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F Michelassi

Publications and source records attributed to F Michelassi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Chromosome 8 Losses in Colorectal Carcinoma: Localization and Correlation With Invasive Disease.

Background: Allelic losses from the short arm of chromosome 8 (8p) are frequent in a variety of epithelial malignancies. In colorectal cancer, there are two discrete regions of 8p loss of hterozygosity (LOH), suggesting the existence of two putative tumor suppressor genes. Previous studies have shown an association of 8p LOH with tumor invasiveness. To better define the deletion extent and the clinical significance of these losses, a series of 41 colorectal cancers were examined for 8p LOH and correlated with clinical features. Methods and Results: Paired normal and enriched tumor DNA from the same individual was typed by polymerase chain reaction for 11 microsatellite polymorphisms and scored as positive or negative for 8p LOH. Loss of 8p markers was observed in 44% of the cases. Most cases had large deletions, but several had localized interstitial losses, enabling specification of two nonoverlapping regions of LOH. The telomeric region of loss is defined by the markers D8S262 and D8S133 at 8p22, and the centromeric region is proximal to NEFL. Clinical, histopathologic, and molecular data were obtained and a significant correlation of 8p LOH with microinvasion (invasion of lymphatics, vessels, or perineurium, ascertained by light microscopy) (P=.01) and also with loss of chromosome arm 18q (P=.001) was found. Conclusions: An association of 8p allelic loss with poor outcome was demonstrated. The correlation between 8p loss and 18q loss suggests that 8p LOH is a late event in the multistep model of colorectal carcinogenesis. 8p LOH may provide a clinically useful prognostic marker in colorectal cancer, thereby warranting further testing. The involvement of two independent loci on 8p is confirmed, and the refined localization of these sites will contribute to the eventual identification of these genes, which appear to play an important role in the progression of epithelial malignancies.

Journal Article↗
PubMed1996

Prospective study of the incidence, timing and treatment of pouchitis in 104 consecutive patients after restorative proctocolectomy.

OBJECTIVE: To determine the incidence timing and effectiveness of treatment of symptomatic pouchitis following restorative proctocolectomy with ileal J-pouch anal anastomosis. DESIGN: A cohort analytical study. SETTING: University hospitals, a tertiary referral center; all subjects entered into the study followed up for a minimum of 12 months (mean follow-up, 40 months). PATIENTS: One hundred four consecutive patients undergoing restorative proctocolectomy with ileal J-pouch anal anastomosis for either ulcerative colitis (n = 97) or familial adenomatous polyposis (n = 7) between June 1986 and December 1994. INTERVENTIONS: Patients with symptomatic pouchitis were treated with either oral metronidazole or ciprofloxacin. OUTCOMES: Diagnosis of pouchitis was determined by clinical symptoms and confirmed with endoscopy. Response to oral antibodies was determined by resolution of symptoms. RESULTS: Fifty-two patients (50%) experience at lest 1 episode of pouchitis. The first episode of pouchitis occurred within the first 12 months after restoration of intestinal continuity in 56% of the cases. In 2 patients it occurred after 30 months. Response to antibiotic treatment was 96%. Two thirds of patients had multiple episodes. Chronic pouchitis occurred in 6 patients, necessitating pouch removal in 2. CONCLUSIONS: The incidence of pouchitis after ileal J-pouch anal anastomosis is approximately 50% with two thirds of these patients having multiple episodes. Chronic pouchitis occurs in a minority of patients. In chronic pouchitis, the risk of pouch loss is substantial.

Adenomatous Polyposis Coli↗
PubMed1996

Ploidy as a prognostic feature in colonic adenocarcinoma.

OBJECTIVE: To determine whether DNA content and cell-cycle kinetic characteristics in Dukes stage B colonic adenocarcinomas provide additional prognostic information in the context of clinicopathologic variables of known significance. DESIGN: Archival, paraffin-embedded tissue blocks from 210 Dukes B colonic adenocarcinomas were retrieved. After confirming stage, tumor cell nuclei were extracted, suspended, and stained. Cell nuclei from adjacent normal colon mucosa were used as controls. SETTING: University-based, tertiary cancer referral center. INTERVENTIONS: Samples obtained from tumors resected at our institution between 1965 and 1984 were analyzed by flow cytometry for DNA index (DI) and percentages of cells in synthesis (S) phase (%S) and in G2 and mitosis (M) phases (%G2M). The data were correlated with 5-year survival. Follow-up was complete in all patients to at least 5 years. RESULTS: Univariate analysis showed that the highest survival rates were associated with DI values near 1 and 2 (diploid and tetraploid tumors, P = .02) and the lowest %G2M values (tumors with fewer mitoses; P = .01). Five-year survival rates also differed significantly between patients with diploid (DI < 1.1) and those with aneuploid (1.1 < DI < 2) tumors (80% vs 64%, respectively; P = .02). Multivariate analysis revealed that race (P < .01), lymphatic or capillary microinvasion (P < .03), and ploidy (P < .05) were significantly associated with outcome. The influence of ploidy, race, and microinvasion on 5-year survival was estimated with logistic regression, and 8 subgroups of patients emerged with 5-year survival probabilities ranging from 39% for black patients with aneuploid tumors and microinvasion to 88% for white patients with diploid tumors and no microinvasion. CONCLUSIONS: Tumor DNA content provides additional independent information that allows further refinement of our prognostic ability in patients with Dukes B colonic adenocarcinoma. This may aid in the identification of a cohort of patients who may potentially benefit from aggressive adjuvant therapy.

Adenocarcinoma↗
PubMed1996

Side-to-side isoperistaltic strictureplasty for multiple Crohn's strictures.

BACKGROUND: Strictureplasties are being used with increased frequency in the surgical treatment of severe and extensive Crohn's disease of the small bowel; concerns regarding their use have been raised in the presence of long and rigid strictures or when strictures are located in close proximity to each other. METHODS: A new surgical technique, a side-to-side isoperistaltic strictureplasty, has been used in three patients with severe Crohn's disease of the small bowel extending up to three feet in length. RESULTS: Three patients (3 males; mean age, 42 years) had recurrent Crohn's jejunoileitis extending over the length of 22, 37, and 14 inches. This represented 19, 16, and 24 percent, respectively, of the entire length of their small bowel. In the first two patients, resection of 5 and 7 inches, respectively, from the middle third of the diseased segment facilitated performance of the side-to-side isoperistaltic strictureplasty; in the last patient, the procedure was performed after resection of a 57-inch bypassed loop. All patients had an uncomplicated postoperative course and, at a recent follow-up visit between 4 and 24 months, they continue to be asymptomatic and do not require steroid medications. CONCLUSIONS: We believe that the side-to-side isoperistaltic strictureplasty is a useful adjunct to the armamentarium of the surgeon dealing with patients affected by inflammatory bowel disease. With this technique, bowel is not resected, blind or bypassed loops are avoided, and stenoses are palliated.

Adult↗
PubMed1996

Introduction of human adenomatous polyposis coli gene into Min mice via cationic liposomes.

BACKGROUND: The adenomatous polyposis coli (APC) gene is a tumor-suppressor gene involved in familial polyposis coli (FAP), a hereditary disease heralded by the development of hundreds of colorectal adenomas. A mouse model for FAP, the multiple intestinal neoplasia (Min) mouse, develops multiple adenomatous polyps of the large and small intestine similar to their human counterparts. To test the feasibility of introducing normal human APC as a means of either preventing or reversing polyp formation, we describe a method of in vivo transfection of APC into colonic epithelium of the Min mouse. METHODS: Anesthetized young (4 weeks) Min mice were treated with enemas containing lipofectant and a normal human APC cDNA plasmid every 72 hours for 2 months and then euthanized at 24, 48, and 72 hours after the last treatment. Polymerase chain reaction (PCR) was used to detect the presence of the plasmid DNA. RESULTS: PCR on the extracted colonic epithelial DNA showed the presence of plasmid DNA up to 72 hours after the last treatment. Expression of the plasmid construct was confirmed by reverse transcriptase-PCR. CONCLUSIONS: We have demonstrated the repeated introduction and detection of normal human APC in the colonic epithelium of the Min Mouse in vivo during an extended period of time with no toxic side effects by means of our prolonged therapy.

Adenoma↗
PubMed1996

Endorectal color Doppler imaging of primary and recurrent rectal wall tumors: preliminary experience.

OBJECTIVE: The purpose of our study was to assess whether color Doppler imaging is a useful adjunct to endorectal sonography in evaluating rectal wall neoplasms and in distinguishing recurrent or residual tumor from postoperative changes. MATERIALS AND METHODS: Thirty-two patients underwent endorectal sonography with color Doppler imaging for one of two indications: evaluation and staging of a suspected primary rectal wall cancer, or distinguishing tumor recurrence from postoperative scarring in patients with previously resected lesions. Rectal wall lesions were evaluated for hypervascularity, and their corresponding flow patterns were graded from 0 to 4. Local tumor staging with endorectal sonography and color Doppler imaging was performed before the results of pathological staging were available. RESULTS: Ninety-five percent of patients with malignant rectal wall tumors demonstrated hypervascularity during color Doppler imaging. In 61% of patients with rectal cancers, prominent perirectal vessels were identified supplying the tumor and were never identified in patients with benign lesions. Endorectal sonography alone correctly identified perirectal fat invasion with a 100% sensitivity and an 83% specificity. Color Doppler imaging during endorectal sonography correctly identified perirectal fat invasion with a sensitivity of 91% and a specificity of 83%. Of the 8 patients with previously resected lesions (five adenomas and three cancers), two patients had recurrent tumor, and both of these demonstrated grade 3 abnormality. Six patients with biopsy-proven fibrosis only had grades of 0 or 1. CONCLUSIONS: Both benign and malignant rectal wall tumors demonstrate abnormal intratumoral hypervascularity when seen with color Doppler imaging. Advanced rectal cancers (T3 or greater) are also associated with abnormal perirectal vascularity. Color Doppler imaging during endorectal sonography does not appear to improve discrimination of benign from T2 (or less) rectal wall cancers, nor does it appear to improve the ability to locally stage rectal wall cancers during endorectal sonography. However, endorectal sonography with color Doppler imaging may add significant information in distinguishing recurrent tumor from postsurgical scarring.

Female↗
PubMed1995

Chromosome 17p allelic loss in colorectal carcinoma. Clinical significance.

OBJECTIVE: To correlate allelic losses on chromosomes 5q, 8p, 17p, and 18q in colorectal adenocarcinomas with histopathologic features of known prognostic significance. DESIGN: DNA was extracted from paired samples of 56 fresh-frozen colorectal adenocarcinomas (one classified as Dukes' stage A, 22 as Dukes' stage B, 27 as Dukes' stage C, and six as Dukes'stage D) and adjacent normal mucosa. SETTING: Specimens were resected at the University of Chicago (Ill) and the University of Padova (Italy) in 1991. PATIENTS: Samples were obtained from consecutive patients. INTERVENTIONS: Chromosomes 5q, 8p, 17p, and 18q were studied for loss of heterozygosity by means of Southern hybridization blot analysis of restriction fragment length polymorphisms, and the results were correlated with pathologic tumor stage, degree of differentiation, and lymphatic and/or vascular microinvasion. RESULTS: Chromosomes 17p and 18q exhibited the highest frequency of loss of heterozygosity (40.6% and 48.8%, respectively). Most of the allelic losses were found in advanced tumors (60% in Dukes' stages C and D combined). A statistically significant correlation was found between loss of heterozygosity on chromosome 17p and the presence of lymphatic and/or vascular microinvasion (P < .01, Fisher's Exact Test). CONCLUSIONS: There was a significant correlation between loss of heterozygosity on chromosome 17p and the presence of lymphatic and/or vascular microinvasion in colorectal adenocarcinoma, a known stage-independent negative prognostic risk factor. Detection of loss of heterozygosity on chromosome 17p may identify a group of patients who may benefit from more aggressive surgical and/or early adjuvant therapy.

Alleles↗
PubMed1995

Morbidity of subtotal colectomy in patients with severe ulcerative colitis unresponsive to cyclosporin.

PURPOSE: The aim of this study was to document the morbidity of urgent subtotal colectomy and ileostomy in patients with severe ulcerative colitis who failed cyclosporin treatment. METHODS: We reviewed the charts of patients with severe ulcerative colitis who did not respond to cyclosporin treatment and underwent urgent subtotal colectomy and Brooke ileostomy at two inflammatory bowel disease centers over the 12-month period ending April 1994. RESULTS: Fourteen patients (6 males; mean age, 34 years) required an urgent subtotal colectomy and Brooke ileostomy after failing treatment with cyclosporin. There were no deaths. Eight patients (57 percent) developed post-operative complications, which included ileus (3), deep vein thrombosis (2), wound infection (2), and partial dehiscence of rectal stump (1). Mean length of postoperative hospital stay was 8.8 days. CONCLUSIONS: These initial data suggest that cyclosporin treatment may not influence the safety of urgent surgical treatment in severe ulcerative colitis.

Adolescent↗
PubMed1995

Prospective analysis of perioperative morbidity in one hundred consecutive colectomies for ulcerative colitis.

BACKGROUND: This study was undertaken to evaluate prospectively the indications for surgical treatment and perioperative morbidity for patients with idiopathic ulcerative colitis (UC). METHODS: Between January 1985 and August 1994, 145 patients were referred to the senior author (F.M.) for treatment of UC. Data were prospectively collected. One hundred patients have completed all stages of their surgical treatment and have been followed up for at least 1 year. These 100 patients form the basis of this study. RESULTS: Thirty patients underwent a proctocolectomy with end-ileostomy in one (25) or two (5) stages. Seventy patients underwent a restorative proctocolectomy with ileal J-pouch anal anastomosis in either one (2), two (37), or three stages (31). In total 100 patients underwent 204 procedures. Failure of medical treatment was by far the most common indication. The initial colectomy was performed electively in 61 patients and urgently in the remaining 39. The rate of perioperative complications for elective and urgent colectomy was 26% and 44%, respectively (p < 0.05). CONCLUSIONS: The overall perioperative morbidity rate remains high and almost doubles for urgent cases. Reducing the need for urgent procedures by earlier elective colectomy may allow for a reduction in perioperative morbidity.

Colectomy↗
PubMed1995

Loss of alveolar macrophages during anesthesia and operation in humans.

Pulmonary macrophages play an important role in the host defense against infection, and the importance of this role is probably enhanced when the upper airway defenses are circumvented by endotracheal intubation. Studies in animals suggest that exposure to volatile anesthetics compromises the viability and function of alveolar macrophages. We studied the effect of surgery and anesthesia on the alveolar macrophages of 41 human subjects undergoing lower abdominal procedures of varying lengths during nitrous oxide-isoflurane anesthesia. Alveolar macrophages were harvested from bronchoalveolar lavage fluid obtained before incision and compared to those recovered just before emergence from anesthesia. Macrophages were analyzed for aggregation and viability, assessed by the ability of viable cells to exclude trypan blue dye. Operations lasting 2 h or less led to little aggregation and had little effect on viability. However, there was a strong correlation between loss of macrophages and the duration of surgery and anesthesia. Aggregation increased and viability decreased as a function of procedure length. Studies are needed to determine whether prolonged surgery contributes to the incidence of postoperative pulmonary complications by disturbing the function and survival of alveolar macrophages in humans.

Adolescent↗
PubMed1995

Prognostic value of bcl-2 oncoprotein expression in stage II colon carcinoma.

The bcl-2 proto-oncogene encodes a Mr 25,000 protein that has been shown to prevent apoptosis or programmed cell death. The bcl-2 protein is detectable in basal cells of normal colonic epithelium, and an altered topographic distribution of this protein is found in colonic neoplasms. However, the clinical significance of abnormal bcl-2 expression in colon carcinomas remains unknown. We examined the prognostic value of the bcl-2 protein in TNM stage II colon carcinomas and its relationship to DNA ploidy, cell proliferation indices, p53 expression, and clinicopathological features. We analyzed 119 resected and otherwise untreated, paraffin-embedded stage II colon carcinomas for bcl-2 and p53 protein expression using immunohistochemistry. DNA ploidy and proliferative index (% S-phase + % G2-M) were determined by flow cytometry, and tumor grade and vascular microinvasion were assessed on histological sections. Cytoplasmic expression of the bcl-2 protein was detected in 72 (66%) of 110 carcinomas, and a high level of expression was significantly correlated with diploid DNA content (P = 0.02) and low proliferative activity (P = 0.005). bcl-2 was not associated with nuclear p53 expression. In a univariate analysis, a higher fraction of bcl-2-positive tumor cells was associated with better relapse-free survival (P = 0.02) and overall survival (P = 0.05) rates. Moreover, a high level of bcl-2 expression was an independent predictor of better relapse-free survival (P = 0.04), but not overall survival (P = 0.14), after adjustment for other variables, including proliferative index, DNA ploidy, and race. In conclusion, bcl-2 overexpression is associated with favorable prognostic features and may predict clinical outcome in stage II colon carcinomas.

Adult↗
PubMed1994

Relationship of P-glycoprotein and carcinoembryonic antigen expression in human colon carcinoma to local invasion, DNA ploidy, and disease relapse.

BACKGROUND: The clinical significance of expression of the MDR1 gene product P-glycoprotein (P-gp) in relation to the intrinsic drug resistance and progression of human colon cancer is largely unknown. To elucidate the role of P-gp in these cancers further, the frequency and intensity of P-gp and carcinoembryonic antigen (CEA) immunostaining were measured at the single-cell level and correlated with known prognostic indices (i.e., DNA ploidy, vessel/lymphatic microinvasion, histologic grade, and disease relapse). METHODS: Fifty-two untreated Dukes' Stage B2 colon cancers were immunostained with the anti-P-gp monoclonal antibodies JSB-1 and HYB-241, and anti-CEA. DNA content and cell proliferation were measured by flow cytometry. RESULTS: JSB-1 and HYB-241 detected P-gp in 44 and 42 of 52 carcinomas, respectively, and CEA was found in 50 of the 52 tumors. The level of P-gp expression was not associated with DNA ploidy, indices of local invasiveness, or histologic grade. In a multivariate analysis, however, a high level of P-gp expression (as assessed by JSB-1), DNA aneuploidy, microinvasion, and single carcinoma cell invasion individually predicted disease relapse (P < 0.05). CONCLUSIONS: The results indicate that diffuse P-gp immunostaining is present in the majority of Stage B2 human colon cancers and therefore may be an important contributor to their intrinsic drug resistance. The association between a high level of P-gp expression and disease relapse suggests that P-gp can be of prognostic value in Stage B2 colon cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Cyclosporine in severe ulcerative colitis refractory to steroid therapy.

BACKGROUND: There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced almost 40 years ago. In an uncontrolled study, 80 percent of 32 patients with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy. METHODS: We conducted a randomized, double-blind, controlled trial in which cyclosporine (4 mg per kilogram of body weight per day) or placebo was administered by continuous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least 7 days of intravenous corticosteroid therapy. A response to therapy was defined as an improvement in a numerical symptom score (0 indicated no symptoms, and 21 severe symptoms) leading to discharge from the hospital and treatment with oral medications. Failure to respond to therapy resulted in colectomy, but some patients in the placebo group who had no response and no urgent need for surgery were subsequently treated with cyclosporine. RESULTS: Nine of 11 patients (82 percent) treated with cyclosporine had a response within a mean of seven days, as compared with 0 of 9 patients who received placebo (P < 0.001). The mean clinical-activity score fell from 13 to 6 in the cyclosporine group, as compared with a decrease from 14 to 13 in the placebo group. All five patients in the placebo group who later received cyclosporine therapy had a response. CONCLUSIONS: Intravenous cyclosporine therapy is rapidly effective for patients with severe corticosteroid-resistant ulcerative colitis.

Adolescent↗
PubMed1994

Deletion mapping reveals two regions of chromosome 8 allele loss in colorectal carcinomas.

Colorectal carcinogenesis is associated with the accumulation of genetic changes involving both dominant oncogenes and tumor suppressor genes. Although at least four different genes have been implicated in the process, the detection of allele loss from other regions of the genome suggests the involvement of additional genes. The short arm of chromosome 8 is one of these regions; loss of heterozygosity occurs at rates ranging from 30 to 50%. To define the region of common deletion containing the putative tumor suppressor gene, we analyzed a series of 87 carcinomas for allele loss in different regions of the short arm of chromosome 8 by using Southern blot analysis and a panel of polymorphic probes. We found allele loss in 33% of our cases, which involves two separate regions, one in the p-terminal region of the chromosome, 8p23.1-pter, where 45% of informative cases demonstrated loss, and the other in the mid-p region, at 8p21, where 31% of cases showed allele loss. No tumors showed loss of heterozygosity for both regions. These findings suggest the presence of two discrete genes related to colorectal carcinogenesis on the short arm of chromosome 8.

Alleles↗
PubMed1994

Loss of heterozygosity in 8p is associated with microinvasion in colorectal carcinoma.

Loss of heterozygosity (LOH) from the short arm of chromosome 8 is frequent in a variety of malignancies, suggesting the presence of a tumor suppressor gene in this region. Previous studies suggested that this deletion may correlate with higher clinicopathologic stages in colorectal cancer, but others did not support this finding; in part, this difficulty is due to the low heterozygosity of the RFLP markers that were used. Here we report on a preliminary investigation in which we used highly informative microsatellite markers to determine whether deletions of 8p are correlated with poor prognostic features. Paraffin-embedded tumor tissue from 15 patients was analyzed with a panel of three microsatellite markers that are known to be sites of frequent LOH. Fourteen of the 15 cases were informative with at least one marker, and 7 showed LOH. Analysis of clinical features showed that there was no relation of 8p LOH with patient age or tumor stage, grade, location, or pattern of growth. However, a statistically significant correlation was seen between LOH and lymphatic, vascular, or perineural microinvasion (Fisher exact test, P = 0.01). This histologic feature is known to be a stage-independent indicator of prognosis. Our data suggest that 8p LOH may be associated with poor outcome and demonstrate the utility of these microsatellite markers for its detection.

Adenocarcinoma↗
PubMed1994

Analysis of clinicopathologic prognostic features in patients with gastric adenocarcinoma.

BACKGROUND: We evaluated the influence of several clinicopathologic variables on 5-year actuarial survival rate after curative resection of gastric adenocarcinoma. METHODS: Clinical characteristics were retrieved from the records of all patients who underwent gastric resection for curative intent between 1965 and 1986 at The University of Chicago Medical Center, and follow-up was obtained from our tumor registry. Pathologic characteristics were determined from a detailed review of all available histopathologic slides. RESULTS: One hundred seventy-eight patients underwent a curative resection during the study period at our institution. Overall 5-year actuarial survival rate was 29%. The relationship between clinicopathologic variables and 5-year survival rate was evaluated by Kaplan-Meier survival curve construction and chi-squared analysis. Lymphatic and/or capillary microinvasion (absent vs present, p < 0.001), tumor location (antrum and body vs gastroesophageal junction, p = 0.05), local extent of disease (limited to the gastric wall versus involving adjacent organs, p = 0.003), stage (absence versus presence of lymph node metastases, p < 0.001), Lauren type (intestinal versus diffuse, p < 0.01), and Ming type (expanding versus infiltrative, p < 0.02) significantly influenced survival. When a multivariate analysis with logistic regression of 5-year survival was performed, lymphatic and/or capillary microinvasion emerged as the only statistically significant, independent prognostic factor associated with long-term survival (p = 0.039). If microinvasion was omitted from the analysis, lymph node metastases (p < 0.05) and the extension to adjacent organs (p < 0.04) became the only statistically significant variables. Multiple correlation analyses suggested that microinvasion is an early histopathologic finding that correlates with a more aggressive natural history. CONCLUSIONS: Lymphatic and/or capillary microinvasion is a more powerful predictor of 5-year survival than lymph node metastases or tumor extension to adjacent organs. Correlation among clinicopathologic variables suggests that microinvasion may represent an early finding, serving as a potential marker for a biologically more aggressive tumor.

Adenocarcinoma↗