Breast cancer multifocality was studied in mastectomy specimens by correlated specimen radiography and histologic techniques. The patients chosen for study were comparable to those eligible for breast-conserving surgical therapy. Two study groups, one with 282 invasive cancers (Tl-2) and the other with 32 intraductal cancers, were selected from a group of 399 consecutive cases by omitting patients who were clearly, or very probably, not candidates for breast-conserving surgical therapy according to current trial criteria. Omitted patients included those with clinically and/or radiologically multifocal cancers and patients with tumor extension into the chest wall or skin (7%). Also excluded were the so-called diffuse invasive cancers @%), the clinically and radiologically occult tumors (3%), and the invasive cancers larger than 5 cm (3%). Of the 282 invasive cancers, 105 (37%) showed no tumor foci in the mastectomy specimen around the reference mass. In 56 (20%) tumor foci were present within 2 cm, and in 121 (43%) tumor was found more than 2 cm from the reference tumor. In 75 (27%) the tumor foci beyond 2 cm were histologically noninvasive cancers, and in 46 cases (16%) they contained invasive cancers as well. A comparison between the group with reference tumors less than 2 cm and the group with reference tumors more than 2 cm in size showed no significant difference between the groups in terms of presence or absence of tumor foci or distance of tumor foci from the reference tumor. If the 264 invasive cancers in this series that were 4 cm or less in diameter had been removed with a margin of 3 to 4 cm, 7% to 9% of the patients would have had invasive cancer left in the remaining breast tissue, and 4% to 9% would have had foci of noninvasive cancer left in the remaining breast tissue. On the basis of the data on the distribution of tumor at different distances from the reference tumor, the current study estimates the expected rates of local recurrences after breast-conserving surgical procedures relative to the extensiveness of the excision. The possible impact of postoperative local radiation therapy on the rates of expected local recurrence is discussed. Cancer 56:979-990, 1985. EPORTED HIGH rates of multifocality of breast cancer R approximately 40%-60%, based on pathologic studies, have been for many years a major deterrent to attempts to treat breast cancer with less mutilating surgical procedures than radical or total mastectomy. Nevertheless, a few nonrandomized studies were camed out that indicated that, in selected groups of patients, the extensiveness of the local surgical therapy does not
Previous studies of patients with infiltrating ductal breast cancer treated with conservative surgery (ie, limited excision) and radiotherapy have indicated that the presence of an extensive intraductal component (EIC) in the excision specimen is highly associated with subsequent breast recurrence. The reason for this association is not clear, but possible explanations include the presence of more extensive disease in the breast or increased radiation resistance among tumors with an EIC (EIC+) compared with those without (EIC-) tumors. To investigate this association further, we related the presence or absence of an EIC in the primary tumors of 214 women who underwent mastectomy to the likelihood of finding additional foci of cancer in their mastectomy specimens using a correlated pathologic-radiologic mapping technique. Primary tumors that were EIC+ were significantly more likely to have carcinoma in the remainder of the breast than those which were EIC--(74% v 42%; P = .00001). This difference was primarily due to the presence of residual intraductal carcinoma. Seventy-one percent of EIC+ patients had residual intraductal carcinoma compared with 28% of EIC-patients (P less than .00001). In particular, 44% of EIC+ patients had "prominent" residual intraductal carcinoma compared with 3% of EIC-patients (P less than .00001). We conclude that patients whose tumors contain an EIC more frequently have a large subclinical tumor burden in the remainder of the breast compared with patients whose tumors do not contain an EIC. This observation may explain the association between EIC and subsequent breast recurrence when patients are treated with a limited excision before radiotherapy.
Cervical intraepithelial neoplasia (CIN I, II, and III) and cases of CIN III associated with micro-invasive cervical carcinoma (CIN III & mCA) were analysed for evidence of episomal or integrated human papillomavirus (HPV) 16/18 DNA by fluorescence in situ hybridization (FISH). In parallel, numerical aberrations of chromosomes 1, 17, and X were determined in these lesions as indicators of genomic instability. HPV 16/18 DNA was present in 2 of 12 CIN I, 19 of 23 CIN II/III, and 10 of 12 CIN III & mCA. None of the CIN I and only two of the 19 HPV 16/18-positive solitary CIN II/III showed an integrated HPV pattern. However, all ten cases of HPV-positive CIN III & mCA showed this pattern. Transition of CIN II/III to CIN III & mCA therefore correlates strongly with viral integration (p<0.001). Chromosomal aberrations were detected in 23 of 31 HPV 16/18-positive lesions (14 solitary CIN I-III and nine CIN III & mCA) and 5 of 16 HPV-negative lesions. Nine of 21 HPV 16/18-positive solitary CIN I-III showed tetrasomy for all chromosomes tested, while trisomies for a single chromosome were seen in a further five of these HPV-positive lesions. In eight of ten HPV-positive CIN III & mCA, predominantly aneusomies and/or polysomies were detected. A significant correlation (p<0.02) was found between the chromosome copy number and the physical status of HPV, indicating that in its episomal form HPV induces genomic changes such as tetrasomies and single trisomies, while HPV integration correlates with aneusomies and polysomies, predominantly detected in CIN III & mCA. These data indicate that integration of HPV 16/18 DNA is a pivotal step in the transition of CIN to micro-invasive carcinoma.
Aims-To investigate the effect of eradication of Helicobacter pylori infection on gastric epithelial damage and gastritis, scored according to the Sydney system. Methods-Gastritis scores and epithelial damage were assessed in gastric biopsy specimens before, and five weeks and one year after anti-H pylori therapy in 66 patients with H pylon related gastritis. Results-The mean initial levels of activity, inflammation, atrophy, intestinal metaplasia, and H pylon scores were higher in the antrum than in the corpus or fundus. Eradication ofHpyloni resulted in an improvement in the mean inflanumatory score in antral biopsy specimens from 2-23 before treatment to 1*32 and 1-06, respectively, five weeks and one year after treatment. Corresponding values for fundic biopsy specimens were 1*30, 036 and 0-35. Activity scores improved from 1P41 before treatment to 0-13 and zero, respectively, five weeks and one year after treatment in antral biopsy specimens and from 0-60 before treatment to zero in fundic biopsy specimens. Before treatment, epithelial damage was present in 51% of biopsy specimens taken from the antrum and 23% of those from the corpus. Five weeks after eradication of H pyloni none of the biopsy specimens revealed evidence of epithelial damage. Conclusion-Eradication ofHpylon is followed by a rapid, significant improvement in the gastritis score and resolution of epithelial damage in antral and fundic mucosa.(J7 Clin Pathol 1995;48:250-256)
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