Ultrasound elastography as an adjuvant to conventional ultrasound in the preoperative assessment of axillary lymph nodes in suspected breast cancer: a pilot study.

AIMS: To compare the performance of ultrasound elastography with conventional ultrasound in the assessment of axillary lymph nodes in suspected breast cancer and whether ultrasound elastography as an adjunct to conventional ultrasound can increase the sensitivity of conventional ultrasound used alone. MATERIALS AND METHODS: Fifty symptomatic women with a sonographic suspicion for breast cancer underwent ultrasound elastography of the ipsilateral axilla concurrent with conventional ultrasound being performed as part of triple assessment. Elastograms were visually scored, strain measurements calculated and node area and perimeter measurements taken. Theoretical biopsy cut points were selected. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) were calculated and receiver operating characteristic (ROC) analysis was performed and compared for elastograms and conventional ultrasound images with surgical histology as the reference standard. RESULTS: The mean age of the women was 57 years. Twenty-nine out of 50 of the nodes were histologically negative on surgical histology and 21 were positive. The sensitivity, specificity, PPV, and NPV for conventional ultrasound were 76, 78, 70, and 81%, respectively; 90, 86, 83, and 93%, respectively, for visual ultrasound elastography; and for strain scoring, 100, 48, 58 and 100%, respectively. There was no significant difference between any of the node measurements CONCLUSIONS: Initial experience with ultrasound elastography of axillary lymph nodes, showed that it is more sensitive than conventional ultrasound in detecting abnormal nodes in the axilla in cases of suspected breast cancer. The specificity remained acceptable and ultrasound elastography used as an adjunct to conventional ultrasound has the potential to improve the performance of conventional ultrasound alone.

Breast surgical specimen radiographs: how reliable are they?

Radiography of the excised surgical specimen following wire guided localisation of impalpable breast lesions is standard surgical practice. The aims of the study were to establish the reliability of the breast specimen radiograph (SR) in determining lesion excision and to determine whether the radiographic margin correlated with the histological margin. The clinical, imaging, SR and pathological details of 106 patients with a pre-operative diagnosis of breast cancer were retrospectively reviewed. The reliability of orientation was estimated and the appearance and distance from the mammographic abnormality to each radial margin were measured and correlated with surgical histological findings. The overall accuracy of the specimen radiograph in determining whether the mammographic lesion was present was 99%. The SR could be orientated "very reliably" or "reliably" in 80% of patients however in only 48% of patients did the closest margin on the SR correspond with the same nearest margin at final histology. A maximum measurement of 11 mm or more from the lesion to the specimen edge was associated with a 77% likelihood of having a clear final histological margin (taken as 5mm or more) and if <11 mm a 58% chance of having involved final histological margins. There was however a wide overlap in the results with patients having an apparently wide SR margin but histologically involved margins and vice versa. The SR is reliable at determining whether the target lesion has been removed. The correlation of SR margin orientation and measurement with final histological measurement is however far less reliable.

Measuring performance in clinical breast examination.

BACKGROUND: Clinical breast examination (CBE) remains an essential part of triple assessment of breast lumps, but to date there are no performance measures for clinicians using this technique. The aim of this retrospective audit was to compare the performance and accuracy of CBE to identify key indicators that could be used to monitor performance prospectively. METHODS: Clinical examination findings (E1, normal, to E5, malignant) for 16,585 patients who had CBE as part of triple assessment were obtained from electronic medical records. The performance of CBE, by age group, mammographic density and clinician, was assessed by calculating the sensitivity, specificity and area under the receiver operating characteristic (ROC) curve. RESULTS: There was marked variation in sensitivity between clinicians (range 44.6-65.9 per cent). There was a strong downward trend in the percentage classified as E5 as sensitivity for breast cancer detection decreased, and a corresponding strong downward trend in the proportion of E4 and E5 cancers classified as E5. Both of these measures could be used as indicators to monitor CBE performance. CONCLUSION: The performance measures outlined here could help to identify clinicians who have a lower sensitivity for CBE and who may therefore require feedback and further training.

The accuracy of digital infrared imaging for breast cancer detection in women undergoing breast biopsy.

BACKGROUND: Mammography has a lower sensitivity for breast cancer detection in younger women and those with dense breasts. Recent improvements in digital infrared breast imaging suggest there may be a role for this technology and we have studied its performance in 100 women prior to breast needle core biopsy (CB). METHODS: All patients were imaged using a digital infrared breast (DIB) scan (Sentinel BreastScan) prior to breast biopsy. Analysis of the infrared scans was performed, blinded to biopsy results, in four different ways: Sentinel screening report, Sentinel artificial intelligence (neural network), expert manual review and NoTouch BreastScan a novel artificial intelligence programme. RESULTS: Of 106 biopsies performed in 100 women, 65 were malignant and 41 were benign. Sensitivity of Sentinel screening (53%) and Sentinel neural network (48%) was low but analysis with NoTouch software (70%) was much closer to expert manual review (78%). Sensitivity (78%) and specificity (75%) using NoTouch BreastScan were higher in women under 50 and the combination of mammography and DIB, with NoTouch interpretation, in this age group resulted in a sensitivity of 89%. CONCLUSION: DIB using NoTouch is an effective adjunctive test for breast cancer detection in women under 70 and appears to be particularly effective in women under 50 where maximal sensitivity (78%) and specificity (75%) were observed. The combined sensitivity of NoTouch BreastScan and mammography in women under 50 was encouraging at 89%, suggesting a potential way forward for a dual imaging approach in this younger age group.

Radiological staging in breast cancer: which asymptomatic patients to image and how.

BACKGROUND: Approximately 4% of patients diagnosed with early breast cancer have occult metastases at presentation. Current national and international guidelines lack consensus on whom to image and how. METHODS: We assessed practice in baseline radiological staging against local guidelines for asymptomatic newly diagnosed breast cancer patients presenting to the Cambridge Breast Unit over a 9-year period. RESULTS: A total of 2612 patients were eligible for analysis; 91.7% were appropriately investigated. However in the subset of lymph node negative stage II patients, only 269 out of 354 (76.0%) investigations were appropriate. No patients with stage 0 or I disease had metastases; only two patients (0.3%) with stage II and < or =3 positive lymph nodes had metastases. Conversely, 2.2, 2.6 and 3.8% of these groups had false-positive results. The incidence of occult metastases increased by stage, being present in 6, 13.9 and 57% of patients with stage II (> or =4 positive lymph nodes), III and IV disease, respectively. CONCLUSION: These results prompted us to propose new local guidelines for staging asymptomatic breast cancer patients: only clinical stage III or IV patients require baseline investigation. The high specificity and convenience of computed tomography (chest, abdomen and pelvis) led us to recommend this as the investigation of choice in breast cancer patients requiring radiological staging.

Patient-led breast cancer follow up.

The audit aimed to assess patient satisfaction and GP workload following the introduction of patient-led breast cancer follow up (PLFU), comprising regular mammographic surveillance and easy access self-referral to the breast clinic if required. A questionnaire was sent to 217 patients at low risk of recurrence or death following breast cancer treatment and to 302 GPs. From 217 patients there were 130 respondents (60%) and of these 126 (97%) patients had a clear idea of how to contact the breast unit, and only 5 of 130 patients (4%) required a breast clinic appointment. All 106 respondents (100%) were satisfied with the process to contact the breast unit. Only 10 of 277 GP respondents (3.6%) referred a patient on PLFU back to the breast unit during the study period. PLFU has been well received by patients following breast cancer treatment with little increase in GP workload.

Use of ultrasound-guided axillary node core biopsy in staging of early breast cancer.

The aim of this study was to see how effective ultrasound-guided needle biopsy was at detecting lymph node involvement in patients with early breast cancer. Patients with newly diagnosed invasive breast cancer underwent axillary ultrasound (US) where lymph node size and morphology were noted. A core biopsy (CB) was undertaken of any node greater than 5 mm in longitudinal section. Patients with benign CBs proceeded to sentinel lymph node (SLN) biopsy, whereas those with malignancy underwent axillary lymph node dissection (ALND). US and CB findings were correlated with final surgical histology in all cases. One hundred and thirty-nine patients were examined, of whom 52.5% had lymph node metastases on final histology. One hundred and twenty-one patients (87%) underwent axillary node CB. The overall sensitivity of CB for detecting lymph node metastases was 53.4% (60.3% for macrometastases; 26.7% for micrometastases). The US morphological characteristics most strongly associated with malignancy were absence of a hilum and a cortical thickness greater than 4 mm. However, one third of patients with normal lymph node morphology had nodal metastases, and only 12% of these were diagnosed on CB. CB of axillary lymph nodes can diagnose a substantial number of patients with lymph node metastases, allowing these patients to proceed directly to ALND, avoiding unnecessary SLN biopsy.

Ultrasound guided percutaneous axillary lymph node core biopsy: how often is the sentinel lymph node being biopsied?

Patients with breast cancer now frequently undergo axillary ultrasound and core biopsy (CB) in an attempt to reduce the number of unnecessary sentinel lymph node (SLN) biopsies. This study aimed to establish the frequency of successful targeting of the SLN by ultrasound guided biopsy. A total of 137 patients had axillary ultrasound of which 121 underwent CB. 73 (60%) patients proceeded to SLN after negative CB. All SLNs were examined for evidence of metastases and previous CB. Of the 73 patients, 51 had no evidence of malignancy in the SLN (true negative=70%). However nodal deposits were found in the remaining 22 patients, representing a false negative rate for CB of 30%. Overall histopathological evidence of previous CB was identified in 47 (64%) of 73 patients undergoing SLN biopsy. The reason for false negative findings in the 22 (30%) patients was failure to sample the sentinel lymph node in 10 (45%) and failure to sample the metastatic disease in the sentinel node in 11 (55%). This study suggests that both better methods of identifying the sentinel lymph node and more adequate sampling are required.

Screen-detected vs symptomatic breast cancer: is improved survival due to stage migration alone?

This paper examines whether screen-detected breast cancer confers additional prognostic benefit to the patient, over and above that expected by any shift in stage at presentation. In all, 5604 women (aged 50-70 years) diagnosed with invasive breast cancer between 1998 and 2003 were identified by the Eastern Cancer Registration and Information Centre (ECRIC) and mammographic screening status was determined. Using proportional hazards regression, we estimated the effect of screen detection compared with symptomatic diagnosis on 5-year survival unadjusted, then adjusted for age and Nottingham Prognostic Index (NPI). A total of 72% of the survival benefit associated with screen-detected breast cancer can be accounted for by age and shift in NPI. Survival analysis by continuous NPI showed a small but systematic survival benefit for screen-detected cancers at each NPI value. These data show that although most of the screen-detected survival advantage is due to a shift in NPI, the mode of detection does impact on survival in patients with equivalent NPI scores. This residual survival benefit is small but significant, and is likely to be due to differences in tumour biology. Current prognostication tools may, therefore, overestimate the benefit of systemic treatments in screen-detected cancers and lead to overtreatment of these patients.

Can breast MRI help in the management of women with breast cancer treated by neoadjuvant chemotherapy?

Contrast-enhanced (CE) MRI was used to monitor breast cancer response to neoadjuvant chemotherapy. Patients underwent CE MRI before and after therapy, together with conventional assessment methods (CAM). CE MRI was carried out at 1.5 T in the coronal plain with 3D sequences before and after bolus injection. An expert panel determined chemotherapy response using both CE MRI and CAM. Histopathological response in the surgical specimen was then used to determine the sensitivity and specificity of CE MRI and CAM. In total, 67 patients with 69 breast cancers were studied (mean age of 46 years). Tumour characteristics showed a high-risk tumour population: median size 49 mm: histopathological grade 3 (55%): oestrogen receptor (ER) negative (48%). Histopathological response was as follows: - complete pathological response (pCR) 17%; partial response (pPR) 68%; no response (NR) 15%. Sensitivity of CAM for pCR or pPR was 98% (CI 91-100%) and specificity was 50% (CI 19-81%). CE MRI sensitivity was 100% (CI 94-100%), and specificity was 80% (CI 44-97%). The absolute agreement between assessment methods and histopathology was marginally higher for CE MRI than CAM (81 vs 68%; P=0.09). In 71%, CE MRI increased diagnostic knowledge, although in 20% it was judged confusing or incorrect. The 2nd MRI study significantly increased diagnostic confidence, and in 19% could have changed the treatment plan. CE MRI persistently underestimated minimal residual disease. In conclusion, CE MRI of breast cancer proved more reliable for predicting histopathological response to neoadjuvant chemotherapy than conventional assessment methods.

The management of radial scars of the breast - does core biopsy help?

PURPOSE: To compare the effectiveness of fine needle aspiration cytology (FNAC) with core biopsy (CB) in the pre-operative diagnosis of radial scar (RS) of the breast. PATIENTS AND METHODS: A retrospective analysis was made of all radial scars diagnosed on surgical histology over an 8-year period. Comparison was made between the results of different preoperative needle biopsy techniques and surgical histology findings. RESULTS: Forty of 47 patients with a preoperative radiological diagnosis of radial scar were included in this analysis. Thirty-eight patients had impalpable lesions diagnosed on mammography and two presented with a palpable lump. FNAC (n=17) was inadequate in 47% of patients, missed two co-existing carcinomas found in this group, and gave a false positive or suspicious result for malignancy in 4 patients. CB (n=23) suggested a RS in 15 patients, but only diagnosed 4 out of 7 co-existing carcinomas found in this group. CONCLUSION: CB is more accurate than FNAC in the diagnosis of RS. However, these data demonstrate that CB may offer little to assist in the management of patients with RS. In summary, this paper advocates the use of CB in any lesion with a radiological suspicion of carcinoma and diagnostic excision of all lesions thought to be typical of RS on mammography.

Radiological peer review of interval cancers in the East Anglian breast screening programme: what are we missing? East Anglian Breast Screening Programme.

OBJECTIVE: To determine whether association between classification of interval cancers (false negative, minimal sign, true interval, occult) and tumour characteristics can indicate areas for improvement in effectiveness of screening. SETTING: East Anglian regional Breast: Screening Programme. METHOD: The consensus classification of interval cases, obtained through peer review, was compared with tumour characteristics: size; grade; and nodal status, and with radiological signs. A set of 923 cancers with known tumour characteristics, presenting in unscreened women, was available for comparison. RESULT: In total, 385 interval cases were analysed. Prognosis of interval cancers was at least as good as that of cancers in unscreened women, with fewer node positive cases. No significant relation was found between classification of cases and age of patients. True intervals tended to present later after a negative screen, although false negatives commonly presented earlier. Occult cancers were significantly smaller than false negatives. Analysis of histological type yielded little of relevance, and mammographic appearance was similar in all classifications. At diagnosis, cancers in the low risk group were more likely to be seen as spiculate masses, whereas high risk cases more often appeared as opacities. A higher proportion of interval cases had been assessed than in the normal screened population. CONCLUSION: Sensitivity may be improved by reducing false negative and minimal sign cases (21% of interval cancers in East Anglia). These will include tumours in all risk groups, and with all radiological features, thus no particular age group or radiological feature may be targeted for improvement. Misdiagnosis at assessment reduces sensitivity and therefore merits particular study.

Interval cancer peer review in East Anglia: implications for monitoring doctors as well as the NHS breast screening programme.

AIM: To devise a method for reviewing interval cancers that will both educate radiologists and facilitate improvement of breast screening practice. To evaluate different methods for case classification to find one that best serves this purpose. METHOD: The method of peer review and the means by which interval cancers are classified is described. The way in which cases are designated false-negative is an issue of acceptability for radiologists, and so three different methods are evaluated. Each is applied to the data set collected in this region over a 3-year period. RESULTS: For cases read by five readers, when a consensus method was used for classifying cases, the proportion of cases classified as false-negative was 14%. Using a method in which only one of the five readers had to classify a case as false-negative for it to be categorized as such, the proportion of false-negative cases rose to a maximum of 38%. The minimum proportion of cases that could be considered to be false-negative was 6% and was obtained when all five readers had to classify a case as false-negative for it to be so categorized. Consistent with its majority viewpoint, the consensus method gave results for proportions of total cases classified as false-negative which were similar to those given by methods in which cases are classified as false-negative if either three of five readers, or at least 60% of readers, classified it as such. CONCLUSION: For the peer review method to achieve its dual aims of educating radiologists and auditing performance, the participating radiologists must share ownership of the results and view the analysis as fair. The method used to classify interval cancers as false-negative will influence the number so classified. A consensus method has been found to give a result that is both fair and acceptable to our radiologist. Using this method 16% of all reviewed cases were classified as false-negative and 60% as true interval cancers. Britton, P. D. (2001). Clinical Radiology56, 44-49.

How reliable is modern breast imaging in differentiating benign from malignant breast lesions in the symptomatic population?

AIM: To assess the ability of mammography and ultrasound individually and in combination to predict whether a breast abnormality is benign or malignant in patients with symptomatic breast disease. MATERIALS AND METHODS: Patients included were those in whom histological confirmation of the abnormality following surgical excision was available. Mammographic and ultrasound appearances were prospectively classified using a four-point scale (1 = no significant lesion, 2 = benign lesion, 3 = possibly malignant, 4 = probably malignant). RESULTS: Histological confirmation following surgical excision was available in 559 patients, of which 303 were benign and 256 were malignant. The imaging classification was correlated with histology in these 559 lesions. In predicting final histology, the sensitivity and specificity of mammography alone were 78.9 and 82.7%, respectively, of ultrasound alone were 88.9 and 77.9%, respectively, and of mammography and ultrasound in combination were 94.2 and 67.9%, respectively. Only one patient had both a mammogram and ultrasound reported as normal (category 1 for both tests) in whom subsequent histology revealed a carcinoma (0.4% of all carcinomas). CONCLUSION: We found that the extensive use of ultrasound increases the cancer detection rate in this selected population by 14%.

Changing to core biopsy in an NHS breast screening unit.

We recently changed from using fine needle aspiration cytology to using core biopsy exclusively in the assessment of screen detected abnormalities. Two hundred and two biopsies (1% of women screened) were performed. Surgical histological confirmation was obtained in 111 patients (101 malignant and 10 benign). The remaining patients were either returned to standard 3-yearly screening or early repeat screening after 1 year. Analysis of the results was performed in accordance with the standards specified in the National Health Service Breast Screening Programme (NHSBSP) Publication Number 22. Absolute sensitivity was 89.3%, complete sensitivity was 93.2%, specificity (including patients undergoing both surgical excision and follow-up) was 88.7%. The predictive value of a positive (malignant) core biopsy result was 100%. The false negative rate was 3.9%. Twelve (5.9%) biopsies were classified inadequate for diagnosis. Core biopsy is a safe and accurate way of assessing screen detected abnormalities and can be used as a substitute for fine needle aspiration cytology with results that exceed the National Health Service Breast Screening Programme target standards, even in the learning phase.

A comparison of MR and duplex Doppler ultrasound for vascular assessment prior to orthotopic liver transplantation.

A prospective blinded comparison of duplex Doppler ultrasound (DDU) and a magnetic resonance angiography (MRA) 2-D time-of-flight technique was performed to assess the hepatic vasculature in 23 adult patients referred for orthotopic liver transplantation. Both techniques confirmed patency of the inferior vena cava in all patients, demonstrated a complete portal vein occlusion in one patient, and accurately defined the vascular and organ anatomy in a patient with situs inversus. The results were confirmed at surgery in 18 of the patients who have subsequently undergone liver transplantation. In one patient a partial portal vein thrombosis was found at surgery which was not detected by either imaging technique. MRA was more sensitive overall in detecting porto-systemic collaterals (31 locations in 17 patients) compared with ultrasound (24 locations in 17 patients), although ultrasound detected more patients with recanalized para-umbilical veins (DDU: 10 patients; MRA: 8 patients). These results indicate that a simple MRA technique can equal duplex Doppler ultrasound for the non-invasive assessment of patency of the hepatic vasculature and should be considered when DDU examination is equivocal or technically inadequate. MRA may provide additional information on the presence and size of porto-systemic collaterals which may be of value in monitoring portal hypertension.

Duplex Doppler measurements of the portal vein in portal hypertension.

In order to assess the validity of quantitative duplex Doppler measurements of portal vein flow, 10 patients with proven diffuse liver disease and portal hypertension were examined serially by two independent observers over a 3 month period. Multiple measurements of the portal vein were made using a consistent technique in an attempt to minimize observer errors. One patient proved unsuitable for ultrasound examination. In the remaining nine patients the intra-observer portal vein measurements for one observer (19 paired examinations) correlated significantly for flow velocity (r = 0.80, P < 0.001) and derived bulk flow (r = 0.54, P < 0.02) but not for cross-sectional area (r = 0.27, P > 0.05). The intra-observer measurements for the second observer (11 paired examinations) were significantly correlated for cross-sectional area (r = 0.64, P < 0.05) and derived bulk flow (r = 0.61, P < 0.05) but not for flow velocity (r = 0.5, P > 0.05). The inter-observer measurements (28 paired examinations) of the portal vein were all highly significantly correlated for cross-sectional area (r = 0.63, P < 0.001), flow velocity (r = 0.79, P < 0.001) and derived bulk flow (r = 0.73, P < 0.001). These results suggest that this quantitative Doppler technique may be valid for the serial study of portal vein flow in selected groups of patients with diffuse liver disease and portal hypertension.

Pictorial review: benign and malignant enlargement of the pterygo-masseteric muscle complex.

Seven cases of unilateral enlargement of the pterygoid and/or masseter muscles due to haemangioma (1), benign masseteric hypertrophy (2), rhabdomyosarcoma (2), leukaemic infiltration (1) and non-Hodgkin's lymphoma (1) are presented. The differential diagnosis of pterygo-masseteric muscle enlargement is outlined and the usefulness of computed tomography (CT) discussed.

Duplex Doppler ultrasound for the detection of vascular occlusion following liver transplantation in children.

Sixty-three children and adolescent patients who received 78 consecutive orthotopic liver transplants and had serial duplex ultrasound monitoring were retrospectively reviewed for episodes of occlusion of the hepatic artery or portal vein. There were 13 documented episodes of complete occlusion of the main hepatic artery or a major branch, of which nine were diagnosed by the absence of flow during duplex ultrasound examination. Four occlusions were not detected, two affected hepatic artery branches, one an accessory hepatic artery, and one the main hepatic artery. The overall sensitivity of the method was 69% and specificity 100%. Six portal vein occlusions were documented in five patients and all six were successfully diagnosed on ultrasound examination, giving a sensitivity and specificity of 100%. Three of the patients had simultaneous occlusions of both vessels. In the early post-operative period duplex Doppler ultrasound examination has proved an effective non-invasive method for the detection of vascular occlusion, but is not yet sensitive enough to replace angiography fully for the detection of hepatic artery occlusion, particularly when this occurs distal to the main hepatic artery.

Doppler ultrasound of the hepatic veins: normal appearances.

Doppler ultrasound of the hepatic veins gives a pulsatile velocity profile which mirrors the cardiac cycle. We describe the physiological basis for the complex waveform and suggest a venous pulsatility index (VPI) which can be used to quantify it. We have studied normal volunteers under differing conditions to establish a normal range of VPI. This provides a baseline against which abnormal patterns of hepatic vein Doppler can be judged.