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Biomedical subjects

F P Rossini

Publications and source records attributed to F P Rossini.

At least 19 recordsLinked to original sources

Microsatellite instability is associated with the histological features of the tumor in nonfamilial colorectal cancer.

Replication errors (RERs) at microsatellite loci were examined in 46 specimens of nonfamilial colorectal cancer. Somatic microsatellite alterations in at least two genetic loci, D11S904, D13S175, D2S123, and D10S197, consistent with a RER(+) phenotype were found in four cases (8.7%). Six additional cases (13%) showed alterations at a single locus. Mucinous differentiation was observed in 3 of 4 (75%) adenocarcinomas with a RER(+) phenotype and only in 19% (8 of 42) of RER(-) adenocarcinomas (P < 0.05). A distinct cap of inflammatory cells at the advancing edge of the tumor and Crohn's-like reaction in peritumoral stroma were histologically identified in 50 and 25% of RER(+) and in 5 and 0% of RER(-) tumors, respectively (P < 0.05). Also, the plexiform pattern of growth of carcinoma turned out to be significantly associated with the RER(+) phenotype (P < 0.05). Mucinous differentiation and stromal inflammatory reactions are frequent features of hereditary nonpolyposis colorectal cancer in which germ-line mutations of mismatch repair genes cause genetic instability. Our results indicate that a link exists between such histological features and somatic genetic instability consistent with a RER(+) phenotype also in nonfamilial colorectal cancer.

Adenocarcinoma

Apoptosis, cell replication, and Western-style diet-induced tumorigenesis in mouse colon.

In this study, feeding Western-style diets (WDs) to mice for a duration of two years without any chemical carcinogen led to the development of gross colonic lesions that were histologically classified as dysplastic crypts and focal hyperplasias with or without atypical nuclei. To better understand early biological events contributing to the development of colonic neoplasia, grossly normal colonic mucosa was investigated; mitotic and apoptotic colonic epithelial cells, atypical mitosis, and atypical nuclei were studied. A significant and transient increase of mitotic activity in the basal and intermediate portions of the colonic crypts was seen in young mice after feeding them the WDs. This was accompanied by diffuse activation of apoptosis of the colonic epithelial cells. In the middle of the rodents' life span, after administration of both the WDs and control diet, the rodents developed a marked depletion of apoptotic epithelial cells in the mid-region of the colonic crypts; this was followed by the expansion of an epithelial cell population containing atypical nuclei, and the emergence of the gross lesions noted above. With this sequence of events, prolonged feeding of WDs to mice produced single-crypt dysplastic lesions and focal hyperplasias indicative of tumorigenesis.

Animals

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

Clinical enteroscopy.

We prospectively evaluated the diagnostic yield of push enteroscopy using either the Olympus SIF 10-LY fiberscope or the SIF-100 video enteroscope in 120 patients suspected of having small-bowel pathology. Insertion beyond the ligament of Treitz, checked by fluoroscopy, ranged from 30 to 150 cm (median 100). The source of bleeding was identified in 25 (41%) of 61 patients referred for gastrointestinal bleeding of obscure origin; vascular malformations were the most common finding, followed by neoplasias. Of 16 patients with inherited polyposis syndromes, multiple distal duodenal or jejunal hamartomas were diagnosed in five of six with Peutz-Jeghers syndrome and multiple duodenal or jejunal adenomas in six of 10 with familial adenomatous polyposis. Overall, isolated vascular malformations were successfully cauterized in three patients, and polypectomy was performed in 12 patients. Endoscopic and histological alterations, in both duodenum and jejunum, were found in 16 of 43 patients with diarrhea and/or malabsorption of unclear origin. The remaining 27 had normal duodenal and jejunal mucosal appearances; six had abnormal histological findings only in the jejunum and one both in the duodenum and in the jejunum. If we take jejunal histology as diagnostic, the sensitivity of duodenal histology was 74% and the specificity was 100%. We conclude that push enteroscopy provides useful diagnostic information and has therapeutic capabilities in patients with small-bowel pathology.

Adenomatous Polyposis Coli

High prevalence of adenomas and microadenomas of the duodenal papilla and periampullary region in patients with familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) are traditionally considered to be at high risk for duodenal-papillary and periampullary adenomas and cancer. AIM: To evaluate prospectively the prevalence, histology and clinical significance of ampullary and periampullary macroscopic and microscopic lesions in our population of affected patients. SETTING: Three gastroenterological departments of northern Italian hospitals. PATIENT AND METHODS: Twenty-five affected patients were carefully investigated over a 24-month period by end-viewing and side-viewing upper panendoscopy. Biopsies were performed on representative macroscopic lesions and randomly on normal-appearing papillary and periampullary mucosa. RESULTS: Seven patients had macroscopic adenomas of the duodenal papilla, three of the periampullary region and five at both sites (cumulative prevalence 40%). An additional six patients had macroadenomas in the rest of the duodenum (overall prevalence 64%). Microscopic adenomas were identified in nine and two patients in the papilla and periampullary region, respectively, and in three at both sites (overall prevalence 44%). Thus, a total of 17 (68%) patients presented macro- or microadenomas at these locations. The prevalence rose to 72%, when a further patient with macroadenomas in the rest of the duodenum only was included. Malignancy was not encountered and severe dysplasia was observed only in a macroadenoma of the second duodenal portion. A higher frequency of macroadenomas in the papilla and periampullary region was significantly correlated with the presence and number of such lesions in the rest of the duodenum (P = 0.04). No other significant association was detected either between micro- or macroadenomas at different sites or with the demographic, clinical and pathological features. CONCLUSION: This study confirms that the duodenal papilla and periampullary region are sites with high prevalence of macro- and microscopic adenomas in patients with FAP. However, our data do not seem to support a higher frequency and malignancy potential of such lesions as compared to polyps in the rest of the duodenum. Nevertheless, these findings warrant a periodic, careful examination of the duodenum with either end-viewing or side-viewing endoscopy, the need for random biopsies of the papilla and periampullary region and the removal of any larger or rapidly growing lesions detected.

Adenoma

Screening for colorectal cancer by once only sigmoidoscopy: a feasibility study in Turin, Italy.

OBJECTIVES: To assess the impact on compliance of three invitation methods, as well as the acceptability and efficacy of two bowel preparation regimens, for endoscopic screening in the general population. METHODS: 1170 subjects (men and women aged 55 to 59, in the rosters of a sample of general practitioners (GPs) in Turin), were randomly allocated to one of three invitation groups (A: personal letter, signed by GP, with a pre-fixed appointment; B: same as for A + letter supporting the study by a well known scientist; C: letter signed by the study coordinator, NS) and two preparation regimens (i: one enema, self administered at home two hours before the test; ii: two enemas, administered the night before and two hours before the test). A postal reminder was mailed to non-attenders. A sample of non-responders was contacted for a telephone interview by a trained nurse. Written consent was obtained from all subjects undergoing the test. RESULTS: A total of 278 subjects attended for sigmoidoscopic screening. An invitation from the GP alone produced the highest response rate (compliance: A = 29.3%; B = 24.9%; C = 26.8%). A single enema was as effective as two enemas in achieving satisfactory preparation for the test: the proportion of subjects invited to repeat the test was 8.1% in the single enema group, and 9.6% in the group receiving two enemas. CONCLUSIONS: Compliance with this screening procedure tends to be low. One enema, self administered two hours before sigmoidoscopy, can ensure a satisfactory bowel preparation.

Colorectal Neoplasms

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

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

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

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

Octreotide in the treatment of bleeding due to angiodysplasia of the small intestine.

Three patients with a history of bleeding due to small bowel angiodysplasia (repeated melena or occult fecal blood with serious anemia) were treated for 10-40 months with octreotide, a somatostatin analog that reduces the splanchnic flow. A dose of 0.1 mg subcutaneously twice a day was followed by an increase in hemoglobin, and reduction or elimination of the need for transfusions. There were no further melena episodes, and stool hemoglobin became stably negative in two cases. Suspension of the drug after 6 months in one case was followed by renewed bleeding, and resumption led to a further response. Lower doses tried in another case were ineffective. Although these uncontrolled clinical cases do not prove its efficacy, octreotide appears to be beneficial in the control and prevention of bleeding due to diffuse small bowel angiodysplasia. There is no evidence that it results in regression of angiodysplasias, as they persisted in the patient subjected to control jejunoileoscopy.

Adolescent

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

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

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

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

Comparison between single morning and bedtime doses of 40 mg famotidine for the treatment of duodenal ulcer.

The aim of this study was to compare the duodenal ulcer healing effects of morning (08.00 hours) vs. single bedtime (22.00 hours) doses of 40 mg famotidine, bearing in mind that the known efficacy of bedtime doses of H2-antagonists is regarded as evidence of the predominance of nocturnal gastric acidity in the pathogenesis of duodenal ulcer. This randomized double-blind multicentre trial was conducted in a total of 127 patients with endoscopically proven active duodenal ulcer. Nine patients dropped out and thus 118 were included in the final analysis. The duration of treatment was 4 weeks, and this was extended to 8 weeks in patients whose ulcers failed to heal by week 4. The patients in the two treatment groups were well matched for age and sex. The therapeutic efficacy parameters were endoscopic healing of the ulcer lesion and disappearance of pain. Results were compared using the chi-square method. The 4- and 8-week (cumulative) ulcer healing rates in the patients treated with the morning dose of famotidine were 77.2% and 86%, respectively, compared with 78.6% and 91.8% in those who received the bedtime dose. The differences failed to prove statistically significant either at week 4 (P = 0.85) or at week 8 (P = 0.31). The percentages of patients with ulcer pain, evaluated weekly, were similar in the two treatment groups. The equivalent efficacy of the morning and bedtime famotidine regimens raises doubts concerning the predominance of nocturnal gastric acidity in the pathogenesis of duodenal ulcer.

Adolescent