Adding retinal photography to screening for diabetic retinopathy: a prospective study in primary care.

OBJECTIVE--To evaluate whether adding retinal photography improved community screening for diabetic retinopathy. SETTING--Mobile screening unit at rural and urban general practices in south west England. SUBJECTS--1010 diabetic patients from primary care. DESIGN--Prospective study; patients were examined by ophthalmoscopy by general practitioners or opticians without fundal photographs and again with photographs, and assessments were compared to those of an ophthalmologist. MAIN OUTCOME MEASURES--Whether fundal photography improved the sensitivity of detection of retinopathy and referrable diabetic retinopathy, and whether this sensitivity could be improved by including a review of the films by the specialist. RESULTS--Diabetic retinopathy was detected by the ophthalmologist in 205 patients (20.5%) and referrable retinopathy in 49 (4.9%). The sensitivity of the general practitioners and opticians for referrable retinopathy with ophthalmoscopy was 65%, and improved to 84% with retinal photographs. General practitioners'' sensitivity in detecting background retinopathy improved with photographs from 22% to 65%; opticians'' sensitivity in detecting background retinopathy improved from 43% to 71%. The sensitivity of detecting referrable retinopathy by general practitioners improved from 56% to 80% with photographs; for opticians it improved from 75% to 88%. CONCLUSIONS--Combining modalities of screening by providing photography with specialist review of all films in addition to direct ophthalmoscopy through dilated pupils improves assessment and referral for diabetic retinopathy by general practitioners and opticians. With further training and experience, primary care screeners should be able to achieve a sensitivity that will achieve an effective, acceptable, and economical community based screening programme for this condition.     

Fine Needle Aspiration Cytodiagnosis As A Pre-Requisite For Primary Medical Treatment of Breast Cancer

The accurate non-surgical diagnosis of breast lumps allows assessment of breast cancer patients for conservation or neoadjuvant primary treatment before surgical intervention. We have analysed the accuracy of clinical assessment, fine needle aspiration cytology (FNAC), and mammography in over 868 women seen in a symptomatic breast clinic. Clinical examination by an experienced breast physician, together with FNAC, detected over 99% of the cancers with a 12% false positive rate. A cytological diagnosis of definite carcinoma was obtained in 69% of women with breast cancer with no false positive result from the women with benign conditions producing a 100% positive predictive value. These results indicate that it would be acceptable to give pre-surgical systemic endocrine or chemotherapy to women with positive cytology which is therefore a prerequisite for a neoadjuvant therapy programme.     

MicroRNA target prediction based on second-order Hidden Markov Model

MicroRNAs are one class of small single-stranded RNA of about 22 nt serving as important negative gene regulators. In animals, miRNAs mainly repress protein translation by binding itself to the 3′ UTR regions of mRNAs with imperfect complementary pairing. Although bioinformatics investigations have resulted in a number of target prediction tools, all of these have a common shortcoming—a high false positive rate. Therefore, it is important to further filter the predicted targets. In this paper, based on miRNA:target duplex, we construct a second-order Hidden Markov Model, implement Baum-Welch training algorithm and apply this model to further process predicted targets. The model trains the classifier by 244 positive and 49 negative miRNA:target interaction pairs and achieves a sensitivity of 72.54%, specificity of 55.10% and accuracy of 69.62% by 10-fold cross-validation experiments. In order to further verify the applicability of the algorithm, previously collected datasets, including 195 positive and 38 negative, are chosen to test it, with consistent results. We believe that our method will provide some guidance for experimental biologists, especially in choosing miRNA targets for validation.     

Factors Influencing Intracavitary Electrocardiographic P-Wave Changes during Central Venous Catheter Placement

Amplitude changes in the P-wave of intracavitary electrocardiography have been used to assess the tip placement of central venous catheters. The research assessed the sensitivity and specificity of this sign in comparison with standard radiographic techniques for tip location, focusing on factors influencing its clinical utility. Both intracavitary electrocardiography guided tip location and X-ray positioning were used to verify catheter tip locations in patients undergoing central venous catheter insertion. Intracavitary electrocardiograms from 1119 patients (of a total 1160 subjects) showed specific amplitude changes in the P-wave. As the results show, compared with X-ray positioning, the sensitivity of electrocardiography-guided tip location was 97.3%, with false negative rate of 2.7%; the specificity was 1, with false positive rate of zero. Univariate analyses indicated that features including age, gender, height, body weight, and heart rate have no statistically significant influence on P-wave amplitude changes (P>0.05). Multivariate logistic regression revealed that catheter insertion routes (OR = 2.280, P = 0.003) and basal P-wave amplitude (OR = 0.553, P = 0.003) have statistically significant impacts on P-wave amplitude changes. As a reliable indicator of tip location, amplitude change in the P-wave has proved of good sensitivity and excellent specificity, and the minor, zero, false positive rate supports the clinical utility of this technique in early recognition of malpositioned tips. A better sensitivity was achieved in placement of centrally inserted central catheters (CICCs) than that of peripherally inserted central catheters (PICCs). In clinical practice, a combination of intracavitary electrocardiography, ultrasonic inspection and the anthropometric measurement method would further improve the accuracy.     

Computer system for assisting with clinical interpretation of tumour marker data.

OBJECTIVE--To design and evaluate a computer advisory system for the treatment of gestational trophoblastic tumour. DESIGN--A comparison of clinicians'' treatment decisions with those of the computer system. Two datasets were used: one to calibrate the system and one to independently evaluate it. SETTING--Department of medical oncology. PATIENTS--Computerised records of 290 patients with low risk gestational trophoblastic tumour for whom the advisory system could predict the adequacy of treatment. The calibration set comprised patients admitted during 1979-86(227) and the test set patients during 1986-89(63). MAIN OUTCOME MEASURES--The system''s accuracy in predicting need to change treatment compared with clinicians'' actions. The mean time faster that the system was in predicting the need to change treatment. RESULTS--On the calibration dataset the system was 94% (164/174) accurate in predicting patients whose treatment was adequate, recommending change when none occurred in only 10 (6%) patients. In patients whose treatment was changed the system recommended change earlier than clinicians in 39/53 cases (74%), with a mean time advantage of 14.9 (SE 2.02) days. On the test dataset the system had an accuracy of 91% (31/34) in predicting treatment adequacy and a false positive rate of 9% (3/34). The system recommended change earlier than clinicians in 22/29 cases (76%), with a mean time advantage of 12.5 (2.22) days. CONCLUSIONS--The computer advisory system could improve patient management by reducing the time spent receiving ineffective treatment. This has implications for both patient time and clinical costs.     

Detection of inflammatory bowel disease in adults and children: evaluation of a new isotopic technique.

The distribution of radioactivity after the oral administration of sucralfate labelled with technetium-99m was studied in 33 patients with Crohn''s disease (13 adults, 20 children), 10 with ulcerative colitis (four adults), and 29 controls (23 with upper intestinal disease, four irritable bowel, one hypolactasia, and one malrotation of the gut). Positive scans were obtained in all patients with ulcerative colitis and 29 of 31 with active Crohn''s disease. The scans of two patients with inactive Crohn''s disease were negative. There were two false negative scans in patients with Crohn''s colitis and one false positive scan. Overall, sensitivity was 95% and specificity 97%. Comparison with radiology in 39 patients showed similar distribution of disease in 24 and more extensive disease in 12. The scan was inexpensive, simple to perform, well tolerated, allowed small and large bowel to be visualised simultaneously, and used a lower dose of radiation than barium studies. It may prove useful as a screening test for inflammatory bowel disease and in the serial assessment of disease activity.     

Factors Affecting the Ability of the Spectral Domain Optical Coherence Tomograph to Detect Photographic Retinal Nerve Fiber Layer Defects

Purpose

To evaluate the ability of normative database classification (color-coded maps) of spectral domain optical coherence tomograph (SDOCT) in detecting wedge shaped retinal nerve fiber layer (RNFL) defects identified on photographs and the factors affecting the ability of SDOCT in detecting these RNFL defects.

Methods

In a cross-sectional study, 238 eyes (476 RNFL quadrants) of 172 normal subjects and 85 eyes (103 RNFL quadrants with wedge shaped RNFL defects) of 66 glaucoma patients underwent RNFL imaging with SDOCT. Logistic regression models were used to evaluate the factors associated with false positive and false negative RNFL classifications of the color-coded maps of SDOCT.

Results

False positive classification at a p value of <5% was seen in 108 of 476 quadrants (22.8%). False negative classification at a p value of <5% was seen in 16 of 103 quadrants (15.5%). Of the 103 quadrants with RNFL defects, 64 showed a corresponding VF defect in the opposite hemisphere and 39 were preperimetric. Higher signal strength index (SSI) of the scan was less likely to have a false positive classification (odds ratio: 0.97, p = 0.01). Presence of an associated visual field defect (odds ratio: 0.17, p = 0.01) and inferior quadrant RNFL defects as compared to superior (odds ratio: 0.24, p = 0.04) were less likely to show false negative classifications.

Conclusions

Scans with lower signal strengths were more likely to show false positive RNFL classifications, and preperimetric and superior quadrant RNFL defects were more likely to show false negative classifications on color-coded maps of SDOCT.     

Influence of imaging on touch imprint cytology of breast lesions

Purpose: Touch imprint cytology (TIC) facilitates rapid diagnosis of breast diseases in women attending triple assessment clinics. Some pathologists, in our centre, feel that pathological interpretation of TIC slides is contentious when the lesions are radiologically indeterminate (R3), as these can lead to potentially higher false positive or false negative cytology results. We hypothesised that: ‘(R3) lesions are more likely to have higher false positive or false negative TIC and/or be inadequate for TIC assessment’. In other words, ‘imaging influences cytological classification especially when indeterminate’. Methods: Review of the data collected in our centre between December 2003 and July 2005. All patients who attended the one stop symptomatic breast clinic and had a TIC performed following an ultrasound (US) guided core biopsy (CB) were included. Demographic, radiological, cytological and core biopsy grading data were collected. Cytology grading was correlated with radiology classification to assess our hypothesis. Results: A total of 248 patients underwent 254 CB/TIC. The average patient's age of the group was 54 years (range of 29–95). On TIC, 186 (73%) were deemed malignant, 23(9%) benign while 33(13%) were inadequate for assessment. There was no false positive or false negative TIC. There was good correlation between TIC and CB results (p < 0.0001). Thirty-three cases were inadequate (C1) for cytology assessment, of these16 (48.5%) were indeterminate on imaging. R3 lesions were 6 times more prone to have C1 cytology (p < 0.0001). Conclusion: Touch imprint cytology is a reliable and efficient method in running a one stop breast clinic, with the backup of full tissue diagnosis. Careful selection of cases that would benefit from this technique is highly recommended as a significant number of radiologically indeterminate lesions are likely to be insufficient for cytological assessment. Further prospective trials are required to assess this further. Until then the diagnosis in this sub-group should depend on core biopsy.     

The role of thyroid fine needle aspiration (FNA) cytology in a district general hospital setting

The pilot study was undertaken to evaluate the role of FNA cytology in the clinical management of patients with thyroid swelling, in a District General Hospital (DGH) setting. One hundred and eleven patients were investigated over a period of 3 years, with a total of 142 fine needle aspirations. Statistical analysis showed a sensitivity of 71%, a specificity of 91% and a false negative rate of 2.7%. These results compare very favourably with other institutions. This study therefore shows that thyroid nodule FNA cytology can be performed in a DGH with a high standard of diagnostic accuracy, the results of which play a key role in patient management.     

初诊腋窝淋巴结阳性乳腺癌新辅助化疗后对腋窝淋巴结转阴性前哨活检的影响分析

摘要 目的：探究对初诊腋窝淋巴结阳性乳腺癌行新辅助化疗患者开展腋窝前哨淋巴结活检的临床意义。方法：选择2017年1月至2020年10月于我院接受改良根治术或保乳术治疗的100例初诊腋窝淋巴结阳性乳腺癌患者,将其中50例病理检测II B、III期行4~8个疗程新辅助化疗后实施前哨淋巴结活检患者设为研究组,将50例I、II A期直接行前哨淋巴结活检患者设为对照组,对比两组患者前哨淋巴结检出率、准确率、假阴性率和灵敏度,同时就患者病理特征与前哨淋巴结检出率的相关性开展分析。结果：（1）比较显示研究组患者与对照组患者在前哨淋巴结检出数、前哨淋巴结检出率以及前哨淋巴结假阴性率方面组间差异不大（P>0.05）;（2）病理学特征分析显示肿瘤直径以及临床N分期同新辅助化疗后患者前哨淋巴结检出阳性率密切相关（P<0.05）。结论：对初诊腋窝淋巴结阳性行新辅助化疗乳腺癌患者实施前哨淋巴结活检具有较显示的临床意义,能够较好的预测患者腋窝淋巴结状况,同时化疗前肿瘤直径、临床N分期是影响前哨淋巴结检出率的重要影响因素。     

Structure-based prediction of RNA-binding domains and RNA-binding sites and application to structural genomics targets

Mechanistic understanding of many key cellular processes often involves identification of RNA binding proteins (RBPs) and RNA binding sites in two separate steps. Here, they are predicted simultaneously by structural alignment to known protein-RNA complex structures followed by binding assessment with a DFIRE-based statistical energy function. This method achieves 98% accuracy and 91% precision for predicting RBPs and 93% accuracy and 78% precision for predicting RNA-binding amino-acid residues for a large benchmark of 212 RNA binding and 6761 non-RNA binding domains (leave-one-out cross-validation). Additional tests revealed that the method makes no false positive prediction from 311 DNA binding domains but correctly detects six domains binding with both DNA and RNA. In addition, it correctly identified 31 of 75 unbound RNA-binding domains with 92% accuracy and 65% precision for predicted binding residues and achieved 86% success rate in its application to SCOP RNA binding domain superfamily (Structural Classification Of Proteins). It further predicts 25 targets as RBPs in 2076 structural genomics targets: 20 of 25 predicted ones (80%) are putatively RNA binding. The superior performance over existing methods indicates the importance of dividing structures into domains, using a Z-score to measure relative structural similarity, and a statistical energy function to measure protein-RNA binding affinity.     

Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing

A common goal in the discovery of rare functional DNA variants via medical resequencing is to incur a relatively lower proportion of false positive base-calls. We developed a novel statistical method for resequencing arrays (SRMA, sequence robust multi-array analysis) to increase the accuracy of detecting rare variants and reduce the costs in subsequent sequence verifications required in medical applications. SRMA includes single and multi-array analysis and accounts for technical variables as well as the possibility of both low- and high-frequency genomic variation. The confidence of each base-call was ranked using two quality measures. In comparison to Sanger capillary sequencing, we achieved a false discovery rate of 2% (false positive rate 1.2 × 10⁻⁵, false negative rate 5%), which is similar to automated second-generation sequencing technologies. Applied to the analysis of 39 nuclear candidate genes in disorders of mitochondrial DNA (mtDNA) maintenance, we confirmed mutations in the DNA polymerase gamma POLG in positive control cases, and identified novel rare variants in previously undiagnosed cases in the mitochondrial topoisomerase TOP1MT, the mismatch repair enzyme MUTYH, and the apurinic-apyrimidinic endonuclease APEX2. Some patients carried rare heterozygous variants in several functionally interacting genes, which could indicate synergistic genetic effects in these clinically similar disorders.     

Is it possible to exclude a diagnosis of myocardial damage within six hours of admission to an emergency department? Diagnostic cohort study

ObjectiveTo assess the clinical efficacy and accuracy of an emergency department based six hour rule-out protocol for myocardial damage.DesignDiagnostic cohort study.SettingEmergency department of an inner city university hospital.Participants383 consecutive patients aged over 25 years with chest pain of less than 12 hours'' duration who were at low to moderate risk of acute myocardial infarction.InterventionSerial measurements of creatine kinase MB mass and continuous ST segment monitoring for six hours with 12 leads.ResultsOutcome of the gold standard test was available for 292 patients. On the diagnostic test for the protocol, 53 patients had positive results and 239 patients had negative results. There were 18 false positive results and one false negative result. Sensitivity was 97.2% (95% confidence interval 95.0% to 99.0%), specificity 93.0% (90.0% to 96.0%), the negative predictive value 99.6%, and the positive predictive value 66.0%. The positive likelihood ratio was 13.9 and the negative likelihood ratio 0.03.ConclusionsThe six hour rule-out protocol for myocardial infarction is accurate and efficacious. It can be used in patients presenting to emergency departments with chest pain indicating a low to moderate risk of myocardial infarction.

What is already known on this topic

Many patients with chest pain in emergency departments indicating a low to moderate risk of myocardial infarction are admitted to rule out myocardial damageSome 6% of those discharged have undiagnosed myocardial damage

What this study adds

An emergency department based chest pain assessment unit protocol to rule out myocardial damage is sensitive enough to allow safe discharge of patients at low to moderate risk of myocardial infarction within six hoursSuch units can also reduce the number of patients admitted unnecessarily     

On minimizing assignment errors and the trade‐off between false positives and negatives in parentage analysis

Genetic parentage analyses provide a practical means with which to identify parent–offspring relationships in the wild. In Harrison et al.'s study (2013a), we compare three methods of parentage analysis and showed that the number and diversity of microsatellite loci were the most important factors defining the accuracy of assignments. Our simulations revealed that an exclusion‐Bayes theorem method was more susceptible to false‐positive and false‐negative assignments than other methods tested. Here, we analyse and discuss the trade‐off between type I and type II errors in parentage analyses. We show that controlling for false‐positive assignments, without reporting type II errors, can be misleading. Our findings illustrate the need to estimate and report both the rate of false‐positive and false‐negative assignments in parentage analyses.     

Fine needle aspiration cytology in the management of male breast masses. Nineteen years of experience.

OBJECTIVE: To determine the utility and accuracy of fine needle aspiration cytology (FNAC) as well as its sensitivity, specificity and predictive value in the diagnosis of male breast masses. STUDY DESIGN: Data on male breast FNAC done between 1978 and 1997 were retrieved from the records of the cytopathology laboratory. FNAC diagnoses were categorized as positive, negative, inconclusive or unsatisfactory. Cytohistologic correlation was done with data from histopathology records. Sensitivity, specificity, diagnostic accuracy and predictive values of FNAC were calculated using standard statistical methods. RESULTS: Five hundred seven of 13,175 patients undergoing breast FNAC were males. Of them, 393/507 had satisfactory aspirates. Of these, 70 were positive (13.8%), 295 were negative (58%), and 29 were inconclusive (5.7%). A total of 114 FNACs (22.5%) were unsatisfactory. Histopathology was available in 97/507 cases. There were no false positive or false negative diagnoses. FNAC had a sensitivity, specificity and diagnostic accuracy of 100% for male breast lesions. CONCLUSION: This large study shows that FNAC is a very accurate tool for diagnosis of male breast lesions. It is highly sensitive and specific, with good cytohistologic correlation. FNAC should therefore be an integral part of the primary assessment of breast lumps in males.     

Le MorphoTEP au FDG est un examen utile dans les cancers différenciés de la thyroïde avec élévation des anticorps antithyroglobuline

AimAssessment of the clinical impact of a PET/CT with FDG for the follow-up of differentiated thyroid cancer (DTC) with rising or positive thyroglobulin autoantibodies (AbTg) level and negative or inconclusive conventional imaging work-up.MethodologyThis retrospective study involves 15 patients seen in follow-up with confirmed DTC primarily treated with total thyroidectomy and Iodine-131. Patients presenting increased AbTg and a negative or non informative conventional workout were included. The results of the PET/CT were correlated with histology and/or clinical follow-up. The clinical impact was determined on a change of intention to treat, which was decided upon in multidisciplinary meetings, based on the PET/CT result.ResultsWe observed 10 true positive exams confirmed via histology in seven patients and via clinical follow-up in three on the average 33 months (20–53 months), three real negative exams with negative follow up of on the average 39.5 months (30–47 months), one false positive and one false negative. The intention to treat was modified in 73.3 % (11/15 patients). PET/CT showed sensitivity, specificity, positive predictive value, negative predictive value and accurancy of 91, 75, 90, 75, 86.6% respectively. There was a large and comparable dispersion of the AbTg values in both the true positive and the true negative groups, the kinetic of AbTg evolution could have a predictive value of a positive PET.Discussion/ConclusionPET/CT with FDG seems to be very useful in the therapeutic management of DTC in the case of AbTg increased or positive, in particular for the patients with N1 in the initial staging. Further studies are suggested to confirm the very promising negative predictive value and specificity of this exam in a larger number of patients.     

SDOCT imaging to identify macular pathology in patients diagnosed with diabetic maculopathy by a digital photographic retinal screening programme

Introduction

Diabetic macular edema (DME) is an important cause of vision loss. England has a national systematic photographic retinal screening programme to identify patients with diabetic eye disease. Grading retinal photographs according to this national protocol identifies surrogate markers for DME. We audited a care pathway using a spectral-domain optical coherence tomography (SDOCT) clinic to identify macular pathology in this subset of patients.

Methods

A prospective audit was performed of patients referred from screening with mild to moderate non-proliferative diabetic retinopathy (R1) and surrogate markers for diabetic macular edema (M1) attending an SDOCT clinic. The SDOCT images were graded by an ophthalmologist as SDOCT positive, borderline or negative. SDOCT positive patients were referred to the medical retina clinic. SDOCT negative and borderline patients were further reviewed in the SDOCT clinic in 6 months.

Results

From a registered screening population of 17 551 patients with diabetes mellitus, 311 patients met the inclusion criteria between (March 2008 and September 2009). We analyzed images from 311 patients’ SDOCT clinic episodes. There were 131 SDOCT negative and 12 borderline patients booked for revisit in the OCT clinic. Twenty-four were referred back to photographic screening for a variety of reasons. A total of 144 were referred to ophthalmology with OCT evidence of definite macular pathology requiring review by an ophthalmologist.

Discussion

This analysis shows that patients with diabetes, mild to moderate non-proliferative diabetic retinopathy (R1) and evidence of diabetic maculopathy on non-stereoscopic retinal photographs (M1) have a 42.1% chance of having no macular edema on SDOCT imaging as defined by standard OCT definitions of DME when graded by a retinal specialist. SDOCT imaging is a useful adjunct to colour fundus photography in screening for referable diabetic maculopathy in our screening population.     

A rapid immunochromatographic assay for the detection of Mycobacterium tuberculosis antigens in pulmonary samples from HIV seropositive patients and its comparison with conventional methods

As tuberculosis generates a highly heterogeneous antibody repertoire, its diagnosis requires tests based on cocktails of antigens. We describe a new, rapid method called rapid immunochromatographic assay (RICA) for cocktail-based diagnosis, which can detect Mycobacterial antigens in sputum specimens. Six antigenic fractions of pathogenic Mycobacterium tuberculosis were used in combination as the capture antigens in the control line of the flow-through assay. Antigen detection of 200 sputum samples from HIV seropositive patients by RICA assay gave a sensitivity of 97.9%, specificity of 99.0%, positive predictive value of 98.9%, negative predictive value of 98.0%, false positive rate of 0.9%, false negative rate of 2.0%, prevalence rate of 49%, likelihood ratio for positive results 97 and likelihood ratio for negative results 0.02. The combination of RICA and AFB staining gave a sensitivity of 100%, specificity of 100%, positive predictive value of 100%, negative predictive value of 100%, false positive rate of 0%, false negative rate of 0%, likelihood ratio for negative results 0. The assay was simple, rapid and economical for the detection of M. tuberculosis infection and suitable for large scale screening of samples in endemic areas without any sophisticated equipment. The results of the assay proved to be superior to conventional methods and combined with clinical data, could form the basis for starting an earlier course of treatment.     

Fine needle aspiration biopsy of vertebral lesions

OBJECTIVE: To evaluate the accuracy of fine needle aspiration biopsy (FNAB) in the diagnosis of vertebral lesions. STUDY DESIGN: Eighty-nine FNAB cases of vertebral lesions from January 1996 to December 2001 were retrieved from the Allegheny General Hospital laboratory information system. The cases were reviewed and correlated with clinical findings, including previous clinical history, primary site of malignancy and final pathologic diagnosis. RESULTS: ENAB diagnoses were malignant in 43 cases, benign in 35, suspicious in 1, unsatisfactory in 7 and false negative in 3. Previous clinical history included malignancy (37 patients), osteomyelitis and systemic disease (11), and nonspecific or no history (41). In 34 cases (38.2%) both aspirates and core biopsies were available, and the diagnoses correlated in 29/34 cases (85%). Surgical or core biopsies in the unsatisfactory/suspicious group showed malignancy in 4 cases (50%). The sensitivity of FNAB of vertebral lesions was 96%, specificity 100%, positive predictive value 100% and negative predictive value 92%, with no false positive cases. CONCLUSION: FNAB of vertebral lesions is an effective, sensitive and specific procedure in the diagnostic workup of a patient with or without a prior history of malignancy. Surgical pathology examination, including core biopsies of unsatisfactory or suspicious lesions, can further improve the diagnostic yield.