Adequacy of diagnostic tests and surgical management of symptomatic invasive lobular carcinoma of the breast

Introduction

Invasive lobular carcinoma (ILC) presents diagnostic and therapeutic challenges as it produces subtle radiological changes. It has been suggested that it is not suitable for breast conserving surgery (BCS). The aim of this study was to ascertain the diagnostic adequacy of modern mammography and ultrasonography in the context of a fast track symptomatic diagnostic clinic in the UK. It also sought to compare the mastectomy, re-excision and BCS rates for ILC with those for invasive ductal carcinoma (IDC).

Methods

A retrospective analysis of prospectively collected data was carried out on all new symptomatic cancers presenting to the one-stop diagnostic clinic of a single breast unit between 1998 and 2007.

Results

Compared with IDC, ILC was significantly larger at presentation (46mm vs 25mm), needed re-excision after BCS more often (38.8% vs 22.3%) and required mastectomy more frequently (58.8% vs 40.8%). Although mammography performs poorly in diagnosing ILC compared with IDC, when combined with ultrasonography, sensitivity of the combined imaging was not significantly different between these two histological types.

Conclusions

Provided ultrasonography is performed, standard radiological imaging is adequate for initial diagnosis of symptomatically presenting ILC but some additional preoperative workup should clearly be employed to reduce the higher number of reoperations for this histological type.     

Isolation and characterization of the factor X Friuli variant

Factor X Friuli was isolated from plasma by immunoaffinity and ion exchange chromatography and compared with normal factor X purified by the same method. Similar molecular weights were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the intact or activated factor X molecules including their respective heavy and light chains. These data indicated that there were no gross structural differences between the normal and variant proteins. Immunochemical assays employing either polyclonal or 46 monoclonal antibodies (MoAbs) did not reveal any structural deviations. Two- dimensional peptide maps indicated that while the light chains of normal and Friuli factor X were very similar, the heavy chains of the native and activated molecules contained a limited number of differences. These data suggested that the defect in factor X Friuli may be a point mutation which lies within the activated heavy chain defined by the 195-424 amino acid sequence. Activation of factor X Friuli in purified systems showed that Russell's viper venom cleaved the molecule at 70% of the normal rate, while the rate of proteolysis of the variant protein was reduced 98% and 75% when incubated with the extrinsic and intrinsic activation complexes, respectively. These data support the clinical laboratory findings and the hypothesis that the defect associated with the Friuli variant may reflect an abnormal interaction between factor X Friuli and the nonproteolytic cofactors of the extrinsic and intrinsic factor X activation complexes. Fluorescence polarization studies suggested that a bound dansylated inhibitor of factor Xa was not oriented to the same extent within the active site of the variant enzyme relative to normal factor Xa until the addition of phospholipid and factor Va. Activated factor X Friuli generated thrombin from prothrombin in a purified system, but at one third the normal rate that was attributed to the Kcat suggesting a secondary effect of this defect.     

Screening potential blood donors at risk for human immunodeficiency virus

Even though all blood donated for transfusion is tested for the presence of human immunodeficiency virus (HIV) antibodies, there exists a period of time after infection by the virus before these antibodies can be detected. Blood donated during this window period is capable of transmitting the virus. Therefore, the blood of persons who are at risk for acquired immune deficiency syndrome (AIDS) should not enter the blood supply. Over a period of 4 months, 6573 potential blood donors who entered fixed and mobile blood collection sites in two cities were exposed to alternative interventions the aim of which was to exclude persons at risk for AIDS. We compared the interventions to one another and to existing materials in terms of the numbers of at-risk persons who did or did not donate for transfusion, the amount of attention paid to the materials, the scores on a comprehension test, and the self-reports by the subjects of attitudes towards the various interventions. At-risk donors who were asked direct AIDS risk behavior questions in addition to the current health history questions were more likely to be screened out than those who underwent alternative health history interviews (p less than 0.01). Potential donors paid more attention to the experimental brochures than to the experimental video or current materials (p less than 0.05). Comprehension scores were better for the new brochure and the video than for the current brochure (p less than 0.05). Donors were not offended by the experimental interventions.(ABSTRACT TRUNCATED AT 250 WORDS)     

CYCLICAL ETIDRONATE INCREASES LUMBAR SPINE BONE DENSITY IN PATIENTS ON LONG-TERM GLUCOCORTICOSTEROID THERAPY

To determine whether cyclical etidronate modifies bone density in patients on chronic glucocorticosteroid therapy, annual bone density measurements were performed on 55 patients receiving glucocorticosteroids who were randomised to either continuous calcium supplementation or cyclical etidronate plus calcium supplementation in this secondary prevention study. Median L1-L4 lumbar spine bone density decreased by 0.7% in the calcium treated group after one year but increased by 3.1% in the group treated by calcium and etidronate (p=0.00116). Median L1-L4 bone density decreased by 2.8% from baseline after two years in the calcium treated group but increased by 4.7% from baseline In the group treated by calcium and etidronate (p=0.04). There were no significant effects of treatment on femoral neck density. Cyclical etidronate and calcium increased lumbar spine bone density in patients established on prednisolone treatment over a two-year period but had no effect on femoral density.     

Effects of Treatments by Calcium and Sex Hormones on Vertebral Fracturing in Osteoporosis

Lateral radiographs of the thoracic and lumbar spine were takenperiodically in 49 patients with osteoporosis. Thirty patientswere postmenopausal, and 19 nonmenopausal with osteoporosisdue to steroids, male hypogonadism, alcoholism, thyrotoxicosisor unknown cause. Patients were studied before, during and aftertreatment with high calcium alone, or with combined calciumand sex steroids. Calcium was given as effervescent calciumlactate gluconate, and sex hormones as oestradiol valerate,testosterone oenanthate, or methenolone oenanthate. A totalof 964 films covering 409 patient-years were available for measurement.On each vertebra, deformity due to loss of anterior height wasmeasured and assigned to one of four grades. For the time intervalbetween each consecutive pair of films, a patient's vertebralfracture rate score was calculated and expressed per thousandpatient-years. In comparison with the corresponding pretreatment fracture ratescore, both the postmenopausal and the nonmenopausal groupswho had not received sex hormones previously, failed to showsignificant changes (p=0.144; p=0.017) on high calcium aloneduring mean periods of 4.3 and 2.8 years respectively. If thefirst 2 years on high calcium were excluded for the postmenopausalgroup, they still failed to show a reduction in fracture ratescore (observed for a mean period of 5.0 years; p=0.04). When treated with combined calcium and sex hormones, both postmenopausaland nonmenopausal groups showed a lower fracture rate scoreof 20 and 207 respectively when compared with the pretreatmentlevels of 1500 and 1697 (in mean treatment periods of 3.2 and4.4 years; p<0.001 in each case). When given high-dose calciumalone, but after treatment with sex hormones as well, the postmenopausalgroup showed no change in fracture rate score from pretreatment(in a mean of 3.1 years; p=0.069); however the nonmenopausalgroup still showed a significant reduction in fracture ratescore from 1697 to 42 over a mean period of 2.3 years (p=0.001).The postmenopausal group, after stopping all treatment, showeda higher fracture rate score of 1286 (in a mean of 2.6 years)than did those on combined calcium and sex hormones, in whomthe fracture rate score was 20 (in a mean of 3.2 years; p=0.008).A subgroup of 11 patients with osteoporosis of both the menopausaland nonmenopausal types, had data both before (in a mean of5.5 years) and during (for a mean of 2.5 years) treatment withcalcium alone; the fracture rate scores were 1473 and 918 (p=0.247).Data were available for nine patients both before (for meanof 5.5 years) and during (for a mean of 5.5 years) treatmentwith calcium and sex hormones; the fracture rate score fellfrom 1397 to 100 (p=0.001). It is concluded that in groups with both menopausal and nonmenopausalosteoporosis, vertebral fracturing was reduced by treatmentwith combined calcium and sex hormones, but no significant effectfrom calcium alone was shown. In both groups, cessation of therapywas associated with a return to near the pretreatment fracturerate score, strongly suggesting the need for lifelong treatment.     

Direct demonstration of an HLA-DR allotypic determinant on the low molecular weight (beta) subunit using a mouse monoclonal antibody specific for DR3

A murine monoclonal antibody directed against a human B cell surface antigen with the characteristics of HLA-DR is described. The antigen detected is tightly linked to HLA and is correlated with the alloantigen HLA-Dw/DR3. Reactivity with a fraction of Dw/DRw6 cells is also observed. The determinant recognized by this antibody has been shown to be present on the smaller molecular weight β subunit of the HLA-DR antigen.