What to do about mammographically detected ductal carcinoma in situ?
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Breast Neoplasms↗
Biomedical subjects
S J Schnitt
Publications and source records attributed to S J Schnitt.
Long-term results of directional coronary atherectomy: predictors of restenosis.
OBJECTIVES: This study was performed to obtain better understanding of the long-term clinical efficacy of directional coronary atherectomy. BACKGROUND: Although this procedure yields favorable acute results, its acceptance has been limited by the perception that late results (that is, freedom from restenosis) are no better than those of conventional angioplasty. METHODS: A total of 225 atherectomies performed in 190 patients between August 1988 and July 1991 were examined. Minimal lumen diameter of the treated segments was measured on angiograms obtained before, after and 6 months after intervention. RESULTS: Although most lesions (97%) had one or more characteristics predictive of unfavorable short- or long-term results after conventional angioplasty, atherectomy was successful in 205 lesions (91%) with a mean residual stenosis of 7 +/- 16%. After subsequent balloon angioplasty in 16 unsuccessful atherectomy attempts, procedural success was 98%. There were no deaths or Q wave myocardial infarctions, and one patient (0.5%) underwent emergency bypass surgery. Six-month angiographic follow-up was obtained in 77% of the eligible patients. The overall angiographic restenosis rate was 32%. Predictors of a lower restenosis rate included a postprocedure lumen diameter > 3 mm (24% vs. 39%, p = 0.047), serum cholesterol < or = 200 mg/dl (18% vs. 40%, p = 0.018) and recent myocardial infarction (16% vs. 37%, p = 0.034). Life-table analysis showed a 2% mortality rate and a 26% incidence of other events (myocardial infarction, repeat revascularization) within the 1st year. The annual 5% mortality rate and 7% incidence of other events during years 2 and 3 were related in large part to the existence or progression of disease at other locations. CONCLUSIONS: Six-month angiographic follow-up of patients who underwent directional coronary atherectomy during the 1st 3 years of our experience shows an overall restenosis rate of 32%, with lower rates in patients with a postatherectomy lumen diameter > or = 3 mm, cholesterol level < or = 200 mg/dl or a recent myocardial infarction. Few if any events relating to the site of atherectomy developed after the 1st year of follow-up.
Atherectomy, Coronary↗
Acute and long-term outcome of narrowed saphenous venous grafts treated by endoluminal stenting and directional atherectomy.
Angioplasty of the narrowed saphenous vein bypass grafts remains a difficult challenge. Over a 37-month period at this institution, 119 of 176 interventions (68%) on saphenous vein grafts (average age 8.3 years from bypass surgery to graft intervention) were performed using either directional coronary atherectomy (n = 35) or Palmaz-Schatz intracoronary stents (n = 84), representing 37% of all stents and 15% of all atherectomies during the study period, respectively. Of the 57 saphenous vein graft lesions treated with conventional balloon angioplasty during this period, 49 (86%) had 1 or more contraindications to stenting or directional atherectomy (thrombus, total occlusion, reference vessel less than 3 mm in diameter). The acute success rate was 99% for stents (1 failure to dilate) and 94% for directional atherectomy (2 failures to cross the lesion with the atherectomy device). Lumen diameter increased from 0.9 to 3.6 mm (reference vessel 3.6) for stents, and from 0.9 to 3.5 mm (reference 3.8) for atherectomy (for all comparisons, p = not significant), with no major complications (abrupt or subabrupt closure, emergent coronary bypass surgery, death, or Q-wave myocardial infarctions). During the same time period 50 of 57 vein grafts (88%) rejected for stenting or atherectomy were dilated successfully by conventional balloon angioplasty, with 3 patients (5%) requiring emergent coronary bypass surgery. Angiographic follow-up was available for 50 of 64 eligible patients (78%).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Estrogen receptor immunohistochemistry in carcinoma in situ of the breast.
Although estrogen receptor (ER) content and its clinical significance have been extensively evaluated in invasive breast cancer, ER expression in carcinoma in situ (CIS) of the breast and its correlates are less well understood. Thus, using an indirect immunoperoxidase technique and paraffin-embedded tissue, the authors studied ER expression in 100 breast tumors containing CIS with or without invasive carcinoma. The percentages of positive and of strongly positive nuclei were compared among histologic categories of CIS and between CIS and invasive carcinoma. The relationships between histologic features of CIS (cell size, nuclear pleomorphism, necrosis, extent of CIS) the patient's age, and the ER status of CIS also were evaluated. ER expression in pure CIS was compared with that of CIS with adjacent invasive carcinoma. Significant differences were observed between comedo CIS, which was frequently ER negative, and non-comedo and lobular CIS, which usually were positive. A predominance of large cells, independently from other features, was the best morphologic predictor of ER negative status in CIS. ER in CIS correlated with ER in invasive carcinoma in 98% of cases (r2 = 0.677). CIS without invasive carcinoma was more frequently ER weak or negative than CIS associated with invasive carcinoma. There was no difference in the overall percentage of nuclear staining in CIS of women of premenopausal versus postmenopausal age; however, a higher proportion of strongly positive cells occurred in the postmenopausal group. The authors conclude that the ER expression in CIS correlates with pathologic features of differentiation and is similar to that of invasive carcinoma.
Adult↗
A prospective study of benign breast disease and the risk of breast cancer.
OBJECTIVE: To examine the relation between proliferative benign breast disease with and without atypical hyperplasia and the subsequent risk of breast cancer. DESIGN: Case-control study nested within a prospective cohort study. Median follow-up after breast biopsy was 8 years (25th to 75th percentile, 5 to 14 years). PARTICIPANTS: Selected from a prospective cohort of 121,700 US registered nurses followed up from 1976 to 1986. Cases were women with breast cancer who had a prior biopsy for benign breast disease. Controls were randomly selected and matched on year of biopsy and year of birth from among women in the cohort who had a benign breast biopsy but who did not develop breast cancer. Included in the analysis were 121 cases and 488 controls. MAIN OUTCOME MEASURE: Development of breast cancer. RESULTS: Slides from the first benign breast biopsy were reviewed by two breast pathologists blinded to the outcome. The multiply adjusted relative risks (RRs) for breast cancer, relative to women with no proliferative disease, were 1.6 for proliferative disease without atypia (95% confidence interval [Cl], 1.0 to 2.5) and 3.7 for atypical hyperplasia (95% Cl, 2.1 to 6.8). Breast cancer risk was more strongly associated with atypical hyperplasia among premenopausal women (RR = 5.9; 95% Cl, 2.9 to 13.2) than postmenopausal women (RR = 2.3; 95% Cl, 0.9 to 5.9), but the association of breast cancer risk with proliferative disease without atypia did not differ across menopausal status. CONCLUSION: These results confirm the marked increase in breast cancer risk among women with atypical hyperplasia, particularly in premenopausal women, and suggest that these women should be encouraged to undergo frequent breast cancer screening.
Breast↗
Histologic findings in specimens obtained by percutaneous directional coronary atherectomy.
Percutaneous directional coronary atherectomy is a second-generation, catheter-based technique for the treatment of coronary artery disease that provides a unique opportunity to study tissue obtained from coronary artery stenoses. We reviewed the histologic findings in 131 coronary atherectomy specimens from 116 patients, including 79 primary lesions and 52 restenosis lesions that developed after a prior coronary intervention. Although atherosclerotic plaque was seen in 95% of cases, an important observation was the finding of deep arterial wall components in the majority of patients, including media in 61% and adventitia in 31%. Despite the relatively common finding of deep wall components, this was not associated with acute clinical complications. Intimal hyperplasia was seen in 64% of cases, including 96% of restenosis lesions. However, intimal hyperplasia was also seen in 45% of primary lesions. The intimal hyperplasia in primary and restenosis lesions was histologically identical and was characterized by cells that showed staining for vimentin and muscle-specific actin, consistent with a myogenous and/or myofibroblastic phenotype. Restenosis was seen in 29 of 94 lesions (31%) with angiographic follow-up an average of 6.3 months after atherectomy. The risk of restenosis was not significantly related to the vessel treated, the nature of the lesion treated (ie, primary v restenosis lesion), or any of the histologic features evaluated. In conclusion, (1) deep arterial wall components are commonly observed in coronary atherectomy specimens without acute complications and (2) intimal hyperplasia is a sensitive, but not specific, marker for restenosis lesions.
Cardiology↗
Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer.
Using permanent-section immunohistochemistry, we investigated the role of HER-2/neu in the development and progression of human breast cancer by measuring its overexpression in a series of hyperplastic (n = 30), dysplastic (n = 15), and malignant neoplastic (n = 708) lesions of ductal epithelium and by evaluating the relationships between overexpression and clinicopathologic features known to have prognostic significance in these lesions. The neoplasms included pure ductal carcinoma in situ (DCIS; n = 59) and infiltrating ductal carcinoma (IDC; n = 649). The latter were all node negative and stratified into IDC combined (n = 237) or not combined (n = 412) with a "significant amount" of DCIS (defined as DCIS greater than or equal to 10% of total tumor cellularity). Overexpression of HER-2/neu was not observed in any of the hyperplastic or dysplastic lesions. In contrast, it was present in 56% of pure DCIS and in 77% of the comedo subtype of this group. Only 15% of IDC overexpressed HER-2/neu. However, the rate of overexpression was significantly higher in the subset of IDC combined with DCIS compared with the subset of IDC not combined with DCIS (22% v 11%, respectively; P less than .0001). These results are consistent with the hypothesis that HER-2/neu plays a more important role in initiation than in progression of ductal carcinomas. They also suggest that overexpression decreases within individual tumors as they evolve from in situ to increasingly invasive lesions or, alternatively, that many invasive carcinomas arise de novo (ie, without progressing through a significant in situ stage) by mechanisms not involving HER-2/neu. In addition, overexpression of HER-2/neu was associated with several poor prognostic features (younger patient age, premenopause, negative estrogen receptor status, negative progesterone receptor status, and high nuclear grade) in the subset of IDC combined with DCIS. With one exception (negative estrogen receptor status) these associations were lost in IDC not combined with DCIS, also suggesting that the role of HER-2/neu changes during the progression of human breast cancer.
Biomarkers, Tumor↗
Processing and evaluation of breast excision specimens. A clinically oriented approach.
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Biopsy↗
Interobserver reproducibility in the diagnosis of ductal proliferative breast lesions using standardized criteria.
Although the categorization of proliferative breast lesions provides valuable information regarding subsequent risk of breast cancer, the ability of pathologists to classify such lesions in a reproducible fashion has not been adequately evaluated. To assess further interobserver reproducibility in the categorization of proliferative breast lesions, six pathologists each reviewed 24 proliferative ductal lesions and classified them as either usual hyperplasia (H), atypical hyperplasia (AH), or carcinoma in situ (CIS). Before evaluation of the study slides, all the participants were instructed to use the diagnostic criteria of Page and co-workers and were provided with both a written summary of these criteria and a set of teaching slides with representative examples of each type of lesion. Complete agreement among all six pathologists was seen in 14 cases (58%); five or more agreed in 17 cases (71%); and four or more arrived at the same diagnosis in 22 cases (92%). No pathologist consistently rendered more "benign" or "malignant" diagnoses than any other. After assigning numerical values for each diagnostic category (H = 1, AH = 2, CIS = 3), the scores for the group of 24 cases did not differ significantly by pathologist (p = 0.68; average score range, 1.7-2.0). Our results indicate that with the use of standardized criteria, interobserver concordance in the diagnosis of proliferative ductal breast lesions can be obtained in the majority of cases.
Breast↗
Endomyocardial biopsy: is it of clinical value?
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Biopsy↗
FNA identification of familial breast disease.
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Biopsy, Needle↗
Nature and significance of cells with irregular nuclear contours in esophageal mucosal biopsies.
Esophageal mucosal biopsies from patients with upper gastrointestinal symptoms often contain intraepithelial cells with irregular nuclear contours (CINC). To investigate their nature and significance, we retrospectively studied biopsies and resection specimens from symptomatic patients that showed the following histologies: unremarkable mucosa (11 cases), active esophagitis (11 cases), infection (herpes: two cases; fungus: five cases), Barrett's esophagus (five cases), adenocarcinoma (three cases), and squamous cell carcinoma (two cases). H&E sections were reviewed to determine the number of intraepithelial CINC, neutrophils, eosinophils, and mononuclear cells with small, round nuclei typical of lymphocytes in five high-power fields. All specimens were also stained for S-100 protein, and six additional biopsies with numerous CINC were stained for leukocyte common antigen (LCA), L-26 (a B-cell marker), and Leu-22 and UCHL-1 (both T-cell markers). Clinical charts were reviewed to analyze endoscopic findings. The CINC had the immunohistochemical profile of T-lymphocytes: LCA (+), Leu-22 (+), UCHL-1 (+), L-26 (-), and S-100 protein (-). Their average number per high-power field was low in benign squamous epithelium away from tumors (average 0.8/high-power field) but much higher in biopsies with the other categories of histology, especially those with active esophagitis and infection (6.3/high-power field). The difference between the mean of the two tumor groups (0.8) and that of esophagitis (6.3) was statistically significant (p = 0.005). Of 11 patients with unremarkable biopsies, there was endoscopic evidence of esophagitis in five. The biopsies of these five showed an average number of CINC of 6.4, whereas the number was only 3.5 in the six with normal endoscopy (p = 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Recurrence in the breast following conservative surgery and radiation therapy for early-stage breast cancer.
This report summarizes the experience of the Joint Center for Radiation Therapy (JCRT) in treating patients with clinical stage I and II breast cancer with conservative surgery and radiation therapy. The study population consisted of 1396 patients treated between 1968 and 1985. All patients underwent a gross excision of the tumor and received breast irradiation (with or without nodal irradiation) including a "boost" to bring the primary tumor site to a total dose of at least 60 Gy. The method of treatment evolved over the study-time period. During the interval from 1968 to 1982, patients typically underwent a limited gross excision of the tumor without regard to the microscopic margins of resection. During the period 1983 to 1985, film-screen mammography, inking of specimen margins, and reexcisions for inevaluable or involved margins were more commonly performed. With a median follow-up of 80 months, the 5-year crude rate of failure in the breast (as the first site of failure) was 8% (106/1396) and the crude rate of regional nodal/distant failure (as the first site of failure) was 16% (228/1396). The time-course of failures in the breast was protracted, occurring at a fairly constant rate over the first 7 years after treatment, but still seen beyond that point. Most recurrences in the breast (75%) developed at or near the original tumor site. The most important risk factor for developing a breast recurrence was the presence of an extensive intraductal component in the tumor. The cosmetic results following treatment were excellent or good in the majority of patients (87%) and were most adversely affected by extensive surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Breast Neoplasms↗
Results of treating ductal carcinoma in situ of the breast with conservative surgery and radiation therapy.
To determine the frequency, pattern, and time course of tumor recurrence in the breast, the outcome of 38 women with ductal carcinoma in situ (DCIS) treated with conservative surgery and radiation therapy between 1976 and 1985 was studied. Surgery typically consisted of local excision without evaluation of the microscopic margins of resection. The median radiation dose to the tumor site was 6400 cGy. With a median follow-up time of 81 months, eight patients (21%) have experienced a recurrence in the breast. The time course to recurrence was protracted in some cases, with failures occurring at 17, 27, 43, 63, 71, 83, 92, and 104 months. The 5-year and 8-year actuarial rates of tumor recurrence in the breast were 8% and 27%, respectively. Seven patients had a recurrence at or near the primary tumor site, four with invasive carcinoma, and one had an invasive recurrence at a site elsewhere in the breast. No clinical or pathologic factor was significantly associated with an increased risk of recurrence, but the number of patients in the study population was small. The authors reached the following conclusions for patients with DCIS treated with conservative surgery and radiation therapy without careful mammographic and pathologic evaluation: (1) recurrence in the breast may be seen in at least one fifth of the patients; (2) recurrence typically occurs at or near the primary site; and (3) recurrence can occur long after treatment. Careful mammographic and pathologic assessment may be useful in reducing the local recurrence rate and should be considered essential if patients are considered for conservative surgery and radiation therapy.
Adult↗
Early ostial vein graft stenosis: management by atherectomy.
During the initial perioperative period (1 mo to 1 yr) after saphenous vein coronary grafting, early stenosis and occlusion occurs in 5-8% of grafts due to intimal hyperplasia. We report a patient who developed ostial stenosis within 4 mo of bypass surgery at the aortotomy site of two vein grafts. Balloon angioplasty of the elastic stenoses did not provide significant luminal enlargement, but successful treatment of the lesions was obtained using directional atherectomy. Histological examination demonstrated intimal hyperplasia. Directional atherectomy may be an excellent technique for treatment of elastic ostial vein graft stenoses in lieu of conventional balloon dilatation.
Aged↗
Laser balloon angioplasty: clinical, angiographic and histologic results.
Laser balloon angioplasty combines conventional coronary angioplasty with laser energy to transiently heat vascular tissue. Laser balloon angioplasty, was performed in 21 patients (aged 56 +/- 13 years), including 10 patients treated urgently after acute failure of conventional angioplasty and 11 patients treated with elective laser balloon angioplasty. Immediately after conventional angioplasty, laser doses (1 to 10 doses of 205 to 380 J each) were delivered during inflation of the laser balloon to a pressure of 4 atm. Seven (70%) of 10 patients with acute failure of conventional angioplasty were successfully treated with laser balloon angioplasty, but 3 (30%) were unsuccessfully treated with the laser procedure and required emergency coronary artery bypass surgery. In all three failures, the 3 mm laser balloon angioplasty catheter was not the optimal size for the vessel. In the 11 patients treated with elective laser balloon angioplasty (reference diameter 2.94 +/- 0.22 mm), the minimal luminal diameter increased from 0.45 +/- 0.25 to 1.85 +/- 0.46 mm after conventional angioplasty and to 2.44 +/- 0.29 mm after laser balloon angioplasty (p less than 0.001). This corresponded to a decrease in diameter stenosis from 84 +/- 9% before to 35 +/- 16% after conventional angioplasty and to 15 +/- 10% after laser balloon angioplasty (p less than 0.001). There were no instances of myocardial infarction, emergency coronary artery bypass surgery or death and no acute complications related to delivery of laser energy in this group. Follow-up coronary angiography was performed 5.5 +/- 1.1 months after laser balloon angioplasty in 18 patients discharged from the hospital after a successful procedure. Ten patients (56%) had angiographic restenosis, defined as recurrent diameter stenosis greater than 50%. Six patients were subsequently treated by directional coronary atherectomy, which revealed intimal proliferation indistinguishable from that in patients with restenosis after conventional angioplasty. In conclusion, laser balloon angioplasty may be effective in sealing severe coronary dissections and reversing abrupt closure associated with failed conventional angioplasty. After uncomplicated conventional angioplasty, laser balloon angioplasty improves immediate luminal dimensions, but restenosis appears to be mediated by intimal hyperplasia, similar to that seen after conventional angioplasty.
Angiography↗
The optimal extent of resection for patients with stages I or II breast cancer treated with conservative surgery and radiotherapy.
The optimal extent of breast resection before irradiation for treatment of early breast cancer has not been defined. Increasing the size of the resection may decrease the risk of local recurrence but will also have an adverse impact on the cosmetic outcome. The 5-year likelihood of a recurrence of the tumor was analyzed in relation to the volume of resected breast tissue in 507 patients with infiltrating ductal carcinoma treated with conservative surgery and radiation therapy between 1968 and 1982. Patients were stratified by clinical T-stage and for each T-stage patients were divided into three groups of equal numbers based on the volume of excised tissue. All patients had at least a gross excision of the tumor and the extent of breast resection was determined at the discretion of the surgeon without knowledge of the histologic features of the tumor. The median follow-up time was 100 months. The 5-year actuarial recurrence rates were analyzed in relation to clinical T-stage (T1 or T2) and the presence or absence of an extensive intraductal component (EIC+ or EIC-). For patients with EIC+ tumors, the largest resections were associated with a substantially lower risk of recurrence in the breast than the smallest resections. This effect was seen both for T1 tumors (10% versus 29%, p = 0.07) and for T2 tumors (9% versus 36%, p = 0.04). For patients with EIC-tumors, recurrence rates were significantly lower than for EIC+ tumors and were not influenced by the volume of resection to the same degree as EIC+ tumors. In the absence of an EIC, recurrence rates for the largest and smallest resections were 0% and 9% (p = 0.02) for T1 tumors and 3% and 6% (p = NS) for T2 tumors. It is concluded that a limited breast resection is acceptable for an EIC- tumor but that a more extensive resection is required for an EIC+ tumor. These results stress the importance of assessing the presence or absence of an EIC in determining the optimal extent of breast resection required before radiation therapy.
Breast Neoplasms↗
Microwave fixation provides rapid, primary fixation for light and electron microscopy and for immunohistochemistry and immunocytochemistry.
A relatively new approach to specimen preservation for morphologic studies uses microwave energy and chemicals. Microwave fixation can produce fixation results equal in quality to chemical fixation methods and equal in speed to freeze fixation methods. The importance of this microwave fixation technology lies in its potential to provide a standardized fixation approach in histopathology, immunohistochemistry, and immunocytochemistry.
Animals↗