Screening for metastasis in primary breast cancer patients having four or more axillary lymph node involvement: is it really necessary?

PURPOSE: To evaluate the necessity and direct cost effectiveness of screening and staging procedures in breast cancer patients having ≥4 positive axillary lymph nodes and to identify further possible biopathological risk factors associated with increased risk of metastasis. METHODS: We reviewed the demographic and clinicopathological data from the medical records of 1897 newly diagnosed breast cancer patients. Patients having ≥4 positive axillary lymph nodes after primary surgery for breast cancer and who had staging examinations for metastasis were eligible. The impact of staging procedures (thoracoabdominal CT, bone scan etc.) for detecting metastasis, decision of adjuvant treatment and direct costs were analyzed in 329 patients with operable breast cancer. RESULTS: Thirty-five (10.6%) patients were found with metastasis at diagnosis. Seven (20.0%) among them had multiple metastases. Eighteen (51.4%) had lung, 17 (48.6%) bone, and 7 (20.0%) liver metastasis. Twenty-one (60.0%) patients needed further radiological investigation for metastasis confirmation. Treatment decision was changed in 27 (77.1%) patients. No statistically significant risk factor was identified among the metastatic patients by means of conventional demographic and biopathological parameters. The cost of screening was lower when compared to the cost of treatment without any screening procedure. CONCLUSION: Since the conventional clinicopathological data seems not sufficient to define the risk of developing metastasis in breast cancer patients with ≥4 axillary lymph node involvement, all of them should undergo full staging examinations until new parameters based on genomic level are defined. Staging procedures need modification for high risk breast cancer patients.

Long-term evaluation of chromosomal breakages after radioisotope synovectomy for treatment of target joints in patients with haemophilia.

Radioisotope synovectomy (RS) is defined as the intra-articular injection of radioisotopic agents with the aim of fibrosis on hypertrophic synovium in the target joint. The aim of this study was to investigate genotoxic effects on lymphocytes and malign transformation induced by Yttrium(90) (Y(90)) and Rhenium(186) (Re(186)) in children with haemophilia undergone RS. Forty haemophilia patients were enrolled. The mean age was 16.4 +/- 6.2 years (range: 8-40). Y(90) was used for knees, Re(186) was used for other joints. For safety, cytogenetic analysis was performed to determine potential chromosomal changes after RS procedure at three different time points as prior to procedure, 3rd day and 90th day. For the stimulation of chromosomal breakages, diepoxybutane was used (DEB test). Chromosomal breakages (CBs) were found in 23 patients (67.6%) prior to RS. We have found CBs additionally in nine of 11 patients who had no CBs prior to RS after 3 days of radioisotope exposure. At that time, the patients who had CBs were 29 (85.2%). At day 90, only 21 patients revealed (61.7%) CBs. The mean frequency of CBs slightly but not significantly increased in the 3rd day. However, there was a significant decreasing trend between 3rd and 90th days. Radioisotope synovectomy with Y(90) and Re(186) does not seem to induce the genotoxic effects significantly on peripheral blood lymphocytes. However, CBs even after one year in the re-evaluation of four patients, significant decrease in the number of CBs between the 3rd and 90th days and de novo CBs after exposure may be accepted as warning signals for young population. It should also be pointed out that families and patients be informed properly related with historical and potential dangers of radioisotopic agents.

Correlation of 99mTc-sestamibi uptake with blood-pool and osseous phase 99mTc-MDP uptake in malignant bone and soft-tissue tumours.

Technetium-99m-sestamibi (99mTc-MIBI) imaging is a well-established modality in oncologic investigations. The current study aimed to investigate whether any relationship could be found between 99mTc-MIBI uptake and local perfusion in malignant bone and soft-tissue tumours. It also aimed to compare 99mTc-MIBI images with those of technetium-99m-methylene diphosphonate (99mTc-MDP) bone scintigraphy with regard to the activity distribution pattern, intensity and lesion extension. The study group included 24 patients with various bone and soft-tissue tumours. Three-phase bone scintigraphy and 99mTc-MIBI studies were performed within the same week before any surgical and therapeutic intervention. Images were evaluated visually and quantitatively using regions of interest (ROIs) over the lesion and adjacent normal tissue. The 99mTc-MIBI study was positive with varying degrees of uptake (range, 1.4-5.3). The mean 99mTc-MIBI uptake and 99mTc-MDP blood-pool and osseous phase activity ratios were 2.5 +/- 0.5, 2.8 +/- 1.0 and 5.5 +/- 4.0, respectively. The correlation between the 99mTc-MIBI uptake and blood-pool ratios was 0.70 (P<0.05). While activity distribution patterns were in agreement in 99mTc-MIBI and blood-pool images in the majority of cases, 99mTc-MIBI better delineated tumour viability and extension in five cases. In conclusion, 99mTc-MIBI accumulation shows a reasonable correlation with blood-pool uptake assuming the presence of multifactorial mechanisms in addition to local hyperaemia. Better delineation of tumour outlines and cellular activity seems to be an advantage of 99mTc-MIBI scintigraphy which may be helpful in the evaluation of musculoskeletal tumours.

Detecting inflammation with 131I-labeled ornidazole.

The aim of this study was to demonstrate the accumulation of 131I-labeled ornidazole (131I-ORN) in experimental abscesses. 131I-ORN was prepared by electrophilic radioiodination of ORN, using radioiodide in the presence of Iodogen. An in vivo inflammation model was prepared by intramuscular injection of turpentine into the thigh of rabbits. Four days later 131I-ORN was intravenously administered to rabbits. Serial scintigrams were performed at different periods, using a Sophy DX Gamma Camera. 131I-ORN was visualized at 10 min after injection. 131I-ORN was also administered intraperitoneally to rats with turpentine-induced inflammation, for quantitative biodistribution studies. Counts of selected tissues were taken by a NaI(Tl) scintillation detector (gamma counter) after rats were decapitated. The target-to-non-target muscle ratios were 2.5, 2.6, 2.9 and 1.9 at 1, 3, 5 and 24 h, respectively.

The role of 99Tcm-sestamibi scintigraphy in the staging and prediction of the therapeutic response of stage IV neuroblastoma: comparison with 131I-MIBG and 99Tcm-MDP scintigraphy.

In this study, we investigated prospectively the diagnostic role of 99Tcm-MIBI for staging and for predicting the therapeutic response of stage IV neuroblastoma compared with 131I-MIBG imaging and 99Tcm-MDP bone scintigraphy. Nine patients (4 girls and 5 boys aged 1-7 years) with suspected or proven stage IV neuroblastoma were studied with 99Tcm-MIBI at initial diagnosis and after 12-18 months of multidrug therapy. After the injection of 80 MBq.kg-1 99Tcm-MIBI, early (10 min) and delayed (1 h) images were obtained. The data were correlated with 131I-MIBG scans, bone scintigraphy, ultrasound, computed tomography and/or magnetic resonance imaging, and bone marrow biopsy. Eight of nine primary tumours and 41 metastatic lesions were detected by 131I-MIBG scintigraphy. None of the primary lesions demonstrated significant 99Tcm-MIBI accumulation. Sestamibi was positive in 16 of 41 MIBG-avid metastatic lesions. After six courses of multidrug chemotherapy, 30 131I-MIBI-avid neuroblastoma metastases that were 99Tcm-MIBI-negative at the time of diagnosis still did not show significant sestamibi accumulation. Follow-up demonstrated that all lesions that were 99Tcm-MIBI-avid at the time of diagnosis remained negative. Of these 16 lesions, seven were positive for 131I-MIBG accumulation with no reduction in size, and nine showed resolution after therapy. New metastatic foci detected by MIBG scintigraphy did not accumulate 99Tcm-MIBI. Clinical evaluation of patients with no 99Tcm-MIBI uptake in primary and secondary sites of neuroblastoma confirmed that they were resistant to multidrug chemotherapy. All 99Tcm-MIBI-positive lesions, irrespective of clinical outcome, demonstrated significant clearance of tracer on the delayed images. We conclude that 99Tcm-MIBI has no role in the staging of neuroblastoma. Sestamibi is a well-documented transport substrate for P-glycoprotein-related multidrug resistance and serial imaging may provide prognostic information on the therapeutic value of chemotherapy.

False-negative scintigraphy with Tc-99m sestamibi in stage IV neuroblastoma.

Tc-99m sestamibi, originally developed for myocardial studies, has been used as a tumor-seeking agent. Recently, the agent also was reported to be a functional tracer to predict multidrug resistance-related p-glycoprotein expression in tumor tissue. The current report presents the authors' experience with sestamibi tumor scintigraphy in a neuroblastoma. Although I-131 MIBG tumor imaging and Tc-99m MDP bone scanning accurately demonstrated the extent of the disease, Tc-99m sestamibi showed no accumulation in primary and metastatic foci. Lack of sestamibi uptake was initially thought to be suggestive of failure to respond to chemotherapy because of p-glycoprotein expression. However, the patient responded well to chemotherapy and complete remission was achieved. The failure of Tc-99m sestamibi to detect a neuroblastoma and the lack of sestamibi accumulation in the tumor may not always be related to chemotherapy resistance.

Assessment of chemotherapy-induced changes in bone sarcomas: clinical experience with 99Tcm-MDP three-phase dynamic bone scintigraphy.

The aim of this study was to evaluate the value of three-phase dynamic bone scintigraphy (TPBS) in the assessment of the response of bone sarcomas to pre-operative chemotherapy and to correlate serial scintigraphic changes with histological findings. The study group comprised 27 patients (osteogenic sarcoma, n = 20; Ewing's sarcoma, n = 5; malignant fibrous histiocytoma, n = 2) with a mean age of 19.2 years. All patients received 99Tcm-methylene diphosphonate TPBS before and after pre-operative chemotherapy. Each phase of the imaging procedure was interpreted qualitatively and quantitatively. The percentage of tumour necrosis was analysed on resection materials following surgery. Histologically, 12 patients were non-responsive (tumour necrosis less than 90%) and 15 patients were responsive (tumour necrosis more than 90%). A decrease in the tumour blood flow ratio and extension were the most notable findings in the responders. The mean change in the tumour blood flow ratio following therapy was 58.7 +/- 8.3% and 19.9 +/- 26.6% (P < 0.005) in responders and non-responders respectively. The accuracy of three-phase imaging and static bone scintigraphy was 88% and 74% respectively. Since bone scintigraphy is a valuable technique owing to its ability to detect distant metastases in clinically early disease, TPBS should be helpful in monitoring therapy effects without any additional cost or radiation dose.

Labeling of zopiclone with iodine-131.

Zopiclone (ZPC) was labeled with 131I by using the halogen exchange method. Temperature and reaction time effects to labeling yields were studied. Infrared, nuclear magnetic resonance, and gas chromatography-mass spectroscopy spectra were undertaken to identify chemical structure. High performance liquid chromatography (HPLC) was performed to determine purity of cold zopiclone. Biodistribution studies were performed on rabbits and rats. 131IZPC was administered intravenously to rabbits. Static images were taken by a Sophy DX Gamma Camera. 131IZPC was also administered intraperitoneally to rats. Activities were counted in a NaI(Tl) scintillation detector for several organs (liver, brain, spleen, lung, blood, fat) after rats were decapitated on different times. Biodistribution profiles were obtained depending on the time.

Evaluation of palpable breast masses with 99Tcm-MIBI: a comparative study with mammography and ultrasonography.

We evaluated the feasibility of 99Tcm-methoxyisobutylisonitrile (MIBI) as a tumour localizing agent in patients with palpable breast masses in comparison with mammography and ultrasonography (US). Forty-one patients with palpable masses were studied. An additional 12 women with no palpable breast anomaly also underwent 99Tcm-MIBI breast study. Multiple views were obtained and semiquantitative evaluation was applied. Mammography and US revealed all of the malignant breast masses but differential diagnosis of fibroadenomas could not be achieved. Twenty-five of 27 breast carcinomas were detected using 99Tcm-MIBI scintigraphy. Two patients with invasive lobular carcinoma showed absent MIBI accumulation. Eight of 14 axillary lymph-node metastases showed positive uptake (57%). Twelve of 14 patients with pathologically proven benign breast lesions did not demonstrate any MIBI accumulation. Focal MIBI uptake could be observed in two fibroadenomas. The sensitivity and the specificity of semiquantitative MIBI analysis were 93 and 86%, respectively. Subjective grading offered no additional help in the further differentiation of malignant breast masses. There was no significant difference between histopathological types of breast carcinomas and uptake grades. Our results indicate that 99Tcm-MIBI scintigraphy may provide additional information in the differentiation of malignant pathologies from benign lesions in patients with palpable breast anomalies.

Effect of pulsatile flow during cardiopulmonary bypass on thyroid hormone metabolism.

Changes in thyroid hormone levels during and after cardiopulmonary bypass (CPB) are well documented. However, little is known about the effects of pulsatile flow during CPB on thyroid hormone metabolism. To examine the effect of flow pattern, a prospective study was carried out using 30 patients undergoing coronary artery bypass grafting. Fifteen patients had pulsatile flow during CPB and 15, nonpulsatile flow. Serum samples were obtained preoperatively, during bypass, and at 2 and 24 hours postoperatively. Thyroid-stimulating hormone, thyroxine (T4), triiodothyronine (T3), free T4, and free T3 levels were measured by radioimmunoassay. All measured hormone levels except free T4 and thyroid-stimulating hormone decreased after the initiation of CPB. There were no differences in preoperative values between the two groups. However, levels of T3 and free T3 during and after CPB showed a significant difference between the two groups, with a smaller decrease in patients in whom pulsatile flow was used during bypass (p < 0.05). Thyroxine, and thyroid-stimulating hormone free T4 values showed no difference between the two groups at any sampling time. These data provide support for the use of pulsatile flow during CPB to establish a more physiologic state and maintain better thyroid hormone metabolism.

Detection of splenosis by radionuclide scanning.

Splenosis is the autotransplantation of splenic tissue following trauma. The presence of residual nodules following splenectomy has been investigated by a sensitive scanning method employing reinjection of 99Tcm-labelled, heat-damaged autologous erythrocytes. Splenosis was detected in 11 of 19 patients who had had splenectomy for traumatic rupture of spleen. Four of them had multiple nodules, the others a single nodule. In one case, the splenic nodule did not take up the sulphur colloid, although it could be visualised on selective splenic scan. We found no splenic nodules in 23 patients who had splenectomy for non-traumatic reasons. It is concluded that the key factor in splenosis is trauma.