Microvessel density, p53 overexpression, and apoptosis in invasive breast carcinoma

AIM: To investigate the possibility of a correlation among microvessel density, p53 overexpression, and apoptosis in invasive breast carcinoma. METHODS: Microvessel density was analysed in 105 cases of invasive breast carcinoma by immunohistology using antifactor VIII related antibody. The results were correlated with the immunohistochemical expression of p53 and the apoptotic index, detected using the in situ end labelling of fragmented DNA method (TUNEL). Assessment was made with a CAS 200 image analyser. All these studies were performed on formalin fixed, paraffin wax embedded tissue sections of tumour samples. RESULTS: The mean (SD) microvessel count was 47.2 (51.1), with a range from 7 to 250. Thirty five (33%) carcinomas showed overexpression of p53 protein. The apoptotic index of tumours ranged from 0.0 to 28.0, with a mean (SD) of 1.7 (3.2). The results showed that there was a significant inverse correlation between microvessel density and p53 expression (p = 0.04; odds ratio, 0.37). In contrast, no correlation was identified between the microvessel density and apoptotic index. CONCLUSIONS: These results suggest that in invasive breast carcinoma the p53 overexpression phenotype downregulates tumour neoangiogenesis, as does the wild-type of p53 protein. In addition, they suggest that apoptosis and neoangiogenesis in these tumours are independent processes.     

Gd-DTPA enhanced multi-shot echo-planar MRI: improvement of contrast between metastatic liver cancer and liver parenchyma

Budd-Chiari syndrome is a rare and serious thrombotic event with significant morbidity and mortality. Recommendations regarding future conception and management during pregnancy have not been defined. We present a patient with history of idiopathic Budd-Chiari Syndrome and subsequent orthotopic liver transplantation who was successfully managed during pregnancy. A 24-year-old white female, gravida 1 para 0, status postorthotopic liver transplantation 5 years previously for Budd-Chiari syndrome with post-transplant insulin-dependent diabetes mellitus presented to our clinic at 7 weeks of gestation for initial prenatal evaluation. Maintenance immunosuppressive therapy and prophylactic heparin anticoagulation was administered throughout the pregnancy, which was uneventful until 35 weeks gestation, at which time pre-eclampsia and premature preterm rupture of membranes prompted labor induction. The patient developed no evidence of acute or chronic hepatic rejection and no evidence of recurrent Budd-Chiari syndrome during the pregnancy or post-partum convalescence. Prudent use of prophylactic anticoagulation, close immunosuppressive monitoring, and periodic fetal and maternal surveillance are warranted in patients with previous orthotopic liver transplantation for idiopathic Budd-Chiari syndrome and may reduce risk of recurrence during pregnancy.     

Capillary transfer constant of Gd-DTPA in the myocardium at rest and during vasodilation assessed by MRI

The purpose of this study was to determine whether the capillary transfer constant (Ki) of gadolinium-DTPA was sensitive to perfusion changes and whether ischemic regions in the myocardium could be identified using the modified Kety formula. Ki was measured at rest and during dipyridamole-induced vasodilation in 10 healthy volunteers and in 10 patients with ischemic heart disease. Ki increased by a factor of 2.5+/-1.2 (mean +/- SD) from 55+/-16 ml 100 g(-1)min(-1) at rest to 136+/-46 ml 100 g(-1)min(-1) (P < 0.01) during vasodilation in the healthy subjects. In the patients, there were no changes in Ki during vasodilation in ischemic regions (50+/-18 versus 49+/-30 ml 100 g(-1)min(-1) (P > 0.4)). Ki increased in nonischemic regions by a factor of 2.0+/-0.8 from 44+/-17 to 81+/-32 ml 100 g(-1)min(-1) during vasodilation (P < 0.02). It is concluded that the capillary transfer constant is sensitive to perfusion changes and that regional ischemia can be detected with MRI. This noninvasive and quantitative method may prove useful in the evaluation of patients with ischemic heart disease.     

Tubulolobular invasive breast cancer: a variant of lobular invasive cancer

Attention is directed to an apparently unique form of invasive breast cancer designated as tubulolobular invasive cancer. These neoplasms exhibit small tubules as well as cords of neoplastic cells in a lobular configuration reminiscent of lobular invasive carcinoma. The clinical and pathologic characteristics encountered in 24 examples were statistically compared with those of infiltrating ductal carcinomas without special specific features, pure tubular, and pure lobular invasive cancer. The results of these analyses as well as the morphologic characteristics of these lesions prompt the conclusion that this lesion represents a tubular variant of lobular invasive carcinoma. Short term treatment failure rates in patients with tubulolobular invasive carcinoma are intermediate between those of pure tubular cancer and lobular invasive carcinoma.     

A case of macrocystic cervical neurinoma diagnosed by MRI with Gd-DTPA

The authors report a rare case of a large cystic cervical neurinoma. A 45-year-old female was admitted to our clinic because of motor weakness of the right upper extremity, numbness of the right fingers and right posterior cervical pain. Metrizamide CT myelography demonstrated the outline of a low density mass. MRI showed a mass revealing low signal intensity on T1-weighted image, high signal intensity on T2-weighted image and marginal enhancement on contrast image with Gd-DTPA. The mass which was diagnosed as cystic tumor, was located in the intradural extramedullary space between C4 to C5 segments. After C4 through C5 laminectomy, the tumor was found to originate from the C5 anterior motor root. The tumor consisted mostly of a cystic part with a very thin solid compartment beneath the capsule. Postoperative course of the patient was uneventful. Although spinal neurinoma is one of the most common spinal tumors, an almost completely degenerated large cystic spinal neurinoma is extremely rare. MRI with Gd-DTPA was useful for the diagnosis of the cystic neurinoma by clearly enhancing the margin of the tumor.     

Microvessel density predicts survival in prostate cancer patients subjected to watchful waiting

The biological potential of prostate cancer is highly variable and cannot be satisfactorily predicted by histopathological criteria alone. Angiogenesis, the formation of new blood vessels, has been suggested to provide important prognostic information in prostate cancer. The aim of this study was to investigate whether microvessel density (MVD) at diagnosis was correlated with disease-specific survival in a non-curative treated population of prostate cancer patients. MVD was immunohistochemically (factor VIII-related antigen) quantified in archival tumours obtained at diagnosis in 221 prostate cancer patients. Median length of follow-up was 15 years. The maximal MVD was quantified inside a 0.25 mm2 area of the tumour and the median MVD was 43 (range 16-151) mm2. MVD was statistically significantly correlated with clinical stage (P < 0.0001) and histopathological grade (P < 0.0001). When dichotomized by the median counts, MVD was shown to be significantly associated (P = 0.0001) with disease-specific survival in the entire population as well as in the theoretically curable clinically localized subpopulation. A multivariate analysis demonstrated that MVD was a significant predictor of disease-specific survival in the entire cancer population (P = 0.0004), as well as in the clinically localized cancer population (P < 0.0001). These findings suggest that quantitation of angiogenesis reflects the spontaneous clinical outcome of prostate cancer.     

Is axillary dissection always indicated in invasive breast cancer?

In light of the changing trends in the diagnosis and management of invasive breast cancer, the practice of routine axillary dissection should be reevaluated. A growing number of patients with breast cancer are diagnosed as having small tumors with an associated low risk of lymph node metastases. The pathologic features of the primary tumor are increasingly being used as a prognostic guide for recommendations about adjuvant systemic therapy, and there are recent reports suggesting a superior prognostic value for tumor cells detected in bone marrow, as compared to axillary lymph node metastases. Consequently, axillary lymph node status is no longer the single prognostic guide for recommendations about adjuvant systemic therapy. For treatment of the axilla, there is evidence that, in clinical N0 patients, radiation therapy to the axilla is an effective alternative to axillary dissection. Finally, there are cost and morbidity considerations for patients undergoing axillary dissection in whom the indications of the procedure are equivocal. In the management of invasive breast cancer, a selective policy toward axillary lymph node dissection should be considered. This review discusses the nonsurgical management of the axilla; ie, radiation therapy to the axilla and observation of the axilla as an alternative to axillary dissection.     

Three-dimensional gadolinium-enhanced dynamic MRI of whole liver using spectrally selected enhanced fast gradient recall sequence]

Although scribing has been used in ophthalmology for many years, the real benefits could not be realized until the entry of managed care into medicine in the United States. Everyone benefits in an office that uses scribes. The patient and the physician benefit by having a record that is much closer to being complete. The technician benefits as a result of becoming a pivotal reference for every patient encounter.     

Modulation of cell surface components of human breast cancer cells by retinoic acid: enhanced HLA-DR expression

A finite volume method in a boundary-fitted coordinate system together with a zonal grid method is employed to compute the flow fields and shear stresses in a two-dimensional aortic bifurcation. Eddy is found distal to plaques during pulsatile flow, whereas permanent eddies are observed only during steady flow. The computed flow fields are consistent with those visualized experimentally by other authors. It is also found that although the time averaged shear rates in a pulsatile flow are similar to those of a steady flow with mean Reynolds number in most regions, they are different in recirculation zones. This result implies that care should be taken if a steady flow shear rate were to be used in modeling shear-dependent physiological processes. The non-Newtonian viscosity has only a minor effect on the flows.     

Analysis of mammographic density and breast cancer risk from digitized mammograms

To evaluate the association between mammographic density and breast cancer risk, a simple, observer-assisted technique called interactive thresholding was developed that allows reliable quantitative assessment of mammographic density with use of a computer workstation. Use of this technique helps confirm that mammographic density is one of the strongest risk factors for breast cancer and is present in a large proportion of breast cancer cases. The strong relationship between mammographic density and breast cancer risk suggests that the causes of breast cancer may be better understood by identifying the factors associated with mammographically dense tissue and determining how such tissue changes as these factors vary. Furthermore, because it can be modified, mammographic density may also be a good vehicle for the development and monitoring of potential preventive strategies. Areas of ongoing investigation include evaluating a potential genetic component of mammographic density by comparing density measurements in twins and understanding changes in density relative to age, menopausal status, exogenous hormone use, and exposure to environmental carcinogens. In addition, work is ongoing to establish measurements from imaging modalities other than mammography and to relate these measurements directly to breast cancer risk.     

Efficacy of dynamic susceptibility contrast MRI using echo-planar imaging in differential diagnosis of breast tumors

It has been shown that T1-weighted dynamic MR imaging is a useful method in differentiating malignant breast tumors from benign lesions. Invasive breast carcinomas enhance more rapidly than benign lesions such as fibroadenomas, papillomas, and proliferative fibrocystic diseases. However, significant overlap in the dynamic profile of benign and malignant lesions may occur, resulting in relatively low specificity, which is an inherent limitation of this technique. The author attempted to improve diagnostic accuracy by utilizing dynamic susceptibility contrast MR imaging (DSC-MRI) with a single-shot echo-planar imaging sequence. Twenty-two patients underwent DSC-MRI using a 1.5-T unit (Magnetom Vision, Siemens). Images were obtained before, during and after the bolus injection of 20 mL of gadopentetate dimeglumine. The signal reduction rate within the first 30 seconds (delta RT2) was calculated by the following equation: delta RT2 = (postcontrast signal intensity-precontrast signal intensity)/precontrast signal intensity. A rapid, strong decrease in signal intensity was observed on the first pass of the contrast material in all cases of carcinoma, whereas no or only a minimal decrease in signal intensity was observed in all but one of the benign lesions. This method seems to be more accurate than T1-weighted dynamic MR imaging in the differentiation benign and malignant breast lesions. Since DSC-MRI can be performed quickly, subsequent conventional T1-weighted imaging can provide additional information about the morphologic features of lesions, to further support the diagnosis. In conclusion, DSC-MRI seems to be a promising method for the accurate preoperative assessment of breast lesions.     

A new, more invasive approach in the radiation diagnosis of breast cancer

The authors discuss the state-of-the-art techniques and the increasingly invasive approach to the diagnosis of breast diseases and also summarise their own experiences. Special attention is called to the nonpalpable, preclinical stage of breast cancers. The newest techniques like MR-mammography, stereo-taxic and ultrasound directed cytology and core biopsy are demonstrated, as well as the present place of traditional breast imaging methods: mammography and diagnostic ultrasound. The preoperative localisation of nonpalpable cancers improves the safety of surgical procedures. The authors emphasize the importance of the detection of early breast cancer, for the sake of a more favourable prognosis compared to that of the palpable, advanced cases. The results of mass screening is detailed, based on statistical data.     

The role of radiation therapy after local excision of invasive and noninvasive breast cancer

An international survey of health service user fee and exemption policies in 26 low- and middle-income countries assessed whether user fee policies were supported by measures that protect the poor. In particular, it explored whether governments were introducing a package of supportive measures to promote service improvements that benefit disadvantaged groups and tackle differential ability to pay through an effective series of exemptions. The results show that many countries lack policies that promote access for disadvantaged groups within user fee systems and quality improvements such as revenue retention at the health care facility and expenditure guidelines for local managers. More significant policy failures were identified for exemptions: 27 percent of countries had no policy to exempt the poor; in contrast, health workers were exempted in 50 percent of countries. Even when an official policy to exempt the poor existed, there were numerous informational, administrative, economic, and political constraints to effective implementation of these exemptions. The authors argue that user fee policy should be developed more cautiously and in a more informed environment. Fees are likely to exacerbate existing inequities in health care financing unless exemptions policy can effectively reach those unable to pay.     

Cyclin D1 expression in invasive breast cancer. Correlations and prognostic value

Cyclin D1 overexpression, detected by standard immunohistochemistry, was correlated with other prognostic variables and its prognostic value was evaluated in a group of 148 invasive breast cancers with long-term follow-up. Overexpression of cyclin D1 (59% of cases) was negatively correlated (chi 2 test) with histological grade (P = 0.0001), mean nuclear area (P = 0.004), mean nuclear volume (P = 0.02), and mitotic activity (P = 0.03) and positively correlated with estrogen receptor (P = 0.0001). There was a strong correlation between cyclin D1 overexpression and histological type (P = 0.0001). Positive cyclin D1 staining was seen in 11 of 13 tubular carcinomas, 3 of 3 mucinous carcinomas, 4 of 4 invasive cribriform carcinomas, and 17 of 20 lobular carcinomas. Of 102 ductal cancers, 52 were positive, and all 6 medullary carcinomas were negative. There were no significant correlations with lymph node status, tumor size, or DNA ploidy. In survival analysis, cyclin D1 overexpression did not provide significant univariate or multivariate prognostic value. In conclusion, cyclin D1 is mainly overexpressed in the well differentiated and lobular types of invasive breast cancer and is strongly associated with estrogen receptor positivity. It is negatively correlated with the proliferation marker mitoses count and with the differentiation markers nuclear area and nuclear volume. However, cyclin D1 overexpression does not seem to have prognostic value in invasive breast cancer when no adjuvant treatment is given.     

Electron density of tissues and breast cancer radiotherapy: a quantitative CT study

PURPOSE: To obtain more accurate data on the electron density of tissues to be used in the treatment planning of breast cancer patients. METHODS AND MATERIALS: Single kVp quantitative computed tomography was applied in 70 women, 20 to 77 years old, to study the electron density of the breast, the thoracic wall close and parallel to the breast, and the lung parenchyma. RESULTS: The electron density of the entire breast decreases with increasing age in premenopausal women and remains practically constant in postmenopausal women (8% less than that of water). No difference was found in the electron densities of the right and left breast. The electron density of the lung parenchyma in proximity to the breast is lower than the density in the entire lung parenchyma. CONCLUSIONS: Whenever no accurate data is available on individual patients, the electron density values to be used in treatment planning for breast and thoracic wall have to take into account both age and menstrual status. The regional differences in electron density of the lung also have to be considered.     

Multiple machine implementation of enhanced dynamic wedge

PURPOSE: After acquiring 4 years of experience with Dynamic Wedge, a software-driven one-dimensional (1D) compensation system, we implemented a new software version called Enhanced Dynamic Wedge (EDW). The EDW allows larger (30 cm) and asymmetric field sizes and additional angles for wedged fields. We implemented this software on four similar dual-energy accelerators that also possess upper and lower physical wedge sets. Our goal was to implement EDW with one common wedge factor (WF) table and one set of treatment-planning files. METHODS AND MATERIALS: We measured WFs with an ionization chamber and isodose profiles with both film and a diode array. We used a calculation scheme that requires only entry of the wedge angle and fixed jaw value. Filters for computerized treatment planning were configured for each wedge angle. We also examined to what degree the multileaf collimation (MLC) orientation, which is orthogonal to the EDW direction, was compromised for specific treatment sites. As a comparative test, we examined the dosimetric consistency for the 8 sets of physical wedges on the four machines. Finally, we updated our DW quality assurance program for EDW. RESULTS: The measured EDW WF was common for all four machines to within +/- 1.5% and the calculation scheme held to within 1.5%. The EDW isodoses were consistent among the machines as measured by film and diode array. The treatment-planning filters provided computed isodose profiles that were nearly identical to measured profiles. Regarding MLC orientation, we found that the collimator angle needed for EDW did not compromise isodose distributions, as apparent in measured isodoses and calculated dose-volume histograms. The consistency of the physical wedges did not fare as well. Two of the lower wedge sets had Wfs and profiles different (> 3%) from the other wedge sets. CONCLUSIONS: We have successfully implemented EDW on four machines using only one WF table and one set of treatment-planning filters. The EDW provides for improved treatment techniques for particular sites due to the large field sizes and additional angles available. Daily treatment efficiency has increased because of the remote capability provided by EDW.     

Determination of connectivity density in human iliac crest bone biopsies assessed by a computerized method

The aim of the present study was to design a computer program (based on the ConnEulor principle) for direct measurement of 3-D connectivity density in iliac crest bone sections, as used for conventional histomorphometry. We used the physical disector principle and developed an algorithm for nonlinear alignment of the disector pairs. 3-D connectivity was evaluated in transiliac specimens from 30 nonselected autopsy cases of 14 men (age range 20-84 years) and 16 women (age range 20-96 years). In order to visualize the findings from the disector pairs, 3-D reconstruction was performed for two of the iliac crest biopsies. The designed computer program aligns the two sections forming a disector pair and automatically depicts the differences between the images, thereby making correct, direct connectivity density measurements available for conventional bone research.