Factors predicting late mortality from breast cancer.

Survival data of a cohort of 160 patients with breast cancer, who were still alive 10 years after the primary diagnosis, and who had been followed up for at least 22 years, were investigated to find out those factors that predict late mortality from breast cancer. The 13 factors investigated included age at diagnosis, histological type and grade, mitotic count, type of tumour margin, inflammatory cell reaction, extent of tumour necrosis, primary tumour size, axillary nodal status, DNA ploidy and index, S-phase fraction and occurrence of a second primary breast cancer. Advanced age at diagnosis (greater than 49 years, P = 0.002), occurrence of a second primary breast cancer during the follow-up (P = 0.01), and primary tumour size (T3-4, P = 0.03) were significantly associated with mortality from breast cancer after the 10th year of follow-up in a multivariate analysis, and the ductal invasive histological type (P = 0.03) and a large DNA index (greater than 1.2; P = 0.06) in univariate analyses.

A comparison of human papillomavirus detection rates by dot blot assay from smear and biopsy specimens with regard to human papillomavirus type and histologic diagnosis.

Colposcopic biopsy and cervical smear sampling techniques for human papillomavirus (HPV) DNA dot hybridization were compared to reveal differences related to the level of the histopathologic detection of HPV type 16. The authors used a previously published dot blot assay to analyze 814 pairs of concurrent biopsy and smear DNA specimens for the presence of DNA of HPV 6, 11, 16, and 18. The overall HPV detection rate was 38%, the most prevalent type being HPV 16 (39% of all HPV-positive cases). In detection and typing of HPV DNA, a 81% concordance (658 of 814 pairs) was noted between the smear and biopsy specimens, with a significant correlation in detection of any of the HPV types in the specimens (kappa, .609). The rate of smear-negative cases among all biopsy-positive cases was similar for HPV 11 and HPV 16 (41% and 42%, respectively). Further analysis of distribution of the smear-negative and biopsy-positive cases among different histopathologic levels of disease showed no significant difference between neoplastic and nonneoplastic lesions for either virus type. In 56 cases, only the smear specimen was positive for DNA of the studied HPV types. Both biopsy and smear specimens should be used for HPV detection in cervical dysplasias.

Preliminary characterization of a toxin isolated from the cyanobacterium Nodularia spumigena.

A peptide toxin was isolated from the cyanobacterium Nodularia spumigena by high performance liquid chromatography (HPLC). The i.p. LD50 of the toxin was 50 micrograms/kg mouse with death within 1-3 hr. The major effects of the toxin were seen in the liver in the form of extensive haemorrhages. Amino acid analysis showed the presence of equimolar amounts of glutamic acid, beta-methyl-aspartic acid, and arginine. The toxicological and some of the chemical properties of the isolated toxin were similar to those reported for hepatotoxins isolated from the cyanobacterium Microcystis aeruginosa.

Use of the mitotic counts for the prognosis and grading of breast cancer. Method evaluation study.

Reproducibility of the volume fraction-corrected mitotic index (M/VV index) was studied in 144 unselected breast cancer specimens. The influence on decision making of variation in determining the index was also analysed. In the complete series of specimens the correlation between two observers, one subjectively estimating the epithelial fraction of tumor epithelium and the other using point-counting (10 x 10 ocular grid), was good (Pearson's r = 0.82, p < 0.001, 95% CI 0.70-0.92). A subset of 30 specimens was used to evaluate the grading efficiency (GE) of the M/VV index method. The mean grading efficiency as estimated from this subset varied between 90% and 93%. The average minimum GE value was 82.8% (SD = 3.4%). The findings suggest that when the M/VV index method is used, the grading is correct on average in 90% or more of the cases, but dependent on the cutoff point. The over-all grading efficiency of the M/VV index method was comparable to that obtained from published S-phase fraction data on breast cancer specimens from three independed laboratories. We conclude that the M/VV index in breast cancer analysis is a sufficiently reproducible method in mitosis counting, and that it can be used with subjective or point count estimation of the area fraction of neoplastic epithelium.

Section thickness and mitotic counts in ovarian mucinous carcinoma. Methodological study with scanning confocal microscopy.

To study the effect of section thickness on mitotic counts, paraffin sections of 28 cases of mucinous ovarian carcinomas were analyzed. Mitotic counts, estimated with the number of mitoses per mm2 of neoplastic epithelium (M/Vv index) and per mm3 from optical sections and through the whole section thickness were done. Section thickness was measured with scanning confocal microscopy from each specimen of 3 series of sections with different nominal thicknesses (5, 8, and 10 microns). Section thickness varied considerably within each series of sections. The sections of the 5-microns group tended to be thicker and the sections of the 10-microns group thinner than expected on the basis of their nominal values. As expected, mitotic counts through the section gave higher M/Vv index values than counts done using optical sections. M/Vv values obtained using optical sections increased with increasing nominal section thickness. The study suggests that, when the section thickness cannot be measured, it is advisable to do mitosis counting by using optical sections in lightly stained tissue sections in the thickness range of 8-15 microns.

Risk of gastric stump carcinoma after gastric resection for benign ulcer disease.

This follow-up study concerns 537 patients who underwent gastric resection for gastric or duodenal ulcer disease 10-13, 21-22, or 31-32 years ago. 12 (2.2%) gastric stump carcinomas were found. The development of gastric stump cancer among these patients was compared with the development of gastric cancer in a general Finnish population. In the oldest male follow-up group the observed: expected ratio for cancer was 9:3.5. This was statistically almost significant (p less than 0.05). No statistical difference could be seen in the other follow-up groups. Gastric stump carcinoma showed a strong male preponderance, with a male:female ratio of 11:1. The primary ulcer disease, whether gastric or duodenal, had no influence on the development of gastric stump carcinoma. Endoscopic screening is recommended for all male patients operated on aged 45 years or younger when 15 years have elapsed since the original gastric operation.

Retrospective analysis of gastric stump carcinoma patients treated during 1946-1981.

Thirty-seven (1.1%) cases of gastric stump carcinoma were found among 3 441 gastric carcinomas treated during 1946-1981. The findings and treatment of gastric stump carcinoma were compared with gastric carcinoma without previous Billroth II resection. The mean age of patients with gastric stump carcinoma and with gastric carcinoma without previous Billroth II resection was identical. Gastric stump carcinoma showed a strong male preponderance, with a male:female ratio of 36:1. The average time interval from the original operation to the discovery of the stump carcinoma was 23.3 years. The interval was greater with lower age at the gastric resection. The primary ulcer disease, whether gastric or duodenal, had no influence on the development of gastric stump carcinoma. The resectability and amount of radical operations were lower than in gastric carcinomas and prognosis poorer with a 5-year survival rate of 7.1%. The differences were statistically not significant, however. The proportion of gastric stump carcinoma showed an increasing tendency toward the end of the study. The frequency was 3.3% during the last period (1976-1981). After a time interval of 15 years from gastric resection, all male patients at the age of 55-60 years should be examined endoscopically.

Placental expression of syndecan 1 is diminished in preeclampsia.

OBJECTIVE: Syndecan 1 is a cell surface heparan sulfate proteoglycan that binds growth factors and antithrombin III. The objective of this study was to examine whether placental expression of syndecan 1 in preeclampsia differs from that in normal pregnancy and whether gestational age and fetal growth affect syndecan 1 expression. STUDY DESIGN: An immunohistochemical analysis of 30 placentas of women with severe preeclampsia and 15 placentas of women without preeclampsia was performed with the monoclonal anti-syndecan 1 antibody B-B4. RESULTS: In 47% of preeclamptic placentas the immunoreactivity with antibody B-B4 was faint or absent, whereas 93% of the normal placentas exhibited strong immunoreactivity. The reduction in placental expression of syndecan 1 in preeclampsia was not associated with gestational age or impaired fetal growth. CONCLUSION: The expression of syndecan 1 on the chorionic villi is reduced in preeclampsia irrespective of gestational age or fetal growth.

A comparison of toxins isolated from the cyanobacteria Oscillatoria agardhii and Microcystis aeruginosa.

1. A toxin isolated from a strain of Oscillatoria agardhii var. was compared to a peptide toxin isolated from Microcystis aeruginosa. 2. The Oscillatoria toxin possessed similar hepatotoxic properties on mice as the Microcystis toxin but had a higher LD50 than the latter; 320 micrograms/kg compared to 43 micrograms/kg (i.p. mouse), respectively. 3. Ultra-violet and infra-red spectra showed that the Oscillatoria toxin is a peptide which is not identical to the Microcystis toxin. 4. The spectra also indicated some structural similarities in these toxins.

Endoscopic follow-up after resection for gastric or duodenal ulcer.

Patients who had undergone resection for gastric or duodenal ulcer 10-13, 21-22 or 31-32 years previously were offered endoscopic follow-up examination. Of the 272 surviving patients, 145 (53%) attended. No gastric stump carcinoma was found. Histologic studies showed atrophic gastritis in 79% and intestinal metaplasia in the gastric mucosa in 72% of the patients, but no definite dysplastic changes. The changes appeared soon after gastric resection and increased equally with patient age. Atrophic gastritis was more prominent after resection for gastric than for duodenal ulcer 10-13 years previously, but 20 years after the operation this difference was no longer significant. Hyperplastic polyps in the stomal region were found in 20% of cases 21-22 and 31-32 years postoperatively, but in only 4% after 10-13 years. Enterogastric reflux was endoscopically seen in most cases, but showed no clear correlation with the atrophic changes or polyps found in the gastric remnant mucosa. Endoscopic screening of all patients following gastric resection does not seem to be an effective method in selecting patients for further follow-up.

Second follow-up study of mucosal changes in the gastric remnant after resection for peptic ulcer disease.

Second follow-up 36-37, 26-27 and 15-18 years after gastric resection for peptic ulcer disease was performed for 72 patients who in the first screening five years earlier had severe atrophic gastritis and/or intestinal metaplasia in the gastric remnant mucosa. Of the 72 patients 60 were still alive. The death certificates revealed no gastric stump carcinomas among the 12 deceased patients. Neither were any cases of gastric stump carcinoma found among the 38 endoscopically screened patients. Severe atrophic gastritis, which was present in 37 patients in 1982-83, had regressed in 14 cases (p less than 0.01) and proceeded in one case. The extent of intestinal metaplasia had increased in 11 cases and decreased in five cases (p = 0.149, NS). Dysplasia, which was not seen five years ago, was now detected in four cases (10.5%). There was an association between dysplasia and incomplete intestinal metaplasia in three cases. Although these mucosal changes may be premalignant it is not possible to be categorical about the prognosis. Thus, endoscopic screening of all patients whose stomach has been resected for peptic ulcer disease cannot be recommended. Endoscopy, however, is always indicated when gastric symptoms appear in a patient with history of gastric resection.

Alveolar integrity and ultrastructure in pigs remain undamaged after exposure to sevoflurane.

Previous studies have shown that both halothane and isoflurane have adverse but reversible effects on alveolar physiology. The present study was designed to test the hypothesis that also sevoflurane may affect alveolar integrity. Fifteen pigs were randomly selected to receive either thiopentone infusion (control group, n=8) or sevoflurane (n=7) at 4.0% inspiratory concentration (1.5 MAC) in air for 6 h. Tissue samples from the lungs were obtained at the end of the experiment. Both histopathological light microscopy and electron microscopy were used to assess the structural integrity of the alveoli. Pulmonary hemodynamics were comparable in both groups. Light microscopy showed no difference between the groups in the amount of alveolar macrophages, red blood cells or edema. Electron microscopy showed minor changes such as moderate local swelling of alveolar epithelium in both study groups. Alveolar type II cells were ultrastructurally unaltered in both study groups. We conclude that long-term, high concentration exposure to sevoflurane has no detrimental effect on the alveolar integrity in pigs.