Can scintimammography with (99m)Tc-MIBI identify multifocal and multicentric primary breast cancer?

Scintimammography with (99m)Tc-MIBI has been shown to be an effective adjunct to imaging of the breast with mammography. Uptake of (99m)Tc-MIBI is particularly high in sites of non-calcified cancer and ductal carcinoma in situ (DCIS), and as a consequence it may be possible to use this method of imaging in identifying multifocal or multicentric disease. The aim of this study was to evaluate the efficacy of preoperative scintimammography in the detection of multifocal and multicentric breast cancer and compare these results with mammography. A retrospective review was performed of 353 women imaged with (99m)Tc-MIBI as part of the clinical assessment of their suspected primary breast cancer. The results of the scintimammography and mammography were then compared with the final pathological diagnosis obtained after mastectomy in all patients. Histopathological assessments of breast tissue from mastectomy confirmed 40 women (12%) had multifocal (34) or multicentric (six) breast cancer. Scintimammography correctly identified 39 of these cancers and the multifocal or multicentric character of the cancer was identified in 22 (52%) of these patients. Anatomical imaging performed in all 40 patients including 25 with mammography alone, mammography and ultrasound in 11 cases and ultrasound alone in four patients. Anatomical imaging identified cancer to be present in 28 patients (70%) and the combination of mammography and ultrasound identified correctly that the cancer was multifocal or multicentric in eight patients (22%). In this study scintimammography was able to identify more cases of multifocal and multicentric cancer than mammography and/or ultrasound. In patients where pre-operative identification of multicentric or multifocal disease can alter treatment scintimammography may be a useful investigative tool.

The role of scintimammography and mammography in recurrent breast cancer. Evaluation of their accuracy using ROC curves.

BACKGROUND: With the increasing demand for breast conservation surgery, the probability of recurrent tumour within the breast increases. Traditionally x-ray mammography (XMM) was used to assess the post-surgical breast, but post-surgery and radiotherapy changes have reduced the accuracy of this method. Scintimammography (SMM) has also been proposed and appears to be more accurate than XMM. MATERIAL AND METHODS: A total of 101 women received (Tc99m) MIBI SMM and 88 had a subsequent XMM. There were 142 sites suspected of loco-regional recurrence breast cancer. During the study the patients did not receive any treatment other then hormonotherapy. SMM was performed by the standard Diggles-Khalkhali method and XMM was performed using standard 2 views. Analysis was performed and the results of each type of imaging compared with histology. In the ROC curve analysis 5 points of certainty were used: from 1 being definitely normal to 5 being definitely cancer; grades 4 and 5 were counted as positive. RESULTS: The overall sensitivity value of SMM was 84% and specificity was 85%, compared with a sensitivity of 52% for XMM and a specificity of 84%. Analysis of areas under ROC curves provides statistically significant difference between SMM and XMM (p < 0.05). Combining the two tests did not significantly improve the diagnostic accuracy of sequence imaging over SMM. CONCLUSION: ROC curve analysis demonstrates that scintimammography should be the primary investigation in suspected local recurrence following breast conservation surgery.

Correlation between uptake of Tc-99m sestaMIBI and prognostic factors of breast cancer.

UNLABELLED: The purpose of this retrospective study was assessment of correlation between Tc-99m sestaMIBI uptake and some prognostic factors of breast cancer. The following prognostic factors have been included in this study: size of the tumour, age of the patients, axilla node involvement, oestrogen and progesterone receptor (ER, PR) status, grading system of Bloom-Richardson and Ki-67 antigen expression. METHODS: 79 patients were enrolled in this study, with 85 lesions confirmed as primary breast cancers. Mean age of patients was 53 years. Scintimammography (SMM) was performed after intravenous injection of 740MBq. At 5-10 min after injection standard planar images were obtained in prone lateral and anterior supine views. Assessment of correlation between known prognostic factors of breast cancer and uptake of MIBI (evaluated as a tumour to background ratio-TBR) was performed used non-parametric (Kendall-tau correlation) statistical analysis. RESULTS: There were 85 breast cancers (73 invasive ductal carcinomas, 11 DCIS (ductal carcinoma in situ) and 1 lobular carcinoma. There was positive correlation between TBR Tc-99m MIBI uptake and size of the tumour (t = 0.19, p = 0.01), presence of axilla node involvement (t = 0.2, p = 0.006) and also grade of the IDC tumours evaluated using Bloom-Richardson's criteria (t = 0.18, 0.03). There were negative correlation between TBR and presence of PR (t = -0.16, p = 0.02) and borderline negative correlation between TBR and age of patients (t = -0.137, p = 0.06) and also TBR and ER status (t = -0.135, p = 0.065). Patients who are younger and/or have PR or ER negative cancers have higher Tc-99m MIBI uptake. Patients who presented with high grade of malignancy (B-R) also have higher uptake of radiotracer. Also those with higher uptake of radiotracer often had axillary node involvement. This would suggest that more aggressive tumours have higher uptake of Tc-99m MIBI. Finally this study suggest correlation between in vivo uptake of MIBI and some of the known prognostic factors of breast cancer.

Prone SPET scintimammography.

Prone single photon emission tomography (SPET) was performed in 24 patients with suspected primary or recurrent breast cancer to determine if this technique offers more accurate imaging than that obtained from planar scintimammography. All patients were imaged on a specially designed couch with two cushion inserts. The first insert was lined with lead and was used to perform prone lateral planar scintimammography 5 min after the injection of 740 MBq 99Tcm-MIBI. The second insert did not contain lead and was used to perform a prone SPET acquisition for 30 min immediately after planar imaging. The results of both studies were read independently and there was agreement between the two techniques in 23 cases (96%). All cases of cancer proven on histology were found on planar imaging, but a 4-mm ductal cancer was missed on prone SPET. This was thought to be due to activity from this medial cancer being obscured by the star artefact produced by back-projection reconstruction from activity in the heart. There were two false-positive studies with both techniques. However, prone SPET enabled better localization and characterization of breast cancers than planar imaging. Prone SPET imaging of the breast produces results similar to prone lateral imaging and may be used instead of planar imaging if a reduced total acquisition time is desirable. Care must be taken when reading scans in the presence of small tumours near the heart when back-projection reconstruction techniques are used.

Use of 99Tcm-MIBI in the assessment of patients with suspected recurrent breast cancer.

A prospective trial was performed to assess the accuracy of 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) scintimammography and X-ray mammography in 18 patients (mean age 58 years, range 46-79 years) with suspected recurrent breast cancer in the breast and/or loco-regional tissues. All patients had been diagnosed to have breast cancer 1-23 years before scintimammography. Two patients had undergone mastectomy, so that a total of 34 breasts were studied with X-ray mammography and with prone-lateral and anterior scintimammography. Any abnormalities on X-ray mammograms and scintimammograms were noted, as was any additional local or nodal uptake of 99Tcm-MIBI. The nature of any lesion seen with either modality, or in which there was a clinical suspicion of recurrence, was confirmed by cytological or histological examination of tissue samples. There were nine breasts with recurrent cancer in eight patients. X-ray mammography identified six of these cancers. 99Tcm-MIBI scintimammography identified eight of nine recurrent breast cancers (the one cancer not seen was positive on X-ray mammography). In the 26 breasts without cancer, two were reported as having changes consistent with cancer and one was reported equivocal. There were three false-positive and one equivocal scintimammograms. The accuracy of 99Tcm-MIBI scintimammography within the breast (85%) was similar to X-ray mammography (82%). Axillary lymph node recurrence occurred in five patients, four of whom were positive with 99Tcm-MIBI. An additional patient had focal uptake of 99Tcm-MIBI at the site of recurrent cancer on the anterior chest wall. In conclusion, 99Tcm-MIBI scintimammography may provide useful complementary information in patients with suspected recurrence of cancer in the breast or loco-regional tissues.

Comparison of accuracy of scintimammography and X-ray mammography in the diagnosis of primary breast cancer in patients selected for surgical biopsy.

Mammography, whilst remaining the first line imaging investigation of suspected primary breast cancer, can be difficult to interpret in patients with fibrous or dense breasts. Radionuclide imaging of the breast (scintimammography) has been suggested as an additional test. The aim of this study was to perform prospectively a comparison of the two techniques in a population with suspected breast cancer. Seventy such patients, mean age 54 years (range 57 years, 28-85) with 74 suspicious breast lesions were studied. They were imaged 5-10 min after intravenous injection of 740 MBq of Tc-99m sestamibi. Prone lateral and anterior supine views with and without markers were performed. All patients had histological confirmation of the nature of the breast lesions by limited incisional biopsy or definitive wide local excision, or cytological confirmation on fine needle aspiration. All patients had X-ray mammography. There were 53 malignant breast tumours and 21 benign lesions. Scintimammography correctly diagnosed 47 breast cancers, and yielded true-negative results in 12 benign breast lesions. There were six cases of false-negative results and nine false-positive results. Four scans were reported as equivocal. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 89%, 52%, 84% and 67%, respectively. X-ray mammography diagnosed correctly 37 malignant tumours, and in 12 benign lesions the results were true negatives. Ten studies were reported as equivocal. The sensitivity, specificity, PPV and NPV were 70%, 57%, 80% and 43%, respectively. The accuracy of Tc-99m sestamibi scintimammography was better than X-ray mammography though this was not significant (McNemar's test). Fewer equivocal results were obtained with scintimammography. Scintimammography may therefore have a role in the diagnosis of primary breast cancer when X-ray mammography is equivocal or unhelpful.

The effect of chemotherapy on the uptake of technetium-99m sestamibi in breast cancer.

Technetium-99m sestamibi scintimammography has been used primarily in the diagnosis of breast cancer. It has also been suggested that this technique could be used to monitor response to chemotherapy and possibly to predict those patients in whom no response can be expected. An initial study was performed in nine patients with primary breast cancer. All patients underwent prone lateral and anterior 99mTc-sestamibi imaging at diagnosis and 4-7 months later, after they had received cytotoxic chemotherapy. The uptake of 99mTc-sestamibi in the breast was compared with that in normal surrounding breast tissue and this ratio was expressed as the target to background ratio. In all patients treated there was a reduction in uptake of 99mTc-sestamibi after treatment, such that whilst all the tumours could be seen before treatment, only three were visible following chemotherapy. There was a significant fall in the mean target to background ratio of the patients undergoing chemotherapy: the tumour to background ratio was 2.48 before chemotherapy and 1.40 after treatment (P<0.001, paired Student's t test). This fall in tumour activity was observed both in those patients in whom a clinical response was seen and in the two patients in whom the tumour enlarged despite chemotherapy. It appears that the reduced uptake of 99mTc-sestamibi seen after chemotherapy may be a non-specific change and therefore may not be predictive of the clinical response to treatment.

Laser Doppler perfusion imaging--a new technique for measuring breast skin blood flow.

Future detection of breast cancer will probably be based on tissue function such as altered vascularity and blood flow. Assessment of tumour blood flow and its pattern may be significant for prognostic prediction, and early evaluation of treatment response. An ideal method of assessment of perfusion would therefore measure a wide area of the breast without the necessity for surface contact. A possible method for achieving this ideal is the recent development of a laser Doppler imager (LDI) that creates an image of tissue perfusion. The method is based on the recording of Doppler shift caused by movements of red blood cells in the backscattered light of a laser beam that successively scans a certain tissue area. This method reflects the vascularity of overlaying skin. We have applied this technique to 101 patients, 47 normal, 25 benign, and 29 carcinoma. Our findings were correlated with breast imaging and tissue diagnosis. The mean blood flow in 'normal' patients was 299 +/- 155 and 311 +/- 157 flux (+/- SD) for right and left breast, in patients with benign breast change it was 482 +/- 209 flux and in patients with carcinoma it was 711 +/- 280 flux. Patients with benign breast change have higher skin blood flow than symptomatic normal patients but the highest levels have been recorded in patients with breast cancer. We believe that LDI may have an important role in improving our understanding of the physiology of the normal breast and may provide a practical method of monitoring breast skin blood flow changes in clinical situations.

Primary breast carcinoma in patients with malignant melanoma.

Malignant melanoma and primary breast cancer are tumours which have an association based on genetic and hormonal factors. It is not generally appreciated that there is an increased incidence of melanoma in patients with breast cancer and vice versa. We present two cases of patients who developed breast carcinoma following previous treatment for melanoma. We review previous reports of this association and examine the theoretical reasons why this should be so. Medical practitioners should be aware of this association in order to alter their index of suspicion appropriately.

Haemolytic anaemia in the Gunn rat following transplantation of isolated hepatocytes injected with Haemobartonella muris.

Extensively purified preparations of isolated rat hepatocytes derived from Wistar rats infected with Haemobartonella muris induced haemolytic anaemia when injected into congenitally jaundiced Gunn rats. In the absence of overt parasitaemia and marked falls in haematocrit, elevation of total plasma bilirubin levels was a valuable indicator of red-cell destruction. Evidence is presented that the parasite is removed by the spleen from the surface of infected red cells which then remain in the circulation.

An explanation for the reduction in bilirubin levels in congenitally jaundiced Gunn rats after transplantation of isolated hepatocytes.

Isolated hepatocytes prepared from Wistar rats by mechanical means were infused into the liver of congenitally jaundiced Gunn rats. Red cell survival was determined in the recipients and their total plasma bilirubin was measured just before and 20 days after transplantation. Similar measurements were made in transplanted Gunn rats receiving the immunosuppressant drug cyclophosphamide at 5 mg/kg/day and in a group of splenectomized Gun rats. Red cell survival was significantly prolonged in all transplanted rats and in the splenectomised group. Total plasma bilirubin also fell significantly in all three groups by up to 25%, a change we attribute to reduced red cell turnover, haemoglobin synthesis and hence reduced bilirubin synthesis. Blockade of the splenic reticuloendothelial system by hepatocyte debris is suggested as a possible cause.

The plain abdominal radiograph in acute pancreatitis.

The radiographs of 100 patients with acute pancreatitis were reviewed and compared with 100 controls by two radiologists and a surgeon. Our aim was to assess the frequency and usefulness of the signs described in the literature. Calcification of the pancreas was seen in one case only. Abnormalities of the biliary tree (visible gallbaldder, biliary gas and gallstones) were seen in 10%. The left psoas shadow was more frequently absent in the pancreatitis series. Paucity of gastrointestinal gas although observed in 12 cases was ascribed to vomiting. A more important sign was the gaseous outline of an adynamic duodenal loop which was seen in half of the patients examined in the left lateral decubitus position. Dilated jejunum was seen in 31 cases, associated with sentinel loops in 10 and multiple fluid levels in 25 patients. Dilatation of thet ransverse colon was the most constant colonic sign (18%), but the colon 'cut-off' sign was not seen. It was concluded that the most prominent signs in order of importance are a gaseous distension of the duodenal loop, gas in the duodenal cap, a dilated transverse colon and the sentinel loop. The gasless abdomen is a striking but rare sign and in our series was always associated with severe pancreatitis.