Flow injection immunoanalysis based on a magnetoimmunosensor system

To establish criteria for the differentiation of benign and malignant tumors of the parotid gland using color Doppler sonography (CDS) and pulsed Doppler sonography (PDS) we examined 37 patients with parotid tumors by gray-scale ultrasound, CDS, and PDS. Tumor vascularization displayed by CDS was graded subjectively on a 4-point scale (0 = no vascularization, 3 = high vascularization). From the Doppler spectrum, the highest systolic peak flow velocity, the resistive index (RI), and the pulsatility index (PI) were calculated. There were 11 malignant and 26 benign tumors. Tumor vascularization by CDS was grade 0 or 1 in 88.5% of benign lesions, whereas it was grade 2 or 3 in 82% of malignant lesions (P < 0.0001). The highest systolic peak flow velocity was statistically significantly higher in malignant lesions than in benign lesions. Using a threshold systolic peak flow velocity of 25 cm/s, sensitivity was 72% and specificity was 88% for the detection of a malignant tumor. Evaluation of tumor vascularization by CDS and PDS cannot differentiate between benign and malignant parotid tumors with certainty. However, high vascularization and high systolic peak flow velocity in tumor vessels should raise the suspicion of malignancy, even if tumor morphology on gray-scale sonography indicates a benign lesion.     

Analysis of blood flow in adnexal tumors by using color Doppler imaging and pulsed spectral analysis

Because of various contradictory reports in the literature and an increasingly urgent need for preoperative evaluation of adnexal masses before laparoscopic surgery, our aim was to disclose if examination by means of color Doppler ultrasound is useful in distinguishing benign from malignant adnexal tumors in our population. Prior to surgery, pulsed color Doppler velocimetry of the adnexal blood supply was performed in a prospective study in 80 patients with benign and 40 with malignant adnexal tumors. Vascularization was equally frequent in both groups of tumors. Blood vessels of benign tumors had a diffuse, intraseptal or intraproliferative location significantly more often and malignant tumor vessels more often exhibited a diffuse, intraseptal or intraproliferative location (p < 0.01). The mean value of RI+/-SD was 0.56+/-0.14 in benign and 0.33+/-0.13 in malignant tumors. The differences in RI between benign and malignant tumors are statistically significant (p < 0.01). In detecting malignant adnexal tumors, the sensitivity of RI < or = 0.40 is 82%, its specificity 97%, positive predictive value 94%, negative predictive value 92% and its accuracy 92%. The analysis of vascularization presence seems not to have any value in predicting the nature of adnexal tumors, and blood vessels arrangement, as well as measured RI < or = 0.40, allows us to predict the presence of malignancy with limited reliability.     

Fluorine-18-fluorodeoxyglucose assessment of glucose metabolism in bone tumors

In our study, we investigate the glucose metabolism of various types of bone lesions with 18F-fluorodeoxyglucose (FDG) PET. METHODS: Twenty-six patients showing clinical and radiographic symptoms of a malignant bone tumor were included. Histological examination after the PET study revealed 19 malignant and 7 benign tumors. PET images were corrected for attenuation. Arterial blood samples were taken to establish the input function. The metabolic rate of glucose consumption (MRglc) was calculated for the whole tumor, for the 10 pixels with maximum activity and for contralateral normal muscle tissue. RESULTS: All lesions were clearly visualized with 18F-FDG PET except for a small infarction of the humerus. All the other lesions had increased glucose metabolism compared to surrounding and contralateral muscle tissue. Both maximum and average MRglc for benign, as well as malignant, lesions were significantly higher than for contralateral normal tissue. The maximum and average MRglc were not higher for malignant as opposed to benign lesions. There was a large overlap between the MRglc of benign and malignant lesions. CONCLUSION: Fluorine-18-FDG PET appears suitable to visualize bone tumors. With the quantification of glucose metabolism, it is not possible to differentiate between benign and malignant bone tumors. There does not seem to be a clear correlation between the MRglc and the biologic aggressiveness of the neoplasms.     

Value of bronchoscopic pneumonia diagnosis: prospective study

The frequent detection of benign liver lesions during ultrasound routine examination and a possible curative therapy of early detected malignant tumors require a reliable method of differentiation. Conventional gray-scale ultrasound, according to this problem, has been extended by the Duplex technique and color Doppler ultrasound. Measurement of blood flow velocity by Doppler in the center and at the periphery of liver lesions is not reliable enough to distinguish between benign and malignant lesions. Color Doppler ultrasound possesses some reliable criteria for differentiation. A central spot could be detected in 2 out of 12 hemangiomas, a giant spot in 1 out of 3 giant cavernous hemangiomas. The halo sign without detectable blood flow is considered to be specific for malignancy. We found this sign in 26 out of 81 malignant liver lesions and only in one benign lesion (sensitivity 32%, specificity 97%). The vascularization of focal liver lesions is excellently demonstrated with color Doppler ultrasound. This is very helpful for the diagnosis (e.g. "chaotic blood vessel architecture' in malignant tumors) and for the therapy of focal liver lesions (e.g. follow-up examinations after chemotherapy or chemoembolization). Therefore, application of Duplex and color Doppler ultrasound is highly recommended as a noninvasive diagnostic method of first choice for unknown liver lesions.     

Glutathione movements during cold preservation of rat hepatocytes

PURPOSE: Power-Doppler sonography is regarded as a very sensitive method for detecting low-velocity and low-volume blood flows. The purpose of our study was to investigate whether increased vascularity in breast carcinoma can be visualized by power-Doppler sonography and whether new criteria for differentiating benign and malign lesions can be found. METHOD: 315 patients were examined with a 13-MHz high-resolution linear transducer. If a suspicious lesion was found, it was evaluated further by power-Doppler sonography. Compared to normal breast parenchyma (reference structure), a focal increase in blood flow signals was registered using a 3-step grading system with a 4th step for no flow increase. RESULTS: In 97 cases the sonographic findings were correlated with histology (n = 95) or cytology (n = 2). There were 50 benign lesions, 42 cases of invasive and 5 cases of in-situ carcinoma. 73.5% benign lesions showed no or just minimal increases in flow signal. 81% of invasive cancer presented middle- or high-flow increases compared to normal breast parenchyma. The extend of flow increase was linked to tumor size in invasive cancer. In stage T1b to T4, 94.3% of invasive carcinoma presented middle or high flow increases. CONCLUSION: Power-Doppler sonography is able to visualize vascularization in breast tumors. According to first clinical results PD sonography is a promising additional diagnostic tool which seems to offer new criteria for differential diagnosis in breast tumors.     

Ophthalmic findings with partial trisomy (duplication) of the long arm of chromosome 7

BACKGROUND: The sensitivity of diagnostic imaging of processes in the parotid gland has been increased by improved spatial resolution, yet specificity remains unchanged. The purpose of this study was to determine whether the low-flow color duplex technique alters the specificity of B-mode ultrasonography. PATIENTS AND METHODS: Forty-one patients with tumors of the parotid gland were examined by color duplex echography as well as histologically. Twenty-eight of the 41 patients had benign tumors and 13 had malignant disease. In 17 of 41 patients, color duplex ultrasonography failed to detect any vascularization within the tumor. Histopathological examination showed that 3 of these 17 tumors were malignant and 14 of 17 were benign. Intranodal vascularization was detected in 24 cases. Ten of these patients were found to have malignant tumors of the parotid gland; 14 had benign parotid tumors. RESULTS: Our present findings show that marked intratumoral vascularization especially appears in malignant tumors. In contrast to lymph nodes, the location and texture of intranodal blood vessels do not provide information about the nature of the neoplasm. CONCLUSIONS: Low flow duplex ultrasonography does not increase the specificity of preoperative examination in tumors of the parotid gland.     

Estimation of vascular blood flow velocity in the breast neoplasms

Based on examinations of 133 females having the normal breast, benign and malignant tumors, the potentialities of color Doppler mapping of breast vessels are shown. Cancers showed an increased vascularity in the peritumor areas and high flow velocity (Vmax' Vmean) in the surrounding tumor vessels. These criteria are not related to the size of a malignant tumor.     

Late outcome after surgical treatment of perilunar dislocation and dislocation fractures

53 cases of ovarian tumors were diagnosed and operated in the Clinic of Obstetrics and Gynecology of Medical Academy in Bydgoszcz in years 1996-1997. Retrospective analysis of 58 results of ultrasonographic examination with color-Doppler estimated flows and histopathological diagnoses in cases of ovarian tumor was performed. On the ground of sonographically estimated morphology, presence or absence of vascularization and pulsation and resistance indices (PI and RI respectively) an attempt to discriminate benign and malignant tumors was made. Values of RI > 0.6 and PI > 1.0 in absence of morphologically suspicious features in ultrasonographic examination correlated with benign forms of ovarian tumors in histological examination.     

Interaction of ozone and allergen challenges on bronchial responsiveness and inflammation in sensitised guinea pigs

We studied the potential of PET with L-[1-11C]-tyrosine (TYR) to visualize tumors outside the central nervous system and to quantify their protein synthesis rates (PSRs). METHODS: Twenty-two patients suspected of having a malignant tumor underwent a PET study with TYR before biopsy. The PSR in nanomoles per milliliter tumor tissue per minute as well as the PSR in contralateral normal tissue, standardized uptake values (SUVs) and tumor-to-nontumor-ratios (T/N ratios) were calculated. RESULTS: Fifteen of the 16 malignancies (94%) were correctly visualized as a hot spot. A chondrosarcoma of the sacrum was not visualized. Of the six patients with benign lesions, cold spots were correctly identified in four (67%). A benign schwannoma and an intramuscular hemangioma of the forearm were visualized as hot spots. PSR in tumor tissue was higher than in the corresponding contralateral normal tissues. PSR and SUV in malignant tumors were higher than in benign tumors. CONCLUSION: TYR appears to be a good tracer for imaging malignancies. The PSR, which was higher in malignant tumors than in normal tissue and the studied benign lesions, could be quantified and correlated with the SUV.     

Cyclic adenosine 3',5'-monophosphate-binding proteins in human ovarian cancer: correlations with clinicopathological features

The regulatory subunits of protein kinase A, or cyclic AMP-binding proteins, were measured in a series of 107 human ovarian tumors (89 malignant, 7 borderline, and 11 benign tumors) and related to tumor clinicopathological features and patient survival. Total cyclic AMP-binding protein levels were not significantly different between malignant tumors and either borderline or benign tumors. However, serous tumors showed significantly higher levels of total cyclic AMP-binding proteins than other malignant tumors (P = 0.007). Poorly differentiated tumors also possessed significantly higher levels of binding proteins as compared with well/moderately differentiated tumors (P < 0.01). Retrospective analysis of follow-up data also revealed a significant trend for patients with high tumor cyclic AMP-binding proteins to have poorer survival (P = 0.03). Individual binding proteins were identified by photoaffinity labeling, and the RI (Mr 48,000) protein was expressed as a percentage of total cyclic AMP-binding proteins detected. The percentage of the RI protein was not significantly different among malignant, borderline, or benign pathologies and was not associated with tumor stage, differentiation, or debulk status. The percentage of RI was significantly increased in serous tumors compared to other common epithelial malignancies (P = 0.01). In malignant tumors there was a significant positive correlation between the percentage of the RI protein and total cyclic AMP-binding proteins (P = 0.01). These data indicate that high tumor levels of cyclic AMP-binding proteins are associated with serous histology, poor differentiation, and poor patient survival.     

Comparative signal intensity measurements in dynamic gadolinium-enhanced MR mammography

Increases in signal intensity enhancement were measured in defined regions of interest (ROIs) to allow distinction between malignant and benign tumors with dynamic gadolinium-enhanced magnetic resonance (MR) mammography. Twenty patients with palpable breast lesions (15 malignant, five benign) underwent MR mammography. The dynamic gradient-echo sequence was performed with intravenous bolus injection of gadopentetate dimeglumine and consisted of 25 images with a time resolution of 30 seconds. Contrast enhancement was calculated by comparing user-defined ROIs on pre- and postcontrast images. An increase in signal intensity of 70% or more on the 1-minute postcontrast image was used as the criterion of malignancy. MR mammographic results correlated with histopathologic findings in all patients when the defined ROI was in the most enhancing part of the tumor. For the ROI in areas of submaximal enhancement or when the ROI surrounded the whole lesion, only five and nine tumors, respectively, fulfilled the malignancy criterion. All malignant tumors showed large variations in signal intensity enhancement that depended on the position of the ROI in the tumor. Dynamic, gadolinium-enhanced MR mammography allows distinction of benign from malignant breast tumors when the selected ROI is in the most enhancing part of the lesion.     

Metabolic characterization of breast tumors with positron emission tomography using F-18 fluorodeoxyglucose

PURPOSE: To evaluate the diagnostic value of position emission tomographic (PET) imaging with F-18 fluorodeoxyglucose (FDG) in differentiating between benign and malignant breast tumors. PATIENTS AND METHODS: Fifty-one patients, with suspicious breast lesions newly discovered either by physical examination or by mammography, underwent PET imaging before exploratory surgery. FDG-PET images of the breast were analyzed visually and quantitatively for objective assessment of regional tracer uptake. RESULTS: Primary breast cancer was identified visually with a sensitivity of 68% to 94% and a specificity of 84% to 97% depending on criteria used for image interpretation. Quantitative analysis of FDG uptake in tumors using standardized uptake values (SUV) showed a significant difference between benign (1.4 +/- 0.5) and malignant (3.3 +/- 1.8) breast tumors (P < .01). Receiver operating characteristic (ROC) curve analysis exhibited a sensitivity of 75% and a specificity of 100% at a threshold SUV value of 2.5. Sensitivity increased to 92% with a corresponding specificity of 97% when partial volume correction of FDG uptake was performed based on independent anatomic information. CONCLUSION: PET imaging allowed accurate differentiation between benign and malignant breast tumors providing a high specificity. Sensitivity for detection of small breast cancer ( < 1 cm) was limited due to partial volume effects. Quantitative image analysis combined with partial volume correction may be necessary to exploit fully the diagnostic accuracy. PET imaging may be helpful as a complimentary method in a subgroup of patients with indeterminate results of conventional breast imaging.     

Standardized uptake value and quantification of metabolism for breast cancer imaging with FDG and L-[1-11C]tyrosine PET

The aims of the study were to compare the value of L-[1-11C]tyrosine (TYR) and [IBF]fluoro-2-deoxy-D-glucose (FDG) as tumor tracers in patients with breast cancer, to investigate the correlation between quantitative values and standardized uptake values (SUVs) and to estimate the value of SUVs for the evaluation of therapy. METHODS: Eleven patients with one or more malignant breast lesions and two patients with one or more benign breast tumors were studied with TYR and FDG. Doses of 300 MBq of TYR and 230 MBq of FDG were given intravenously. All PET sessions were performed using a Siemens ECAT 951/31 camera. Of 10 malignant tumors and the 3 benign lesions, glucose consumption and protein synthesis rate were quantified. All lesions were studied using SUVs based on body weight, body surface area and lean body mass, with and without correction for plasma glucose or tyrosine levels. RESULTS: All malignant tumors were visualized with both FDG and TYR, but the visual contrast was better with FDG. Increased uptake of the tracers was seen in patients with fibrocystic tissue and complicated the visual assessment and the outlining of tumor tissue. Uptake in fibrocystic disease was more prominent with FDG than with TYR. No difference in tumor/nontumor ratio between the two tracers could be established. FDG showed a false-positive result in one benign lesion. No major differences between the SUVs as defined above were found, although the best correlation between glucose consumption and the SUV was observed when the SUV was based on body surface area and corrected for plasma glucose level (r = 0.85-0.87). The SUV based on lean body mass was found to correlate best with protein synthesis rate (r = 0.83-0.94). CONCLUSION: In this group of patients, TYR appears to be a better tracer than FDG for breast cancer imaging, because of lower uptake in fibrocystic disease. SUVs correlate well with quantitative values, but future studies must determine whether treatment evaluation is also reliable with SUVs.     

Expression of c-met proto-oncogene product (c-MET) in benign and malignant bone tumors

The expression of c-met proto-oncogene product (c-MET) has been reported to be related to invasive growth or tumor stage in some tumors, but little is known concerning the significance of c-MET expression in bone tumors. With use of formalin-fixed, paraffin-embedded tissue specimens and polyclonal antibody for c-MET, we studied the expression of c-MET in 122 cases of malignant bone tumors (43 osteosarcomas, 24 chondrosarcomas, 21 malignant fibrous histiocytomas of bone, 16 Ewing's sarcoma versus primitive neuroectodermal tumors, 18 chordomas), 65 cases of benign tumors and tumor-like lesions (including 8 giant cell tumors of bone, 8 chondroblastomas, 12 enchondromas, 7 osteochondromas, 10 fibrous dysplasias), 7 cases of articular cartilaginous tissue, and 10 cases of fetal vertebral tissue consisting of foci of enchondral ossification and notochordal tissue. In malignant tumors, c-MET expression was most frequently detected in chordoma (94.4%), followed by chondrosarcoma (54.2%) and osteosarcoma (23.3%). Among the osteosarcoma specimens, c-MET expression was frequently detected in the chondroblastic subtype (66.7%), but the incidence was low in the cases with other subtypes of osteosarcoma. We found no significant correlation between the c-MET expression and the histologic grade of malignancy in either osteosarcoma or chondrosarcoma. c-MET expression was either rarely observed or completely negative in malignant fibrous histiocytomas of bone (4.8%) and primitive neuroectodermal tumors (0%). In benign tumors and tumor-like lesions, c-MET expression was frequently detected in cartilaginous tumors, such as chondroblastoma (62.5%), enchondroma (66.7%), and osteochondroma (71.4%), but no expression was observed in giant cell tumors of bone or any other benign tumors or tumor-like lesions. In normal tissue, c-MET expression was frequently detected in the articular cartilage (100%) and notochord (70.0%) specimens examined. We conclude that c-MET expression as frequent as that observed in the notochordal tissue, chordomas, articular cartilage, and cartilaginous tumors is related to the development of both normal tissue and chondroid tumors.     

Use of resistance index for the diagnosis of breast tumours

AIM: To determine whether the resistance index (RI) contributes to the differential diagnosis of breast masses. PATIENTS AND METHODS: In 56 breast tumours colour-coded Doppler sonography was performed and their resistance indices calculated from their spectral Doppler tracings. Histologic evaluation was obtained by excision biopsy. RESULTS: In seven of 28 benign tumours (25%) no lesion was seen on ultrasound. In another seven benign tumours, no intratumoral vessels were demonstrated. The resistance index of the remaining 14 lesions (50%) varied between 0.5 and 0.75 with a mean value of 0.62 (standard deviation 0.08). Ultrasound missed one of 28 carcinomas (3.5%) and in one other tumour (3.5%) no flow was demonstrable. The resistance index of 26 malignant tumours varied between 0.56 and 0.9 with a mean value of 0.7 (standard deviation 0.08). CONCLUSION: Breast malignancies have higher resistance indices with a wider range as assessed by colour-coded Doppler ultrasound (81% exceed 0.6) than do benign lesions. Due to the considerable overlap of the range of the resistance index, the measurements in any single patient may not be diagnostic. The absence of flow does not definitively exclude malignancy.     

Citrate values in the whole blood of patients with malignant tumors of various locations

Based on reports on elevated concentrations of 2-oxoglutarate in the blood of human subjects with tumors of various locations, data are presented on the concentration of citrate and pyruvate in the whole blood of 41 patients with malignant tumors (mainly of the female breast and of the digestive tract), 30 patients with benign surgical diseases and 12 healthy subjects. Adopting a level of significance of 2P=0.10 differences of concentration were found between the following collectives: (1) The mean value of citrate for the patients in tumor stage T4 was decreased by 23%, compared with healthy persons, and by 19%, compared with patients with benign surgical diseases. (2) The mean value of pyruvate for the patients with malignant tumors was increased by 40%, compared with healthy subjects and by 17%, compared with patients with benign surgical diseases. (3) The maximum of the pyruvate concentration was reached in tumor stage T3, where an increase of 52% was noted, compared with healthy subjects. (4) The pyruvate value of the patients with tumors of the digestive tract was increased by 34%, compared with healthy subjects. With regard to the total group of patients with malignant tumors, even with a low level of significance, no differences in citrate values were found as compared with the control groups. Thus the results do not indicate a disturbance of the citric acid cycle in the organism of tumor bearing hosts in general.     

Angiogenesis of gynecologic tumors studied with color Doppler

Angiogenesis is obligatory event in solid tumors growth. Weak muscular layer in the newly formed tumoral vessels results in decreased resistance to blood flow and characteristic Doppler signal. The number and arrangement of the blood vessels differ between benign and malignant lesions as well. Parameters mentioned above enable a precise ultrasound differential diagnosis between benign and malignant tumors. Malignant uterine tumors are better perfused and have lower resistance to blood flow than benign ones. Benign lesions with secondary changes (necrosis) may have lowered resistance indices. The finding of pathological perfusion makes the diagnosis of endometrial carcinoma also very accurate. High sensitivity of the transvaginal color Doppler in detecting newly formed blood vessels in an early stages of ovarian cancer may establish this technique as a screening method for this still very high lethality disease.     

Breast hamartoma with invasive ductal carcinoma. Report of two cases and review of the literature

Two cases of well-defined masses also containing clinical and radiographical abnormalities suggestive of malignancy, subsequently found to be invasive ductal carcinomas in breast hamartomas are described. The patients were 53 and 78 years old. Both presented with a generally soft palpable breast lump, containing a firm area which in one case invaded and ulcerated the skin. Mammography demonstrated two typical hamartomas: one containing a spiculated opacity, the other irregular opacities with suspicious calcifications, suggesting the presence of carcinomas in these benign lesions. The cut surface of these well-circumscribed masses measured 5 cm and 7 cm. The microscopic appearance was characteristic of breast hamartoma (sharp circumscribed "pseudocapsule" surrounding breast fibrocystic changes with variable amounts of adipose tissue) with the firm area in each case corresponding to invasive ductal carcinoma. In one case the invasive ductal carcinoma was confined to the hamartoma, whereas in the other malignant tumor, cells extended beyond the surrounding breast tissue and infiltrated the skin. These findings raise the question of secondary involvement of a hamartoma by invasive carcinoma. Breast hamartomas are probably underrecognized lesions. In our view, these findings do not justify a more aggressive approach towards the management of breast hamartomas.     

Surgical treatment of primary neurogenic mediastinal tumors

In the years 1968-1989 out of 300 patients with surgically treated mediastinal tumors in 63 (21%) they were of neurogenic origin. Eighteen of these (29%) proved to be malignant. These tumors occurred in 23 males and 40 females, age range 14 months-67 years (mean 36 years). In all 45 patients with benign tumors and in 12 (66.7%) with malignant tumors the tumors were totally resected. In 4 patients the tumor was only partially resected in further two only a biopsy of the lesion was taken. During postoperative period one patient with a malignant tumor died. Ten (71.4%) patients survived 5 years with malignant lesions, while only 8 (61.5%) survived ten years. All patients that underwent resection of the benign tumor survived 10 years.