scholarly journals A targeted folate receptor-α near-infrared fluorescent agent used for in vitro diagnosis of endometrial cytology

Author(s):  
Dongxin Liang ◽  
Xiaoqian Tuo ◽  
Lanbo Zhao ◽  
Kailu Zhang ◽  
Yiran Wang ◽  
...  

AbstractThe aim of this study is to perform the synthesis and evaluation of the new near-infrared targeting fluorescent dye folic acid-ZW800-1 (ZW-FA) and to explore its potential feasibility for in vitro diagnosis of endometrial cancer. Characterisation and Folate receptor-α (FR-α) targeting verification of ZW-FA were performed first and 92 patients were recruited, after liquid-based cytology preparations, during a 15-month period. ZW-FA and Hematoxylin-Eosin (H&E) staining were performed on all cytological slides successively; the histological diagnoses were regarded as the gold standard for ROC curve analysis. The cut-off value of ZW-FA fluorescence intensity is 62.9745; the sensitivity (Se), specificity (Sp), false-negative rate (FNR), false-positive rate (FPR), positive predictive value (PV+) percentage and negative predictive value (PV–) of the ZW-FA method are 84.6%, 85.2%, 15.4%,14.8%, 93.2% and 69.7%, respectively. ZW-FA is potentially efficient for in vitro diagnosis of endometrial lesions based on the FR-α expression level of different endometrial lesions.

2020 ◽  
Author(s):  
Dongxin Liang ◽  
Xiaoqian Tuo ◽  
Lanbo Zhao ◽  
Kailu Zhang ◽  
Yiran Wang ◽  
...  

Abstract Background Endometrial cancer is the second-most prevalent cancer after breast cancer. Endometrial cytology test is a new diagnosis method for endometrial lesions. However, some unresolved issues limited the application of endometrial cytology test (ECT) in early diagnosis and screening of endometrial cancer. Evidence suggests that FRα is overexpressed in various solid tumors such as endometrial cancer, breast carcinoma, ovarian cancer and so on. Based on the expression of FR-α, the agent used in intraoperative imaging, FRα-targeting antibody drugs and diagnosis were developed previously. Nevertheless, research regarding agents used in the diagnosis of endometrial cancer is rarely carried out yet. Methods To obtain a promising and efficient method for in vitro and screening diagnosis of endometrial cytology, we performed the synthesis and evaluation of the new near-infrared targeting fluorescent dye folic acid-ZW800-1 (ZW-FA) and to explore its potential feasibility for in vitro diagnosis of endometrial cancer. Characterisation and Folate receptor-α (FR-α) targeting verification of ZW-FA were performed first and 92 patients were recruited, after liquid-based cytology preparations, during a 15-month period. ZW-FA and Hematoxylin-Eosin (H&E) staining were performed on all cytological slides successively; the histological diagnoses were regarded as the gold standard for ROC curve analysis. Results The cut-off value of ZW-FA fluorescence intensity is 62.9745; the sensitivity (Se), specificity (Sp), false-negative rate (FNR), false-positive rate (FPR), positive predictive value (PV+) percentage and negative predictive value (PV–) of the ZW-FA method are 84.6%, 85.2%, 15.4%,14.8%, 93.2% and 69.7%, respectively. Conclusions ZW-FA is potentially efficient for in vitro diagnosis of endometrial lesions based on the FR-α expression level of different endometrial lesions. This research offers a promising and efficient method for in vitro and screening diagnosis of endometrial cytology. Trial registration: ChiCTR1800020123. Registered December 15, 2018.


2018 ◽  
Vol 29 (4) ◽  
pp. 435-441 ◽  
Author(s):  
Kazuyoshi Kobayashi ◽  
Kei Ando ◽  
Ryuichi Shinjo ◽  
Kenyu Ito ◽  
Mikito Tsushima ◽  
...  

OBJECTIVEMonitoring of brain evoked muscle-action potentials (Br[E]-MsEPs) is a sensitive method that provides accurate periodic assessment of neurological status. However, occasionally this method gives a relatively high rate of false-positives, and thus hinders surgery. The alarm point is often defined based on a particular decrease in amplitude of a Br(E)-MsEP waveform, but waveform latency has not been widely examined. The purpose of this study was to evaluate onset latency in Br(E)-MsEP monitoring in spinal surgery and to examine the efficacy of an alarm point using a combination of amplitude and latency.METHODSA single-center, retrospective study was performed in 83 patients who underwent spine surgery using intraoperative Br(E)-MsEP monitoring. A total of 1726 muscles in extremities were chosen for monitoring, and acceptable baseline Br(E)-MsEP responses were obtained from 1640 (95%). Onset latency was defined as the period from stimulation until the waveform was detected. Relationships of postoperative motor deficit with onset latency alone and in combination with a decrease in amplitude of ≥ 70% from baseline were examined.RESULTSNine of the 83 patients had postoperative motor deficits. The delay of onset latency compared to the control waveform differed significantly between patients with and without these deficits (1.09% ± 0.06% vs 1.31% ± 0.14%, p < 0.01). In ROC analysis, an intraoperative 15% delay in latency from baseline had a sensitivity of 78% and a specificity of 96% for prediction of postoperative motor deficit. In further ROC analysis, a combination of a decrease in amplitude of ≥ 70% and delay of onset latency of ≥ 10% from baseline had sensitivity of 100%, specificity of 93%, a false positive rate of 7%, a false negative rate of 0%, a positive predictive value of 64%, and a negative predictive value of 100% for this prediction.CONCLUSIONSIn spinal cord monitoring with intraoperative Br(E)-MsEP, an alarm point using a decrease in amplitude of ≥ 70% and delay in onset latency of ≥ 10% from baseline has high specificity that reduces false positive results.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246438
Author(s):  
Akihiro Shitara ◽  
Kazumasa Takahashi ◽  
Mayumi Goto ◽  
Harunori Takahashi ◽  
Takuya Iwasawa ◽  
...  

This prospective study evaluated the accuracy of non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) using cell-free DNA in spent culture medium, as well as that of preimplantation genetic testing for aneuploidy (PGT-A) using trophectoderm (TE) biopsy after culturing beyond implantation. Twenty frozen blastocysts donated by 12 patients who underwent IVF at our institution were investigated. Of these, 10 were frozen on day 5 and 10 on day 6. Spent culture medium and TE cells were collected from each blastocyst after thawing, and the embryos were cultured in vitro for up to 10 days. The outgrowths after culturing beyond implantation were sampled and subjected to chromosome analysis using next-generation sequencing. Chromosomal concordance rate, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), false-positive rate (FPR), and false-negative rate (FNR) of niPGT-A and PGT-A against each outgrowth were analyzed. The concordance rate between the niPGT-A and outgrowth samples was 9/16 (56.3%), and the concordance rate between the PGT-A and outgrowth samples was 7/16 (43.8%). NiPGT-A exhibited 100% sensitivity, 87.5% specificity, 88.9% PPV, 100% NPV, 12.5% FPR, and 0% FNR. PGT-A exhibited 87.5% sensitivity, 77.8% specificity, 87.5% PPV, 75% NPV, 14.3% FPR, and 22.2% FNR. NiPGT-A may be more accurate than PGT-A in terms of ploidy diagnostic accuracy in outgrowths.


2016 ◽  
Author(s):  
Akanksha Mangla ◽  
Renuka Sinha

Objective: Cervical cancer is the second most common gynecologic malignancy worldwide. India alone accounts for one fifth of total number of cases worldwide. The aim of our study was to calculate sensitivity, specificity, positive predictive value, negative predictive value, false positive rate and false negative rate of complementary cytology and colposcopy with histopathology as gold standard for detection of premalignant and malignant cervical lesions. Methods: A cross sectional study was conducted at Vardhman Mahavir Medical College and Safdarjung hospital, Delhi, India. 100 non pregnant females with complaint of post coital or irregular vaginal bleeding and those who had unhealthy cervix on visual inspection were included in study. Results: Colposcopy exhibited a high degree of accuracy in diagnosis of high grade lesions. Overall sensitivity of cytology was 50% whereas that of colposcopy was 83.3%. Cytology had specificity of 93.4% whereas colposcopy had specificity of 89.4%. 100% of high grade and invasive cancers on colposcopy were associated with similar findings on histology. The degree of agreement between cytology and colposcopy with histology was significant (p<0.001). Conclusion: Colposcopy is sensitive method as compared to cytology, especially in the higher grade lesions and combination of both methods appears to be of higher diagnostic importance.


Author(s):  
Onur Doğan

In recent years, the use of various digital devices that continuously generate massive amounts of heterogeneous, structured or unstructured data has increased. In parallel to generation, data collection, storage, and analysis technologies have developed. Big data sources have a variety of data quality. Preparing and clearing data is one of the first step of mining big data. It is often important to address the full data set found in different data sources to achieve the right result. Various techniques have been used to increase the accuracy of the data comparison. Deterministic and probabilistic linkage algorithms are the two main techniques used in literature. They have different steps to reach qualified and integrated results. To easily interpret the results of the linkage algorithm, a confusion matrix can be used. Measurements such as sensitivity, specificity, positive predictive value, negative predictive value, false positive rate, and false negative rate, are considered to evaluate output quality.


Author(s):  
Josiane Steinmetz ◽  
Joseph Henny ◽  
René Gueguen

AbstractThe aim of the present work was to compare in a supposed healthy population of 680 subjects several algorithms for positive selection of urine samples requiring microscopic examination for erythrocytes and leukocytes after screening by automated test-strip measurement and particle counting on a Sysmex UF-50™ flow cytometer. Four strategies have been formulated and the sensitivity, specificity, positive predictive value, negative predictive value, false positive rate, false negative rate, and microscopic review rate were measured. The strategy combining test strip analysis and automated counting on all samples, followed by microscopic examination of only discordant samples gave the best results. When the two methods of haematuria screening were in agreement (91% of samples), the false negative rate for microscopy was 1.1%, with a false positive rate of 0.8%, sensitivity of 66% and specificity of 99%, and the results are acceptable without any other examination. When the two methods of haematuria screening were discrepant, visual microscopic analysis was necessary to obtain definitive results. For leukocyturia screening, 80% of results were in agreement by test strip and automatic sediment urinalysis, with only ten results considered as false negatives (1.8%) and four as false positives (0.7%). Agreement was good and the other criteria were good (sensitivity 79%, specificity 99%). On conflicting samples, there was no agreement between methods and microscopic analysis was essential. The benefit of such an algorithm would be optimisation of the workflow without any loss of sensitivity and specificity at the expense of a two-fold increase in cost.


2021 ◽  
Vol 162 (20) ◽  
pp. 790-799
Author(s):  
Zoárd Tibor Krasznai ◽  
Zsuzsa Bagoly ◽  
Eszter Nagy ◽  
Zsolt Farkas ◽  
Róbert Póka ◽  
...  

Összefoglaló. Bevezetés: Bevezetés: A citológiai alapú méhnyakrákszűrés átmeneti kategóriáinak optimális menedzselése a humán papillomavírus (HPV) szűrése és tipizálása ellenére jelenleg is kihívás. Vizsgálatunk célja a modern cervixspektroszkópiának (multimodális hiperspektroszkópia – MHS), egy azonnali eredményt nyújtó, digitális technológiára épülő módszernek a vizsgálata volt a citológiai alapú méhnyakszűrés találati biztonságának javítására. Betegek és módszer: Vizsgálatainkat 208, 18 és 75 év közötti nőbeteg bevonásával végeztük, akiknél már indikálásra került valamely, a méhnyakon végzendő műtét, citológiai eredményük rendelkezésre állt (a HPV-tesztet, amennyiben nem történt meg, elvégeztük), valamint valamennyi betegnél elvégeztük a műtét előtt az MHS-vizsgálatot. A szövettani mintavétel 166 betegnél történt meg. Eredmények: A citológiai vizsgálatot (az összes betegre tekintve) magas álpozitív arány jellemezte (69,28%), amely megfigyelések mindenképpen utalnak az újabb komponens alkalmazásának igényére a triázsban. Az összes citológiai kategóriára nézve az MHS-eredmények közül kiemelendő az álnegatív leletek rendkívül alacsony aránya (3/166 = 1,8%), mely a HPV-teszt esetén ennél magasabb volt (11/165 = 6,66%). A spektroszkópiás vizsgálat álpozitív aránya ugyanakkor kedvezőtlenebbnek bizonyult (91/166 = 54,81%) a HPV-vizsgálat álpozitív arányánál (40/165 = 24,24%). Az atípusos laphámsejt (ASC-US/ASC-H) citológiai kategória esetén a spektroszkópia álnegatív eredményeinek aránya (3/126 = 2,38%) szintén kedvezőbb volt, mint a HPV-vizsgálaté (9/126 = 7,14%). A cervicalis intraepithelialis neoplasia-2 vagy súlyosabb fokozatú hámelváltozások azonosításában a spektroszkópia szenzitivitása 94% (95% CI = 0,84–0,99), specificitása 22% (95% CI = 0,15–0,31), negatív prediktív értéke 90% (95% CI = 0,73–0,98), pozitív prediktív értéke 34% (95% CI = 0,26–0,43) volt (p = 0,00130). Következtetés: Az MHS fejlett innovatív technológián alapuló, azonnali eredményt adó vizsgálóeljárás, amely kiemelkedően alacsony álnegatív eredménye miatt nagy segítséget nyújt a citológiai eltéréssel rendelkező betegek további vizsgálatában. Orv Hetil. 2021; 162(20): 790–799. Summary. Introduction: Despite the use of human papillomavirus (HPV) testing, the management of the transitional categories of cytology-based screening still remains a challenge. The modern multimodal hyperspectroscopy (MHS) of the cervix is a novel digital technology based on artificial intelligence, providing an instant result in the assessment of cytology-based screening abnormalities. Patients and methods: 208 women (age 18–75) were enrolled. The patients already had cytology results and an operation on the cervix indicated at the time of inclusion. HPV and the hyperspectroscopy examination was performed pre-operatively. The pre-indicated operation was performed on 166 patients. Results: Cytology-based screening alone (in the category of all patients) resulted in a high false-positive rate (69.28%). In this category, the MHS had an outstanding false-negative rate (3/166 = 1.80%) compared to the HPV (11/165 = 6.66%). The false-positive rate of the spectroscopy examination (91/166 = 54.81%) was higher than that of the HPV testing (40/165 = 24.24%). In the atypical squamous cell (ASC-US/ASC-H) category, the false-negative rate of the spectroscopy (3/126 = 2.38%) was also lower than that of the HPV test (9/126 = 7.14%). In the detection of high-grade abnormalities (cervical intraepithelial neoplasia 2 and worse), the spectroscopy had a 94% sensitivity (95% CI = 0.84–0.99), with a 22% specificity (95% CI = 0.15–0.31), an 90% negative predictive value (95% CI = 0.73–0.98), and a 34% positive predictive value (95% CI = 0.26–0.43) (p = 0.00130). Conclusion: In the case of cytological abnormality, the MHS provides an immediate result based on advanced digital technology, and because of its outstanding false negative rate it is a great aid and should be considered in the triage of such patients. Orv Hetil. 2021; 162(20): 790–799.


Author(s):  
Sabahattin Yüzkan ◽  
Duygu Cengiz ◽  
İlhan Hekimsoy ◽  
Özlem Sezgin Okçu ◽  
Ayşenur Oktay

Abstract Objective To compare the diagnostic performance of contrast-enhanced mammography (CEM) with MRI and mammography (MG) based on histopathological results. Methods In this IRB-approved study, written informed consent was obtained from all patients. Images from 40 patients (62 lesions) with suspicious findings on US between March 2018 and August 2018 were evaluated. Sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CEM, MRI, and MG were evaluated and compared within a 95% confidence interval. Maximum dimensions of lesions were measured and correlations of results were evaluated with Spearman’s Rho test. Results In the histopathological analysis, 66% (41/62) of lesions were malignant and 34% (21/62) lesions were benign. Contrast-enhanced mammography, MRI, and MG had sensitivities of 100% (41/41), 100% (41/41), and 80% (33/41), respectively. The sensitivity of CEM and MRI was significantly better than that of MG (P = 0.03). The NPVs of CEM (100%, 7/7) and MRI (100%, 14/14) were statistically higher than the NPV of MG (60%, 12/20) (P = 0.03). The false-positive rates for CEM, MRI, and MG were 33% (7/21), 66% (14/21), and 42% (9/21), respectively. Contrast-enhanced mammography had a significantly lower false-positive rate than MRI (P &lt; 0.001). Mammography had the highest false-negative rate, missing 19% (8/41) of malignant lesions. Conclusion Contrast-enhanced mammography has similar performance characteristics to MRI and improved performance characteristics relative to MG. In particular, CEM and MRI have similar sensitivity and NPVs and both are superior in each of these metrics to MG.


2021 ◽  
Vol 11 ◽  
Author(s):  
Dongxin Liang ◽  
Xiaoqian Tuo ◽  
Qing Wang ◽  
Lanbo Zhao ◽  
Kailu Zhang ◽  
...  

The lack of cytopathologists delays the advancement of screening for endometrial cancer. It was urgent to develop a new dye for rapid diagnosis. Our study aimed to synthesize a targeted folate receptor-α near-infrared (NIR) fluorescent agent, folic acid-zwitterionic NIR fluorophore (ZW-FA), and explore the feasibility for screening of endometrial cancer and precancerous change. Folic acid was conjugated with zwitterionic NIR fluorophore. The preparation of ZW-FA was validated by 1H NMR, mass spectrometric, ultraviolet spectra and fluorescence spectra. ZW-FA was incubated with endometrial cytology samples obtained from patients who underwent dilation and curettage or total hysterectomy. Diagnostic utility was calculated by applying laser confocal microscope, Image-J and statistical models, such as enumeration, receiver operating characteristic curve, logistic regression, support vector machine and decision tree were used. The purity of ZW-FA was &gt; 95% determined by 1H NMR. ZW-FA had the strongest absorption peak at 633 nm in ultraviolet spectra. Photostability of ZW-FA was over 8 hours. In clinical validation, a total of 92 patients were enrolled. The cut-off value of ZW-FA was 49 in enumeration, which was used to distinguish the type of samples. Indicators about diagnostic utility are as follows: sensitivity 90.77%, specificity 62.96%, false-positive rate 37.04%, false-negative rate 9.23%, positive predictive value 85.51% and negative predictive value 73.91%. The samples processed by ZW-FA did not affect further Hematoxylin-Eosin staining and pathological diagnosis. It was an effective cytologic strategy for in vitro diagnosis of endometrial cancer and precancerous change by using ZW-FA.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifier ChiCTR1800020123.


2017 ◽  
Vol 2 (2) ◽  
pp. 127-131
Author(s):  
Rareș Georgescu ◽  
Adela Luciana Oprea ◽  
Alexandra Contra ◽  
Orsolya Bauer Hanko ◽  
Ioana Colcer ◽  
...  

AbstractObjective:To evaluate and demonstrate the accuracy of fine-needle aspiration (FNA) in thyroid lesions in our department and to highlight probable causes of errors leading to unsatisfactory sampling, which may depend on the characteristics of the nodule.Methods:This is a retrospective study conducted on 319 diagnosed cases of thyroid nodules referred to the Surgery Unit of Puls hospital, Tîrgu Mureș in the January 2014 – December 2015 period, who underwent fine-needle aspiration. Histological examination was considered to be the gold standard; therefore we compared the cytological diagnosis with the histological one.Results:Of the 319 cases, 289 (90.6%) were female and 30 (9.4%) male patients; 210 cases (69.3%) were interpreted as benign, 46 cases (15.2%) as follicular lesion of undetermined significance, 4 cases (1.3%) as suspect for malignancy, 1 case (0.3%) as malignant sampling, and 42 cases (13.9%) as unsatisfactory. We compared the results of fine-needle aspiration cytology (FNAC) with the corresponding histopathological results (49 in total). FNAC achieved a sensitivity of 76.47%, a specificity of 83.1%, a positive predictive value of 35.1%, a negative predictive value of 96.7%, a false positive rate of 16.9%, a false negative rate of 23%, and an overall accuracy of 82.3%.Conclusions:The results of our study demonstrate the accuracy of the FNA technique in the first-line diagnosis of thyroid nodules.


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