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M L Silverman

Publications and source records attributed to M L Silverman.

At least 19 recordsLinked to original sources

DNA flow cytometric analysis and prognosis of axillary lymph node-negative breast carcinoma.

METHODS: The prognostic significance of flow cytometric analysis in patients with node-negative invasive breast carcinoma was evaluated in a retrospective series of 158 patients with a minimum follow-up study of 9 years. RESULTS: The ploidy status could be assessed in 147 specimens (93%), and the proliferative phase or S-phase fraction (SPF) could be assessed in 136 tumors (86%); 70 tumors (48%) were diploid, 49 tumors (33%) were aneuploid, and 28 tumors (19%) were tetraploid. Ploidy status and SPF were correlated significantly with tumor size, histologic grade, nuclear grade, and mitotic rate. By itself, ploidy was not a statistically significant prognostic factor, although all of the patients with multiploid and hypertetraploid tumors had recurrence of disease. The SPF was related significantly to recurrence of disease (P = 0.04). However, when multivariate analysis of various histopathologic variables was performed, SPF ceased to be a significant prognostic determinant, whereas peritumoral lymphovascular invasion was the most important variable. The combination of tumor size and flow cytometric parameters permitted stratification into three groups with different prognoses at the 9-year follow-up review (P less than 0.001). In the low-risk group (diploid tumors less than or equal to 2 cm in diameter with a low SPF or small tetraploid tumors), the recurrence rate was 12%. In the intermediate-risk group (diploid tumors greater than 2 cm in diameter with a low SPF or aneuploid tumors with a low SPF), the recurrence rate was 21%. In the high-risk group (diploid or aneuploid tumors with a high SPF or large tetraploid tumors), the recurrence rate was 49%. The high-risk group status remained a significant variable in the Cox proportional hazards multivariate analysis model. CONCLUSIONS: These results indicate that flow cytometry in breast carcinoma contributes useful but limited prognostic information and stress the importance of using multiple prognostic factors to improve prognostication and optimize patient management.

Axilla

Crohn's disease and carcinoma: increasing justification for surveillance?

Carcinoma of the colon that arises in patients with Crohn's disease is being reported with increasing frequency. To help clarify the nature of this association, records of 25 patients with Crohn's disease and colorectal carcinoma seen from 1957 through 1989 were reviewed. One patient had leiomyosarcoma of the rectum, and two patients had the onset of Crohn's disease after the diagnosis and treatment of colorectal carcinoma. Therefore, 22 patients were available for complete retrospective analysis. The median age at diagnosis of Crohn's disease was 37 years (range, 15-67 years), and the median age at diagnosis of carcinoma was 54.5 years (range, 32-76 years). The median duration of symptoms preceding the discovery of colorectal carcinoma was 18.5 years (range, 0-32 years). Carcinoma arose in colonic segments with known Crohn's disease in 77 percent of patients, and six patients (27 percent) had associated colonic mucosal dysplasia. One lesion was classified as Dukes A, nine lesions were Dukes B, five lesions were Dukes C, and seven lesions were Dukes D. Patients with an onset of Crohn's disease before the age of 40 years had primarily Dukes C or D lesions and consequently poor survival. Most patients presented with nonspecific signs and symptoms, with nothing to distinguish the activity of the Crohn's disease from the presence of colorectal neoplasm. Younger patients with long-standing Crohn's disease should be considered for colonic surveillance to permit earlier diagnosis and treatment of potential colorectal carcinoma.

Adolescent

Microvessel quantitation and prognosis in invasive breast carcinoma.

The prognostic significance of microvessel quantitation in invasive breast carcinoma was analyzed in a study group that comprised 88 patients with axillary node-negative carcinoma and 32 patients with axillary node-positive carcinoma who had a minimum follow-up period of 9 years. Microvessels were identified by immunohistochemistry using antibodies to endothelial markers, including factor VIII-related antigen and blood group isoantigens (ABH). Factor VIII-related antigen staining provided more consistent results for microvessel quantitation than did staining for ABH isoantigens. The three most vascular areas within a tumor were selected, and the microvessels within a x200 microscopic field of each area were counted by two investigators simultaneously. Node-positive carcinomas demonstrated significantly higher microvessel counts than did node-negative carcinomas (mean +/- SD, 99 +/- 42 and 73 +/- 22, respectively; P less than .001). In node-negative carcinomas, tumors from patients who experienced distant recurrence had higher microvessel counts than did tumors from patients who were disease-free (84 +/- 19 and 70 +/- 22; P = .01). Similarly, in patients with node-positive carcinoma, microvessel counts were considerably higher in tumors from patients who experienced distant recurrence than in patients who did not, although the difference did not reach statistical significance (113 +/- 44 and 93 +/- 34, respectively). Among patients with node-negative carcinoma, those with a microvessel count of less than 84 had a recurrence rate of 20% compared with 57% in patients with counts greater than 84 (P = .003). Microvessel counts were independent of histologic parameters, ploidy status, and S-phase fraction but correlated with peritumoral vascular invasion. Both microvessel counts and vascular invasion were independent prognostic parameters by multivariate analysis. High vessel counts may represent increased tumor angiogenesis and are correlated with tumor aggressiveness. Microvessel quantitation may be an additional prognostic factor that, when used in conjunction with more established parameters, can help in appropriate patient management.

Breast Neoplasms

Sucrase-isomaltase expression in chronic ulcerative colitis and dysplasia.

Sucrase-isomaltase (SI) is a mucosal disaccharidase that is present in normal small intestine and fetal colon. It also has been noted in colonic adenomas and adenocarcinomas. We used a polyclonal antibody to human SI to investigate enzyme presence and utility in detecting dysplastic changes in chronic ulcerative colitis. Sections from 32 cases were reviewed for the presence or absence of active colitis and dysplasia. Immunostaining of these cases for SI was performed and the results were reported based on location of immunoreactivity (ie, membrane and cytoplasmic staining in superficial and crypt epithelial cells) and percentage of positivity. Of 81 sections examined, 48 were rated negative for dysplasia (23 inactive colitis, 20 active, and five probably negative) and 28 were rated positive (eight low grade and 20 high grade). Surface membrane staining of epithelial cells was noted in all 28 dysplastic slides and positive cases (sensitivity, 100%) but also in 29 of 48 negative sections (P less than .001). In contrast, cytoplasmic positivity was present in 25 of 28 dysplastic and in only two of 48 negative slides (P less than .0001). The presence of cytoplasmic staining of SI in the superficial or crypt cells revealed a sensitivity of 92% and a specificity of 94%. There were five additional sections rated as indefinite for dysplasia (probably positive or unknown); two showed staining patterns typical of negative slides and three showed positive staining patterns. Of the 18 samples of transitional mucosa next to areas of dysplasia, surface membrane staining of SI was seen in all samples and cytoplasmic staining was seen in 15. We conclude that membrane staining of SI can be detected in inflammatory, regenerative, and dysplastic mucosa in ulcerative colitis. Cytoplasmic staining, however, correlates strongly with the presence of dysplastic change and may help in its detection.

Adult

Quantitative DNA analysis and proliferation in breast carcinomas. A comparison between image analysis and flow cytometry.

The DNA content and proliferation in 100 invasive breast carcinomas were evaluated by computerized image analysis (IA) and flow cytometry (FCM). For DNA content, image analysis of Feulgen-stained slides of fresh tumor imprints were compared with flow cytometry of propidium iodide-stained disaggregated fresh tumor tissue. The DNA indices obtained by the two methods showed close correlation by linear regression analysis (r = 0.89, p less than .001). There were 44 (44%) diploid and 56 (56%) aneuploid tumors. There was agreement between the two methods in detection of aneuploidy in 81% of tumors. Image analysis required smaller tissue samples, permitted direct visualization and selection of tumor cells, and was more sensitive in detecting tetraploid and highly aneuploid cell populations. In contrast, flow cytometry histograms provided better resolution, and were more effective in detecting multiploid tumors and near-diploid aneuploid tumors. Aneuploidy was significantly related to various adverse prognostic parameters, namely, negative estrogen receptor, high mitotic rate, high histologic and nuclear grades. Proliferation was evaluated by measuring the FCM S phase fraction (SPF), and by image analysis quantitation of immunohistochemical staining using Ki-67 monoclonal antibody. SPF and Ki-67 count showed modest correlation (r = 0.42). Both SPF and Ki-67 count were significantly related to the mitotic rate, histologic and nuclear grades. Our results indicate that the two methods provide comparable results, but offer individual advantages and are complementary techniques in analyzing DNA ploidy and proliferation in breast carcinomas.

Adenocarcinoma, Mucinous

DNA ploidy, proliferation, and neu-oncogene protein overexpression in breast carcinoma.

DNA content, proliferative activity (Ki-67 immuno-staining and S-phase fraction by flow cytometry), and neu-oncogene overexpression were studied in 135 patients with invasive breast carcinoma. Image analysis and flow cytometry of fresh tumors showed good correlation between the two methods and yielded 39% diploid tumors and 61% aneuploid tumors. Aneuploidy, including tetraploidy, was significantly related to the loss of estrogen (p = 0.0002) and progesterone (p = 0.03) receptors, high histologic (p = 0.014) and nuclear (p less than 0.0001) grades, and mitotic rate (p = 0.0001). Immunohistochemical evaluation of proliferation by staining with Ki-67 monoclonal antibody and of neu-oncogene protein overexpression was performed in fresh frozen tissue from 83 tumors. The Ki-67 score, quantitated by the CAS-200 image analyzer, correlated only moderately with S-phase fraction obtained by flow cytometry by linear regression analysis (r = 0.39, p less than 0.001). However, both of these proliferation markers correlated strongly with the mitotic rate (p less than 0.0001). Aneuploid and tetraploid tumors demonstrated higher Ki-67 scores and S-phase fractions than diploid tumors. Neu-oncogene protein overexpression was seen in 24 tumors (29%) overall and was much higher in aneuploid tumors (38%) and tetraploid tumors (50%) than in diploid tumors (7%). However, the concentration of neu-oncogene protein positive tumors in the tetraploid region reported by others was not observed. Neu-oncogene protein overexpression was also associated with higher Ki-67 scores (p = 0.016) and S-phase fractions (p = 0.037).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal

DNA quantitation by image analysis of paraffin-embedded colorectal adenocarcinomas and its prognostic value.

DNA content was measured by image analysis in a retrospective study of formalin-fixed paraffin-embedded colorectal carcinomas from 213 patients who were followed up for at least 5 yr. DNA histograms were classified as diploid, aneuploid, or tetraploid. Diploid tumors comprised 29% of all cases, aneuploid 50%, and tetraploid 21%. Aneuploid tumors were found more often in patients with advanced disease and in carcinomas arising in the rectum. Pathologic stage, histologic grade, and ploidy were individually related to survival and recurrence. However, after stage stratification, histologic grade was no longer a significant prognostic factor. In patients without regional or distant metastases (Dukes' Stage A and Stage B), patients with aneuploid tumors had a statistically worse prognosis than patients with diploid or tetraploid tumors (P less than 0.01). The prognostic value of ploidy in this group of patients was maintained only in tumors arising in the distal colon and rectum (P less than 0.04). In patients with regional or distant metastases, DNA content did not provide additional prognostic information. In conclusion, DNA quantitation can be evaluated reliably by image analysis of archival material and can provide valuable prognostic information, especially in patients with Dukes' Stage A and Stage B disease. It may prove useful in guiding adjuvant therapy in these patients.

Adenocarcinoma

Splenic hamartoma and capillary hemangioma are distinct entities: immunohistochemical analysis of CD8 expression by endothelial cells.

The histologic and immunohistologic features of two morphologically similar splenic tumors, a capillary hemangioma and a splenic hamartoma, are reported. The hemangioma was composed predominantly of small vascular channels lined by endothelium expressing factor VIII-related antigen and lacking T-subset antigen (CD8). In contrast, the splenic hamartoma was predominantly a spindle cell lesion with numerous vascular channels coursing through the tumor; these contained splenic-type endothelium expressing both CD8 and factor VIII-related antigen. Our results justify the concept that the splenic hamartoma is a tumor of splenic origin or a true hamartoma and is distinct from the splenic capillary hemangioma.

Aged

Quantitative DNA analysis in breast carcinomas: a comparison between image analysis and flow cytometry.

We compared the results of quantitative DNA analysis of fresh tumor tissue from 50 invasive breast carcinomas by image analysis and flow cytometry. For image analysis, Feulgen-stained slides of tumor imprints and of disaggregated tumor cytospin preparations were evaluated with the CAS-200 image analyzer. For flow cytometry, propidium iodide-stained disaggregated tumor cells were analyzed with the Coulter EPICS-C flow cytometer. The two methods yielded comparable results. The DNA indices obtained by the two methods showed close correlation by linear regression analysis (r = 0.86, P less than 0.001). There were 26 diploid (52%) and 24 nondiploid (48%) carcinomas. The ploidy pattern between the two methods showed agreement in 41 carcinomas (82%) and discordance in two (4%). Three tumors (6%) were equivocal by flow cytometry and four (8%) by image analysis. The equivocal cases presented potential sources of error in the evaluation of histograms in the near-tetraploid region by flow cytometry and in the near-diploid region by image analysis. Image analysis required smaller tissue samples and permitted direct visualization and selection of tumor cells. It also detected more tetraploid carcinomas. In contrast, flow cytometry analyzed larger cell samples and provided histograms with better resolution. It more readily detected the presence of multiple aneuploid peaks and also the presence of aneuploid peaks in the near-diploid range. The presence of aneuploidy was significantly related to the loss of hormone receptor expression, high mitotic rate, and high histologic and nuclear grades. Our study indicates that image analysis and flow cytometry provide comparable results in a majority of breast carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms

Clinical and pathologic correlations in patients with periampullary tumors.

Perioperative data on 87 patients undergoing pancreatoduodenectomy for periampullary tumors were correlated with pathologic study of operative specimens to identify the accuracy of diagnosis and the factors affecting survival. Accuracy of endoscopic retrograde cholangiopancreatography and computed tomography in locating lesions was 75% and 44%, respectively. Histologic diagnosis before or at the time of resection was available in only 61% of the patients. Carcinoma was correctly diagnosed clinically by the pathologist or the surgeon in 95% (83/87) of patients with 4 patients found to have benign disease on final pathologic examination. Intraoperative diagnosis of site of origin was incorrect in 18% (16/87) of patients. In 28% (23/83) of patients, pathologists identified nodal metastatic disease missed by the surgeon. Survival correlated with nodal and margin status and tumor grade. Tumor size demonstrated no predictive capacity. Although preoperative diagnostic accuracy is less than optimal, surgeons can usually diagnose malignant lesions but more often fail to identify tumor origin and nodal disease. We continue to advocate resection for patients with periampullary lesions thought to be malignant and resectable without a positive histologic diagnosis.

Adult

Long-term results of pancreatic resection and segmental pancreatic autotransplantation for chronic pancreatitis.

Thirteen patients who underwent extensive pancreatic resection and segmental autotransplantation and who have a median follow-up of 62 months are presented. Eleven patients had technically successful grafts. Three of six patients who underwent total pancreatectomy and three of five patients who underwent near-total resection remain insulin-independent. Those patients who require insulin require small doses and have stable diabetes. Pain has recurred in 7 of the 11 patients who underwent distal subtotal resection; 5 of them required pancreatoduodenectomy and completion pancreatectomy for pain relief. Because of the high rate of recurrence of pain after distal resection, we favor pancreatoduodenectomy as the initial procedure of choice. When distal near-total or total pancreatectomy is required, the addition of segmental autotransplantation offers definitive, although at times transient, benefits in glucose homeostasis compared with no transplantation.

Adult

Prognostic significance of peritumoral lymphatic and blood vessel invasion in node-negative carcinoma of the breast.

The prognostic significance of intramammary lymphatic and blood vessel invasion was evaluated in a retrospective series of 221 patients with node-negative carcinoma of the breast treated with modified radical mastectomy. To facilitate identification of lymphatic and blood vessel invasion, the tumors were studied with an immunohistochemical technique using antibodies to endothelial markers. Peritumoral lymphatic and blood vessel invasion (PLBI) (encompassing both lymphatic and blood vessel invasion) was an adverse prognostic indicator independent of menopausal status, tumor size, and other histologic variables. Recurrence of disease and death resulting from carcinoma were significantly higher for patients with PLBI-present (+) tumors compared with patients with PLBI-absent (-) tumors (P less than .0001). The risk of recurrence for patients with PLBI+ tumors was 4.7 times that for their PLBI- counterparts. The presence of intratumoral lymphatic and blood vessel invasion (ILBI) is less important because few examples were found without concomitant PLBI. When PLBI was separated into lymphatic invasion and blood vessel invasion individually, the prognostic significance was retained in both groups. The immunohistochemical approach reduced both false-negative and false-positive observations and identified about 40% of PLBI that would have been missed by routine histologic examination alone. The presence of PLBI appears to be a potentially useful discriminant in predicting the outcome of patients with node-negative carcinoma of the breast.

Breast Neoplasms

Gastric adenocarcinoma. A disease in transition.

Two hundred eleven gastric adenocarcinomas diagnosed from 1967 to 1982 were analyzed. Thirty-four percent had a proximal location, a proportionate increase from previous decades that suggested a distinctive epidemiology. Diffuse histology occurred in 49% of cases overall and in 55% of unresectable cases, which were also increases from previous decades. No deaths followed curative resections, two (4%) of 50 patients with palliative resections died, and three (6%) of 54 patients who underwent exploration without resection died, indicating improved operative management. Superficial gastric cancer constituted 6% of cases; 91% were cured. Seventeen percent of cases were linitis plastica and required total gastrectomy in 77% of resections; only 13% of patients had curative operations; none were cured. Seventy-nine percent of cases were polypoid or ulcerated focal cancers. Of operable focal cancers, 72% were resected; 27 (47%) of 57 patients who underwent resection for cure survived five years, a distinct improvement from previous reports, as was the overall survival of 21%.

Adenocarcinoma

Adenocarcinoma arising in an ileostomy. Report of two cases and review of the literature.

Adenocarcinoma arising in an ileostomy is rare. Two cases are reported, one of a 58-year-old woman and the other of a 54-year-old man who had each undergone a colectomy for chronic ulcerative colitis. Seven other cases previously reported in the literature are reviewed. Though the exact pathogenesis is uncertain, several possibilities, particularly with regard to antecedent dysplasia and backwash ileitis, are discussed. Routine yearly follow-up and examination of the stoma by a physician or enterostomal therapist may lead to earlier detection of this rare complication.

Abdominal Neoplasms

Experimental study of hollow, absorbable polyglycolic acid tube as stent for vasovasostomy.

Bilateral vasovasostomy in 16 rats permitted evaluation of a microsurgical technique using an original absorbable hollow stent made of polyglycolic acid. Advantages of this stent included ease of anastomosis, maintenance of luminal patency, satisfactory approximation of vasal ends, and reduction of perivasal inflammation possibly due to reduction of extravasation of sperm. Absorbable stents were eliminated within four weeks of placement, and patency was confirmed by histologic studies performed two, four, and six weeks after vasovasostomy.

Animals

Anatomy and pathology of the adrenal glands.

The adrenals are paired glands that lie in the retroperitoneum and have a close anatomic relation to the kidneys. Each gland has a cortex and a medulla, which act as separate entities. The adrenals are affected by various pathologic conditions, including congenital abnormalities, hypofunction, nodular enlargement, hyperplasia, and malignant and benign tumors. Newer developments in pathologic evaluation are fine-needle aspiration biopsy, immunohistochemistry, and ploidy and oncogene analysis.

Adrenal Gland Diseases