Number Of False Negative Cases Research Articles

A cost-effectiveness evaluation of latent tuberculosis infection screening of a migrant population in Malaysia

To estimate the costs and benefits of screening for latent tuberculosis infection (LTBI) in a migrant population in Malaysia. An economic model was developed from a Malaysian healthcare perspective to compare QuantiFERON-TB Gold Plus (QuantiFERON) with the tuberculin skin test (TST). A decision tree was used to capture outcomes relating to LTBI screening followed by a Markov model that simulated the lifetime costs and benefits of the patient cohort. The Markov model did not capture the impact of secondary infections. The model included an R shiny interactive interface to allow adaptation to other scenarios and settings. QuantiFERON is both more effective and less costly than TST (dominant). Compared with QuantiFERON, the lifetime risk of developing active TB increases by approximately 40% for TST due to missed LTBI cases during screening (i.e. a higher number of false negative cases for TST). For a migrant population in Malaysia, QuantiFERON is cost-effective when compared with TST. Further research should consider targeted LTBI screening for migrants in Malaysia based on common risk factors.

Non-invasive prenatal testing for everybody or contingent screening?

To compare the advantages and disadvantages of two main implementation strategies for non-invasive prenatal testing (NIPT) for the detection of trisomies 21, 13 and 18 in public healthcare settings. These concern NIPT as a first-tier screening test for all pregnant women, or NIPT contingent on an increased risk first-trimester combined test (FCT) result. Comparison based on (un)published data and literature. Despite the lower prevalence of trisomies in the low-risk population, data show that the positive predictive value (PPV) and detection-miscarriage ratio of first-tier NIPT are comparable to NIPT used as contingency test. Advantages of NIPT as a first-tier test compared to FCT with contingent NIPT are that there is no time-window for testing, sensitivity is higher, fewer women need follow-up testing (PPV of NIPT is higher than PPV of FCT), less anxiety for pregnant women and partners. When given the choice, pregnant women prefer first-tier NIPT. Although contingency testing still seems to be the cheaper option, the differences in costs are becoming increasingly smaller and might soon disappear. We argue that NIPT should preferably be offered as a first-tier test for the detection of fetal aneuploidies for all pregnant women, provided that women are supported to make informed decisions. This article is protected by copyright. All rights reserved.

Diagnostic Accuracy of Rapid Antigen Test for COVID-19 Infection: A Retrospective Analysis

Introduction: For the diagnosis of Coronavirus Disease 2019 (COVID-19) disease, Real-Time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) is a laboratory-based technique and is considered a gold standard test, but is time consuming. A Rapid Antigen Test (RAT) is used for screening which is an immunoassay that identifies the presence of a viral antigen causing infection at the point of care. The RAT is quick, inexpensive, easily accessible and doesn’t need lab handling or sample preprocessing. Aim: To measure the sensitivity, specificity, Negative Predictive Value (NPV) and Positive Predictive Value (PPV) of RAT in comparison to RT-PCR. Materials and Methods: This retrospective study was conducted in Department of Community Medicine at Government Medical College (tertiary care centre), Surat, Gujarat, India, using secondary data from 1st July 2020 to 5th Dec 2020. The samples were collected from all the patients of Acute Respiratory Illness (ARI), Severe Acute Respiratory Illness (SARI), Influenza Like Illness (ILI), the suspected COVID-19 cases and all walk in patients for testing or treatment purposes. A total of 264 participants enrolled in the study underwent both the RAT and RT-PCR tests. The sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were calculated using MS Excel Statistical Package for the Social Sciences (SPSS) version 17.0. Results: Total 264 cases were analysed, amongst which 161 (60.9%) were males and 103 (39.1%) were females and the mean age of the patient was 41.6 years and 36.8 years for males and females, respectively. The overall sensitivity was 52.47%, specificity was 87.11%, PPV was 71.62% and the NPV was 74.73%. While among symptomatic patients sensitivity was 55.55%, specificity was 88.54%, PPV was 76.97% and NPV was 74.35%. Conclusion: Because of the low sensitivity of the RAT, if used alone a high number of false negative cases will be resulted. Hence, it is employed in community and clinical settings as sequential screening in conjunction with RT-PCR, which results in improved net gain and aids in disease transmission control.

False negative results in testosterone doping in forensic cases: Sensitivity of the urinary detection criteria T/E and T/LH.

At the Swedish national forensic toxicology laboratory, a measured testosterone/epitestosterone (T/E) ratio ≥ 12 together with testosterone/luteinizing hormone (T/LH) in urine > 400 nmol/IU is considered as a proof of exogenous testosterone administration. However, according to the rules of the World Anti-Doping Agency (WADA), samples with T/E ratio > 4 are considered suspicious and shall be further analysed by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) to confirm the origin of testosterone and its metabolites. The aim of this study was to investigate the possibility of false negative results and to estimate the frequency of negative results using the current criteria for detection of abuse of testosterone in forensic investigations. Urine and serum samples were collected by the police at suspected infringement of the doping law in Sweden. Fifty-eight male subjects were included in the study. Urinary testosterone was determined by gas chromatography-mass spectrometry (GC-MS), serum testosterone and LH-by immunoassay. The origin of testosterone and its metabolites was confirmed by means of GC-C-IRMS. Twenty-six of the 57 analysed subjects tested positive for exogenous testosterone using the criteria T/E ≥ 12 combined with T/LH > 400 nmol/IU. The IRMS analyses confirmed 47 positives; thus, 21 were considered false negatives. Negative predictive value was 32% (95% confidence interval [CI]: 16%-50%) and sensitivity 55%. No false positive subjects were found. The number of false negative cases using the current criteria for the detection of testosterone abuse and hence the low sensitivity indicates a need to discuss introduction of new strategies in forensic doping investigations.

To evaluate the sensitivity of cytological examination of endobronchial biopsy, BAL, bronchial brushing and sputum in diagnosing lung carcinoma

All the cases of suspected bronchial malignancy were included in present study in which broncho-alveolar lavage (BAL) and bronchial biopsy samples were received in pathology department for evaluation. Respective bronchial brushings & sputum samples were also studied where ever available. Cross sectional study.In our study, correctly diagnosed adenocarcinoma of lung on BAL were 27.7%, sqaumous cell carcinoma were 26.6%, small cell carcinoma were 40% and BAL cytodiagnosis from miscellaneous tumor could only be made in 14.2% cases. Endobronchial biopsy and BAL, both were studied, sensitivity of cases increases and number of false negative cases decreases for diagnosis. Bronchial brushing has better sensitivity than BAL for diagnosis of lung carcinoma. Sputum is less sensitive than bronchial brushing for diagnosis of lung carcinoma.

Tiroid Nodüllerinin Değerlendirilmesinde Bethesda Sistemi ve İnce İğne Aspirasyon Biopsisinin Yeri

Aim: In this study, the role of fine needle aspiration biopsy (FNAB) evaluated with the Bethesda System in the diagnosis of thyroid nodules was investigated. Materials and Methods: Total 2284 FNAB materials of 1846 patients were performed in the Pathology Department of Kutahya Health Sciences University, Evliya Celebi Traning and Research Hospital between 2016 and 2019 and reported according to the Bethesda category. Among these cases, diagnostic sensitivity, specificity, accuracy, positive and negative predictive values of FNAB were calculated by making cytohistopathologica comparison in 328 cases who underwent total thyroidectomy. Results: In the study, 1538 of the 1846 patients included were female (83.31%) and 308 (16.68%) were male. The average age was 49.92 years (Age range 19-87). The final cytological diagnoses of 2284 FNABs were as follows: 287 (12.57%) nondiagnostic or unsatisfactory, 1517 (66.42%) benign cytology, 316 (13.83%) atypia of undetermined significance/follicular lesion of undetermined significance, 63 (2.75%) follicular neoplasm or suspicious for a follicular neoplasm, 59 (2.59%) suspicious for malignancy and 42 (1.84%) malignant cytology. Histologically, 245 (74.70%) of the 328 cases were benign, while 83 (25.30%) were malignant. The number of true negative cases was 216 (65.85%), the number of true positive cases was 62 (19.90%), the number of false positive cases was 29 (8.84%) and the number of false negative cases was 21 (6.40%). In this case, diagnostic sensitivity, specificity, accuracy rates, positive and negative predictive values were 74.7%, 88.16%, 84.76%, 68.13% and 91.14%, respectively. Conclusion: In our study, it was observed that the sensitivity, specificity, accuracy rates, positive and negative predictive values of thyroid FNABs were compatible with the literature. We think that as the experience of the clinician and cytopathologist increases, false negative and positive results will decrease and at the same time, the confidence in thyroid FNABs will increase even more with the participation of some recent molecular methods (BRAF and RET/PTC, AX8/PPARG and RAS) applied to FNABs.

Percentage volume of delayed kinetics in computer-aided diagnosis of MRI of the breast to reduce false-positive results and unnecessary biopsies

To investigate the best cut-off percentage volume of delayed kinetics using magnetic resonance imaging (MRI) with computer-aided diagnosis (CAD) to reduce unnecessary biopsies in patients with newly diagnosed breast cancer. Between January 2017 and December 2018, 94 malignant and 56 benign masses were analysed using MRI CAD. All malignant and benign masses measured <2 cm and were confirmed histopathologically. The optimal cut-off values for washout, plateau, and persistent components were determined using the maximum Youden Index. The positive predictive value (PPV) was analysed using morphological descriptors and combining the percentage volume of delayed kinetics. The area under the curve (AUC) was highest at ≤73% persistent component (AUC=0.759). In the subgroup analyses of masses <1 cm, the AUC was highest a plateau of >26% (AUC=0.697). When the persistent ≤73% criterion was applied to the lesions of C4a, the positive predictive value (PPV) increased from 61.9% to 72.44% with reduced false-negative cases and when applied to the lesions of C4a and C4b, the PPV increased from 61.9% to 78.1% with slightly increased false-negative cases. For subcentimetre lesions, the PPV increased from 46.77% to 54.72% with the same number of false-negative cases, when a plateau of >26% was applied to C4a, and the PPV increased from 46.77% to 61.36% with five false-negative cases when applied to C4a and C4b. The percentage volume of delayed kinetics has the potential to improve the PPV of breast MRI. When suspicious masses <2 cm do not show ≤73% persistence, follow-up rather than biopsy could be considered; however, to avoid increasing false-negative cases, delayed kinetic information should be used with caution and accurate margin assessment is essential.

Impact of hybrid supervision approaches on the performance of artificial intelligence for the classification of chest radiographs

PurposeTo evaluate the impact of different supervision regimens on the training of artificial intelligence (AI) in the classification of chest radiographs as normal or abnormal in a moderately sized cohort of individuals more likely to be outpatients. Materials and methodsIn a retrospective study, 7000 consecutive two-view chest radiographs obtained from 2012 to 2015 were labeled as normal or abnormal based on clinical reports. A convolutional neural network (CNN) was trained on this dataset and then evaluated with an unseen subset of 500 radiographs. Five different training approaches were tested: (1) weak supervision and four hybrid approaches combining weak supervision and extra supervision with annotation in (2) an unbalanced set of normal and abnormal cases, (3) a set of only abnormal cases, (4) a set of only normal cases, and (5) a balanced set of normal and abnormal cases. Standard binary classification metrics were assessed. ResultsThe weakly supervised model achieved an accuracy of 82%, but yielded 75 false negative cases, at a sensitivity of 70.0% and a negative predictive value (NPV) of 75.5%. Extra supervision increased NPV at the expense of the false positive rate and overall accuracy. Extra supervision with training using a balance of abnormal and normal radiographs resulted in the greatest increase in NPV (87.2%), improved sensitivity (92.8%), and reduced the number of false negatives by more than fourfold (18 compared to 75 cases). ConclusionExtra supervision using a balance of annotated normal and abnormal cases applied to a weakly supervised model can minimize the number of false negative cases when classifying two-view chest radiographs. Further refinement of such hybrid training approaches for AI is warranted to refine models for practical clinical applications.

Diagnostic Value of Cytomegalovirus IgM Antibodies at Birth in PCR-Confirmed Congenital Cytomegalovirus Infection.

Although cytomegalovirus (CMV) DNA detection in urine is the standard method for diagnosing congenital cytomegalovirus infection (CCMVI), polymerase chain reaction (PCR) is not comprehensively available. Currently, the efficacy of CMV-specific IgM (CMV-IgM) and CMV-specific IgG (CMV-IgG) detection remains unclear. To determine the sensitivity and specificity of CMV-specific antibodies at birth, we investigated CMV-IgM and CMV-IgG titers in CCMVI cases and non-CCMVI controls, with confirmed diagnoses by urine quantitative real-time PCR within 3 weeks after birth. We included 174 infants with suspected CCMVI in whom serological testing was performed within the first 2 weeks after birth during 2012–2018. We classified the participants into a CCMVI group (n = 32) and non-CCMVI group (n = 142) based on their urine PCR results. The CMV-IgM-positive rate was 27/32 (84.4%) in the CCMVI group, compared with 1/142 (0.7%) in the non-CCMVI group (p < 0.0001). The positive CMV-IgG rates were 32/32 (100%) in the CCMVI group and 141/142 (99.3%) in the non-CCMVI group. The positive predictive value for CMV-IgM was high at 96.4% (27/28). This value may be sufficient for clinical use, especially in settings with limited resources where PCR is unavailable. However, CCMVI screening by CMV-IgM alone appears insufficient because of the considerable number of false-negative cases.

Diagnostic accuracy of shear wave elastography – Virtual touch™ imaging quantification in the evaluation of breast masses: Impact on ultrasonography’s specificity and its ultimate clinical benefit

ObjectivesTo evaluate the diagnostic performance and the clinical benefit of Shear-Wave Elastography - Virtual Touch™ Imaging Quantification (SWE-VTIQ) as a complement to ultrasonography (US). MethodsFrom October 2016 through Jun 2017, B-mode US and SWE-VTIQ were prospectively performed in 396 breast masses in 357 women who consented to undergo this study. Quantitative elastography values were recorded: Vmax (maximum elasticity), Vmean (median elasticity), Vratio(max) (ratio of Vmax and surrounding parenchyma) and Vratio(mean) (ratio of Vmean and surrounding parenchyma). The histopathology of the lesions was considered the reference standard for benign or malignant definition. The performance of the four elastographic parameters was evaluated trough sensitivity, specificity and AUC. The parameter with the best performance was tested in six different diagnostic approaches defined based on clinical practice. ResultsOf the 396 masses, 122 (30.8%) were benign and 274 (69.2%) were malignant. All SWE parameters were significantly higher in malignant masses (all p < 0.01). Vmax and Vratio(max) performed significantly better then Vratio(mean) (p = 0.01 and p = 0.03, respectively). SWE-VTIQ improved US specificity in all diagnostic approaches, except when applied to BI-RADS 3 lesions. SWE-VTIQ reduced the false positive rate in 25% if applied only to BI-RADS 4A masses, maintaining a high sensitivity (98.9%, 95% confidence interval 97.1–100%) and a negative predictive value of 95.5%. When applied to BI-RADS 4A and 4B masses, SWE-VTIQ reduced the false positive rate in 54.4%. However, 13 malignant cases would be missed in this approach (4.7% of all malignant cases). ConclusionsSWE-VTIQ increases US specificity when applied to BI-RADS 4 A lesions, significantly reducing unnecessary interventions and preserving the diagnosis of malignant lesions. When applied also to BI-RADS® 4B lesions, SWE-VTIQ increases the number of false negative cases, which should be evaluated with caution.

Modified Alvarado scoring system as a diagnostic tool for acute appendicitis at a tertiary care teaching hospital, Central India: a cross sectional study

Background: Acute Appendicitis forms an important emergency in the day-to-day surgical practice. It affects human beings irrespective of age, nationality and religion. Early diagnosis and prompt operative intervention is the key for successful management of acute appendicitis. However, the picture of acute appendicitis may not be classical, and in such situations, a policy of early intervention to avoid perforation may lead to high negative appendicectomy rates.Methods: A total of 80 patients were enrolled in the present cross sectional study. Their ages ranged from eleven to 72 years (mean 32.89 ± 15.87). A proforma containing general information about the patient plus eight variables based on the modified Alvarado scoring system was filled.Results: Histological examination confirmed appendicitis in 54 patients (67.5%). The remaining 26 patients were found to have normal appendix giving a negative appendicectomy rate of 32.5% being 36.8% and 28.3% for males and females respectively.Conclusions: This scoring system is easy, simple and cheap complementary aid for supporting the diagnosis of acute appendicitis. MASS can be used effectively in Indian setup to reduce the incidence of negative appendectomies. The patients are not unduly exposed to risks of delay in intervention or significant increase in number of false negative cases.

Concordance and discrepancy between subjective and objective cognitive assessment in bipolar disorder: What is influencing this discrepancy?

IntroductionEvidence has shown that some patients with bipolar disorder have a relatively accurate sense of their cognitive abilities, whereas others may overreported or underreported cognitive difficulties, which causes a discrepancy in this measures.ObjectivesTo investigate concordance and discrepancy between subjective and objective cognitive measures, as well as to identify factors that could influence this discrepancy.MethodsPatients who met DSM IV-TR criteria for bipolar disorder in partial or full remission (HDRS-17 score ≤ 12; YMRS score ≤ 7) were recruited from outpatient clinic at Barcelona and Porto Alegre. Objective cognitive assessment was performed by the Letter-Number Sequencing (LNS-WAIS III). Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA) was used as a subjective cognitive measure.ResultsWere included 179 patients. We found a concordance between COBRA and LNS in 62 cases, and discrepancy in 117 cases (Fig. 1). The incongruent group (COBRA–and LNS + ) have less years of study (8.10 ± 4.01) than the incongruent group (COBRA+ and LNS–) (13.44 ± 4.05, P = 0.001), and than congruent group (COBRA–and NLS–) (13.75 ± 4.04, P = 0.003). Finally, the congruent group (COBRA+ and LNS + ) was the group with higher functioning impairment.ConclusionsA few number of false-negative cases were detected, suggesting that COBRA can be used as a screening instrument. A special attention should be provided for subjects with a few years of study, because possibly these subjects presents more difficulty in express its cognitive difficulties.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Abstract P3-07-07: The updated ASCO/CAP guidelines for HER2 testing create more uncertainty for clinicians

Abstract Background: Accurate assessment of the Human Epidermal Growth Factor Receptor 2 (HER2) status has been an integral part of clinical decision making in treatments of breast cancer. In 2007, American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) published a series of guidelines on how to determine the status of HER2. The guidelines were updated in 2013 with the goal of reducing the numbers of false negative cases. The new guidelines are based on a combination of HER2:CEP17 ratio and average HER2 copy number. We sought to assess the overall effect of the new guidelines. Methods: We retrospectively identified all cases of invasive breast cancer with HER2 testing done in 2014 from the pathology database of Mount Sinai Beth Israel, Mount Sinai St. Luke's and Roosevelt Hospitals. Our pathology department guideline is to perform initial testing for HER2 with immunohistochemistry (IHC) by the HercepTest (Dako) method. Those with IHC of 2+ would be followed by reflex HER2 dual probe FISH. The HER2:CEP 17 ratio and average HER2 copy number were then reviewed for each IHC 2+ case using the 2013 guidelines. These cases were then rescored using the 2007 guidelines. All equivocal cases as determined by the new 2013 guidelines (HER2:CEP17 ratio &amp;lt;2.0 with an average HER2 copy number ≥4.0 and &amp;lt;6.0 signals/cell) were further evaluated to determine whether repeat HER2 testing was performed as suggested by the new guidelines and whether HER2 directed therapy was recommended for patient. Results: Among 853 cases identified in the database, 337 were IHC 2+. Using 2007 guidelines, 27/337 cases (8.0%) were amplified (HER2:CEP 17 ratio &amp;gt;2.2), 6 (1.8%) were equivocal (HER2:CEP 17 ratio 1.8-2.2), and 305 cases (90.2%) were non-amplified (HER2:CEP 17 ratio &amp;lt;1.8). Using the 2013 guidelines, 29/337 cases (8.6%) were amplified (HER2:CEP 17 ratio ≥2 or HER2 copy number ≥6), 23 (6.8%) were equivocal (HER2:CEP17 ratio &amp;lt;2.0 with an average HER2 copy number ≥4.0 and &amp;lt;6.0), and 284 (84.3%) were non-amplified (HER2:CEP 17 ratio &amp;lt;2 with an average HER2 copy number &amp;lt;4.0). The new guidelines resulted in change in HER2 status in 24 cases (7.1%): 2 cases changed from equivocal to amplified, 1 case changed from equivocal to non-amplified, but 20 cases changed from non-amplified to equivocal. Of the 23 equivocal cases determined using the 2013 guidelines, only 13 cases had repeat HER2 analysis. On repeat HER2 testing, one case was found to be HER2 amplified, 4 cases were non-amplified, and 8 cases remained equivocal. Only one equivocal case received HER2 directed treatment. Conclusion: The 2013 ASCO/CAP guidelines for HER2 assessment identified a slightly increased number of patients eligible for HER2 directed therapy, but also resulted in a significant increase in the number of equivocal cases. The new guidelines appear to have generated more uncertainty for the clinician due to the rise in equivocal cases. Further studies are needed to determine whether patients with equivocal HER2 status would benefit from HER2 directed therapy. Citation Format: Chen J, Klein P, Shao T. The updated ASCO/CAP guidelines for HER2 testing create more uncertainty for clinicians. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-07.

Restaging Clear Cell Renal Carcinoma With 18F-FDG PET/CT

The aim of our retrospective study was to assess the usefulness of F-FDG PET/CT in the restaging of clear cell renal cell carcinoma (RCC) patients. Sixty-nine patients (median age = 62 years; range = 36-86 years) affected by clear cell RCC (TNM at staging: T1, 42 patients; T2, 13 patients; T3, 11 patients; T4, 3 patients; Fuhrman grade: G2, 47 patients; G3, 20 patients; G4, 2 patients) underwent whole-body F-FDG PET/CT to restage the disease after nephrectomy for clinical or radiological suspicion of metastases. Areas of abnormal uptake at PET/CT were classified, taking the liver uptake as reference, as follows: 1 = faint uptake, lower than liver; 2 = moderate uptake, equal to liver; and 3 = high uptake, higher than liver. Validation of F-FDG PET/CT results was established by (1) biopsy (23 patients) and (2) other imaging modalities (addressed BS; c.e.CT; MRI; F-fluoride PET/CT; subsequent F-FDG PET/CT), and/or clinical and radiological follow-up of 12 months (46 patients). F-FDG PET/CT was positive in 42 patients and negative in 27 patients. Sixteen patients presented single lesions and 26 patients presented multiple localizations of the disease. On a patient basis, 40 patients resulted true positive, 2 patient false positive, 23 patients true negative, and 4 patients false negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 90%, 92%, 91%, 95%, and 85%, respectively. On a lesion basis, PET/CT detected 114 areas of abnormal uptake in 42 positive patients of which 112 resulted to be true positive. FDG uptake of the true positive lesions resulted to be high in 83 cases, moderate in 17 lesions, and finally faint in 12 lesions. F-FDG PET/CT demonstrated a good sensitivity in the restaging of clear cell RCC. Most of the lesions showed intense activity. According to our results, it seems that the use of F-FDG PET/CT in the restaging of RCC is feasible because the number of false-negative cases is limited.

Thyroid Nodule with Benign Cytology: Is Clinical Follow-Up Enough?

ObjectiveIn this multicenter study, we investigated the management algorithm for thyroid nodules with benign cytology using US features from data collected from 7 institutions.Materials and MethodsThe institutional review board approved this retrospective study. Data on 700 focal thyroid nodules in 673 consecutive patients were collected from 7 university-affiliated hospitals. This study included nodules that were diagnosed as benign at initial cytologic evaluation and that underwent pathologic or follow-up study. The risk of malignancy was compared according to the US assessments of each institution as well as looking at all the nodules together as a whole.ResultsOf the 700 nodules, 688 (98.3%) were benign and 12 (1.7%) were malignant. If initial cytologic results were benign, the likelihood of the nodule actually being malignant was from 1 to 3%, varying by institution. The likelihood of a cytologically benign nodule with positive US being malignant (4.7%, 8/169) was higher than that of one without positive US (0.8%, 4/531) (P = .002).ConclusionBased on our multicenter study, repeat FNA should be performed in thyroid nodules with initial benign cytology showing suspicious US features in order to decrease the number of false negative cases.

Prostate Cancer: All Aspects

Prostate Cancer: All Aspects

Ultrasound-guided diagnostic breast biopsy methodology: retrospective comparison of the 8-gauge vacuum-assisted biopsy approach versus the spring-loaded 14-gauge core biopsy approach

BackgroundUltrasound-guided diagnostic breast biopsy technology represents the current standard of care for the evaluation of indeterminate and suspicious lesions seen on diagnostic breast ultrasound. Yet, there remains much debate as to which particular method of ultrasound-guided diagnostic breast biopsy provides the most accurate and optimal diagnostic information. The aim of the current study was to compare and contrast the 8-gauge vacuum-assisted biopsy approach and the spring-loaded 14-gauge core biopsy approach.MethodsA retrospective analysis was done of all ultrasound-guided diagnostic breast biopsy procedures performed by either the 8-gauge vacuum-assisted biopsy approach or the spring-loaded 14-gauge core biopsy approach by a single surgeon from July 2001 through June 2009.ResultsAmong 1443 ultrasound-guided diagnostic breast biopsy procedures performed, 724 (50.2%) were by the 8-gauge vacuum-assisted biopsy technique and 719 (49.8%) were by the spring-loaded 14-gauge core biopsy technique. The total number of false negative cases (i.e., benign findings instead of invasive breast carcinoma) was significantly greater (P = 0.008) in the spring-loaded 14-gauge core biopsy group (8/681, 1.2%) as compared to in the 8-gauge vacuum-assisted biopsy group (0/652, 0%), with an overall false negative rate of 2.1% (8/386) for the spring-loaded 14-gauge core biopsy group as compared to 0% (0/148) for the 8-gauge vacuum-assisted biopsy group. Significantly more (P < 0.001) patients in the spring-loaded 14-gauge core biopsy group (81/719, 11.3%) than in the 8-gauge vacuum-assisted biopsy group (18/724, 2.5%) were recommended for further diagnostic surgical removal of additional tissue from the same anatomical site of the affected breast in an immediate fashion for indeterminate/inconclusive findings seen on the original ultrasound-guided diagnostic breast biopsy procedure. Significantly more (P < 0.001) patients in the spring-loaded 14-gauge core biopsy group (54/719, 7.5%) than in the 8-gauge vacuum-assisted biopsy group (9/724, 1.2%) personally requested further diagnostic surgical removal of additional tissue from the same anatomical site of the affected breast in an immediate fashion for a benign finding seen on the original ultrasound-guided diagnostic breast biopsy procedure.ConclusionsIn appropriately selected cases, the 8-gauge vacuum-assisted biopsy approach appears to be advantageous to the spring-loaded 14-gauge core biopsy approach for providing the most accurate and optimal diagnostic information.

Post-processing analysis of transient-evoked otoacoustic emissions to detect 4 kHz-notch hearing impairment – a pilot study

SummaryBackgroundTo identify a parameter to distinguish normal hearing from hearing impairment in the early stages. The parameter was obtained from transient-evoked otoacoustic emissions (TEOAEs), overcoming the limitations of the usually adopted waveform descriptive parameters which may fail in standard clinical screenings.Material/MethodsAudiometric examinations and TEOAE analysis were conducted on 15 normal ears and on 14 hearing-impaired ears that exhibited an audiometric notch around 4 kHz. TEOAE signals were analyzed through a multivariate technique to filter out the individual variability and to highlight the dynamic structure of the signals. The new parameter (named radius 2-dimension – RAD2D) was defined and evaluated for simulated TEOAE signals modeling a different amount of hearing impairment.ResultsAudiometric examinations indicated 14 ears as impaired-hearing (IH), while the TEOAE ILO92 whole reproducibility parameter (WWR) indicated as IH 7 signals out of 14 (50%). The proposed new parameter indicated as IH 9 signals out of 14 (64%), reducing the number of false negative cases of WWR.ConclusionsIn this preliminary study there is evidence that the new parameter RAD2D defines the topology and the quantification of the damage in the inner ear. The proposed protocol can be useful in hearing screenings to identify hearing impairments much earlier than conventional pure tone audiometry and TEOAE pass/fail test.

Abstract 327: Genomic profiling of sentinel lymph node breast cancer metastasis

Abstract The sentinel lymph node (SLN) is the first node in the axilla to harbor malignant cells in breast tumors with metastasis, and its positivity is an indication for axillary lymph node dissection. Despite significant improvement in the methods for detection of tumor cells at this site, there are a still significant number of false negative cases and the inability to detect malignant cells in lower abundance, such as in the case of micrometastasis. We propose to use methods based on the genomic alterations, which present higher sensitivity and accuracy, and can be used to augment the current methods to identify the epithelial malignant cells at the SLN. In this study, we performed CGH and array-CGH analysis in microdissected tumors cells from the SLN metastatic lesions to identify DNA copy number changes. We compared the changes observed in the SLN lesion to the ones present in the corresponding primary tumors (PT) from the same patients. Here we present the results from the initial analysis of 10 FFPE (formalin-fixed paraffin-embedded) breast cancer samples (5 pairs of SLN and PT). DNA copy number changes were detected by both methods in all the cases analyzed. A remarkable similarity in the DNA profiles between the SLN metastatic lesions and the corresponding PT were observed, despite the high level of heterogeneity observed among the cases. CGH analysis revealed most frequently gains of chromosomal regions (at both lesions) involving 1p, 1q, 6q, 9q, 11p, 11q, 13q, 16p, 17q, 19p, 19q and Xq. Array-CGH analysis detected both amplifications and deletions, affecting mostly the chromosome regions 1p (genes affected KLHL17, NOC2L, PPIAL4), 9q (ANKRD20A, COL5A), 11p (PSMD13, SIRT3), 15q (MAN2C1), 19p (MUC16, AZU1) and 20q regions (PSMA7). In addition, several genes of the HIST, FLJ, SLC and TRIM family as well as the homeobox families HOX and NK were involved in the alterations. FISH analysis is being conducted to confirm the array-CGH findings as well as the analysis of additional matching samples. The assessment of copy number changes in the SLN metastasis (and in its correspondent PT) using genomic profiling is a very sensitive method and will lead to the identification of genomic alterations that can reliably characterize breast tumor cells at the SLN lesions. Once these alterations are validated in larger series of patients, they can be used as molecular markers that can improve the predictive value of the current established methods of SLN evaluation in the identification of patients at higher risk of developing axillary lymph node metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 327.

A comparative study of teledermatoscopy and face-to-face examination of pigmented skin lesions

We examined the agreement between diagnoses of pigmented skin lesions based on an in-person (face-to-face) dermatological examination and diagnoses based on the study of medical records and images transferred through the web (teledermatoscopy). Two experienced dermatologists examined and diagnosed 64 pigmented skin lesions, which had been surgically excised and undergone histopathology examination. Two years later, the same cases were studied and diagnosed once again by the same dermatologists via the web. There was 72% agreement between the in-person diagnoses and the biopsy results (the gold standard), and 66% agreement between the telediagnoses and the biopsy results. Telemedicine had high sensitivity (87%) and specificity (73%), although there were 4 false-negative diagnoses. A web-based dermatoscopic diagnostic service appears to be feasible and would meet the needs for access to specialized services in rural areas. However, further work is required to decrease the number of false negative cases.