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Biomedical subjects

C A Rubio

Publications and source records attributed to C A Rubio.

At least 55 records · Page 3Linked to original sources
PubMed1998

Apoptotic differences in experimentally induced colorectal rat tumours.

The presence of apoptotic bodies and of intraepithelial lymphocytes (IELs) were assessed in colorectal adenomas and adenocarcinomas induced in 158 rats by two different carcinogens: 1,2 dimethylhydrazine (DMH) and glutamic acid pyrolysate (GLU-P-1 and 2). Apoptotic granules were present in 97.5% (n=40) of the 41 GLU-induced adenomas and adenocarcinomas, but only in 20.5% (n=24) of the 117 DMH-induced tumours. IELs were found in 95.1% (n=39) of the 41 GLU-induced tumours but only in 21.4% (n=25) of the 117 DMH-induced neoplasias. The differences were significant (p< 0.001). The presence of IELs and apoptotic granules in GLU tumours (and their absence in the majority of the DMH tumours) is new evidence that IELs are the cells from which many of the apoptotic granules--seen in colorectal neoplasias--derive. GLU neoplasias were induced following daily treatment, for 24 months (about half the life span of the animals) and DMH neoplasias by weekly doses, for a period of only 2.8-6 months. It would appear that 'slowly growing' colorectal GLU neoplasias often attract IELs and trigger lymphocytic apoptosis whereas 'quickly growing' DMH tumours seldom evoke those reactions.

Journal Article↗
PubMed1997

Colorectal adenocarcinoma in Crohn's disease: a retrospective histologic study.

PURPOSE: The aim of this study was to review all histopathologic sections from surgical specimens with inflammatory bowel disease and colorectal carcinoma filed at this hospital between 1951 and 1996. METHOD: A total of 40 surgical (n = 39) or autopsy (n = 1) colon or colorectal specimens were reviewed. Internationally accepted histologic criteria were strictly applied to differentiate Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC). RESULTS: Of the 40 specimens with inflammatory bowel disease and carcinoma, 22 (55 percent) had CD, 16 (40 percent) had UC, and the remaining 2 (5 percent) had IC. Males accounted for 72.7 percent or 16 of the 22 patients with colorectal carcinoma in CD and for 68.7 percent or 11 of the 16 patients with carcinoma in UC. Both patients with IC and carcinoma were males. The median age of patients at diagnosis was as follows: CD, 20 (range, 7-68) years; UC, 23 (range, 5-21) years. In IC, the age was 61 and 81 years, respectively. The median disease duration (before detection of colorectal cancer) was as follows: CD, 18.5 (range, 1-45) years; UC, 19 (range, 6-38) years. For cases with IC, it was 13 and 19 years, respectively. Median age of patients at cancer diagnosis was as follows: CD, 48 (range, 21-78) years; UC, 49 (range, 21-81) years. Ages at cancer diagnosis in IC were 68 and 81 years. Colorectal carcinoma tend to develop among relatively young patients with CD and UC. Mucinous adenocarcinomas accounted for approximately one-third of the carcinomas affecting CD. Thirty percent of old specimens (before the end of 1982) had in fact carcinoma complicating CD and not UC (the latter being the diagnosis appearing in old pathologic reports). During a time lapse of 38 years (i.e., between 1951 and 1989), only 11 cases of colorectal CD with carcinoma (i.e., 0.2 cases/year) were found, but as many as 11 during the past 6.5 years (i.e., 1.7 cases/year) have been diagnosed. Only 42.3 percent (11/26) of cases with colorectal inflammatory bowel disease and carcinoma operated on between 1951 and the end of 1989 had Crohn's colitis but as many as 78.6 percent (11/14) of those operated on between 1990 and May 1996 had Crohn's colitis. Review of the literature indicated that 64.8 percent or 191 of the 295 cases of colorectal carcinomas in CD so far reported occurred in the past 6.5 years. It would seem as if the risk of colorectal carcinoma in Crohn's colitis has increased in later years. CONCLUSIONS: 1) Reports on cancer frequency in UC based on old histopathologic records should be subjected to critical histologic re-evaluation; 2) carcinoma in Crohn's colitis has increased at this hospital, particularly since 1990; 3) the surveillance program strategy used in patients with long-standing UC at this hospital should also embrace patients with Crohn's colitis.

Adenocarcinoma↗
PubMed1997

Intraepithelial lymphocytes vs. colorectal neoplastic cells: who is winning the apoptotic battle?

Intraepithelial lymphocytes (IELs) and Intraepithelial apoptotic granules (AGs) are found in the vast majority of colorectal adenomas, less frequently in incipient carcinomas and occasionally in advanced colorectal carcinomas. In colorectal adenomas, the activated and cytotoxic IELs undergo apoptosis by a Fas-FasL mechanism. In advanced invasive carcinomas lacking IELs, that mechanism cannot be activated. On the other hand, the peritumoural lymphocytes which surround some advanced invasive carcinomas may abrogate to-be-metastatic tumor cells, as treated cancer patients with peritumoural lymphocytes have a better 5-years' survival than those without that peritumoural barrier. In colorectal adenomas the host reaction (IELs) dysplastic cells Fas-dependent confrontation seems to prevent rapidly proliferating adenomas from becoming rapidly invasive carcinomas, since that process takes 10 to 20 years to evolve.

Journal Article↗
PubMed1997

Hyperplastic foveolar gastropathies and hyperplastic foveolar gastritis.

Thirteen gastrectomy specimens having diffuse (n = 5), focal (i.e., nodular, n = 6) or combined (n = 2) giant hypertrophic folds at gross examination were reviewed. Of the five specimens with grossly diffuse hypertrophic fundic mucosal folds, two had at histology tortuous foveolar hyperplasia (without intraepithelial lymphocytosis) and prominent glandular cysts; they were classified as Ménétrier's gastropathy. The other three specimens with diffuse foveolar hyperplasia had serrated foveolar infoldings with marked intraepithelial lymphocytosis; they were classified as Ménétrier-like lymphocytic gastritis. Of the six, specimens with multiple mucosal nodules at gross examination, four had focal foveolar hyperplasia with crest depression and no intraepithelial lymphocytosis; they were classified as varioliform gastropathy. The other two specimens with multiple nodules at gross examination had focal foveolar hyperplasia with marked intraepithelial lymphocytosis; they were classified as varioliform gastritis. In the remaining two cases, both diffuse and nodular hypertrophic gastric mucosa were found at gross examination; at histology, both foveolar hyperplasia and intraepithelial lymphocytosis were found. The diffuse or focal distribution of the lesions, the occurrence of intraepithelial lymphocytosis and the architecture of the upper part of the crypts (in diffuse foveolar hyperplasias) were valuable criteria in the differential diagnosis between the various types of foveolar hyperplasia of the stomach.

Aged↗
PubMed1996

Mutation of p53 tumor suppressor gene in flat neoplastic lesions of the colorectal mucosa.

PURPOSE: In a recent comparative histologic survey of flat colorectal neoplasias, we found more lesions with high-grade dysplasia (HGD) and carcinoma in Japanese than in Swedish patients. The purpose of this work was to assess the p53 protein overexpression in flat colorectal neoplasias in Swedish patients and to compare results with those reported in Japan. METHOD: A total of 57 neoplastic lesions of the colorectal mucosa were investigated: 29 had been regarded both at endoscopy and at histology as flat and the remaining 28 as exophytic. Deparaffinized, rehydrated sections were treated immunohistochemically to detect the p53 protein. Lesions having a moderate (++) or high ( ) staining were considered as overexpressing the p53 protein. RESULTS: Results indicated that 16.7 percent (1/6) of the exophytic adenomas with low-grade dysplasia (LGD) had distinct p53 overexpression as well as 57.1 percent (8/14) of those with HGD and 87.5 percent (7/8) with invasive growth. In flat neoplastic lesions, 7.7 percent (1/13) of the tubular adenomas with LGD, 25 percent (3/12) of tubular adenomas with HGD, and 75 percent (3/4) of adenocarcinomas arising in flat adenomas had p53 overexpression. CONCLUSIONS: In Swedish patients, the proportion of flat and exophytic colorectal neoplasias showing p53 immunoreactivity increased with increasing degree of dysplasia, the highest percent being recorded in lesions with invasive growth. Because a similar stepwise increase was reported for exophytic and flat colorectal neoplasias in Japan, it seems that the comparison of results in both countries is justifiable. One possible conclusion from this comparison is that the higher proportion of flat neoplastic colorectal lesions with HGD and carcinoma in the Japanese (compared with the Swedish) takes place for reasons extraneous to the overexpression of the p53 protein.

Adenocarcinoma↗
PubMed1996

Dose-time-dependent histological changes following irradiation of the small intestine of rats.

The distal ileum of 48 male Sprague-Dawley rats was exteriorized and irradiated either with low dosis (9-12 Gy, N = 18 rats), moderate dosis (15-18 Gy, N = 18 rats) or high dosis (21-24 Gy, N = 12 rats). A shielded segment of the ileum in the same animals as well as the sham-irradiated exteriorized ileum of 10 rats served as controls. The animals were allowed to survive for 3, 10, or 30 days. A total of 16 histologic parameters were found to be relevant for this study. Cell necrosis, loss of goblet cells, crypt abscesses, structural changes of the crypts, loss of Paneth cells, decreased number of mitoses, appearance of clear basal cells, loss of margination of lymphocytes, increased colagen in the submucosa, muscularis propria and subserosa, ectopic mucosal glands, as well as mucosal ulcerations, were found to be dose-time-dependent irradiation changes. Racket-shaped superficial epithelial cells, capillary congestion, and an increased number of round cells in the lamina propria mucosa were found to be time-dependent histological parameters. Preparations from the shielded ileum or from the sham-irradiated control animals showed normal histology. This study appears to be the first in which the systematic analysis of several postirradiation histologic changes have been found to be dose- and/or time-dependent. The knowledge that some radiation changes are dose-time-depeendent, whereas others are exclusively time-dependent, may open new vistas on the study of postradiation enteritis in the rat.

Animals↗
PubMed1996

Paneth cell-rich flat adenoma of the rectum: report of a case.

A patient having familiar adenomatosis polyposis and an ileo-rectal anastomosis developed a flat mucosal lesion in the rectum. A punch biopsy revealed a villous adenoma with high-grade dysplasia. The subsequent surgical specimen indicated that the flat villous adenoma was rich in Paneth cells. Special stains included lysozyme muramidase (to visualize Paneth cells), MIB1 proliferation monoclonal antibody and single and multilabel immunohistochemistry for Paneth cells. Other methods included transmission electron microscopy and quantification with an image quantifier (Program Optilab 2.1) of lysozyme-stained Paneth cells. The subjective evaluation of hematoxylin-eosin-stained preparations demonstrated that the Paneth cells were mainly located in the lower half of the villi. Sections labeled with a specific stain (lysozyme muramidase) revealed more Paneth cells in the villi and electron microscopy showed even more in lysozyme-negative areas. Obviously some migrating dysplastic Paneth cells had retained their characteristic granules on their way towards the tip of the villi. Quantitative studies indicated that the lysozyme muramidase-positive material accounted for 41% of the adenomatous tissue. MIB1 revealed intense cell proliferation at the base of the adenoma and in the entire slopes of the villi. Despite the wide distribution of Paneth cells in intestinal metaplasia of the stomach, in the normal small intestine and in the large bowel with chronic inflammatory diseases, it is surprising that tumors arising in Paneth cells are extremely rare. The causes of the apparent natural resistance of Paneth cells to tumor development deserve to be investigated. This is the first case of Paneth cell-rich flat adenoma of the rectum in the literature.

Adenoma↗
PubMed1996

Flat serrated adenomas of the colorectal mucosa.

A total of 47 flat serrated neoplasias of the colorectal mucosa are presented: 44 were flat serrated adenomas and the remaining 3 flat serrated adenocarcinomas arising in flat serrated adenomas. These lesions were found among 600 flat mucosal lesions removed at colonoscopy during a 3-year period (1992 and 1994) at the Karolinska Hospital. Thirty-five of the 47 patients (74%) were males and the remaining 12 (26%), females. Depending upon the degree of cellular dysplasia within the epithelium, serrated adenomas were divided into those with low-grade dysplasia (LGD), when the dysplastic nuclei were present in the deeper half of the epithelium, and those with high-grade dysplasia (HGD), when the dysplastic nuclei were found even in the upper half of the epithelium. LGD was present in 37 (84.1%) of the 44 serrated adenomas and HGD in the remaining 7 (15.9%). Depending upon the topographic distribution of the dysplastic epithelium within the crypts, flat serrated adenomas were divided into type I, when the dysplastic epithelium was limited to the lower half of the serrated crypts, and type II, when the dysplastic epithelium was even present in the superficial half of the serrated crypts. Of the 44 serrated adenomas, 38 (86.1%) were type I and the remaining 6 (13.9%) type II. The dysplastic epithelium seemed to originate at the base of the crypts and to progress upwards, replacing the scalloped, serrated epithelium of the sides of the crypts. Invasive adenocarcinomas (i.e., with submucosal extension) were seen to arise from flat serrated adenomas with LGD type I (n = 2) or with HGD type II (n = 1). This preliminary survey suggests that flat serrated adenomas of the colorectal mucosa may be lesions with a propensity to evolve into invasive adenocarcinoma, irrespective of the degree of the epithelial dysplasia or of their extension along the crypts.

Adenocarcinoma↗
PubMed1996

Leuchtenberger bodies in flat adenomas of the colorectal mucosa: a comparison between Japanese and Swedish patients.

The dysplastic epithelium of flat colorectal adenomas was found to contain DNA inclusion granules, known as Leuchtenberger bodies (LB). Hematoxylin and eosin-stained sections of 263 colorectal flat neoplastic lesions (i.e., flat adenomas, and flat adenocarcinomas) collected in Japan and Sweden were scrutinized for the presence of such intraepithelial inclusions. LB were recorded in 87.1% of the 263 flat colorectal neoplastic lesions. The frequency of flat colorectal lesions having LB was similar in Japan (160 of 178 or 89.8%) to that in Sweden (69 of 85 flat lesions or 81.2%), suggesting that the occurrence of LB may not be influenced by race or environment. Direct immunoperoxidase detection of nuclear DNA fragmentation and transmission electron microscopy studies indicated that the inclusions contained apoptotic material. The semiquantitative assessment of histochemically labeled apoptotic granules indicated that the number of lesions having moderate to large numbers of apoptotic granules (++/ ) was higher in flat adenomas with high-grade dysplasia, suggesting that the occurrence of these granules may be related to the degree of severity of the dysplastic process. A better knowledge of LB may improve our understanding of the possible relationship between apoptosis, host immune response and carcinogenesis in flat colorectal adenomas.

Adenoma↗
PubMed1996

Image quantitation of intestinal metaplasia in entire gastrectomy specimens from Swedish and Japanese patients.

The aim of this work was to investigate the extension of intestinal metaplasia (IM), as well as to quantitate various components of IM (namely sialomucins, sulfomucins and Paneth cells), in entire gastrectomy specimens from Swedish and Japanese patients. The length of the gastric mucosa was assessed by morphometry. The percent of sections with IM was regarded as the extension of IM in the specimens. Histochemically labeled sialomucins, sulfomucins and Paneth cells (the 3 main findings in gastric IM) were quantified in separate sections with the aid of an image analyzer. In total, 1,321 sections corresponding to 6 gastrectomy specimens were quantified. Sialomucins and sulfomucins were more extensively distributed in the 4 specimens with carcinoma than in the 2 without carcinoma (one having a peptic ulcer and the other, hereditary gastric cancer syndrome (HGCS) without carcinoma). On the other hand, quantitative analysis in Swedish specimens indicated that the highest values for sialomucins, sulfomucins and Paneth cells were present in HGCS. When Swedish and Japanese specimens with adenocarcinoma were compared, only sulfomucins (denoting Types II and III IM) were significantly higher in those carrying an intestinal-type carcinoma (ITC) than in those with diffuse-type carcinoma (DTC). The results substantiate those obtained with gastric biopsies by other authors. On the other hand, the mucosal extension and the amount of sulfomucins are not comparable parameters (since that mucin was not equally distributed, but "concentrated" in certain areas in the mucosa). One possible conclusion is that the focal distribution of acidic mucins and of Paneth cells in the gastric mucosa may strongly influence their detection rate in gastric biopsies. Thus, haphazard biopsy of the gastric mucosa may fail to sample areas with sulfomucins in population studies aiming to detect individuals at risk. Such sampling errors in gastric biopsies may explain the conflicting results on this subject appearing in the literature.

Gastrectomy↗
PubMed1996

Histologic classification of endoscopically removed flat colorectal polyps: a multicentric study.

A total of 594 flat colorectal polyps, removed at endoscopy, were histologically classified into non-neoplastic (n = 49) and neoplastic (n = 545) polyps. Non-neoplastic polyps were subdivided into metaplastic (n = 45) and hyperplastic (n = 4), whereas neoplastic polyps were subdivided into adenomas (n = 481), intramucosal carcinomas (n = 28) and invasive adenocarcinomas (n = 36). Several adenoma phenotypes were discerned: tubular (n = 375), serrated (n = 59), villous (n = 39), mixed (n = 7) and fenestrated (n = 1). Intramucosal carcinomas were subdivided into tubular (n = 26) and serrated (n = 2), and invasive adenocarcinomas into tubular (n = 32), serrated (n = 3) and fenestrated (n = 1). The microscopic characteristics of each histologic phenotype described in this communication are defined and illustrated.

Adenoma↗
PubMed1996

A comparative study between the gastric mucosa of Chileans and other dwellers of the Pacific basin.

A total of 3,289 sections of 120 gastrectomy specimens from Chile were reviewed. Intramucosal cysts were found in 61.7% of the specimens, ciliated metaplastic cells in 33.3%, large vacuolated cells in 20.8% and extensive intestinal metaplasia in 51.7%. The frequency of these non-neoplastic changes was significantly higher in specimens with early adenocarcinoma of intestinal type than in those with early adenocarcinoma of diffuse type or having a peptic ulcer. Similar results have been recorded in other inhabitants of the Pacific basin, but not inhabitants of the Atlantic basin. Interestingly, the gastric cancer incidence in the various populations studied in the Pacific basin is much higher than in those studied in the Atlantic basin. Environmental factors acting in Chile appear to have induced those non-neoplastic changes in the gastric mucosa. The question arises as to whether environmental factors (promoters?) acting in Chile (as well as in Japan, in Hawaii and in New Zealand) have favored the necessary non-neoplastic mucosal conditions required for the subsequent development of gastric adenocarcinoma (in particular of intestinal type.)

Adenocarcinoma↗
PubMed1995

p53 overexpression in flat serrated adenomas and flat tubular adenomas of the colorectal mucosa.

The expression of the p53 protein was investigated in flat serrated neoplasias as well as in other histological phenotypes of flat or exophytic hyperplasias or neoplasias of the colorectal mucosa. A total of 104 such lesions were analyzed: 24 were flat serrated neoplasias (22 flat serrated adenomas and 2 flat serrated adenocarcinomas), 26 flat tubular adenomas, 17 flat hyperplastic polyps, 29 exophytic tubular and/or villous neoplasias (23 adenomas and 6 exophytic adenocarcinomas) and the remaining 8, exophytic hyperplastic polyps. Deparaffinized, rehydrated sections were treated immunohistochemically to detect those overexpressing the p53 protein. Lesions having slight (+), moderate (++) or intense ( ) staining were considered immunoreactive. The results showed that 50% of the flat serrated adenomas with low-grade dysplasia (LGD) and 66.7% of those with high-grade dysplasia (HGD) had p53 immunoreactivity. None of the flat tubular or of the exophytic adenomas with LGD expressed p53, but immunoreactivity was present in 61.5% of the flat tubular adenomas with HGD and in 52.3% of the exophytic adenomas with HGD. All adenocarcinomas had an intense p53 reaction. Weak p53 expression was demonstrated by 11.7% of the flat hyperplastic polyps but none of the exophytic polyps reacted. The occurrence of p53 expression in flat serrated adenomas with LGD suggested that, despite its low histological profile, one-half of those lesions could be biologically already committed to independent growth. The occurrence of p53 expression in nearly 12% of the flat hyperplastic polyps was totally unexpected and deserves further investigation. Flat serrated adenoma emerges as a novel, independent histological entity among the various phenotypes of flat neoplasias of the colorectal mucosa.

Adenocarcinoma↗
PubMed1995

Flat adenomas and flat adenocarcinomas of the colorectal mucosa in Japanese and Swedish patients. Comparative histologic study.

PURPOSE: In recent years, flat adenomas of the colorectal mucosa have been intensively investigated by Japanese pathologists. Results of that work indicate that flat adenomas may antedate the development of colorectal carcinomas. Because of differences in the histologic definition of flat adenomas with severe dysplasia and with intramucosal carcinoma within the group, one single observer having both Western and Asian training in pathology reviewed the material. METHODS: A total of 287 flat colorectal lesions were reviewed: 109 from the Karolinska Hospital, Stockholm, 137 from the Tokyo Medical and Dental University (TMDU) (which included 5 cases from the Nagoya City University), and 41 from the Cancer Institute (CI), Tokyo. Lesions were histologically classified following strict histologic criteria. Thus, flat adenomas were divided into those having low-grade dysplasia (LGD; having dysplastic cells in the deeper half of the epithelium), high-grade dysplasia (HGD; dysplastic cells were found even in the superficial half of the epithelium), intramucosal carcinoma (dysplastic glands displayed molding with buddings and often a cribriform pattern), and adenocarcinoma (braking through the muscularis mucosa, with neoplastic cells in the submucosal layer or deeper). RESULTS: Whereas in Stockholm only 14.7 percent of lesions had HGD, as much as 56.9 percent and 56.1 percent, respectively, had HGD at the two Tokyo Hospitals. Intramucosal carcinomas were not found in the Stockholm material but occurred in 2.2 percent of lesions seen at TMDU and in 4.9 percent of those seen at the CI. Notably, only 2.7 percent of the specimens at Karolinska Hospital had invasive adenocarcinoma, but it was seen in as many as 4.4 percent at TMDU and 21.9 percent at the CI. CONCLUSIONS: This study indicates that there were histologic differences between flat neoplasias of the colorectal mucosa harvested in Stockholm and Tokyo. In Japan lesions were obviously more advanced (in terms of HGD) and more aggressive (in terms of intramucosal and submucosal invasion). The cause for the differences found in those two disparate geographic regions remains poorly understood. The results, however, may help us understand some of the unclear points and discussions appearing in the literature on this subject.

Adenocarcinoma↗
PubMed1995

Flat serrated adenomas and flat tubular adenomas of the colorectal mucosa: differences in the pattern of cell proliferation.

In the present work we have investigated the cell proliferation pattern of flat serrated adenomas and flat tubular adenomas. For this purpose tissue sections from 23 consecutive flat serrated adenomas and 22 consecutive flat tubular adenomas of the colorectal mucosa were challenged with MIB1, a monoclonal antibody directed against a proliferation-related antigen. The results (including semi-quantitative studies) demonstrated that, whereas flat serrated adenomas had a high cell proliferation at the lower part of the crypts, flat tubular adenomas had a high cell proliferation in the upper part of the crypts. In serrated adenomas with invasive adenocarcinoma, high cell proliferation was demonstrated both at the lower portion of the crypts and in the subjacent submucosa. This suggests that the cells of the lower portion of the crypts in serrated adenomas are truly neoplastic, with the capacity to evolve into invasive growth. The difference in cell proliferation between the two types of flat lesions reported here is a new argument in favor of the classification of flat serrated adenomas as a novel and independent type of neoplastic change of the colorectal mucosa.

Adenoma↗
PubMed1995

Clear cell adenocarcinoma of the colon.

A case of clear cell adenocarcinoma of the colon is reported. The histological examination of both the surgical specimen and of the metastases at necropsy showed columnar or polygonal cells with vesicular nuclei. The cytoplasm was usually clear with multiple, often empty looking vacuoles. From a panel of histochemical and immunohistochemical reactions, carcinoembryonic antigen and tissue polypeptide antigen showed strong positivity. The histochemical and immunohistochemical differential diagnosis with another common clear cell tumour, namely clear cell renal adenocarcinoma, is discussed.

Adenocarcinoma, Clear Cell↗