies are being more widely used to treat cartilage lesions. One of the most exploited novel treatments is Platelet-rich Plasma (PRP), whose high content of growth factors is supposed to determine a regenerative stimulus to cartilaginous tissue. Despite many promising in vitro and in vivo studies, when discussing clinical application a clear indication for the use of PRP cannot be assessed. There are initial encouraging clinical data, but only a few randomized controlled trials have been published, so it is not possible to fully endorse this kind of approach for the treatment of cartilage pathology. Furthermore, study comparison is very difficult due to the great variability in PRP preparation methods, cell content and concentration, storage modalities, activation methods and even application protocols. These factors partially explain the lack of high quality controlled trials up to now. This paper discusses the main aspects concerning the basic biology of PRP, the principal sources of variability, and summarizes the available literature on PRP use, both in surgical and conservative treatments. Based on current evidence, PRP treatment should only be indicated for low-grade cartilage degeneration and in case of failure of more traditional conservative approaches. PMID:23730375

Impact of Primary Gleason Grade on Risk Stratification for Gleason Score 7 Prostate Cancers

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

Koontz, Bridget F., E-mail: bridget.koontz@duke.edu; Tsivian, Matvey; Mouraviev, Vladimir

Purpose: To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. Methods: One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Results: Nine hundred seventy-nine patientsmore » had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Conclusions: Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities.« less

Impact of primary Gleason grade on risk stratification for Gleason score 7 prostate cancers.

PubMed

Koontz, Bridget F; Tsivian, Matvey; Mouraviev, Vladimir; Sun, Leon; Vujaskovic, Zeljko; Moul, Judd; Lee, W Robert

2012-01-01

To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Nine hundred seventy-nine patients had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities. Copyright © 2012 Elsevier Inc. All rights reserved.

Mucinous cystic neoplasms of the pancreas: update on the surgical pathology and molecular genetics.

PubMed

Fukushima, Noriyoshi; Zamboni, Giuseppe

2014-11-01

Mucinous cystic neoplasms (MCNs) of the pancreas are primary pancreatic cyst-forming neoplasms that can be a precursor to invasive adenocarcinoma of the pancreas. MCNs occur almost exclusively in the distal pancreas of middle-aged women. MCNs typically show a "cyst-in-cyst" pattern of growth and are well encapsulated by a thick fibrous wall. MCNs are composed of mucin-producing neoplastic epithelial cells and "ovarian-type" subepithelial stroma. The epithelium is dysplastic and the grade can range from low to high grade; some MCNs have an associated invasive carcinoma. It is this associated invasive carcinoma that determines prognosis. MCNs harbor several characteristic genetic and epigenetic alterations, some of which are shared with conventional invasive pancreatic ductal adenocarcinoma. Furthermore, several studies reveal characteristic patterns of gene expression in the ovarian-type stroma that suggest steroidogenesis in the ovarian-type stroma. Better knowledge of the molecular alterations could help in the management of patients with this type of precursor of invasive carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

Barrett’s Esophagus: Frequency and Prediction of Dysplasia and Cancer

PubMed Central

Falk, Gary W.

2015-01-01

The incidence of esophageal adenocarcinoma is continuing to increase at an alarming rate in the Western world today. Barrett’s esophagus is a clearly recognized risk factor for the development of esophageal adenocarcinoma, but the overwhelming majority of patients with Barrett’s esophagus will never develop esophageal cancer. A number of endoscopic, histologic and epidemiologic risk factors identify Barrett’s esophagus patients at increased risk for progression to high-grade dysplasia and esophageal adenocarcinoma. Endoscopic factors include segment length, mucosal abnormalities as seemingly trivial as esophagitis and the 12 to 6 o’clock hemisphere of the esophagus. Both intestinal metaplasia and low grade dysplasia, the latter only if confirmed by a pathologist with expertise in Barrett’s esophagus pathologic interpretation are the histologic risk factors for progression. Epidemiologic risk factors include aging, male gender, obesity, and smoking. Factors that may protect against the development of adenocarcinoma include a diet rich in fruits and vegetables, and the use of proton pump inhibitors, aspirin/NSAIDs and statins. PMID:25743461

Barrett's oesophagus: frequency and prediction of dysplasia and cancer.

PubMed

Falk, Gary W

2015-02-01

The incidence of oesophageal adenocarcinoma is continuing to increase at an alarming rate in the Western world today. Barrett's oesophagus is a clearly recognized risk factor for the development of oesophageal adenocarcinoma, but the overwhelming majority of patients with Barrett's oesophagus will never develop oesophageal cancer. A number of endoscopic, histologic and epidemiologic risk factors identify Barrett's oesophagus patients at increased risk for progression to high-grade dysplasia and oesophageal adenocarcinoma. Endoscopic factors include segment length, mucosal abnormalities as seemingly trivial as oesophagitis and the 12 to 6 o'clock hemisphere of the oesophagus. Both intestinal metaplasia and low grade dysplasia, the latter only if confirmed by a pathologist with expertise in Barrett's oesophagus pathologic interpretation are the histologic risk factors for progression. Epidemiologic risk factors include ageing, male gender, obesity, and smoking. Factors that may protect against the development of adenocarcinoma include a diet rich in fruits and vegetables, and the use of proton pump inhibitors, aspirin/NSAIDs and statins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mucinous Cystic Neoplasms Lined by Abundant Mucinous Epithelium Frequently Involve KRAS Mutations and Malignant Progression.

PubMed

Shibata, Hideki; Ohike, Nobuyuki; Norose, Tomoko; Isobe, Tomohide; Suzuki, Reika; Imai, Hideyuki; Shiokawa, Akira; Aoki, Takeshi; Murakami, Masahiko; Mizukami, Hiroki; Tanaka, Jun-Ichi; Takimoto, Masafumi

2017-12-01

Pancreatic and hepatic mucinous cyst neoplasms (MCNs) have a malignant potential, but indolent MCNs are not uncommon. The pathological and genetic characteristics of resected MCNs (n=15) categorized by the amount of mucin of the lining epithelium were investigated. MCNs were divided into two groups: (i) a rich (r)-MCN group (n=6), in which more than half of the epithelium was lined by abundant mucinous epithelium; and (ii) a poor (p)-MCN group (n=9), which consisted of the remaining cases. Three patients in the r-MCN group showed invasive carcinoma or high-grade dysplasia, whereas all patients in the p-MCN group showed low-grade dysplasia. Mutations of Kirsten rat sarcoma viral oncogene homolog (KRAS) were more frequent in the r-MCN group (83%) (p-MCN; 11%, p<0.05). Mucinous MCNs more frequently have KRAS mutations and higher risk of malignant progression. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Pathological characterisation of male breast cancer: Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program.

PubMed

Vermeulen, Marijn A; Slaets, Leen; Cardoso, Fatima; Giordano, Sharon H; Tryfonidis, Konstantinos; van Diest, Paul J; Dijkstra, Nizet H; Schröder, Carolien P; van Asperen, Christi J; Linderholm, Barbro; Benstead, Kim; Foekens, Renee; Martens, John W M; Bartlett, John M S; van Deurzen, Carolien H M

2017-09-01

Several prognostic histological features have been established in female breast cancer (BC), but it is unknown whether these can be extrapolated to male BC patients. The aim of this study was to evaluate the prognostic value of several histological features in a large series of male BC. Central pathology review was performed for 1483 male BCs collected through part 1 of the European Organisation for Research and Treatment of Cancer (EORTC) International Male BC Program. Pathology review included histological subtype, grade, mitotic activity index (MAI), presence of a fibrotic focus and density of tumour-infiltrating lymphocytes (TILs). These features were correlated with clinical outcome. The relationship between these features and surrogate molecular subtypes using immunohistochemistry was also assessed. Median follow-up for overall survival (OS) was 7.1 years. Overall histological grade was not significantly associated with OS (p = 0.129). MAI, the presence of a fibrotic focus and a low TIL density however were correlated with unfavourable OS (p = 0.023, p = 0.004 and p = 0.011, respectively). BC subtype correlated with TIL density (p = 0.015), as we observed a higher density for human epidermal growth factor receptor type 2 (HER2) positive BC compared to luminal HER2-negative subtype. No association was observed between subtype and fibrotic focus. Histologic grade was not significantly correlated with clinical outcome in this series, unlike what is seen in female patients. These results contribute to our understanding of male BC and indicate the importance of further research on the optimisation of risk stratification and treatment decisions for male BC patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Variation in nuclear size and PD-L2 positivity correlate with aggressive chromophobe renal cell carcinoma.

PubMed

Mostafa, Mohamed E; Abdelkader, Amrou; Kuroda, Naoto; Pérez-Montiel, Delia; Banerjee, Anjishnu; Hes, Ondrej; Iczkowski, Kenneth A

2018-06-01

Chromophobe renal cell carcinoma (CRCC) is not amenable to International Society for Urologic Pathology-endorsed nucleolar grading. Novel grading approaches were proposed, but the rarity of adverse pathology hampers their discriminatory value. We investigate simple linear micrometer measurements and a proposed immunostain in CRCCs. 32 patients' CRCCs were studied: 12 adverse cases (stage pT3, recurrence, or metastasis), 15 controls (stage ≤pT2, no recurrence or metastasis after >3 years), and 8 metastases (3 were paired with primary adverse cases). The ratio of greatest dimensions of largest and smallest nuclei, in each of 5 "worst" high-power fields, excluding those with degenerative features, was designated variation in nuclear size (VNS). Percent multinucleate cells (PMC) were also counted. Mouse anti PD-L2 monoclonal antibody immunostaining was performed. Mean VNS measured in adverse primary and control primary tumors were 3.7 ± 0.5 and 2.4 ± 0.4 respectively (P < .001), and 3.4 ± 0.4 for metastases (P < .001). Optimal VNS cut-off was 2.5, with sensitivity and specificity 0.85 and 0.81, respectively. PMCs were 6.0 ± 3.0 for adverse group, 5.7 ± 2.7 for controls, and 4.1 ± 1.6 for metastases (P = NS). PD-L2 could not discriminate adverse versus good primary tumors (χ 2 1.6, P = .2), but was higher in metastases (χ 2 6.9, P < .01), or metastases plus adverse primary tumors (χ 2 4.8, P = .03), compared to good-pathology primary tumors. In conclusion, VNS is an easily obtained measurement that can predict adverse behavior of chromophobe RCC, and may impart value for needle biopsy reporting and the choice of active surveillance. PD-L2 was elevated in metastases but was less useful for primary tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

Phase II Study of Neoadjuvant Bevacizumab and Radiotherapy for Resectable Soft Tissue Sarcomas

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

Yoon, Sam S., E-mail: syoon@partners.org; Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, PA; Duda, Dan G.

Purpose: Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response. Methods and Materials: Patients with {>=}5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans. Results: The 20 patients had a median tumor sizemore » of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in {>=}80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73%, apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62-72% (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence. Conclusions: The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants additional investigation. Gene expression profiles and other tissue and circulating biomarkers showed promising correlations with treatment response.« less

Perinatal pathology: practice suggestions for limited-resource settings.

PubMed

Roberts, Drucilla J

2013-06-01

The practice of perinatal pathology in much of the world suffers, as do all subspecialties of anatomic pathology, from inadequate resources (equipment, consumables, and both professional and technical personnel), from lack of education (not only of the pathologist but also of the clinicians responsible for sending the specimens, and the technicians processing the specimens), and from lack of appropriate government sector support. Perinatal pathology has significant public health-related utility and should be championing its service by providing maternal and fetal/infant mortality and morbidity data to governmental health ministries. It is with this pathologic data that informed decisions can be made on health-related courses of action and allocation of resources. These perinatal pathology data are needed to develop appropriate public health initiatives, specifically toward achieving the Millennium Developmental Goals as the best way to effectively decrease infant and maternal deaths and to determine causes of perinatal mortality and morbidity. The following overview will focus on the utility of perinatal pathology specifically as related to its public health function and will suggest methods to improve its service in resource-poor settings. This article is offered not as a critique of the current practice that most pathologists find themselves working in globally, but to provide suggestions for improving perinatal pathology services, which could be implemented with the limited available resources and manpower most pathology departments currently have. In addition, we offer suggestions for graded improvements ("ramping up") over time.

Identification of Key Pathways and Genes in the Dynamic Progression of HCC Based on WGCNA.

PubMed

Yin, Li; Cai, Zhihui; Zhu, Baoan; Xu, Cunshuan

2018-02-14

Hepatocellular carcinoma (HCC) is a devastating disease worldwide. Though many efforts have been made to elucidate the process of HCC, its molecular mechanisms of development remain elusive due to its complexity. To explore the stepwise carcinogenic process from pre-neoplastic lesions to the end stage of HCC, we employed weighted gene co-expression network analysis (WGCNA) which has been proved to be an effective method in many diseases to detect co-expressed modules and hub genes using eight pathological stages including normal, cirrhosis without HCC, cirrhosis, low-grade dysplastic, high-grade dysplastic, very early and early, advanced HCC and very advanced HCC. Among the eight consecutive pathological stages, five representative modules are selected to perform canonical pathway enrichment and upstream regulator analysis by using ingenuity pathway analysis (IPA) software. We found that cell cycle related biological processes were activated at four neoplastic stages, and the degree of activation of the cell cycle corresponded to the deterioration degree of HCC. The orange and yellow modules enriched in energy metabolism, especially oxidative metabolism, and the expression value of the genes decreased only at four neoplastic stages. The brown module, enriched in protein ubiquitination and ephrin receptor signaling pathways, correlated mainly with the very early stage of HCC. The darkred module, enriched in hepatic fibrosis/hepatic stellate cell activation, correlated with the cirrhotic stage only. The high degree hub genes were identified based on the protein-protein interaction (PPI) network and were verified by Kaplan-Meier survival analysis. The novel five high degree hub genes signature that was identified in our study may shed light on future prognostic and therapeutic approaches. Our study brings a new perspective to the understanding of the key pathways and genes in the dynamic changes of HCC progression. These findings shed light on further investigations.

Detection of CCNE1/URI (19q12) amplification by in situ hybridisation is common in high grade and type II endometrial cancer

PubMed Central

Noske, Aurelia; Brandt, Simone; Valtcheva, Nadejda; Wagner, Ulrich; Zhong, Qing; Bellini, Elisa; Fink, Daniel; Obermann, Ellen C.; Moch, Holger; Wild, Peter J.

2017-01-01

One TCGA subgroup of endometrial cancer (EC) is characterised by extensive genomic DNA copy number alterations. CCNE1 located at 19q12 is frequently amplified in EC and a target for anti-cancer therapy. The relevance of URI, also located at 19q12, is unknown. To evaluate the prevalence of 19q12 (CCNE1/URI) in EC, we investigated different histologic types by in situ hybridisation (ISH) and copy number assay. We applied a previously established 19q12 ISH for the detection of CCNE1/URI copy numbers in EC (n = 270) using conventional bright field microscopy. In a subset (n = 21), 19q12 amplification status was validated by OncoScan assay. Manual ISH was controlled by a recently developed computational ISHProfiler algorithm. Associations of 19q12 status with Cyclin E1, URI and p53 expression, and clinico-pathological parameters were tested. Amplification of 19q12 (CCNE1/URI) was found in 10.4% (28/270) and was significantly associated with type II EC (high grade and non-endometrioid; p < 0.0001), advanced FIGO stage (p = 0.001), high Cyclin E1 expression (p = 0.008) and aberrant p53 expression (p = 0.04). 19q12 ISH data were confirmed by OncoScan and computational ISHProfiler techniques. The 19q12 in situ hybridisation is a feasible and robust biomarker assay in molecular pathology. Amplification of CCNE1/URI predominantly occurred in type II endometrial cancer. Prospective clinical trials are warranted to assess the utility of combined 19q12 amplification and Cyclin E1/URI protein expression analysis for the prediction of therapeutic response to chemotherapy and/or cyclin-dependent kinase inhibitors in patients with endometrial cancer. PMID:27582547

Metabolic syndrome and low high-density lipoprotein cholesterol are associated with adverse pathological features in patients with prostate cancer treated by radical prostatectomy.

PubMed

Lebdai, Souhil; Mathieu, Romain; Leger, Julie; Haillot, Olivier; Vincendeau, Sébastien; Rioux-Leclercq, Nathalie; Fournier, Georges; Perrouin-Verbe, Marie-Aimée; Doucet, Laurent; Azzouzi, Abdel Rahmene; Rigaud, Jérome; Renaudin, Karine; Charles, Thomas; Bruyere, Franck; Fromont, Gaelle

2018-02-01

Previous studies have suggested a link between metabolic syndrome (MetS) and prostate cancer (PCa). In the present study, we aimed to assess the association between MetS and markers of PCa aggressiveness on radical prostatectomy (RP). All patients consecutively treated for PCa by RP in 6 academic institutions between August 2013 and July 2016 were included. MetS was defined as at least 3 of 5 components (obesity, elevated blood pressure, diabetes, low high-density lipoprotein (HDL)-cholesterol, and hypertriglyceridemia). Demographic, biological, and clinical parameters were prospectively collected, including: age, biopsy results, preoperative serum prostate-specific antigen, surgical procedure, and pathological data of RP specimen. Locally advanced disease was defined as a pT-stage ≥3. International Society of Urological Pathology (ISUP) groups were used for pathological grading. Qualitative and quantitative variables were compared using chi-square and Wilcoxon tests; logistic regression analyses assessed the association of MetS and its components with pathological data. Statistical significance was defined as a P<0.05. Among 567 men, 249 (44%) had MetS. In a multivariate model including preoperative prostate-specific antigen, biopsy ISUP-score, clinical T-stage, age, and ethnicity: we found that MetS was an independent risk factor for positive margins, and ISUP group ≥4 on the RP specimen (odds ratio [OR] = 1.5; 95% CI: 1.1-2.3; P = 0.035; OR = 2.0; 95% CI: 1.1-4.0; P = 0.044, respectively). In addition, low HDL-cholesterol level was associated with locally advanced PCa (OR = 1.6; 95% CI: 1.1-2.4; P = 0.024). Risks of adverse pathological features increased with the number of MetS components: having ≥ 4 MetS components was significantly associated with higher risk of ISUP group ≥ 4 and higher risk of positive margins (OR = 1.9; 95% CI: 1.1-3.3; P = 0.017; OR = 1.8; 95% CI: 1.1-2.8; P = 0.007, respectively). MetS was an independent predictive factor for higher ISUP group and positive margins at RP. Low HDL-cholesterol alone, and having 4 and more MetS components were also associated with higher risk of adverse pathological features. Copyright © 2018. Published by Elsevier Inc.

Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

PubMed

Rice, Thomas W; Ishwaran, Hemant; Kelsen, David P; Hofstetter, Wayne L; Apperson-Hansen, Carolyn; Blackstone, Eugene H

2016-11-01

We report analytic and consensus processes that produced recommendations for neoadjuvant pathologic stage groups (ypTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 7,773 had pathologic assessment after neoadjuvant therapy. Risk-adjusted survival for each patient was developed. Random forest analysis identified data-driven neoadjuvant pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. An additional analysis produced data-driven anatomic neoadjuvant pathologic stage groups based only on ypT, ypN, and ypM categories. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus neoadjuvant pathologic stage groups. Grade and location were much less discriminating for stage grouping ypTNM than pTNM. Data-driven stage grouping without grade and location produced nearly identical groups for squamous cell carcinoma and adenocarcinoma. However, ypTNM groups and their associated survival differed from pTNM. The need for consensus process was minimal. The consensus groups, identical for both cell types were as follows: ypStage I comprised ypT0-2N0M0; ypStage II ypT3N0M0; ypStage IIIA ypT0-2N1M0; ypStage IIIB ypT3N1M0, ypT0-3N2, and ypT4aN0M0; ypStage IVA ypT4aN1-2, ypT4bN0-2, and ypTanyN3M0; and ypStage IVB ypTanyNanyM1. Absence of equivalent pathologic (pTNM) categories for the peculiar neoadjuvant pathologic categories ypTisN0-3M0 and ypT0N0-3M0, dissimilar stage group compositions, and markedly different early- and intermediate-stage survival necessitated a unified, unique set of stage grouping for patients of either cell type who receive neoadjuvant therapy. © 2016 International Society for Diseases of the Esophagus.

Protein kinase C zeta suppresses low‐ or high‐grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring

PubMed Central

Deevi, Ravi Kiran; Javadi, Arman; McClements, Jane; Vohhodina, Jekaterina; Savage, Kienan; Loughrey, Maurice Bernard; Evergren, Emma

2018-01-01

Abstract Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring. PKCz regulates interdependent processes that control centrosome positioning. Among these, interaction between the cytoskeletal linker protein ezrin and its binding partner NHERF1 promotes the formation of a localized cue for anchoring interphase centrosomes to the cell cortex. Perturbation of these phenomena induced different outcomes in cells with single or extra centrosomes. Defective anchoring of a single centrosome promoted bipolar spindle misorientation, multi‐lumen formation, and aberrant epithelial stratification. Collectively, these disturbances induce cribriform multicellular morphology that is typical of some categories of low‐grade CRC. By contrast, defective anchoring of extra centrosomes promoted multipolar spindle formation, chromosomal instability (CIN), disruption of glandular morphology, and cell outgrowth across the extracellular matrix interface characteristic of aggressive, high‐grade CRC. Because PKCz enhances apical NHERF1 intensity in 3D epithelial cultures, we used an immunohistochemical (IHC) assay of apical NHERF1 intensity as an indirect readout of PKCz activity in translational studies. We show that apical NHERF1 IHC intensity is inversely associated with multipolar spindle frequency and high‐grade morphology in formalin‐fixed human CRC samples. To conclude, defective PKCz control of interphase centrosome anchoring may underlie distinct categories of mitotic slippage that shape the development of low‐ or high‐grade CRC phenotypes. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:29520890

The incidence and effect of fatty atrophy, positive tangent sign, and rotator cuff tears on outcomes after total shoulder arthroplasty.

PubMed

Choate, W Stephen; Shanley, Ellen; Washburn, Richard; Tolan, Stefan J; Salim, Tariq I; Tadlock, Josh; Shealy, Elizabeth C; Long, Catherine D; Crawford, Ashley E; Kissenberth, Michael J; Lonergan, Keith T; Hawkins, Richard J; Tokish, John M

2017-12-01

Treatment choices for total shoulder arthroplasty (TSA) in the absence of full-thickness rotator cuff tears (RCTs) are not clearly defined in current literature. This study investigated the prevalence and effect of preoperative partial-thickness RCTs and muscular degenerative changes on postoperative outcomes after TSA. Medical records and magnetic resonance imaging studies were reviewed for patients who underwent TSA for primary glenohumeral osteoarthritis with minimum 2-year follow-up to determine preoperative tear classification, Goutallier grade, and supraspinatus tangent sign. Postoperative pain on the visual analog scale, range of motion, and patient outcomes scores were obtained to correlate preoperative RCT status, Goutallier grading, tangent sign, and postoperative outcomes. Patients with full-thickness RCT on preoperative magnetic resonance imaging were excluded. Forty-five patients met all inclusion criteria (average age, 65 ± 10 years; average follow-up, 43 months). Of the patients undergoing TSA, 40% had a significant (>50% thickness) partial RCT. Grade 3 to 4 Goutallier changes were noted in 22% of all patients, and 13% demonstrated grade 3 to 4 changes in the context of no tear. Positive tangent sign was present in 7% of all patients. The preoperative Goutallier grade of the infraspinatus was significantly negatively correlated with postoperative forward elevation (P = .02) and external rotation (P = .05), but rotator cuff pathology, including tear status, Goutallier grade, and the presence of a tangent sign, did not correlate with postoperative functional outcome scores. Even in the absence of a full-thickness RCT, rotator cuff atrophy, fatty infiltration, and partial thickness tearing are common findings. Although postoperative range of motion is correlated to Goutallier changes of the infraspinatus, rotator cuff pathology is not correlated to outcomes after TSA; therefore, one may proceed with TSA without concern of their effect on postoperative outcomes. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Ureteroscopic biopsy of upper tract urothelial carcinoma: comparison of basket and forceps.

PubMed

Kleinmann, Nir; Healy, Kelly A; Hubosky, Scott G; Margel, David; Bibbo, Marluce; Bagley, Demetrius H

2013-12-01

To compare two different biopsy devices for upper tract urothelial carcinoma (UTUC) and evaluate the pathologic result obtained by these devices. From January 2008 to December 2010, 414 ureteroscopies were performed and 504 biopsies were taken for evaluation of UTUC. Two biopsy devices were compared: 2.4F stainless steel flat wire basket and 3F cup biopsy forceps. The effect of the biopsy device on obtaining an adequate pathologic specimen was evaluated using univariate and multivariate binary logistic regression analysis. We also investigated whether tumor grade determination was affected by the biopsy device among patients with a diagnostic biopsy. Diagnosis was successful in 63% and 94% in the forceps and basket groups, respectively (P < 0.0001). Among biopsies with a definite diagnosis of UTUC, specific grade was determined in 80% and 93% in the forceps and basket groups, respectively (P = 0.033). In subgroup analysis of tumors larger than 10 mm in diameter, diagnosis was obtained in 80% and 94% in the forceps and basket groups, respectively (P = 0.037). Cytologic evaluation was found to increase diagnostic rates. The stainless steel flat wire basket was shown to be superior to the 3F cup biopsy forceps in terms of obtaining tissue diagnosis and providing specific grade.

Anaplasia is rare and does not influence prognosis in adult medulloblastoma.

PubMed

Giordana, Maria Teresa; D'Agostino, Carla; Pollo, Bianca; Silvani, Antonio; Ferracini, Romano; Paiolo, Anna; Ghiglione, Paolo; Chiò, Adriano

2005-10-01

Histopathologic grading based on increasing anaplasia predicts clinical behavior of pediatric medulloblastomas. The present study was aimed at grading 86 medulloblastomas of adult patients (aged 18 and older) by anaplasia and analyzing the predictive power. Nodularity, desmoplasia, nuclear size, nuclear pleomorphism, necrosis, and endothelial proliferations have been evaluated. Morphometric analysis of nuclear size was performed using the Eclipse Net program. Patients treated with standard postoperative radiotherapy (35 Gy to craniospinal axis and 50 Gy to posterior fossa) were considered for correlation with survival. Pathologic data and total survival were compared by Kaplan-Meier and logrank analysis. No correlation was found between total survival duration and individual pathologic features. Cooccurrence of nuclear pleomorphism, large nuclear diameter, microvascular proliferations, and necroses did not predict outcome. Severe nuclear pleomorphism was found in 4 of 86 cases; the only large-cell medulloblastoma was from an 18-year-old patient. Histopathologic factors have no clinical use for stratification of patients in risk groups. The histologic spectrum of medulloblastoma in adults is different from that in children.

MALDI TOF imaging mass spectrometry in clinical pathology: a valuable tool for cancer diagnostics (review).

PubMed

Kriegsmann, Jörg; Kriegsmann, Mark; Casadonte, Rita

2015-03-01

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) imaging mass spectrometry (IMS) is an evolving technique in cancer diagnostics and combines the advantages of mass spectrometry (proteomics), detection of numerous molecules, and spatial resolution in histological tissue sections and cytological preparations. This method allows the detection of proteins, peptides, lipids, carbohydrates or glycoconjugates and small molecules.Formalin-fixed paraffin-embedded tissue can also be investigated by IMS, thus, this method seems to be an ideal tool for cancer diagnostics and biomarker discovery. It may add information to the identification of tumor margins and tumor heterogeneity. The technique allows tumor typing, especially identification of the tumor of origin in metastatic tissue, as well as grading and may provide prognostic information. IMS is a valuable method for the identification of biomarkers and can complement histology, immunohistology and molecular pathology in various fields of histopathological diagnostics, especially with regard to identification and grading of tumors.

Effect of neoadjuvant chemotherapy on HER-2 expression in surgically treated gastric and oesophagogastric junction carcinoma: a multicentre Italian study.

PubMed

Chiari, Damiano; Orsenigo, Elena; Guarneri, Giovanni; Baiocchi, Gian Luca; Mazza, Elena; Albarello, Luca; Bissolati, Massimiliano; Molfino, Sarah; Staudacher, Carlo

2017-03-01

Predictors of response to neoadjuvant chemotherapy are not available for gastric and oesophago-gastric junction carcinoma. HER-2 over-expression in breast cancer correlates with poor prognosis and high incidence of recurrence. First aim of this study was to evaluate if the HER-2 expression/amplification is predictive of response to neoadjuvant chemotherapy in terms of pathologic regression. Secondary aim was to evaluate if HER-2 expression varies after neoadjuvant treatment. Thirty-five patients with locally advanced gastric or oesophago-gastric junction carcinoma underwent preoperative chemotherapy and surgical resection at San Raffaele Scientific Institute and Spedali Civili of Brescia. HER-2 expression/amplification was evaluated on every biopsy at diagnosis time and on every surgical sample after neoadjuvant chemotherapy. Pathologic response to chemotherapy was evaluated according to TNM classification (ypT status and ypN status) and Mandard's tumour regression grade classification. In our series 10 patients (28.6%) showed a reduction in HER-2 overexpression and in 6 of them (17.1%) HER-2 expression completely disappeared. Only three of the six patients with HER-2 disappearance had a complete pathological response to neoadjuvant chemotherapy. There was a strong correlation between HER-2 negativity on biopsy and absence of lymph node metastasis in surgical samples after neoadjuvant chemotherapy, irrespective of nodal status before chemotherapy. A direct correlation between HER-2 reduction after neoadjuvant chemotherapy and pathologic regression (primary tumour and lymph nodes) in surgical samples was found. HER-2 negativity may represent a predictor of pathologic response to neoadjuvant chemotherapy for gastric and oesophago-gastric junction adenocarcinoma. Neoadjuvant treatment can reduce HER-2 overexpression.

A systematic review of definitions and classification systems of adjacent segment pathology.

PubMed

Kraemer, Paul; Fehlings, Michael G; Hashimoto, Robin; Lee, Michael J; Anderson, Paul A; Chapman, Jens R; Raich, Annie; Norvell, Daniel C

2012-10-15

Systematic review. To undertake a systematic review to determine how "adjacent segment degeneration," "adjacent segment disease," or clinical pathological processes that serve as surrogates for adjacent segment pathology are classified and defined in the peer-reviewed literature. Adjacent segment degeneration and adjacent segment disease are terms referring to degenerative changes known to occur after reconstructive spine surgery, most commonly at an immediately adjacent functional spinal unit. These can include disc degeneration, instability, spinal stenosis, facet degeneration, and deformity. The true incidence and clinical impact of degenerative changes at the adjacent segment is unclear because there is lack of a universally accepted classification system that rigorously addresses clinical and radiological issues. A systematic review of the English language literature was undertaken and articles were classified using the Grades of Recommendation Assessment, Development, and Evaluation criteria. RESULTS.: Seven classification systems of spinal degeneration, including degeneration at the adjacent segment, were identified. None have been evaluated for reliability or validity specific to patients with degeneration at the adjacent segment. The ways in which terms related to adjacent segment "degeneration" or "disease" are defined in the peer-reviewed literature are highly variable. On the basis of the systematic review presented in this article, no formal classification system for either cervical or thoracolumbar adjacent segment disorders currently exists. No recommendations regarding the use of current classification of degeneration at any segments can be made based on the available literature. A new comprehensive definition for adjacent segment pathology (ASP, the now preferred terminology) has been proposed in this Focus Issue, which reflects the diverse pathology observed at functional spinal units adjacent to previous spinal reconstruction and balances detailed stratification with clinical utility. A comprehensive classification system is being developed through expert opinion and will require validation as well as peer review. Strength of Statement: Strong.

Quality of pathology reporting is crucial for cancer care and registration: a baseline assessment for breast cancers diagnosed in Belgium in 2008.

PubMed

De Schutter, H; Van Damme, N; Colpaert, C; Galant, C; Lambein, K; Cornelis, A; Neven, P; Van Eycken, E

2015-04-01

Given the crucial role of pathology reporting in the management of breast cancers, we aimed to investigate the quality and variability of breast cancer pathology reporting in Belgium. Detailed information on non-molecular and molecular parameters was retrieved from the pathology protocols available at the Belgian Cancer Registry for 10,007 breast cancers diagnosed in Belgium in 2008. Substantial underreporting was shown for several clinically relevant non-molecular parameters, such as lymphovascular invasion. High-volume laboratories performed only slightly better than others, and analyses at the individual laboratory level showed clear inter-laboratory variability in reporting for all volume categories. Information on ER/PR and HER2 IHC was mentioned in respectively 91.7% and 90.8% of evaluative cases. HER2 ISH data were available for 78.5% of the cases judged to be 2+ for HER2 IHC. For cases with different specimens analysed, discordance between these specimens was highest for HER2, followed by PR. For HER2, results obtained from different laboratories were even less concordant. In addition, inter-laboratory differences were noted in the used ER/PR scoring systems, the proportion of ER-/PR+ cases, and the relation between histological grade and ER/PR positivity. Data on Ki67 were only available for 43.8% of the investigated cases, and showed inconsistent use of cut-off values. Breast pathology reporting in Belgium in 2008 was suboptimal and showed considerable inter-laboratory variability. Synoptic reporting has been proposed as a facilitator towards increased reporting quality and harmonization, but the lack of aligned informatics remains a major hurdle in its concrete implementation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Argininosuccinate synthetase (ASS) deficiency in high-grade pulmonary neuroendocrine carcinoma: an opportunity for personalized targeted therapy.

PubMed

Walts, Ann E; Bomalaski, John S; Ines, Delma; Orsulic, Sandra

2015-08-01

Cells deficient in argininosuccinate synthetase (ASS) must absorb the arginine they need for growth from circulating blood. Treatment with pegylated arginine deiminase (ADI-PEG 20) selectively eliminates arginine from the circulation and has shown some efficacy against ASS-deficient tumors including small cell lung cancer (SCLC). We sought to assess ASS expression in a cohort of high-grade pulmonary neuroendocrine carcinomas (PNEC) which include SCLC and large cell neuroendocrine carcinoma (LCNEC). Sixty-nine PNEC (49 SCLC and 20 LCNEC) were retrieved from our pathology archives. Formalin-fixed paraffin-embedded sections of the 54 primary tumors, 15 metastases and appropriate positive and negative controls were immunostained using an ASS-specific monoclonal antibody. Positive staining in <30 % of the tumor was scored as weak; staining in ≥30 % of the tumor was scored as strong. The absence of staining in the tumor was recorded as ASS negative. 58 % of the PNEC including 61.2 % of the SCLC and 50 % of the LCNEC were ASS negative. These ASS-negative tumors included 63 % of the primary and 40 % of the metastatic lesions tested. More than 50 % of the high-grade PNEC tested lack immunohistochemically detectable ASS, suggesting that they are auxotrophic for arginine and potential candidates for arginine deprivation therapy. PNEC comprise about 25 % of primary lung cancers and have a 5-year overall survival of only 5-10 %, underscoring the need for new and more effective therapies. Immunostaining for ASS has potential to improve the selection of patients with PNEC for arginine deprivation therapy with ADI-PEG 20.

Comparison of the gas-liquid dual support fixation and Heitzman fixation techniques for preparing lung specimens

PubMed Central

Yu, Dongsheng; Qu, Weili; Xia, Haipeng; Li, Xiaofeng; Luan, Zhenfeng; Yan, Renjie; Lu, Xiaodong; Zhao, Peng

2017-01-01

The aim of the present study was to compare the gas-liquid dual support fixation and Heitzman fixation techniques for the preparation of lung specimens. A total of 40 fresh lung samples were surgically collected from 40 male patients with lung cancer by biopsy. Patients were recruited from the Affiliated Hospital of Qingdao University Medical College (Qingdao, China) between July 2007 and June 2014. Samples were prepared using either the gas-liquid dual support fixation method (group A; n=26) or the Heitzman fixation method (group B; n=14). High-resolution computed tomography (HRCT) scanning was performed prior to surgery and corresponding postoperative HRCT scanning was conducted for the lung specimens; the gross transverse specimen section, cord photography images and histological sections were evaluated. Morphological observations of lung specimens indicated that there were 22 cases in group A with grade I (84.6%) and 4 cases with grade II (15.4%), whereas, in group B, there were 5 cases with grade II (35.7%) and 9 cases with grade III (64.3%). Statistical analysis demonstrated that the grades of specimens between the two groups were significantly different (P<0.01). Results from imaging and histological studies found that the quality of lung specimens was superior in group A, compared with group B. In conclusion, the present study demonstrated that, compared with the Heitzman fixation method, gas-liquid dual support fixation may be a superior technique for the preparation of lung specimens. This finding may facilitate the improvement of lung HRCT and pathological studies. PMID:28673006

Comparison of the gas-liquid dual support fixation and Heitzman fixation techniques for preparing lung specimens.

PubMed

Yu, Dongsheng; Qu, Weili; Xia, Haipeng; Li, Xiaofeng; Luan, Zhenfeng; Yan, Renjie; Lu, Xiaodong; Zhao, Peng

2017-07-01

The aim of the present study was to compare the gas-liquid dual support fixation and Heitzman fixation techniques for the preparation of lung specimens. A total of 40 fresh lung samples were surgically collected from 40 male patients with lung cancer by biopsy. Patients were recruited from the Affiliated Hospital of Qingdao University Medical College (Qingdao, China) between July 2007 and June 2014. Samples were prepared using either the gas-liquid dual support fixation method (group A; n=26) or the Heitzman fixation method (group B; n=14). High-resolution computed tomography (HRCT) scanning was performed prior to surgery and corresponding postoperative HRCT scanning was conducted for the lung specimens; the gross transverse specimen section, cord photography images and histological sections were evaluated. Morphological observations of lung specimens indicated that there were 22 cases in group A with grade I (84.6%) and 4 cases with grade II (15.4%), whereas, in group B, there were 5 cases with grade II (35.7%) and 9 cases with grade III (64.3%). Statistical analysis demonstrated that the grades of specimens between the two groups were significantly different (P<0.01). Results from imaging and histological studies found that the quality of lung specimens was superior in group A, compared with group B. In conclusion, the present study demonstrated that, compared with the Heitzman fixation method, gas-liquid dual support fixation may be a superior technique for the preparation of lung specimens. This finding may facilitate the improvement of lung HRCT and pathological studies.

Analysis of Prognostic Factors and Patterns of Recurrence in Patients With Pathologic Stage III Endometrial Cancer

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

Patel, Samir; Portelance, Lorraine; Gilbert, Lucy

2007-08-01

Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) comparedmore » with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients.« less

Re-evaluating TTF-1 immunohistochemistry in diffuse gliomas: Expression is clone-dependent and associated with tumor location.

PubMed

Pratt, Drew; Afsar, Nina; Allgauer, Michael; Fetsch, Patricia; Palisoc, Maryknoll; Pittaluga, Stefania; Quezado, Martha

TTF-1 is widely used as a marker in routine surgical pathology in the work-up of malignancy. Aberrant expression of TTF-1 in extrapulmonary and extrathyroidal malignancies is a frequently reported phenomenon. In addition to the recently characterized pituicyte-derived tumors of the sella, immunoreactivity has been reported in diffuse gliomas with the SPT24 clone. Here, we sought to evaluate TTF-1 expression with three commercially available clones in a large series of gliomas. Expression was compared across the newly defined diagnostic entities in the 2016 WHO Classification of CNS Tumors. Using tissue microarrays (TMA), 212 diffuse gliomas (WHO grades II - IV) were systematically evaluated with TTF-1 immunohistochemistry using three clones: SPT24, 8G7G3/1, and SP141, and results correlated with clinicopathologic features. 14 high-grade diffuse gliomas demonstrated nuclear staining with the SP141 and SPT24 clones. Two tumors showed weak positivity with the 8G7G3/1 clone. All tumors were high grade by histology (WHO grades III and IV). 86% (12/14) of TTF-1-positive gliomas involved the frontal lobes at diagnosis. No relationship with IDH R132H, ATRX, p53, H3K27M, or EGFR immunohistochemistry was identified. TTF-1 expression in gliomas was not independently prognostic of overall survival. TTF-1 expression in diffuse gliomas is a rare but potentially misleading occurrence. In our cohort, staining occurred with both the SPT24 and SP141 clones at equal intensity and frequency. Clustering of TTF-1-positive tumors in the frontal lobe(s) suggests lineage-specific expression. Due to clone-specific expression in diffuse gliomas, caution must be exercised in the work-up of intracranial tumors with TTF-1.
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Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1-a consensus overview.

PubMed

Miettinen, Markku M; Antonescu, Cristina R; Fletcher, Christopher D M; Kim, Aerang; Lazar, Alexander J; Quezado, Martha M; Reilly, Karlyne M; Stemmer-Rachamimov, Anat; Stewart, Douglas R; Viskochil, David; Widemann, Brigitte; Perry, Arie

2017-09-01

Patients with neurofibromatosis 1 (NF1) develop multiple neurofibromas, with 8% to 15% of patients experiencing malignant peripheral nerve sheath tumor (MPNST) during their lifetime. Prediction of transformation, typically from plexiform neurofibroma, is clinically and histologically challenging. In this overview, after a consensus meeting in October 2016, we outline the histopathologic features and molecular mechanisms involved in the malignant transformation of neurofibromas. Nuclear atypia alone is generally insignificant. However, with atypia, loss of neurofibroma architecture, high cellularity, and/or mitotic activity >1/50 but <3/10 high-power fields, the findings are worrisome for malignancy. We propose the term "atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP)" for lesions displaying at least 2 of these features. This diagnosis should prompt additional sampling, clinical correlation, and possibly, expert pathology consultation. Currently, such tumors are diagnosed inconsistently as atypical neurofibroma or low-grade MPNST. Most MPNSTs arising from neurofibromas are high-grade sarcomas and pose little diagnostic difficulty, although rare nonnecrotic tumors with 3-9 mitoses/10 high-power fields can be recognized as low-grade variants. Although neurofibromas contain numerous S100 protein/SOX10-positive Schwann cells and CD34-positive fibroblasts, both components are reduced or absent in MPNST. Loss of p16/CDKN2A expression, elevated Ki67 labeling, and extensive nuclear p53 positivity are also features of MPNST that can to some degree already occur in atypical neurofibromatous neoplasms of uncertain biologic potential. Complete loss of trimethylated histone 3 lysine 27 expression is potentially more reliable, being immunohistochemically detectable in about half of MPNSTs. Correlated clinicopathological, radiologic, and genetic studies should increase our understanding of malignant transformation in neurofibromas, hopefully improving diagnosis and treatment soon. Published by Elsevier Inc.

Increased plasmatic soluble HLA-G levels in endometrial cancer.

PubMed

Ben Yahia, Hamza; Babay, Wafa; Bortolotti, Daria; Boujelbene, Nadia; Laaribi, Ahmed Baligh; Zidi, Nour; Kehila, Mehdi; Chelbi, Hanène; Boudabous, Abdellatif; Mrad, Karima; Mezlini, Amel; Di Luca, Dario; Ouzari, Hadda-Imene; Rizzo, Roberta; Zidi, Inès

2018-05-03

Human Leukocyte Antigen-G (HLA-G) is known as an immune suppressive molecule; it interacts with several immune cells and inhibits their functions. HLA-G molecule is highly represented in pathological conditions including malignant transformation. To the best of our knowledge this is the first study that focuses on the expression of soluble HLA-G (sHLA-G) in endometrial cancer (EC). We aimed at exploring sHLA-G plasma levels and its prognostic value in EC. We examined total sHLA-G expression as well as the sHLA-G1 and HLA-G5 isoforms expression in plasma samples from 40 patients with EC and 45 healthy controls by a specific sandwich ELISA. Immunoprecipitation and Coomassie blue staining were performed to explore the presence of plasmatic sHLA-G monomers and dimers. sHLA-G plasma level was significantly enhanced in patients with EC compared to healthy controls (p = 0.028). Additionally, HLA-G5 molecules were highly represented than sHLA-G1 molecules in EC, at the borderline of significance (p = 0.061). Interestingly, sHLA-G has been shown to be increased in early stages (Stages I and II) as well as in high grade EC (Grade 3) that is associated with rapid spread of the disease (p = 0.057). sHLA-G positive EC plasma were majorly in monomeric form (75%). Clinically, all the HLA-G dimers were detected in early stages and in high grade of EC. Our data strengthen the implication of HLA-G molecules in EC etiology and especially in progression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Similar protein expression profiles of ovarian and endometrial high-grade serous carcinomas.

PubMed

Hiramatsu, Kosuke; Yoshino, Kiyoshi; Serada, Satoshi; Yoshihara, Kosuke; Hori, Yumiko; Fujimoto, Minoru; Matsuzaki, Shinya; Egawa-Takata, Tomomi; Kobayashi, Eiji; Ueda, Yutaka; Morii, Eiichi; Enomoto, Takayuki; Naka, Tetsuji; Kimura, Tadashi

2016-03-01

Ovarian and endometrial high-grade serous carcinomas (HGSCs) have similar clinical and pathological characteristics; however, exhaustive protein expression profiling of these cancers has yet to be reported. We performed protein expression profiling on 14 cases of HGSCs (7 ovarian and 7 endometrial) and 18 endometrioid carcinomas (9 ovarian and 9 endometrial) using iTRAQ-based exhaustive and quantitative protein analysis. We identified 828 tumour-expressed proteins and evaluated the statistical similarity of protein expression profiles between ovarian and endometrial HGSCs using unsupervised hierarchical cluster analysis (P<0.01). Using 45 statistically highly expressed proteins in HGSCs, protein ontology analysis detected two enriched terms and proteins composing each term: IMP2 and MCM2. Immunohistochemical analyses confirmed the higher expression of IMP2 and MCM2 in ovarian and endometrial HGSCs as well as in tubal and peritoneal HGSCs than in endometrioid carcinomas (P<0.01). The knockdown of either IMP2 or MCM2 by siRNA interference significantly decreased the proliferation rate of ovarian HGSC cell line (P<0.01). We demonstrated the statistical similarity of the protein expression profiles of ovarian and endometrial HGSC beyond the organs. We suggest that increased IMP2 and MCM2 expression may underlie some of the rapid HGSC growth observed clinically.

The use of automated Ki67 analysis to predict Oncotype DX risk-of-recurrence categories in early-stage breast cancer.

PubMed

Thakur, Satbir Singh; Li, Haocheng; Chan, Angela M Y; Tudor, Roxana; Bigras, Gilbert; Morris, Don; Enwere, Emeka K; Yang, Hua

2018-01-01

Ki67 is a commonly used marker of cancer cell proliferation, and has significant prognostic value in breast cancer. In spite of its clinical importance, assessment of Ki67 remains a challenge, as current manual scoring methods have high inter- and intra-user variability. A major reason for this variability is selection bias, in that different observers will score different regions of the same tumor. Here, we developed an automated Ki67 scoring method that eliminates selection bias, by using whole-slide analysis to identify and score the tumor regions with the highest proliferative rates. The Ki67 indices calculated using this method were highly concordant with manual scoring by a pathologist (Pearson's r = 0.909) and between users (Pearson's r = 0.984). We assessed the clinical validity of this method by scoring Ki67 from 328 whole-slide sections of resected early-stage, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. All patients had Oncotype DX testing performed (Genomic Health) and available Recurrence Scores. High Ki67 indices correlated significantly with several clinico-pathological correlates, including higher tumor grade (1 versus 3, P<0.001), higher mitotic score (1 versus 3, P<0.001), and lower Allred scores for estrogen and progesterone receptors (P = 0.002, 0.008). High Ki67 indices were also significantly correlated with higher Oncotype DX risk-of-recurrence group (low versus high, P<0.001). Ki67 index was the major contributor to a machine learning model which, when trained solely on clinico-pathological data and Ki67 scores, identified Oncotype DX high- and low-risk patients with 97% accuracy, 98% sensitivity and 80% specificity. Automated scoring of Ki67 can thus successfully address issues of consistency, reproducibility and accuracy, in a manner that integrates readily into the workflow of a pathology laboratory. Furthermore, automated Ki67 scores contribute significantly to models that predict risk of recurrence in breast cancer.

The Paris System for Reporting Urinary Cytology: The Quest to Develop a Standardized Terminology.

PubMed

Barkan, Güliz A; Wojcik, Eva M; Nayar, Ritu; Savic-Prince, Spasenija; Quek, Marcus L; Kurtycz, Daniel F I; Rosenthal, Dorothy L

2016-07-01

The main purpose of urine cytology is to detect high-grade urothelial carcinoma. With this principle in mind, The Paris System (TPS) Working Group, composed of cytopathologists, surgical pathologists, and urologists, has proposed and published a standardized reporting system that includes specific diagnostic categories and cytomorphologic criteria for the reliable diagnosis of high-grade urothelial carcinoma. This paper outlines the essential elements of TPS and the process that led to the formation and rationale of the reporting system. TPS Working Group, organized at the 2013 International Congress of Cytology, conceived a standardized platform on which to base cytologic interpretation of urine samples. The widespread dissemination of this approach to cytologic examination and reporting of urologic samples and the scheme's universal acceptance by pathologists and urologists is critical for its success. For urologists, understanding the diagnostic criteria, their clinical implications, and limitations of TPS is essential if they are to utilize urine cytology and noninvasive ancillary tests in a thoughtful and practical manner. This is the first international/inclusive attempt at standardizing urinary cytology. The success of TPS will depend on the pathology and urology communities working collectively to improve this seminal paradigm shift, and optimize the impact on patient care.

Magnetic resonance tomography of the knee joint.

PubMed

Puig, Stefan; Kuruvilla, Yojena Chittazhathu Kurian; Ebner, Lukas; Endel, Gottfried

2015-10-01

To compare the diagnostic performance of magnetic resonance imaging (MRI) in terms of sensitivity and specificity using a field strength of <1.0 T (T) versus ≥1.5 T for diagnosing or ruling out knee injuries or knee pathologies. The systematic literature research revealed more than 10,000 references, of which 1598 abstracts were reviewed and 87 full-text articles were retrieved. The further selection process resulted in the inclusion of four systematic reviews and six primary studies. No differences could be identified in the diagnostic performance of low- versus high-field MRI for the detection or exclusion of meniscal or cruciate ligament tears. Regarding the detection or grading of cartilage defects and osteoarthritis of the knee, the existing evidence suggests that high-field MRI is tolerably specific but not very sensitive, while there is literally no evidence for low-field MRI because only a few studies with small sample sizes and equivocal findings have been performed. We can recommend the use of low-field strength MRI systems in suspected meniscal or cruciate ligament injuries. This does, however, not apply to the diagnosis and grading of knee cartilage defects and osteoarthritis because of insufficient evidence.

Perfusion MR Imaging and Proton MR Spectroscopic Imaging in Differentiating Necrotizing Cerebritis from Glioblastoma Multiforme

PubMed Central

Pivawer, Gabriel; Law, Meng; Zagzag, David

2007-01-01

We describe a lesion with the MR imaging characteristics of a glioblastoma mutiforme and demonstrate how perfusion MR imaging and proton MR spectroscopic imaging can be used to differentiate necrotizing cerebritis from what appeared to be a high-grade glioma. A 43 year old woman presented to her physician complaining of progressive visual disturbance and headache for several weeks. Conventional MR imaging demonstrated a parietal peripherally enhancing mass with central necrosis and moderate to severe surrounding T2 hyperintensity suggesting an infiltrating high-grade glioma. However, advanced imaging, including dynamic susceptibility contrast magnetic resonance imaging (DSC MRI) and magnetic resonance spectroscopic imaging (MRSI), suggested a non-neoplastic lesion. The DSC MRI data demonstrated no hyperperfusion within the lesion and surrounding T2 signal abnormality and the MRSI data showed overall decrease in metabolites in this region, except for lactate. Because of the aggressive appearance to the lesion and the patients worsening symptoms, a biopsy was performed. The pathologic diagnosis was necrotizing cerebritis. After the commencement of steroid therapy, imaging findings and patient symptoms improved. This report will review the utility of advanced imaging for differentiating inflammatory from neoplastic appearing lesions on conventional imaging. PMID:17275620

Significance and outcome of nuclear anaplasia and mitotic index in prostatic adenocarcinomas.

PubMed

Kır, Gozde; Sarbay, Billur Cosan; Gumus, Eyup

2016-10-01

The Gleason grading system measures architectural differentiation and disregards nuclear atypia and the cell proliferation index. Several studies have reported that nuclear grade and mitotic index (MI) are prognostically useful. This study included 232 radical prostatectomy specimens. Nuclear anaplasia (NA) was determined on the basis of nucleomegali (at least 20µm); vesicular chromatin; eosinophilic macronucleoli, nuclear lobulation, and irregular thickened nuclear membranei. The proportion of area of NA was recorded in each tumor in 10% increments. The MI was defined as the number of mitotic figures in 10 consecutive high-power fields (HPF). In univariate analysis, significant differences included associations between biochemical prostate-specific antigen recurrence (BCR) and Gleason score, extraprostatic extension, positive surgical margin, the presence of high-pathologic stage, NA≥10% of tumor area, MI≥3/10 HPF, and preoperative prostate-specific antigen. In a stepwise Cox regression model, a positive surgical margin, the presence of a NA≥10% of tumor area, and a MI of≥3/10 HPF were independent predictors of BCR after radical prostatectomy. NA≥10% of tumor area appeared to have a stronger association with outcome than MI≥3/10 HPF, as still associated with BCR when Gleason score was in the model. The results of our study showed that, in addition to the conventional Gleason grading system, NA, and MI are useful prognostic parameters while evaluating long-term prognosis in prostatic adenocarcinoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Helicobacter pylori Eradication Prevents Progression of Gastric Cancer in Hypergastrinemic INS-GAS Mice

PubMed Central

Lee, Chung-Wei; Rickman, Barry; Rogers, Arlin B.; Ge, Zhongming; Wang, Timothy C.; Fox, James G.

2009-01-01

Helicobacter pylori infection results in chronic gastritis, which may progress to gastric cancer. In this study, we investigated the efficacy of H. pylori eradication in preventing the progression of gastritis to gastric cancer in H. pylori–infected transgenic INS-GAS mice. H. pylori infection induced severe dysplasia and gastric cancer classified as high-grade and low-grade gastrointestinal intraepithelial neoplasia (GIN) in INS-GAS mice at 28 weeks postinfection (WPI). H. pylori eradication therapy using omeprazole, metronidazole, and clarithromycin was administered p.o. at 8, 12, or 22 WPI. Compared with untreated infected mice, H. pylori eradication at 8, 12, and 22 WPI significantly reduced the severity of dysplasia (P < 0.01). Moreover, H. pylori eradication at 8 WPI completely prevented the development of GIN (P < 0.001). Although not as effective as early antimicrobial treatment, prevention of progression to high-grade GIN was achieved by H. pylori eradication at 12 and 22 WPI (P < 0.05). Consistent with reduced gastric pathology, H. pylori eradication at all time points significantly down-regulated gastric Interferon-γ, tumor necrosis factor-α, inducible nitric oxide synthase, and Reg 1 mRNA levels (P < 0.05) and reduced epithelial proliferation in the corpus (P < 0.01) compared with untreated infected mice. We concluded that H. pylori eradication prevented gastric cancer to the greatest extent when antibiotics are given at an early point of infection, but that eradication therapy given at a later time point delayed the development of severe dysplastic lesions. PMID:18441088

The modern role of transoesophageal echocardiography in the assessment of valvular pathologies

PubMed Central

Bull, Sacha; Newton, James

2017-01-01

Despite significant advancements in the field of cardiovascular imaging, transoesophageal echocardiography remains the key imaging modality in the management of valvular pathologies. This paper provides echocardiographers with an overview of the modern role of TOE in the diagnosis and management of valvular disease. We describe how the introduction of 3D techniques has changed the detection and grading of valvular pathologies and concentrate on its role as a monitoring tool in interventional cardiology. In addition, we focus on the echocardiographic and Doppler techniques used in the assessment of prosthetic valves and provide guidance for the evaluation of prosthetic valves. Finally, we summarise quantitative methods used for the assessment of valvular stenosis and regurgitation and highlight the key areas where echocardiography remains superior over other novel imaging modalities. PMID:28096184

The modern role of transoesophageal echocardiography in the assessment of valvular pathologies.

PubMed

Wamil, Malgorzata; Bull, Sacha; Newton, James

2017-01-17

Despite significant advancements in the field of cardiovascular imaging, transoesophageal echocardiography remains the key imaging modality in the management of valvular pathologies. This paper provides echocardiographers with an overview of the modern role of TOE in the diagnosis and management of valvular disease. We describe how the introduction of 3D techniques has changed detection and grading of valvular pathologies and concentrate on its role as a monitoring tool in interventional cardiology. In addition, we focus on the echocardiographic and Doppler techniques used in the assessment of prosthetic valves, and provide guidance for evaluation of prosthetic valves. Finally, we summarise quantitative methods used for the assessment of valvular stenosis and regurgitation and highlight the key areas where echocardiography remains superior over other novel imaging modalities. © 2017 The authors.

Pancreatic pseudopapillary tumour: A rare misdiagnosed entity

PubMed Central

Affirul, C.A.; Qisti, F.N.; Zamri, Z.; Azlanuddin, A.; Hairol, A.O.; Razman, J.

2014-01-01

INTRODUCTION Solid pseudo papillary pancreatic tumour is a rare entity. The atypical presentation causes a delayed or misdiagnosis of these pathology. It commonly affects the female population in the 2nd and 3rd decade of life. The presentation varies from non-specific abdominal pain to incidental findings in asymptomatic patients. It is a low-grade premalignant condition that is curable by excision of the tumour. PRESENTATION OF CASE This paper presents a 17-year-old girl with intra-abdominal mass diagnosed with solid pseudo papillary tumour that underwent Whipple's procedure. DISCUSSION We discuss the presentations, diagnosis and pathology findings of this rare pathology. CONCLUSION The diagnosis remains an enigma in view of the nature and location of the tumour. Resection is still the best choice remains for this condition. PMID:25462046

Pancreatic pseudopapillary tumour: A rare misdiagnosed entity.

PubMed

Affirul, C A; Qisti, F N; Zamri, Z; Azlanuddin, A; Hairol, A O; Razman, J

2014-01-01

Solid pseudo papillary pancreatic tumour is a rare entity. The atypical presentation causes a delayed or misdiagnosis of these pathology. It commonly affects the female population in the 2nd and 3rd decade of life. The presentation varies from non-specific abdominal pain to incidental findings in asymptomatic patients. It is a low-grade premalignant condition that is curable by excision of the tumour. This paper presents a 17-year-old girl with intra-abdominal mass diagnosed with solid pseudo papillary tumour that underwent Whipple's procedure. We discuss the presentations, diagnosis and pathology findings of this rare pathology. The diagnosis remains an enigma in view of the nature and location of the tumour. Resection is still the best choice remains for this condition. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

[The relationship between human papillomavirus (HPV) infection and penile cancer].

PubMed

Yumura, Yasushi; Hattori, Yusuke; Noda, Hideyuki; Kondo, Kei-Ichi; Noguchi, Kazumi; Sasaki, Takeshi; Kasuga, Jun; Kubota, Yoshinobu

2009-11-01

Human papillomavirus (HPV) may be carcinogenic effectors in a variety of human lower genital tract malignancies. We evaluated HPV status with respect to clinical and pathological features and prognosis of penile carcinoma. We searched for HPV infected cells (Koilocytosis) within the primary lesion of cancer tissue from 78 patients with penile squamous cell carcinoma. The following variables were recorded : age, tumor size, clinical stage, lymphatic and venous invasion, histologic and nuclear grade, Broders grade, infiltration status, and lymph node and distant metastasis. Koilocytosis were detected 55.1% (43 of 78) of patients. Tumors with Koilocytosis had better differentiation (p=0.0443) and lower grade (better keratinized) in Broders grading system (p=0.0116) than HPV negative tumors. No difference was found in the 5-year survival rate (p=0.5693). Our data suggest that the presence of Koilocytosis does not influence prognosis in penile cancer.

Automated classification of brain tumor type in whole-slide digital pathology images using local representative tiles.

PubMed

Barker, Jocelyn; Hoogi, Assaf; Depeursinge, Adrien; Rubin, Daniel L

2016-05-01

Computerized analysis of digital pathology images offers the potential of improving clinical care (e.g. automated diagnosis) and catalyzing research (e.g. discovering disease subtypes). There are two key challenges thwarting computerized analysis of digital pathology images: first, whole slide pathology images are massive, making computerized analysis inefficient, and second, diverse tissue regions in whole slide images that are not directly relevant to the disease may mislead computerized diagnosis algorithms. We propose a method to overcome both of these challenges that utilizes a coarse-to-fine analysis of the localized characteristics in pathology images. An initial surveying stage analyzes the diversity of coarse regions in the whole slide image. This includes extraction of spatially localized features of shape, color and texture from tiled regions covering the slide. Dimensionality reduction of the features assesses the image diversity in the tiled regions and clustering creates representative groups. A second stage provides a detailed analysis of a single representative tile from each group. An Elastic Net classifier produces a diagnostic decision value for each representative tile. A weighted voting scheme aggregates the decision values from these tiles to obtain a diagnosis at the whole slide level. We evaluated our method by automatically classifying 302 brain cancer cases into two possible diagnoses (glioblastoma multiforme (N = 182) versus lower grade glioma (N = 120)) with an accuracy of 93.1% (p < 0.001). We also evaluated our method in the dataset provided for the 2014 MICCAI Pathology Classification Challenge, in which our method, trained and tested using 5-fold cross validation, produced a classification accuracy of 100% (p < 0.001). Our method showed high stability and robustness to parameter variation, with accuracy varying between 95.5% and 100% when evaluated for a wide range of parameters. Our approach may be useful to automatically differentiate between the two cancer subtypes. Copyright © 2015 Elsevier B.V. All rights reserved.

The performance of the new prognostic grade and stage groups in conservatively treated prostate cancer.

PubMed

Chen, Cheng; Chen, Ye; Hu, Lin-Kun; Jiang, Chang-Chuan; Xu, Ren-Fang; He, Xiao-Zhou

2018-02-27

We evaluated the prognosis of the new grade groups and American Joint Committee on Cancer (AJCC) stage groups in men with prostate cancer (PCa) who were treated conservatively. A total of 13 798 eligible men were chosen from the Surveillance Epidemiology and End Results database. The new grade and AJCC stage groups were investigated on prostate biopsy specimens. Kaplan-Meier survival analysis and multivariable hazards models were applied to estimate the association of new grade and stage groups with overall survival (OS) and PCa-specific survival (CSS). Mean follow-up was 42.65 months (95% confidence interval: 42.47-42.84) in the entire cohort. The 3-year OS and CSS rates stepped down for grade groups 1-5 and AJCC stage groups I-IVB, respectively. After adjusting for clinical and pathological characteristics, all grade groups and AJCC stage groups were associated with higher all-cause and PCa-specific mortality compared to the reference group (all P ≤ 0.003). In conclusion, we evaluated the oncological outcome of the new grade and AJCC stage groups on biopsy specimens of conservatively treated PCa. These two novel clinically relevant classifications can assist physicians to determine different therapeutic strategies for PCa patients.

Multi-slice MRI reveals heterogeneity in disease distribution along the length of muscle in Duchenne muscular dystrophy.

PubMed

Chrzanowski, Stephen M; Baligand, Celine; Willcocks, Rebecca J; Deol, Jasjit; Schmalfuss, Ilona; Lott, Donovan J; Daniels, Michael J; Senesac, Claudia; Walter, Glenn A; Vandenborne, Krista

2017-09-01

Duchenne muscular dystrophy (DMD) causes progressive pathologic changes to muscle secondary to a cascade of inflammation, lipid deposition, and fibrosis. Clinically, this manifests as progressive weakness, functional loss, and premature mortality. Though insult to whole muscle groups is well established, less is known about the relationship between intramuscular pathology and function. Differences of intramuscular heterogeneity across muscle length were assessed using an ordinal MRI grading scale in lower leg muscles of boys with DMD and correlated to patient's functional status. Cross sectional T 1 weighted MRI images with fat suppression were obtained from ambulatory boys with DMD. Six muscles (tibialis anterior, extensor digitorum longus, peroneus, soleus, medial and lateral gastrocnemii) were graded using an ordinal grading scale over 5 slice sections along the lower leg length. The scores from each slice were combined and results were compared to global motor function and age. Statistically greater differences of involvement were observed at the proximal ends of muscle compared to the midbellies. Multi-slice assessment correlated significantly to age and the Vignos functional scale, whereas single-slice assessment correlated to the Vignos functional scale only. Lastly, differential disease involvement of whole muscle groups and intramuscular heterogeneity were observed amongst similar age subjects. A multi-slice ordinal MRI grading scale revealed that muscles are not uniformly affected, with more advanced disease visible near the tendons in a primarily ambulatory population with DMD. A geographically comprehensive evaluation of the heterogeneously affected muscle in boys with DMD may more accurately assess disease involvement.

Audit of paired anal cytology and histopathology outcomes in patients referred to a public sexual health clinic.

PubMed

Williams, Vincent M; Metcalf, Cecily; French, Martyn A; McCloskey, Jenny C

2010-09-01

The level of agreement between anal cytology and histopathology is not clear with only a few studies evaluating the reliability of anal specimen reporting. Australian data in relation to this are limited. The results of paired anal cytology and histopathology specimens received between 2002 and 2008 from patients who were referred within the sexual health clinic were retrieved from the anatomical pathology database. A total of 248 paired samples from 154 (21 females, 133 males) participants were extracted. Concurrent high risk human papilloma virus (hrHPV) DNA assay and HIV status for the study group were also collected. Data were tabulated according to reported grade of squamous abnormality based on the Bethesda system. Using the biopsy result as the gold standard the specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for cytology were calculated and the association between grade of abnormality, HIV status and hrHPV infection estimated. Concordance between cytology and histology showed that in 204 (85%) paired samples both tests were categorised as abnormal (Kappa statistic 0.73, P = 0.013). The cytology result showed a sensitivity of 96%, specificity 14%, PPV 89% and NPV 31% when compared with histopathology. HrHPV assay was positive in 192 (80%) samples. High-grade squamous abnormalities were reported in biopsy specimens from 60% (n = 42/67) of HIV-positive subjects and 25% (n = 22/87) of HIV-negative subjects. HIV-positive individuals were more likely to be hrHPV positive, odds ratio (OR) 6.21 [95% confidence interval (CI) 2.69 to 14.34], when compared with HIV-negative subjects. Anal cytology is highly sensitive for the detection of abnormal squamous cells. While cytology has low specificity for predicting the grade of abnormality compared with biopsy outcome, its application as a screening method in asymptomatic at risk populations warrants further study.

The synovial microenvironment of osteoarthritic joints alters RNA-seq expression profiles of human primary articular chondrocytes

PubMed Central

Lewallen, Eric A.; Bonin, Carolina A.; Li, Xin; Smith, Jay; Karperien, Marcel; Larson, A. Noelle; Lewallen, David G.; Cool, Simon M.; Westendorf, Jennifer J.; Krych, Aaron J.; Leontovich, Alexey A.; Im, Hee-Jeong; van Wijnen, Andre J.

2018-01-01

Osteoarthritis (OA) is a disabling degenerative joint disease that prompts pain with limited treatment options. To permit early diagnosis and treatment of OA, a high resolution mechanistic understanding of human chondrocytes in normal and diseased states is necessary. In this study, we assessed the biological effects of OA-related changes in the synovial microenvironment on chondrocytes embedded within anatomically intact cartilage from joints with different pathological grades by next generation RNA-sequencing (RNA-seq). We determined the transcriptome of primary articular chondrocytes derived from pristine knees and ankles, as well as from joints affected by OA. The GALAXY bioinformatics platform was used to facilitate biological interpretations. Comparisons of patient samples by k-means, hierarchical clustering and principal component analysis reveal that primary chondrocytes exhibit OA grade-related differences in gene expression, including genes involved in cell-adhesion, ECM production and immune response. We conclude that diseased synovial microenvironments in joints with different histopathological OA grades directly alter gene expression in chondrocytes. One ramification of this finding is that sampling anatomically intact cartilage from OA joints is not an ideal source of healthy chondrocytes, nor should they be used to generate a normal baseline for the molecular characterization of diseased joints. PMID:27378743

Next-generation endomyocardial biopsy: the potential of confocal and super-resolution microscopy.

PubMed

Crossman, David J; Ruygrok, Peter N; Hou, Yu Feng; Soeller, Christian

2015-03-01

Confocal laser scanning microscopy and super-resolution microscopy provide high-contrast and high-resolution fluorescent imaging, which has great potential to increase the diagnostic yield of endomyocardial biopsy (EMB). EMB is currently the gold standard for identification of cardiac allograft rejection, myocarditis, and infiltrative and storage diseases. However, standard analysis is dominated by low-contrast bright-field light and electron microscopy (EM); this lack of contrast makes quantification of pathological features difficult. For example, assessment of cardiac allograft rejection relies on subjective grading of H&E histology, which may lead to diagnostic variability between pathologists. This issue could be solved by utilising the high contrast provided by fluorescence methods such as confocal to quantitatively assess the degree of lymphocytic infiltrate. For infiltrative diseases such as amyloidosis, the nanometre resolution provided by EM can be diagnostic in identifying disease-causing fibrils. The recent advent of super-resolution imaging, particularly direct stochastic optical reconstruction microscopy (dSTORM), provides high-contrast imaging at resolution approaching that of EM. Moreover, dSTORM utilises conventional fluorescence dyes allowing for the same structures to be routinely imaged at the cellular scale and then at the nanoscale. The key benefit of these technologies is that the high contrast facilitates quantitative digital analysis and thereby provides a means to robustly assess critical pathological features. Ultimately, this technology has the ability to provide greater accuracy and precision to EMB assessment, which could result in better outcomes for patients.

Correlation of Body Mass Index and Serum Parameters With Ultrasonographic Grade of Fatty Change in Non-alcoholic Fatty Liver Disease

PubMed Central

Abangah, Ghobad; Yousefi, Atefeh; Asadollahi, Rouhangiz; Veisani, Yousef; Rahimifar, Paria; Alizadeh, Sajjad

2014-01-01

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease in the western population and expanding disease in the world. Pathological changes in fatty liver are like alcohol liver damage, which can lead to end-stage liver disease. The prevalence of NAFLD in obese or overweight people is higher than general population, and it seems that people with high Body Mass Index (BMI) or abnormality in some laboratory tests are more susceptible for severe fatty liver and high grade of NAFLD in ultrasonography (U.S). Objectives: This study aimed to evaluate the correlation of BMI and laboratory tests with NAFLD in ultrasonography. Materials and Methods: During a multi-step process, we selected two-hundred and thirteen cases from four hundred and eighteen patients with NAFLD. Laboratory tests performed included: ALT, AST, FBS, Triglyceride and cholesterol levels, hepatitis B surface antigen, hepatitis C antibody, ceruloplasmin, serum iron, TIBC, transferrin saturation, ferritin, AMA, ANA, ANTI LKM1, serum protein electrophoresis, TSH, anti TTG (IgA). BMI and ultrasonography for 213 patients were performed, and then data was analyzed. These parameters and grades of ultrasonography were compared with the values obtained using one way ANOVA. An ordinal logistic regression model was used to estimate the probability of ultrasonography grade. The Statistical Package for the Social Science program (SPSS, version 16.0) was used for data analysis. Results: Two-hundred and thirteen cases including 140 male and 73 female, were studied. In general, 72.3% of patients were overweight and obese. Post-hoc tests showed that only BMI (P < 0.001) and TG (P < 0.011) among variables had statistically significant associations with ultrasonography grade (USG), and ordinal logistic regression model showed that BMI and AST were the best predictors. Discussion: Our results suggest that in patients with NAFLD, BMI and TG are most effective factors in severity of fatty liver disease and ultrasonography grade (USG). On the other hand, BMI as a predictor can be helpful. But, AST has not been a reliable finding, because it changes in many conditions. PMID:24719704

Correlation of Body Mass Index and Serum Parameters With Ultrasonographic Grade of Fatty Change in Non-alcoholic Fatty Liver Disease.

PubMed

Abangah, Ghobad; Yousefi, Atefeh; Asadollahi, Rouhangiz; Veisani, Yousef; Rahimifar, Paria; Alizadeh, Sajjad

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease in the western population and expanding disease in the world. Pathological changes in fatty liver are like alcohol liver damage, which can lead to end-stage liver disease. The prevalence of NAFLD in obese or overweight people is higher than general population, and it seems that people with high Body Mass Index (BMI) or abnormality in some laboratory tests are more susceptible for severe fatty liver and high grade of NAFLD in ultrasonography (U.S). This study aimed to evaluate the correlation of BMI and laboratory tests with NAFLD in ultrasonography. During a multi-step process, we selected two-hundred and thirteen cases from four hundred and eighteen patients with NAFLD. Laboratory tests performed included: ALT, AST, FBS, Triglyceride and cholesterol levels, hepatitis B surface antigen, hepatitis C antibody, ceruloplasmin, serum iron, TIBC, transferrin saturation, ferritin, AMA, ANA, ANTI LKM1, serum protein electrophoresis, TSH, anti TTG (IgA). BMI and ultrasonography for 213 patients were performed, and then data was analyzed. These parameters and grades of ultrasonography were compared with the values obtained using one way ANOVA. An ordinal logistic regression model was used to estimate the probability of ultrasonography grade. The Statistical Package for the Social Science program (SPSS, version 16.0) was used for data analysis. Two-hundred and thirteen cases including 140 male and 73 female, were studied. In general, 72.3% of patients were overweight and obese. Post-hoc tests showed that only BMI (P < 0.001) and TG (P < 0.011) among variables had statistically significant associations with ultrasonography grade (USG), and ordinal logistic regression model showed that BMI and AST were the best predictors. Our results suggest that in patients with NAFLD, BMI and TG are most effective factors in severity of fatty liver disease and ultrasonography grade (USG). On the other hand, BMI as a predictor can be helpful. But, AST has not been a reliable finding, because it changes in many conditions.

Tumour border configuration in colorectal cancer: proposal for an alternative scoring system based on the percentage of infiltrating margin.

PubMed

Karamitopoulou, Eva; Zlobec, Inti; Koelzer, Viktor Hendrik; Langer, Rupert; Dawson, Heather; Lugli, Alessandro

2015-10-01

Information on tumour border configuration (TBC) in colorectal cancer (CRC) is currently not included in most pathology reports, owing to lack of reproducibility and/or established evaluation systems. The aim of this study was to investigate whether an alternative scoring system based on the percentage of the infiltrating component may represent a reliable method for assessing TBC. Two hundred and fifteen CRCs with complete clinicopathological data were evaluated by two independent observers, both 'traditionally' by assigning the tumours into pushing/infiltrating/mixed categories, and alternatively by scoring the percentage of infiltrating margin. With the pushing/infiltrating/mixed pattern method, interobserver agreement (IOA) was moderate (κ = 0.58), whereas with the percentage of infiltrating margins method, IOA was excellent (intraclass correlation coefficient of 0.86). A higher percentage of infiltrating margin correlated with adverse features such as higher grade (P = 0.0025), higher pT (P = 0.0007), pN (P = 0.0001) and pM classification (P = 0.0063), high-grade tumour budding (P < 0.0001), lymphatic invasion (P < 0.0001), vascular invasion (P = 0.0032), and shorter survival (P = 0.0008), and was significantly associated with an increased probability of lymph node metastasis (P < 0.001). Information on TBC gives additional prognostic value to pathology reports on CRC. The novel proposed scoring system, by using the percentage of infiltrating margin, outperforms the 'traditional' way of reporting TBC. Additionally, it is reproducible and simple to apply, and can therefore be easily integrated into daily diagnostic practice. © 2015 John Wiley & Sons Ltd.

The development of confocal arthroscopy as optical histology for rotator cuff tendinopathy.

PubMed

Wu, J-P; Walton, M; Wang, A; Anderson, P; Wang, T; Kirk, T B; Zheng, M H

2015-09-01

MRI, ultrasound and video arthroscopy are traditional imaging technologies for noninvasive or minimal invasive assessment of the rotator cuff tendon pathology. However, these imaging modalities do not have sufficient resolution to demonstrate the pathology of rotator cuff tendons at a microstructural level. Therefore, they are insensitive to low-level tendon diseases. Although traditional histology can be used to analyze the physiology of rotator cuff tendons, it requires biopsy that traumatizes the rotator cuff, thus, potentially comprising the mechanical properties of tendons. Besides, it cannot offer real-time histological information. Confocal endoscopy offers a way to assess the microstructural disorder in tissues without biopsy. However, the application of this useful technique for detecting low-level tendon diseases has been restricted by using clinical grade fluorescent contrast agent to acquire high-resolution microstructural images of tendons. In this study, using a clinical grade sodium fluorescein contrast agent, we have reported the development of confocal arthroscopy for optical histological assessment without biopsy. The confocal arthroscopic technique was able to demonstrate rotator cuff tendinopathy in human cadavers, which appeared macroscopically normal under video arthroscopic examinations. The tendinopathy status of the rotator cuff tendons was confirmed by corresponding traditional histology. The development of confocal arthroscopy may provide a minimally invasive imaging technique for real-time histology of rotator cuff without the need for tissue biopsy. This technique has the potential for surgeons to gain in real time the histological information of rotator cuff tendons, which may assist planning repair strategies and potentially improve intervention outcomes. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

The p53 breast cancer tissue biomarker in Indian women

PubMed Central

Patil, Vinayak W; Tayade, Mukund B; Pingale, Sangeeta A; Dalvi, Shubhangi M; Rajekar, Rajesh B; Deshmukh, Hemkant M; Patil, Shital D; Singhai, Rajeev

2011-01-01

Background Combination chemotherapy is highly effective in locally advanced breast cancer. A negative expression of biomarker p53 indicates a higher chance of responding to this regimen. Patients’ p53 status may be used as a biological cancer marker to identify those who would benefit from more aggressive treatments. Aims The role of p53 in modulating apoptosis has suggested that it may affect the efficacy of anticancer agents. p53 alterations in 80 patients with locally advanced breast cancer IIIB undergoing neoadjuvant chemotherapy were prospectively evaluated. Materials and methods Patients received three cycles of paclitaxel (175 mg/m2) and doxorubicin (60 mg/m2) every 21 days. Tumor sections were analyzed before treatment for altered patterns of p53 expression, using immunohistochemistry and DNA sequencing. Results An overall response rate of 83.5% was obtained, including 15.1% complete pathological responses. The regimen was well tolerated with 17.7% grade 2/3 nausea and 12.8% grade 3/4 leukopenia. There was a statistically significant correlation between response and expression of p53. Of 25 patients who obtained a complete clinical response, only two were classified as p53-positive (P = 0.004, χ2). Of 11 patients who obtained a complete pathological remission, one was positive (P = 0.099, χ2). Conclusion Immunohistochemical (IHC) analysis has been shown to be a prognostic factor for patients with breast cancer in India. Paclitaxel is one of the most promising anticancer agents for the therapy of breast cancer, where it has also shown activity in tumors resistant to doxorubicin. PMID:24367177

Extraprostatic Extension Is Extremely Rare for Contemporary Gleason Score 6 Prostate Cancer.

PubMed

Anderson, Blake B; Oberlin, Daniel T; Razmaria, Aria A; Choy, Bonnie; Zagaja, Gregory P; Shalhav, Arieh L; Meeks, Joshua J; Yang, Ximing J; Paner, Gladell P; Eggener, Scott E

2017-09-01

A significant proportion of men with Gleason score 6 (GS6) prostate cancer undergo treatment with radiation or surgery. To assess pathologic stage of pure GS6 at radical prostatectomy (RP). In the period 2003-2014, 7817 patients underwent RP at two institutions. Of 2502 patients with GS6 at surgery, 60 were identified as stage pT3a-b on initial pathologic review, 55 with pT3a (extraprostatic extension, EPE), and five with pT3b (seminal vesicle invasion; SVI). All cases of GS6 with pT3 disease underwent contemporary pathologic evaluation for Gleason grade, stage, and extent of EPE. At one institution, all GS≥7 pT3b cases were re-reviewed for downgrading. The 2014 International Society of Urological Pathology (ISUP) Gleason grading criteria and 2009 ISUP recommendations on pT3 staging were applied. Calculated incidence (%) of pT3a, pT3b, pT4, and lymph node-positive disease. Of the 60 GS6 pT3a-b cases identified in the period 2003-2014, seven (0.28% of entire GS6 cohort) with GS6 and pT3a were identified after re-review, all focal EPE. Among the re-examined cohort, no cases of GS6 with pT3b were observed. None of the 132 GS≥7 pT3b cases were downgraded to GS6. Limitations include partial embedding of specimens and separate pathologic review at each institution. In a large prostatectomy cohort, GS6 never had seminal vesicle invasion (0%) and was very rarely (0.28%) associated with extraprostatic extension. GS6 prostate cancer rarely spreads outside the prostate. A new finding in this study was that GS6 prostate cancer never spread to the seminal vesicles. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Intra- and inter-rater agreement between an ophthalmologist and mid-level ophthalmic personnel to diagnose retinal diseases based on fundus photographs at a primary eye center in Nepal: the Bhaktapur Retina Study.

PubMed

Thapa, Raba; Bajimaya, Sanyam; Bouman, Renske; Paudyal, Govinda; Khanal, Shankar; Tan, Stevie; Thapa, Suman S; van Rens, Ger

2016-07-18

Early detection can reduce irreversible blindness from retinal diseases. This study aims to assess the intra- and inter-rater agreement of retinal pathologies observed on fundus photographs between an ophthalmologist and two-mid level ophthalmic personnel (MLOPs). A population-based, cross-sectional study was conducted among subjects 60 years and above in the Bhaktapur district of Nepal. Fundus photographs of 500 eyes of 500 subjects were assessed. The macula-centered 45-degree photographs were graded twice by one ophthalmologist and two MLOPs. Intra-rater and inter-rater agreements were assessed for the ophthalmologist and the MLOPs. Mean age was 70.22 years ± 6.94 (SD). Retinal pathologies were observed in 55.6 % of photographs (age-related macular degeneration: 34.2 %; diabetic retinopathy: 4.2 %; retinal vein occlusion: 3.8 %). Twelve (2.4 %) fundus pictures were non-gradable. The intra-rater agreement for overall retinal pathologies, retinal hemorrhage, and maculopathy were substantial both for the ophthalmologist as well as for the MLOPs. There was moderate inter-rater agreement between the ophthalmologist and the first MLOP on second rating for overall retinal pathologies, [kappa (k); 95 % CI = 0.59 (0.51-0.66)], retinal hemorrhage [k; 95 % CI = 0.60 (0.41-0.78)], and maculopathy [k; 95 % CI = 0.52 (0.43-0.60)]. Inter-rater agreement between the ophthalmologist and the second MLOP for second rating was moderate for overall retinal pathologies [k; 95 % CI = 0.52 (0.44-0.60)], substantial agreement for retinal hemorrhage [k; 95 % CI = 0. 68 (0.52-0.84)], moderate agreement for maculopathy [k; 95 % CI = 0.59 (0.50-0.67)]. There is moderate agreement between the MLOPs and the ophthalmologist in grading fundus photographs for retinal hemorrhages and maculopathy.

The effect of progressive hearing loss on the morphology of endbulbs of Held and bushy cells.

PubMed

Connelly, Catherine J; Ryugo, David K; Muniak, Michael A

2017-01-01

Studies of congenital and early-onset deafness have demonstrated that an absence of peripheral sound-evoked activity in the auditory nerve causes pathological changes in central auditory structures. The aim of this study was to establish whether progressive acquired hearing loss could lead to similar brain changes that would degrade the precision of signal transmission. We used complementary physiologic hearing tests and microscopic techniques to study the combined effect of both magnitude and duration of hearing loss on one of the first auditory synapses in the brain, the endbulb of Held (EB), along with its bushy cell (BC) target in the anteroventral cochlear nucleus. We compared two hearing mouse strains (CBA/Ca and heterozygous shaker-2 +/- ) against a model of early-onset progressive hearing loss (DBA/2) and a model of congenital deafness (homozygous shaker-2 -/- ), examining each strain at 1, 3, and 6 months of age. Furthermore, we employed a frequency model of the mouse cochlear nucleus to constrain our analyses to regions most likely to exhibit graded changes in hearing function with time. No significant differences in the gross morphology of EB or BC structure were observed in 1-month-old animals, indicating uninterrupted development. However, in animals with hearing loss, both EBs and BCs exhibited a graded reduction in size that paralleled the hearing loss, with the most severe pathology seen in deaf 6-month-old shaker-2 -/- mice. Ultrastructural pathologies associated with hearing loss were less dramatic: minor changes were observed in terminal size but mitochondrial fraction and postsynaptic densities remained relatively stable. These results indicate that acquired progressive hearing loss can have consequences on auditory brain structure, with prolonged loss leading to greater pathologies. Our findings suggest a role for early intervention with assistive devices in order to mitigate long-term pathology and loss of function. Copyright © 2016 Elsevier B.V. All rights reserved.

Human papillomavirus genotypes in human immunodeficiency virus-positive patients with anal pathology in Madrid, Spain

PubMed Central

2013-01-01

Background We studied anal specimens to determine the distribution of human papillomavirus (HPV) genotypes and co-infection occurrence. This information will contribute to the knowledge of HPV genotype distributions and provide an estimate of the prevalence of different oncogenic HPV genotypes found in patients in Madrid (Spain). Methods We studied a total of 82 anal biopsies from the Hospital General Universitario Gregorio Marañón of Madrid. These included 4 specimens with benign lesions, 52 specimens with low-grade anal squamous intraepithelial lesion, 24 specimens with high-grade anal squamous intraepithelial lesions and 2 specimens with invasive anal carcinoma. HPV genotyping was performed with PCR amplification and reverse dot blot hybridization. Results We detected 33 different HPV genotypes, including 16 HPVs associated with a high risk of carcinogenesis, 3 HPVs associated with a highly likely risk of carcinogenesis and 14 HPVs associated with a low-risk of carcinogenesis. In two specimens, an uncharacterized HPV genotype was detected. The most frequent HPV genotypes found were HPV-16 (10.3%; 95% CI: 6.6%-15.1%), HPV-52 (8.5%; 95% CI: 5.2%-13%) and HPV-43/44 (7.6%; 95% CI: 4.5%-11.9%). HPV-18 was only detected in 0.9% (95% CI: 0.1%-3.2%) of the total viruses detected in all lesions. HPV co-infections were found in 83.9% of all types of lesions. The majority of cases (90.2%) were concomitantly infected with the human immunodeficiency virus (HIV). Conclusion The prevalence of high-risk carcinogenic genotypes in anal pathological samples was remarkable. Therefore, further studies that include a greater number of samples, particularly invasive carcinoma cases are needed to evaluate the potential influence of these HPV genotypes in the appearance of anal carcinomas. Also, the influence of other accompanying infections should be evaluated clarify the appearance of this type of carcinoma. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2075238024106058. PMID:24325764

Integrative, multimodal analysis of glioblastoma using TCGA molecular data, pathology images, and clinical outcomes.

PubMed

Kong, Jun; Cooper, Lee A D; Wang, Fusheng; Gutman, David A; Gao, Jingjing; Chisolm, Candace; Sharma, Ashish; Pan, Tony; Van Meir, Erwin G; Kurc, Tahsin M; Moreno, Carlos S; Saltz, Joel H; Brat, Daniel J

2011-12-01

Multimodal, multiscale data synthesis is becoming increasingly critical for successful translational biomedical research. In this letter, we present a large-scale investigative initiative on glioblastoma, a high-grade brain tumor, with complementary data types using in silico approaches. We integrate and analyze data from The Cancer Genome Atlas Project on glioblastoma that includes novel nuclear phenotypic data derived from microscopic slides, genotypic signatures described by transcriptional class and genetic alterations, and clinical outcomes defined by response to therapy and patient survival. Our preliminary results demonstrate numerous clinically and biologically significant correlations across multiple data types, revealing the power of in silico multimodal data integration for cancer research.

[A case of intragastric wall abscess formation during bevacizumab combined chemotherapy].

PubMed

Mori, Ayano; Kogawa, Takahiro; Arihara, Youhei; Abe, Masakazu; Tamura, Fumito; Abe, Seiichirou; Kukitsu, Takehiro; Ihara, Hideyuki; Sumiyoshi, Tetsuya; Yoshizaki, Naoto; Kondou, Hitoshi; Tsuji, Yasushi

2013-05-01

A 38-year-old man was given a diagnosis of as sigmoid colon cancer and underwent sigmoid colectomy. Post-operative pathological staging was stage IIIb. He then underwent adjuvant chemotherapy. One year and 4 months after the surgery, CT scans revealed multiple liver and lung metastases. He was given mFOLFOX6+bevacizumab, which was changed later to FOLFIRI+bevacizumab. After these chemotherapies, he was admitted to the hospital due to sudden abdominal pain and high grade fever. Obstructive jaundice was initially diagnosed, but detailed study of initial CT revealed intragastric wall abscess. After the drainage of the abscess, his conditions improved. We speculated that the abscess formation was caused by mucosal damage due to bevacizumab.

A Natural Language Intelligent Tutoring System for Training Pathologists - Implementation and Evaluation

PubMed Central

El Saadawi, Gilan M.; Tseytlin, Eugene; Legowski, Elizabeth; Jukic, Drazen; Castine, Melissa; Fine, Jeffrey; Gormley, Robert; Crowley, Rebecca S.

2009-01-01

Introduction We developed and evaluated a Natural Language Interface (NLI) for an Intelligent Tutoring System (ITS) in Diagnostic Pathology. The system teaches residents to examine pathologic slides and write accurate pathology reports while providing immediate feedback on errors they make in their slide review and diagnostic reports. Residents can ask for help at any point in the case, and will receive context-specific feedback. Research Questions We evaluated (1) the performance of our natural language system, (2) the effect of the system on learning (3) the effect of feedback timing on learning gains and (4) the effect of ReportTutor on performance to self-assessment correlations. Methods The study uses a crossover 2×2 factorial design. We recruited 20 subjects from 4 academic programs. Subjects were randomly assigned to one of the four conditions - two conditions for the immediate interface, and two for the delayed interface. An expert dermatopathologist created a reference standard and 2 board certified AP/CP pathology fellows manually coded the residents' assessment reports. Subjects were given the opportunity to self grade their performance and we used a survey to determine student response to both interfaces. Results Our results show a highly significant improvement in report writing after one tutoring session with 4-fold increase in the learning gains with both interfaces but no effect of feedback timing on performance gains. Residents who used the immediate feedback interface first experienced a feature learning gain that is correlated with the number of cases they viewed. There was no correlation between performance and self-assessment in either condition. PMID:17934789