Nuclear medicine and breast cancer: a review of current strategies and novel therapies.

While breast cancer is still increasing in frequency, new diagnostic procedures are now available to challenge existing procedures and to make diagnosis of breast cancer more accurate and reliable. Mammography remains the standard investigation to reveal disease in an asymptomatic population: it can also be used to diagnose breast cancer in symptomatic patients (e.g. those with palpable breast lumps) and for guiding fine needle aspiration (FNA). Because the majority of breast lumps are benign, the challenge is to distinguish benign from malignant lesions without the use of invasive methods and this has attracted nuclear medicine physicians and medical oncologists to investigate the role of scintigraphic procedures to identify which patients require FNA. This review attempts to shed light on the various scintigraphic methods available which are of potential practical use in the assessment of malignant breast disease as well as looking at the possible role of nuclear medicine in the treatment of advanced disease.

Color Doppler sonography of the lateral thoracic (breast-feeding) arteries: a new approach to the diagnosis of breast disease?

OBJECTIVE: The main arteries to the breast are the lateral thoracic artery and to a lesser extent the internal thoracic artery. In this prospective open diagnostic study involving 94 women, we compared the intraindividual differences of Doppler indices in the lateral thoracic (breast-feeding) artery of breasts affected by cancer with those unaffected by disease. METHODS: Sixty-seven consecutive patients were recruited from an outpatient unit for breast surgery and 27 volunteers were studied who were known to be without any breast disease (controls). In each patient we attempted to obtain Doppler indices from the lateral thoracic artery of both breasts. The difference in Doppler indices in each individual was assessed and statistical analysis was performed to assess whether these differences were significantly altered in women with cancer compared to healthy women. RESULTS: Lateral thoracic arteries could be visualized in 88% of the study population. Significantly lower values for pulsatility and resistance indices and systolic/diastolic ratios were obtained in the lateral thoracic arteries of breasts affected by cancer as compared to the contralateral breasts (1.73 +/- 0.39 vs. 2.05 +/- 0.47, P = 0.003; 0.78 +/- 0.06 vs. 0.84 +/- 0.06, P < 0.0001; 4.71 +/- 1.24 vs. 6.75 +/- 3.38, P = 0.0008, respectively). Using the intraindividual difference of pulsatility index, resistance index and systolic/diastolic ratio to screen for malignancy, sensitivities for breast cancer of 78%, 85% and 83%, respectively, were achieved. Depending on the cut-off level, specificity reached 94%. CONCLUSION: The intraindividual difference in Doppler indices in women with breast cancer may be a useful test for the diagnosis of breast lesions.

99m-Tc-tetrofosmin scintigraphy for the evaluation of suspicious palpable and non-palpable breast lesions.

PURPOSE: To assess the value of 99m-Tc-tetrofosmin (tetrofosmin) scintigraphy in patients with palpable and nonpalpable breast lesions. PATIENTS AND METHODS: Prospective, blinded trial. One hundred and fifty-nine consecutive patients with 163 breast lesions detected by clinical examination and mammography were included. Tetrofosmin scintigraphy of the breast was performed additionally to the regular diagnostic procedure. Using histologic assessment as the golden standard, sensitivity, specificity, positive and negative predictive value for tetrofosmin scintigraphy of the breast were assessed. RESULTS: Overall sensitivity and specificity were 82% and 84%. The sensitivity for palpable tumors (65%) was 93% compared to 62% for non-palpable breast lesions. Malignant lesions were nearly twice as big as benign lesions (31.5 mm +/- 2.4 vs. 16.9 mm +/- 2.4). Specificity, positive and negative predictive value (84%, 89%, and 66%) did not differ significantly in palpable versus non-palpable tumors. Of malignant tumors 18% were found false negative by tetrofosmin scintigraphy. CONCLUSION: The results suggest that tetrofosmin scintigraphy is a valuable tool for the evaluation of palpable breast cancer. In patients with non-palpable tumors, tetrofosmin scintigraphy may not add to the work-up of patients with breast cancer due to a low sensitivity rate.

Electrical stimulation of the vestibular system prevents postoperative nausea and vomiting.

BACKGROUND: Electrical stimulation of the vestibular system may prevent nausea and vomiting. We studied the influence of transcutaneous impulse stimulation in prevention of postoperative nausea and vomiting (PONV) following gynaecological surgery. METHODS: In this randomised study 70 women undergoing elective gynaecological surgery under general anaesthesia were assigned to receive either the activated (stimulation group) or the inactivated (non-stimulation group) impulse stimulator. The stimulator comprises the stimulator itself, two negative electrodes on a headset applied over both mastoid processes and a nuchal positive electrode. The device yielded a pulse frequency of 5 Hz direct current, individually adjustable between 0.5 and 4 mA. A trapezoid stimulation of 50 ms was applied. Nausea, vomiting, dizziness and the amount of antiemetic drugs used were assessed during the first 4 h postoperatively. RESULTS: Lower postoperative nausea scores with a lower incidence of vomiting and postoperative dizziness were found in the stimulation group. A lower amount of antiemetic drugs was needed in the stimulation group when compared to the non-stimulation group (P<0.01 between groups). CONCLUSION: This study suggests that electrical stimulation of the vestibular system may be useful in prevention of PONV.

[Testicular feminization--sequelae of chronic neglect of a neoplastic process]. / Zur testikulären Feminisierung--Folgen langdauernder Verschleppung eines neoplastischen Geschehens.

This paper reports on a 56-year-old patient with a history of "testicular feminization syndrome" who was admitted to hospital because of a rapid gain in her abdominal girth (106 cm). A benign cyst was removed laparotomically which, histologically, was equivalent to a cystadenofibroma. Based on this case report, the clinical significance of testicular feminization syndrome and the necessity for gonadectomy due to the risk of growth of a possibly malignant tumor are discussed.

Axillary lymph nodes in breast cancer: is size related to metastatic involvement?

Usually when using imaging procedures, such as axillary mammography or ultrasonography, a cutoff level of 5 mm for lymph node size is postulated to be not only the limit of lymph node visibility but also a sign of metastatic involvement. The aim of this study was to evaluate whether this assumption, used as a basic hypothesis in many reports, is true. A series of 72 axillary specimens from 71 breast carcinoma patients operated at the university hospital of Vienna were analyzed. A comparison of histologically noninvolved axillary specimens with those showing metastatic involvement revealed that the two groups did not differ significantly according to the number or size of lymph nodes per axilla. For lymph nodes <5 mm the probability of being metastatically involved was still 10%. Enlarged lymph nodes (5-20 mm) had a slightly higher risk of being malignant (20%). In contrast, the probability of metastatic involvement for lymph nodes >20 mm was only 40%. We suggest that many reports dealing with the prediction of malignancy in axillary lymph nodes may have used misleading basic assumptions, so the results of these studies must be viewed critically.

Use of 99mTc-furifosmin scintigraphy--planar and SPECT--to evaluate suggestive palpable and nonpalpable breast lesions.

UNLABELLED: Our objective was to evaluate the role of 99mTc-furifosmin scintigraphy--planar and SPECT--in discriminating benign from malignant breast disease. METHODS: The trial was prospective, open, and diagnostic. We recruited 30 consecutive patients with 14 palpable and 16 nonpalpable breast lesions. After receiving informed consent, we injected 555-640 MBq 99mTc-furifosmin intravenously in the arm contralateral to the breast lesion. Planar imaging and SPECT were performed. All patients underwent excision of the tumor within 2 wk. Using histology as the gold standard, we calculated sensitivity, specificity, and positive and negative predictive values for 99mTc-furifosmin in planar and SPECT technique. RESULTS: For 18 malignant and 12 benign breast lesions, a sensitivity of 50% for planar imaging and 72% for SPECT was seen. Specificity and positive and negative predictive values were 83%, 82%, and 53%, respectively, for planar imaging and 50%, 68%, and 55%, respectively, for SPECT. For the 14 palpable tumors (10 malignant, 4 benign), which averaged 17+/-10 mm in size (size range, 4-45 mm), a sensitivity of 60% for planar imaging and 80% for SPECT was achieved. Sixteen lesions were not palpable (median size, 9+/-3 mm [size range, 4-13 mm]). In this subgroup, 99mTc-furifosmin scintigraphy yielded a sensitivity of 37% for planar and 62% for SPECT technique (P>0.05). CONCLUSION: 99mTc-furifosmin scintigraphy is not a potent competitor to established scintigraphic procedures. In comparing this tracer with 99mTc-sestamibi and 99mTc-tetrofosmin, we cannot recommend 99mTc-furifosmin for the diagnosis of breast cancer.

[Increased rate of spontaneous version in breech presentation by Indian bridge? A prospective, randomized study]. / Erhöhung der Rate von Spontanwendungen bei Beckenendlagen durch die Indische Brücke? Eine prospektive, randomisierte Studie.

BACKGROUND: The effectiveness of Indian version to convert fetuses from breech to vertex presentation was evaluated. METHODS: One hundred and nine pregnant women presenting between 30 and 32 weeks of gestation with singleton breech infants were included in our prospective randomized open study making an interim analysis recruitment to estimate the sample sizes after one year. The spontaneous version rate of fetuses in breech presentation was compared with the version rate in women performing Indian version. Indian version is a maternal positioning exercise that consists of raising the pelvis, abduction of the thighs, and relaxed abdominal breathing. Clinical parameters that could influence the result were assessed. RESULTS: In primiparous women, the version rate was 70% in the Indian version group and 63% in the comparison group. In multiparous women, 89% Indian versions and 87% spontaneous versions were observed. Parity was the only clinical parameter found to be related to outcome. CONCLUSION: Indian version does not significantly improve the rate of spontaneous version of breech to vertex presentation.

Single-injection paravertebral block compared to general anaesthesia in breast surgery.

BACKGROUND: Breast surgery is frequently associated with post-operative nausea, vomiting, pain and painful restricted movement. Paravertebral block may be an alternative to general anaesthesia for this type of surgery. We studied the single-injection paravertebral block at the level of T4 and report a comparison of single-injection paravertebral block to general anaesthesia for breast surgery. METHODS: After written informed consent was obtained, 86 patients were enrolled in this prospective study. Forty-four women were randomly allocated to receive a single-injection paravertebral block at the level of T4, while 42 women received general anaesthesia. The surgical procedures varied from lumpectomy (wide local excision of a tumour) to modified radical mastectomy with axillary dissection. The block was performed according to the guidelines described by Eason and Wyatt using 0.3 ml x kg(-1) (maximum dose 150 mg) of bupivacaine 0.5%. The skin and the underlying tissues were infiltrated with local anaesthetic solution two fingers (about 3 cm) from the anatomical midline and level with the cephalad end of the vertebral spine. RESULTS: Time for performance of blocks lasted from 4 to 9 min. Recovery from anaesthesia or sedation was shortened, while postoperative pain scores (VAS), the incidence of vomiting and the requirement for analgesics were lower in the paravertebral group. Less painful restricted movement was observed in the paravertebral block group. Paravertebral block was inadequate in 6.8% of patients. Epidural spread with paraparaesis and Horner triad was assumed in one patient. CONCLUSION: Single-injection paravertebral block at the level of T4 represents a suitable alternative to general anaesthesia in women undergoing breast surgery.

Maternal cigarette smoking increases F2-isoprostanes and reduces prostacyclin and nitric oxide in umbilical vessels.

The objective of this study was to evaluate the influence of smoking on F2-isoprostanes, prostacylin and nitric oxide in human umbilical vessels. Umbilical cords from 13 babies of smoking mothers and from 28 babies of non-smoking mothers were examined for levels of F2-isoprostanes, prostacyclin, L-arginine, and L-citrulline. Forty-one umbilical arteries and eleven umbilical veins were analyzed. Statistical analysis of data was done using modified t-test. Cigarette smoking increased F2-isoprostane levels and reduced the generation of prostacyclin, L-arginine and L-citrulline comparably in umbilical arteries and veins. Notably, in umbilical cords of babies of non-smoking mothers the F2-isoprostane level was significantly higher in arteries. Cigarette smoking correlates with a direct vasoconstrictive effect. We suggest that smoking might enhance the vasoconstrictory capacity in umbilical arteries by increased F2-isoprostanes and by a simultaneous decrease in the production of the vasodilatory compounds, prostacyclin, and nitric oxide.

Identification of women with early breast cancer by analysis of p43-positive lymphocytes.

Regular screening mammographies and increasing knowledge of high-risk groups have resulted in an improvement in the rate of detection of smaller malignant lesions. However, uncertain minimal mammographic features frequently require further costly and often uncomfortable investigation, including repeat radiological controls or surgical procedures, before cancerous lesions can be identified. Placental isoferritin (p43), a protein with immunosuppressive effects, has been detected on the surface of lymphocytes taken from peripheral blood in patients with breast cancer. In this study we evaluated the sensitivity and specificity of the expression of p43-positive lymphocytes as a marker in early stage breast cancer and also investigated its expression on T-cell subpopulations. The presence of p43-positive lymphocytes was investigated using the monoclonal antibody CM-H-9 and flow cytometry in 76 women with controversial, non-palpable mammographic findings who were undergoing surgical biopsy. Patients with early breast cancer (n = 48) had significantly higher p43-positive cell values (median 3.83%, range 0.98-19.4) than patients with benign lumps (n = 28, median 1.43%, range 0.17-3.7) or controls (n = 22, median 1.3%, range 0.4-1.87) (P < 0.0001). At a cut-off level of 2% p43-positive cells a sensitivity of 91.7% and a specificity of 89.3% for detection of breast cancer could be reached. While the median ratio of total CD4+/CD8+ cells was 2.6, a ratio of 1.3 was found for the p43-positive subpopulation (P < 0.001), thus indicating a significant link between p43 and CD8+ cells. The determination of p43-positive lymphocytes in peripheral blood could serve as an additional diagnostic tool in patients with controversial mammographic findings and could also reduce the need for cost-intensive and often uncomfortable management of these patients.

Homocysteine--a pathophysiological cornerstone in obstetrical and gynaecological disorders?

Homocysteine, a product of the methionine cycle, is known to play an important role in cardiovascular diseases, neurological disorders and embryology, and in very important, fast growing fields concerning obstetrics and gynaecology. Therefore, we attempted an actual overview on possible obstetrical and gynaecological disorders as a consequence of an impaired methionine cycle. We tried to evaluate all mechanisms concerning homocysteine metabolism in order to look for hypothetical possibilities of therapeutic interventions. Using MEDLINE starting in January 1966, a search was conducted for articles published in which homocysteine was included as a subject heading or a text word. This search was also specified in combination with other key words such as obstetrics, pregnancy, gynaecology and cancer. Additional sources were identified through cross-referencing. All sources found were examined with regard to providing substantial information on our topic. The information obtained was divided into articles dealing with homocysteine and the methionine cycle itself, homocysteine and pregnancy, and homocysteine and hormones, including menopause, hormone replacement therapy and oral contraceptives. Another group was concerned with other special gynaecological aspects of the methionine cycle. We suggest that elevated concentrations of homocysteine could be a marker and perhaps a cause of, or contributive to, a wide range of obstetrical and gynaecological disorders.

99m-Tc-tetrofosmin scintigraphy and breast cancer.

BACKGROUND: 99m-Tc-tetrofosmin holds significant interest among medical oncologists because of its high positive predictive value (>90%) in pilot trials, exceeding sensitivity and specificity rates of mammography. Objective. Our objective was to assess the diagnostic accuracy of 99m-Tc-tetrofosmin whole-body scintigraphy in outpatients. PATIENTS AND METHODS: Thirty-one patients with an abnormal mammograph (n = 22) or follow-up patients (n = 9), 7 of whom were known to have metastatic disease, were included. Tracer (550 MBq) was injected into the cubital vein. Whole-body planar and single photon emission computed tomography images of regions of interest were obtained. Histology, computed tomography (CT), or magnetic resonance imaging (MRI) were performed to confirm scintigraphic results. Correlation between scintigraphy and CT or MRI was assessed by two independent radiologists. Accuracy, sensitivity, and specificity rates for the diagnosis of local and distant breast cancer lesions were given. RESULTS: Of the 22 first-visit patients, 15 had breast cancer, and 7 had no evidence of any malignant disease. Of all patients examined (n = 31), 21 had distant metastases. Breast tumors were correctly diagnosed in 14/15 patients (93%), with only 1 false-negative result. Extrahepatic metastatic lesions (n = 16) were correctly diagnosed in 14 (88%) patients, whereas the method was not suitable for the diagnosis of liver metastases. CONCLUSION: Tetrofosmin scintigraphy has shown very high detection rates of breast tumors and of metastatic lesions and is therefore a valuable option in breast cancer diagnosis.

Axillary metastases of an occult primary carcinoma of the breast-discovered only by 99mTc-tetrofosmin scintigraphy.

Recent reports consider 99mTc-tetrofosmin scintigraphy to be a powerful new diagnostic tool for discriminating malignant from benign breast disease. We report on a woman suffering from histologically confirmed axillary metastases of a primary unknown, occult carcinoma, whose origin was suspected within the breast. All the diagnostic procedures performed to discover any lesion failed or were inconclusive. The primary cancer was clearly visualized, however, in the right breast by means of 99mTc-tetrofosmin scintigraphy. Conclusion. We suggest that 99mTc-tetrofosmin scintigraphy is a powerful method to detect breast cancer, especially when other diagnostic imaging procedures are inconclusive.

A head-to-head comparison between technetium-99m-tetrofosmin and technetium-99m-MIBI scintigraphy to evaluate suspicious breast lesions.

The aim of this study was to assess the diagnostic value of technetium-99m-tetrofosmin and technetium-99m-MIBI in a head-to-head comparison. Both radiopharmaceuticals are routinely used for detecting breast cancer. In a prospective, open, diagnostic trial, the two radiopharmaceuticals were administered randomly on different days to the same 101 women suffering from 103 breast tumours. Planar images and single photon emission computer tomography (SPET) were performed. After histological examination of the tumours, sensitivity, specificity and positive and negative predictive value were compared. 99mTc-tetrofosmin and 99mTc-MIBI showed low sensitivity in planar images (44% vs 46%, respectively). SPET improved sensitivity (70% vs 69%, respectively). Specificity in planar images was 83% and 87%, and it was even lower using SPET (70% vs 78%, respectively). Positive predictive value in planar images was 76% vs 81%, and it was not changed by SPET. Negative predictive value was low in planar images (54% vs 57%, respectively), but it was improved by using SPET (65% vs 67%, respectively). In conclusion, 99mTc-tetrofosmin and 99mTc-MIBI scintigraphy show similar diagnostic value in assessing suspicious breast lesions.

[Placental isoferritin (PLF): early predictor of fetal growth retardation]. / Früherkennung fetaler Wachstumsretardierung durch Bestimmung des plazentaren Isoferritins.

OBJECTIVE: Maternal immunoreaction against the embryo can be responsible for fetal growth retardation. The secretion of PLF during pregnancy could be reliable for a diminished immunoreaction of maternal lymphocytes against the embryo. The aim of the present study was to elucidate a possible correlation between PLF and fetal growth retardation. METHODS: In this study, blood samples of 402 pregnant women were obtained between the 12th and 16th weeks of gestation. The serum levels of PLF were compared with birth weight, percentile of birth weight, and gestational age. RESULTS: Women with children whose birth weight was below or equal to the 10th percentile for gestational age showed significantly lower PLF levels (11.4 U/ml, n = 107) as compared with women whose newborns were of normal weight (19.9 U/ml, n = 295; p < 0.004). CONCLUSION: Determination of the PLF level could serve to identify women at risk of having growth-retarded babies.

An undetected reason for severe fetal growth retardation.

In a severely growth-retarded fetus, repeated Doppler ultrasound examinations from the 23rd week of gestation on, showed normal and highly pathological blood flow velocities in the umbilical artery. A caesarean section performed in the 39th week of gestation revealed two true umbilical cord knots. Sonographic screening for umbilical cord knots may be valuable in similar cases. The use of color Doppler could help to visualize the entire course of the umbilical cord.

Breech infants: vaginal or cesarean delivery?

BACKGROUND: This study was undertaken to determine whether planned vaginal or elective cesarean delivery is better for singleton term breech infants and their mothers. METHODS: We studied deliveries of 388 singleton term breech infants that were born in our teaching hospital in Vienna. We follow well defined criteria for vaginal delivery versus cesarean section of term breech fetuses. We thus compared 280 (72%) cases scheduled for vaginal delivery with 108 (28%) scheduled cesarean sections with regard to neonatal mortality and morbidity, including Apgar score, umbilical artery pH, and postpartum maternal morbidity. RESULTS: Vaginally delivered fetuses of primiparas had lower five-minute Apgar scores (5% < Apgar 7) and a lower umbilical artery pH (39% below 7.2). This is significantly different from the abdominally delivered primiparas (no Apgar below 7, only 11% with an artery pH below 7.2). Multiparas did not show significantly different results with regard to Apgar scores and umbilical artery pH between the different modes of delivery. Postpartum maternal morbidity was not different between the two groups. CONCLUSION: The results suggest that planned vaginal delivery of singleton breech infants of primiparas result in newborns with lower Apgar-scores, a lower umbilical artery pH and a poorer fetal outcome. On the other hand, it seems that singleton term infants of multiparas do not profit from cesarean delivery.