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M Risio

Publications and source records attributed to M Risio.

At least 37 records · Page 2Linked to original sources
PubMed1996

Deletions at chromosome 1p by fluorescence in situ hybridization are an early event in human colorectal tumorigenesis.

BACKGROUND & AIMS: Deletions at chromosome 1p have been observed frequently in human colorectal adenocarcinomas, suggesting that loss of genes in this chromosome arm is relevant for tumorigenesis. The aim of this study was to investigate whether 1p deletions are already present in adenomas within selected foci of dysplasia and early cancer using two-color fluorescence in situ hybridization. METHODS: Fifty-one sectors characterized by low- and high-grade dysplasia and early cancer were microdissected from 34 adenomas, and isolated epithelial nuclei were subjected to hybridization with probes to the telomeric and centromeric regions of chromosome 1. RESULTS: Deletions of 1p were detected in 13 of 34 adenomas (38%). In particular, low/moderate and high dysplasia and foci of early cancer had 1p deletion frequencies of 31%, 44%, and 50%, respectively. CONCLUSIONS: Compared with classic cytogenetics, fluorescence in situ hybridization seems to be a particularly useful methodology to detect 1p deletions in human colorectal adenomas. The present findings indicate that loss of genes from the 1p chromosome arm may play an important role during the early steps of the colorectal carcinogenesis.

Adenoma↗
PubMed1995

Colorectal cancer in patients with ulcerative colitis. A prospective cohort study in Italy.

BACKGROUND: The aim of this study was to assess the development of dysplasia or cancer in patients with ulcerative colitis and to determine the effectiveness of colonoscopy and biopsy follow-up in colon cancer surveillance. METHODS: From 1980 to 1986, 65 patients who had ulcerative colitis for 7 years or more participated in a surveillance program of colonoscopy and biopsy. This cohort was followed until December 1992. Forty-nine patients (75.4%) had extensive colitis and 16 (24.6%) left-sided colitis. The mean disease duration was 17.2 years. Three hundred four colonoscopies were performed. During each endoscopy, random biopsies were performed. RESULTS: Seven patients had definite dysplasia of the colorectal mucosa. Four of them had high grade lesions and underwent surgery. In all of these patients, colon cancer (3 Dukes' Stage A, 1 Dukes' Stage B) was found. No cancer was found in the other patients. Pedunculated adenomas were excised from 6 other patients during colonoscopy. When dysplasia was diagnosed, these patients were older than those who were dysplasia free, whereas the age at onset of colitis was significantly higher in the former (P < 0.01). Fifteen patients discontinued follow-up. Two of them developed colon cancer diagnosed at an advanced stage. CONCLUSIONS: Dysplasia, especially of high grade, is a marker of colon cancer risk in patients with longstanding ulcerative colitis. Intensive colonoscopy and biopsy surveillance can lead to the diagnosis of colon cancer at a potentially curable stage. In this series, older age appeared to be an additional risk factor. A careful selection of patients with ulcerative colitis seems mandatory to minimize the cost and optimize the benefit of colon cancer surveillance programs.

Adult↗
PubMed1995

K-ras-2 G-C and G-T transversions correlate with DNA aneuploidy in colorectal adenomas.

BACKGROUND/AIMS: K-ras-2 mutations and DNA content heterogeneity represent early events of human colorectal tumor progression. The aim of the study was to investigate if specific K-ras-2 mutations in 58 human sporadic adenomas were correlated with DNA aneuploidization and cell proliferation. METHODS: Multiparameter flow cytometry, based on scatter parameters and DNA content, was performed using 4,6-diamidino-2-phenilindole-2-hydrochloride-stained nuclei obtained from adenoma fragments with either mild-moderate or severe dysplasia. K-ras-2 polymerase chain reaction and spectrum analysis were performed using sorted DNA specific epithelial subclones. RESULTS: We detected six G-A transitions, and four G-C and two G-T transversions. The DNA aneuploid subclones were 25 with DNA index values in the near diploid region (DNA index < 1.3) for the vast majority of cases (80%). DNA aneuploidy among the mutated adenomas with G-A transitions was 1 of 6 (17%) and 6 of 6 (100%) among G-C and G-T transversions. Although DNA aneuploidy and high S-phase values were also present among K-ras-2 wild-type adenomas, their statistical associations with K-ras-2 status were P < 0.005 and P < 0.05, respectively. CONCLUSIONS: The present series of sporadic colorectal adenomas indicates that codon 12 G-C and G-T K-ras-2 transversion mutations and DNA aneuploidy are correlated. The underlying mechanisms that explain such association remain to be investigated.

Adenoma↗
PubMed1995

Clinical evaluation of push-type enteroscopy.

BACKGROUND AND STUDY AIMS: Endoscopic exploration of the small bowel is potentially of prime importance in studying gastrointestinal bleeding of obscure origin, diarrhea and malabsorption, neoplasia, and other clinical conditions, but the method is still problematic because of the limited efficacy of sonde-type enteroscopes. This study evaluates the diagnostic yield of two push-type enteroscopes fitted with tip deflection and a biopsy channel. PATIENTS AND METHODS: Seventy-two consecutive patients underwent enteroscopy using either an Olympus SIF-10 LY fiberscope or an Olympus SIF-100 video enteroscope. The depth of insertion was always checked by fluoroscopy, and ranged 30-120 cm beyond the ligament of Treitz. RESULTS: Angiodysplasia was identified as the source in eight of 20 patients referred for gastrointestinal bleeding of obscure origin, and electrocoagulation was successfully performed in one case. A jejunal polyp was the cause of obscure bleeding in one patient. Radiological evidence of neoplasia/lymphoma located in the third portion of the duodenum or in the upper jejunum was ruled out in 10 of 12 patients. A normal jejunal appearance was found in two patients with lymphoma, subsequently confirmed by a normal enteroclysis. Duodenal or jejunal polyps were removed in seven of nine patients with familial polyposis. Endoscopic and histological alterations were found in nine of 24 patients with diarrhea or malabsorption. In addition, jejunal histology supplied the diagnosis in five patients with a normal endoscopic mucosal appearance. Only 18% of patients described slight, transient pain, and there were no complications. The tolerance and diagnostic efficacy were the same with both instruments. CONCLUSIONS: Even though push-type enteroscope exploration is restricted to the jejunum, the instruments are safe and efficacious in clinical practice, and permit indepth study of small bowel anatomy and pathology.

Adolescent↗
PubMed1995

Mucosal cell proliferation in patients with hyperplastic colorectal polyps.

BACKGROUND: Morphologic, histochemical, and cytoproliferative characteristics differentiate hyperplastic polyps from adenomas. Even so, these polyps are indicators of populations with a high colorectal cancer risk. Since changes in mucosal cell proliferation are highly predictive biomarkers of the adenomacarcinoma sequence, this study examined the cytoproliferative profiles of mucosa bearing hyperplastic polyps, in a search for the significance of such lesions in bowel carcinogenesis. METHODS: Proliferative activity demonstrated by immunohistochemical detection of the in vitro uptake of bromodeoxyuridine was evaluated in the rectal mucosa of 26 patients with hyperplastic polyps, 35 with adenomas < 1 cm, 60 with adenomas > 1 cm, 10 with adenomas + synchronous hyperplastic polyps, and 400 controls. RESULTS: An upward shift of the major DNA synthesis zone to the intermediate and surface crypt compartments was found in all four patients groups. Significant hyperproliferation, on the other hand, was only observed in patients with large adenomas or hyperplastic polyps, or small adenomas and synchronous hyperplastic polyps. CONCLUSIONS: These findings suggest that hyperplastic polyps are morphologic indicators of tumor initiation in the rectal mucosa and its ensuing hyperproliferation. Abnormalities in the distribution of proliferation in the mucosa do not appear to be specifically associated with the morphogenesis of hyperplastics polyps.

Adenoma↗
PubMed1994

Methodological aspects of using immunohistochemical cell proliferation biomarkers in colorectal carcinoma chemoprevention.

In vitro uptake of bromodeoxyuridine (BrdU), expression of proliferating cell nuclear antigen (PCNA), and expression of antigen Ki-67 as revealed by the MIB-1 antibody in fixed and embedded tissues have been regarded as markers of cell proliferation in colorectal tumor progression. Proliferation distribution abnormalities in high-risk mucosa have been illustrated in detail by BrdU labeling of cells in S phase, whereas PCNA and MIB-1 are less informative at this stage of carcinogenesis. The reliability of BrdU labeling is, in any event, dependent on optimization of its tissue uptake and diffusion. Neoplastic deregulation of the synthesis and expression of PCNA, coupled with striking variations in nuclear immunostaining intensity, imposes caution on its use as an intermediate biomarker in intestinal chemoprevention. Validation of MIB-1 must await the standardization of some of the critical procedures (e.g., treatment with microwaves) of antigen retrieval.

Amino Acid Sequence↗
PubMed1993

Small rectosigmoid polyps as markers of proximal neoplasms.

PURPOSE: The aim of this study was to determine the spatial distribution and histotype of small colorectal polyps and to determine the validity of distal-small colorectal polyps as markers of proximal neoplasms. METHODS: In 366 patients who underwent total colonoscopy and removal of all polyps, the presence and features of polyps were recorded. The relationship between proximal neoplasms and distal polyps was investigated in 216 of 366 subjects who had no personal or familial history of colorectal neoplasia. RESULTS: Of 366 patients, 96 were free from polyps. A total of 733 small colorectal neoplasms was removed from the remainder: 79.9 percent neoplastic and 20.1 percent hyperplastic, inflammatory, or hamartomatous. High-grade dysplasia was noted in 2.7 percent of the neoplastic polyps. One adenoma containing invasive carcinoma was observed. In the subset of 216 patients, proximal neoplasms were found in 11.4 percent of those with no distal polyps, 33.8 percent of those with distal-small colorectal polyps only (P < 0.01), and 58.8 percent of those with at least one polyp > 5 mm in diameter (P = 0.001). The proximal neoplasm percentage was the same in patients with at least one adenomatous-small polyp and those with only hyperplastic-small polyps. CONCLUSIONS: A distal-small colorectal polyp, whether adenomatous or hyperplastic, may be a proximal neoplasm marker. Total colonoscopy is thus justified in all patients with distal polyps, regardless of their size and histotype.

Adult↗
PubMed1992

Cell proliferation in colorectal tumor progression: an immunohistochemical approach to intermediate biomarkers.

Cell renewal in the large intestine mucosa is normally tied to a rigidly compartmentalized model. Immunohistochemical identification of cells in S phase through uptake of bromodeoxyuridine is the method of choice for detailed compartmental mapping of proliferation, while immunohistochemical detection of proliferation-associated antigens (Ki-67, PCNA, DNA polymerase alpha) provides information in advanced tumor cases. Mucosal hyperproliferation due to inflammation may be transient (self-limited colitis, Crohn's disease, acute radiation damage) or lasting (ulcerative colitis). Progressive shifting of the proliferation zone to the crypt surface (Stage II abnormality) is a late feature of irradiated rectal mucosa and subgroups of ulcerative colitis patients at high risk for cancer. Hyperproliferation and Stage II abnormality coexist in the mucosa of patients with colorectal neoplasia, but are mutually independent and correlated to different clinical and pathological features of the disease. These cytokinetic abnormalities are highly predictive markers of the adenoma-carcinoma sequence, but are not associated with de novo adenocarcinoma. Proliferation increases progressively in the subsequent steps of this sequence, except in early cancer.

Adenoma↗
PubMed1992

Histology, histochemistry, tumor and serum markers in gastrointestinal tract cancer.

Integration of morphologic and molecular information is being pursued as a result of more extensive use of in situ hybridization techniques. Oncogenes, gene products, and viral genomes involved in the genesis and progression of gastrointestinal tumors have been located in specific histotypes or tumor sectors. The main advances in this area relate to cell-matrix interactions and the biologic mechanisms of tumor invasion. Some aspects of the morphogenetic sequences of gastric and colorectal adenocarcinomas and hepatocellular carcinoma have been elucidated. Studies of DNA ploidy have furnished results consonant with carcinogenesis models envisaging sequential genome alterations due to genetic instability of the transformed cell. The prognostic role of DNA content in gastrointestinal tumors, however, has not been unequivocally established. Research on tumor markers has been directed toward the tissue expression and distribution of apomucins with different molecular structures. Evaluation of tumor markers in body fluids has proved inadequate for the early detection and screening of gastrointestinal neoplasia. Some interesting results have been reported with regard to the monitoring of gastric and colorectal carcinomas by means of serum tumor markers.

Aneuploidy↗
PubMed1991

Correlations between rectal mucosa cell proliferation and the clinical and pathological features of nonfamilial neoplasia of the large intestine.

An in vitro study of proliferative activity as shown by immunohistochemical detection of the uptake of bromodeoxyuridine was run on rectal biopsies from 400 patients with nonfamilial large bowel neoplasia: 200 adenoma; 150 adenocarcinoma; 50 adenoma plus adenocarcinoma. The controls were 400 subjects with negative personal and family histories of colorectal neoplasia. The number and height distribution of bromodeoxyuridine positive cells were determined by dividing the crypt into five longitudinal compartments. The total labeling index and the labeling index of each compartment were higher in all three groups compared with the controls. In subjects with adenoma, total labeling index and labeling index values were correlated with tumor size and decreased in function of the duration of the polyp-free colon state. The major zone of DNA synthesis had shifted to the intermediate and surface crypt compartments in all three groups. This stage II abnormality was more marked in adenoma patients with a high degree of dysplasia and in those with adenoma plus adenocarcinoma. Hyperproliferation and the proliferative compartment shift are cytokinetic abnormalities that coexist in the flat rectal mucosa of patients with colorectal neoplasia. Nonetheless, they are independent, controlled by different factors, and are expressions of different biological aspects of large bowel carcinogenesis.

Adenocarcinoma↗
PubMed1990

Late cytokinetic abnormalities in irradiated rectal mucosa.

Late cytokinetic changes of the colonic crypt epithelium after radiation therapy were investigated. A monoclonal antibody to bromodeoxyuridine (anti-BrdU MAb) was used in tissue specimens previously incubated with BrdU to show S-phase cells by immunohistochemical technique. Endoscopic rectal biopsies were taken from 30 patients previously treated with radiotherapy for gynaecological cancer and from 50 patients with comparable but untreated neoplasms, as controls. Number and height distribution of S-phase cells were evaluated by dividing each crypt column into 5 equal longitudinal compartments. No statistically significant differences were found in total Labelling Index (LI) between controls and irradiated mucosa, whereas LI per crypt compartment, percentage of labelled compartments and percentage of BrdU-positive cells in the middle and superficial portions of the crypt were significantly higher in patients submitted to radiation therapy. This kinetic abnormality corresponds to a progressive shift of the major zone of DNA synthesis to the upper third of the crypt as a late reaction to radiation and represents an early step in the histogenesis of colorectal cancer. These results lend support to the view that there is a higher risk of colorectal carcinoma after pelvic irradiation.

Adult↗
PubMed1990

Needle biopsy of submucosal lesions of the gastrointestinal tract.

Needle biopsy of submucosal lesions is an important addition to the diagnostic capabilities of gastrointestinal endoscopy. A series of 22 cases is described employing a guillotine needle to diagnose submucosal lesions, 4 of which were infiltrating adjacent carcinomas. The specimens obtained were sufficient for firm histological diagnosis in 20 cases. There were no complications apart from minor bleeding in 1 case.

Adolescent↗
PubMed1989

Colorectal adenomas containing invasive carcinoma. Pathologic assessment of lymph node metastatic potential.

Adenomas that contain early invasive carcinoma (ACIC) represent the earliest form of clinically relevant cancer of the colorectum in most patients. In order to assess the incidence of nodal metastases of ACIC, we studied 31 patients in whom the colon was resected after endoscopic polypectomy (EP) done from 1975 to 1987. We also reviewed the pathologic features reported in individual cases and in literature series of ACIC with lymph node metastases published from 1958 to 1986. The lymph node metastatic potential of ACIC is relatively high, ranging from an average value of 8.5% in the literature of to 16.1% in our own study, and is equivalent to the range of 10%-17% that occurs in colorectal carcinomas that invade the submucosa. When an ACIC is seen in an EP specimen in which the polypectomy margin is normal, the decision as to whether the patient should enter a follow-up protocol or have radical surgical resection is determined by the assessment of the probability of the occurrence of nodal metastases. According to several authors, certain histopathologic features make it possible to distinguish between an ACIC with a high-risk of nodal metastases versus those with a low-risk. The most relevant pathologic parameters include the state of the resection margins, the grade of the invasive carcinoma, and the presence or absence of vascular invasion. Of 351 cases of ACIC that were operated on, derived from 16 literature series, 45.6% were high-risk cases and 8.5% had lymph node metastases. In our group of high-risk ACIC that had surgical resection subsequently, the lymph node metastatic rate was 35.7%. Our results help to estimate the nodal metastatic potential of early colorectal carcinomas and stress the importance of adequate pathologic evaluation in order to assess metastatic risk in these patients accurately.

Adenoma↗
PubMed1988

Large bowel adenomas containing carcinoma--a diagnostic and therapeutic approach.

Adenomas containing invasive carcinoma of the large bowel form the majority of early colorectal cancers. Conclusive histological diagnosis of early colorectal cancer depends on two conditions; first, the whole lesion must be examined and second the resection margin must border on healthy tissue. The presence of certain histopathological features makes it possible to distinguish between cases with high and low risk of having lymph node metastases. Sixty-six adenomas containing invasive carcinoma are reported. They comprised 3.15% of 2,095 adenomas removed by colonoscopic polypectomy during the same period. Five cases were lost to follow-up. Forty-nine patients considered to be at low risk of having lymph node metastases have been treated by endoscopic polypectomy only with a rigorous follow-up regime including CEA estimation, ultrasonography and total colonoscopy at regular intervals. In none have distant metastases been found on follow-up examinations at a mean duration of 3 years. Two of these cases have developed a metachronous colorectal carcinoma and 15 (30.5%) have metachronous adenomas. Two low risk patients with no tumour found in the operative specimen have undergone major surgical resection. Ten high risk cases have been referred for major surgery and lymph node metastases have been found in four (40%). The need for careful histological examination for lymphatic and veinous invasion is stressed by the presence of this finding in all four high risk patients with involved lymph nodes.

Aged↗
PubMed1988

Immunohistochemical study of epithelial cell proliferation in hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel.

A monoclonal antibody to bromodeoxyuridine was used in tissue specimens previously incubated with bromodeoxyuridine to show S-phase cells by immunohistochemical technique. Biopsy specimens of normal mucosa (n = 10), hyperplastic polyps (n = 10), adenomas with low-grade dysplasia (n = 20), adenomas with high-grade dysplasia (n = 10), and invasive adenocarcinomas (n = 10) of the large bowel were studied. Labeling index and cell proliferative patterns were analyzed. No statistically significant difference was found in labeling index between normal mucosa and hyperplastic polyps or between adenomas with high-grade dysplasia and adenocarcinomas. The labeling index was significantly lower in normal mucosa and in hyperplastic polyps than in adenomas and adenocarcinomas (p less than 0.001). The difference in labeling index between adenomas with high-grade dysplasia and low-grade dysplasia was also statistically significant (0.01 less than p less than 0.05). In normal mucosa and in hyperplastic polyps the proliferative zone was confined to the lower two-thirds of the crypt; no kinetic activity was found in the upper portions of the crypt or in surface epithelium. In adenomas the labeled cells were either present in the upper third or scattered along the whole axis of the crypt and in the surface epithelium. Labeling patterns in invasive carcinomas were similar to those observed in adenomas with high-grade dysplasia. The difference in proliferative patterns between hyperplastic polyps and adenomas supports a different significance of the two polypoid lesions in the histogenesis of large bowel cancer; our results confirm the subsequent steps of the adenoma-carcinoma sequence. Immunohistochemical labeling patterns observed with monoclonal antibody to bromodeoxyuridine in polypoid and cancer lesions of the large bowel are similar to those described by autoradiographic studies.

Adenocarcinoma↗