Tor J. Eide

Polyps of the large intestine in Northern Norway.

In unselected autopsies on 171 males and 109 females over 20 years of age in Tromsø, Northern Norway, adenomas of the colon and rectum were present in 40% of the males and 33% of the females. The frequency of adenomas increased with age in both sexes. Hyperplastic polyps were found in 20% of all cases with no variation in frequency with sex or age. Before the age of 65 most adenomas were located in the distal half of the large intestine in both sexes. After 65 years in males and 75 years in females the predilection site was shifted to the proximal half of the large intestine. The average size and grade of atypia of adenomas increased with age, but no significant difference in grade of atypia was found between the proximal and distal halves of the large intestine. The occurrence of adenomas was not associated with any of the common chronic diseases thought to be related to a western‐style diet or to malignant or benign neoplasms elsewhere in the body. A significant association was found between the occurrence of adenoma and high body weight. The findings support the role of adenomas as precursors of colorectal carcinoma. Cancer 42:2839–2848, 1978.

Remnants of adenomas in colorectal carcinomas

In consecutive large bowel resectates in patients older than age 20 years, primary colorectal cancer remnants of adenomas were histologically identified in 39 of 169 carcinomas (23%). Remnants of pure tubular adenomas were seen in 17 and of tubulovillous adenomas in 22 cases. There was no significant difference among sexes, intestinal segments, or age groups older than 55 years with the regard to the frequency of adenomas in carcinomas. A very low rate (0.05) was found in patients of both sexes younger than 55 years. The frequency with which adenomas was identified was independent of tumor size. A high rate was found in those carcinomas which were limited to the submucosal layer (0.57), were well differentiated (0.43), and had an exophytic growth (0.54). Coexisting single or multiple adenomas at a distance from the main tumor were significantly more frequent in resectates in which adenomas was detected in the carcinoma (0.51) than in resectates in which no adenoma contiguous with the carcinoma was seen (0.30). The study shows that carcinomas develop from adenomas in all parts of the large intestine, but it cannot be concluded that all carcinomas in noncolitic patients develop from adenomas.

Cell death initiated by 3-deazaadenosine in HL-60 cells is apoptosis and is partially inhibited by homocysteine.

Cell death initiated by the adenosine analog 3-deazaadenosine (c3 Ado) was studied in human promyelocytic leukemia HL-60 cells. A rapid decrease in cell number was seen after 4-hr exposure to 50-100 microM c3 Ado. The dominating mode of cell death was apoptosis as demonstrated by condensation and fragmentation of the nucleus, formation of apoptotic bodies and endonucleolytic degradation of DNA. Four hour treatment with 100 microM c3 Ado resulted in a reduction of early S-phase cells, and appearance of cells with a lower DNA and protein content than that of the G1 population. Whereas 25 and 50 microM c3 Ado only initiated apoptosis in S-phase cells, 75 and 100 microM c3 Ado also initiated apoptosis in G1- and G2 + M-phase cells, suggesting different mechanisms for cell death at different concentrations. Apoptosis initiated by 100 microM c3 Ado was completely inhibited by 1 mM ZnCl2. Addition of homocysteine thiolactone (Hcy) partly inhibited cell death by c3 Ado. Light microscopic examination of cultures treated with 100 microM c3 Ado and 1 mM Hcy showed nuclear condensation and fragmentation consistent with the first stage in apoptosis, however, only a minor formation of apoptotic bodies took place in these cultures compared to that observed in cultures treated with 100 microM c3 Ado alone. The modifying action of Hcy on c3 Ado initiated apoptosis in HL-60 cells and this suggests that c3 Ado and 3-deazaadenosylhomocysteine (c3 AdoHcy) interact with different targets during initiation and progression of cell death in this cell line.

Trends in colorectal cancer incidence and histologic findings in Maori and Polynesian residents of New Zealand.

Background. The aim of this study was to combine an epidemiologic survey of colorectal cancer among Maori, Polynesian, and white inhabitants of New Zealand with a detailed analysis of tumor subsite and histopathology.

Renal and hepatic toxicity after high-dose 7-hydroxymethotrexate in the rat

To examine directly the hepatic and renal toxicity of 7-hydroxymethotrexate (7-OH-MTX) without interference of the parent compound methotrexate (MTX), we purified and gave 100 mg/kg 7-OH-MTX to rats, a dose resulting in serum levels of 7-OH-MTX comparable with those achieved in the clinic after the administration of high-dose MTX (HD-MTX). After only 5 h, the 7-OH-MTX-treated rats demonstrated 2.6-fold increases in serum creatinine values and 2-fold elevations in serum aspartate aminotransferase (ASAT) levels as compared with the controls. Morphologic evidence of toxicity, however, was apparent only in the kidneys. Intraluminal cellular debris containing membranous material and deteriorated organelles was seen, but no precipitate of the delivered drug. The peak serum concentration of 7-OH was up to 939 μM, and concentrations of 7-OH-MTX declined triphasically, showing at1/2α value of 2.45 min, at1/2β value of 30.5 min, and a terminal half-life (t1/2γ) of 240 min. The total clearance value was 14.5 ml min−1 kg, and the postdistributional volume of distribution (Vβ) was 5070 ml/kg. Our results may indicate a direct toxic effect of 7-OH-MTX on kidney and liver cells.

A morphometrical analysis of dysplasia in small adenomas of the large instestine

In a morphometrical study of 40 colorectal adenomas less than 10 mm in diameter and of 10 specimens of normal mucosa, it was found that nuclear size, perimeter and shape-factor of the epithelial cells were significantly different in neoplastic when compared with normal tissues. The same was found for the volume fraction of stroma, gland spaces, goblet and non-goblet epithelium, for the gland diameter, nuclear stratification height and stratification index, but not for the epithelial height nor the total volume fraction of the epithelium. In a multivariate analysis, stratification index and nuclear size of the epithelial cells contributed most significantly to determination of the histological grade of dysplasia in adenomas. By the combination of these two morphometric variables 75% of all adenomas could be correctly allocated to the grade of dysplasia.

Morphological modifications of apoptosis in HL-60 cells: effects of homocysteine and cytochalasins on apoptosis initiated by 3-deazaadenosine.

Using electron microscopy, confocal laser scanning microscopy and measurements of intact DNA we have studied the morphology and DNA degradation of human leukaemia HL-60 cells undergoing drug initiated apoptosis. Apoptosis was initiated by 100 μM 3-deazaadenosine (c3Ado), 25 μM c3Ado plus 1 mM homocysteine thiolactone (Hcy) and 100 μM c3Ado plus 5 μg/ml cytochalasin B (CB). Two different phenotypes of apoptotic cells (APC), blebbed and non-blebbed, were present in the cultures. Blebbed APC dominated in cultures exposed to c3Ado, whereas most APC in cultures treated with c3Ado plus Hcy and all the APC in cultures treated with c3Ado plus CB displayed a non-blebbed phenotype. A more pronounced reduction of the chromatin/cytoplasm ratio, lower volume fractions of uncondensed chromatin and higher volume fractions of highly condensed chromatin (micronuclei) were found in cultures exposed to c3Ado and c3Ado plus Hcy when compared with cultures exposed to c3Ado plus CB. A partial inhibition of c3Ado apoptosis by CB was confirmed by measurements of intact DNA. The inhibitory effect of CB was not reproducible by CE, indicating that CB exerts its effect by an actin independent mechanism. Both blebbed and non-blebbed APC displayed nuclear fragmentation, segregation of organelles and cytoplasmic vesiculation, suggesting that the differences between the phenotypes were restricted to the cytoplasmic membrane. We were not able to demonstrate the presence of F-actin by fluorescein isothiocyanate-phalloidin staining in blebbed APC nor in non-blebbed APC in cultures treated with c3Ado plus Hcy. Non-blebbed APC in cultures treated with c3Ado plus CB displayed foci of F-actin at the internal part of the cytoplasmic membrane. This suggests that F-actin is preserved by the mechanism by which CB inhibits blebbing, and may indicate that blebbing of the cytoplasmic membrane during apoptosis is associated with F-actin deficiency rather than a result of actin-myosin interactions.

IMMUNOLOCALIZATION OF CYSTATIN A IN NEOPLASTIC, VIRUS AND INFLAMMATORY LESIONS OF THE UTERINE CERVIX

Cystatin A was immunohistochemically demonstrated in the normal squamous epithelium of the uterine cervix, particularly in the parabasal and superficial cell layers whereas it was absent or scanty in the basal cells and in areas with parakeratosis. Cystatin A was also found in neoplastic lesions (dysplasia, carcinoma in situ and squamous cell carcinoma), but less abundant than in normal squamous epithelium. The immunoreaction in intraepithelial neoplasia was closely related to the degree of morphological maturation of the squamous cells with more abundant cystatin A in low grade dysplasia and less in high grade dysplasia and carcinoma in situ. In squamous cell carcinoma, cystatin A was often abundant in highly differentiated areas and almost absent in poorly differentiated ones. Cystatin A was found in the squamous epithelium in herpes and in condylomatous lesions. It was also found in the cytoplasm of neutrophils, but not in lymphocytes and plasma cells. In unspecific cervicitis, cystatin A was found extracytoplasmatically as small vesicles in the epithelial-stromal junction. The implications of cystatin A in neoplastic, virus, and inflammatory processes are discussed.

Variant γ-glutamyltransferases in colorectal carcinomas

Abstract Two variants of γ-glutamyltransferase were demonstrated in colorectal carcinomas. When compared to the enzyme in normal large bowel mucosa, one of the variants showed reduced affinity to concanavalin A and considerable charge heterogeneity largely due to variable sialic acid content. The other varia form with no affinity to concanavalin A. The two novel forms were of identical size and antigeneity compared to the normal enzyme.

Malignant appendiceal carcinoid with intussusception of the base manifesting as a cecal tumor: Report of a case

SummaryA case of an appendiceal carcinoid tumor with regional lymph-node metastases is presented. The size of the tumor was remarkable, as the appendix was infiltrated throughout its length. The proximal part of the appendix was intussuscepted into the cecum. Preoperatively, the lesion was diagnosed as a polypoid tumor of the cecum. A primary right hemicolectomy was carried out.