PubMed Health⌕ Search

Biomedical subjects

R D Odze

Publications and source records attributed to R D Odze.

46 records · Page 3Linked to original sources
PubMed1995

Growth factor expression and proliferation kinetics in periampullary neoplasms in familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis develop periampullary adenomas at a high rate. However, little is known regarding the factors that control the growth, the natural history, or the malignant potential of these tumors. METHODS: In this study, the authors systematically evaluated the expression of the intestinal peptide growth factor, transforming growth factor-alpha (TGF-alpha), and its corresponding receptor, epidermal growth factor-receptor (EGF-R), in 49 periampullary adenomas and 6 periampullary carcinomas from 29 patients. Tumor proliferation rates were evaluated with the MIB-1 antibody. RESULTS: All periampullary adenomas and carcinomas (100%) had TGF-alpha expression, whereas 63% of adenomas and 67% of carcinomas expressed EGF-R. The extent of TGF-alpha expression was greater in carcinomas compared with adenomas and increased progressively in adenomas relative to the degree of dysplasia and villous architecture of these lesions. The extent of EGF-R expression correlated only with the degree of dysplasia in adenomas. With regard to proliferation kinetics, higher MIB-1 labeling indices were observed in adenomas that were larger, more severely dysplastic, and villous. Transforming growth factor-alpha, and to a lesser extent, EGF-R expression, correlated directly with the MIB-1 labeling indices. CONCLUSIONS: These results support the adenoma-carcinoma sequence in the progression of malignancy in the duodenum in familial adenomatous polyposis, suggesting a possible involvement for TGF-alpha and EGF-R expression in this process.

Adenoma↗
PubMed1995

Somatic APC and K-ras codon 12 mutations in periampullary adenomas and carcinomas from familial adenomatous polyposis patients.

Periampullary adenomas in the duodenum of Familial Adenomatous Polyposis (FAP) patients are among the most frequent and clinically important extracolonic neoplasms in FAP. The purpose of this study was to characterize the frequency and nature of somatic adenomatous polyposis coli (APC) gene and K-ras codon 12 mutations in periampullary adenomas and carcinomas in FAP. These molecular changes have been shown to be important during the early stages of colorectal carcinogenesis. DNA was prepared from endoscopic periampullary biopsies and paraffin blocks from 49 FAP patients. Of 143 samples, 77 were histologically normal, 29 were biopsies from small periampullary adenomas, 29 biopsies were from 19 large adenomas and eight samples were from periampullary cancers. APC mutations in the mutation cluster region and K-ras codon 12 mutations were detected by polymerase chain reaction based techniques. Somatic APC mutations consisting of deletions at codons 1464 and 1465 were detected in one small and two large periampullary adenomas. Loss of heterozygosity was seen in one periampullary carcinoma. K-ras codon 12 mutations were detected in seven of 19 large periampullary adenomas and in one of eight periampullary carcinomas. These data suggest that K-ras codon 12 mutations may be important during periampullary tumorigenesis in FAP but somatic APC mutations in the mutation cluster region are infrequent. Local environmental factors in the duodenum may contribute to differences in the molecular changes which occur during the adenoma-to-carcinoma sequence in periampullary compared to colonic tumorigenesis.

Adenoma↗
PubMed1995

Epithelial proliferation and differentiation in flat duodenal mucosa of patients with familial adenomatous polyposis.

The colonic mucosa in patients with familial adenomatous polyposis (FAP) exhibits altered epithelial cell proliferation, differentiation, and mucin histochemical properties compared with unaffected controls. However, little is known regarding these parameters in FAP-associated duodenal mucosa, an area in which adenomas also develop at a high rate. The purpose of this study is to evaluate the morphologic, mucin histochemical, and proliferative characteristics of the epithelium in the flat duodenal mucosa from 32 patients with FAP (18 with and 14 without adenomas), and compare the results with those observed in 18 non-FAP age-matched controls. The proliferative properties of the epithelium were analyzed immunohistochemically with the MIB-1 antibody, which recognizes the Ki-67 proliferation-associated nuclear antigen in formalin-fixed tissue. No significant differences were detected with regard to the mucin histochemical properties (sialomucins, sulfomucins, and o-acylated sialomucins) or the proliferative characteristics of the duodenal epithelium in FAP versus non-FAP controls. However, FAP-associated duodenal epithelium showed a significant increase in the number of Paneth cells (P = 0.04) and endocrine cells (P = 0.01) per crypt in comparison with controls. This specialized cell hyperplasia occurred in the flat mucosa of FAP patients regardless of the presence or absence of adenomas and may represent a primary defect in the regulation of stem cell differentiation in the duodenum in FAP.

Adenomatous Polyposis Coli↗
PubMed1994

Prospective evaluation of early morphological changes in pelvic ileal pouches.

BACKGROUND/AIMS: Little is known about the evolution of morphological changes in pelvic ileal-pouch mucosa. This study evaluates prospectively the sequence of early morphological, histochemical, and phenotypic features in pouch mucosal biopsy specimens. METHODS: Twenty-two patients with pelvic ileal pouches constructed after total colectomy for chronic ulcerative colitis had biopsies performed at the time of ileostomy closure and after 6 weeks and 6 months of pouch function and were evaluated to assess the type and degree of inflammation, villus atrophy, Paneth's cell hyperplasia, mucin histochemical changes, the mucosal proliferative activity using the murine monoclonal antibody 1 (MIB-1), and the expression of the enzyme sucrase-isomaltase. RESULTS: Early changes (6 weeks) were characterized by neutrophilic and eosinophilic inflammation, mild villus atrophy, Paneth's cell hyperplasia, a partial transition to colonic mucin phenotype, and an increased MIB-1 proliferation index. These features remained relatively stable after 6 months, except for a greater degree of mononuclear infiltration, a progressive increase in the degree of eosinophilic inflammation and a new higher steady state level of crypt epithelial kinetics. Expression of sucrase-isomaltase remained stable. CONCLUSIONS: Pelvic ileal pouches develop inflammatory, phenotypic, and kinetic changes early in the course of function but have only a limited potential for colonic type metaplasia. The persistence of these changes is evidence in support of an adaptive response to a new luminal environment.

Adolescent↗
PubMed1993

Comparative dual label study of first and second generation antitumor-associated glycoprotein-72 monoclonal antibodies in colorectal cancer patients.

Radiolabeled first-generation anti-tumor-associated glycoprotein-72 (TAG-72) monoclonal antibody (MAb), B72.3, has proven useful in detecting primary and secondary colorectal carcinoma. It has been anticipated that the development of second-generation, higher affinity, anti-TAG-72 MAbs, CC49 and CC83, would be of greater use in cancer detection and of value in radioimmunotherapy of human cancer. We compared the pharmacokinetics, biodistribution, and immune responses of 131I-labeled CC49 and CC83 to 125I-labeled B72.3 by preoperatively coninjecting dual-labeled MAbs into 16 colorectal cancer patients. The imaging properties of radiolabeled CC49 and CC83 were also assessed. Pharmacokinetics of all three MAbs were identical, and there were no differences in the uptake of any of three MAbs in tumor and normal tissues. Maximum tumor uptake was 0.0041% of the injected dose/g for 125I-B72.3, 0.0024% for 131I-CC49, and 0.0029% for 131I-CC83. Radiolabeled CC49 and CC83 detected most known tumor sites on scintigrams without any clear advantage for either MAb. Nonspecific splenic and testicular uptake was frequently observed. Anti-idiotypic human anti-mouse antibody responses were seen more frequently with B72.3 than with CC49 or CC83. We conclude that higher affinity, radiolabeled anti-TAG-72 MAbs can detect colorectal cancer but do not penetrate these tumors more effectively than B72.3. Improvements in tumor detection and radioimmunotherapeutic strategies will likely require the administration of smaller fragments of MAb molecules or novel delivery systems rather than the continued development of higher affinity MAbs.

Adult↗
PubMed1993

Advanced gastroduodenal polyposis with ras mutations in a patient with familial adenomatous polyposis.

Upper gastrointestinal polyps are being recognized with increasing frequency in patients with familial adenomatous polyposis. Duodenal and periampullary adenomas are the most common type and have poorly understood but definite malignant potential. In contrast, the majority of polypoid lesions in the stomach are benign fundic gland polyps. We report a patient with familial adenomatous polyposis who developed dysplasia in a large exophytic hyperplastic gastric tumor that appeared to arise on a background of diffuse fundic gland polyposis and presented with anemia, hypoalbuminemia, and a protein-losing enteropathy. A large periampullary adenoma also was present. Using the polymerase chain reaction with mismatched primers, a GGT to TGT Kras codon 12 mutation was detected within areas of severe dysplasia in the gastric tumor and in the periampullary adenoma. This case serves to further highlight the spectrum of clinical, pathologic, and molecular features of premalignant upper gastrointestinal tract lesions in patients with familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1993

Allergic proctocolitis in infants: a prospective clinicopathologic biopsy study.

Allergic proctocolitis is a major cause of rectal bleeding in infants, but its clinical features and laboratory results are often nonspecific. Our previous retrospective study demonstrated that large numbers of eosinophils in colonic mucosal biopsy specimens were highly associated with cases of allergic proctocolitis. Therefore, we prospectively examined 60 colonic mucosal biopsy specimens from the same sites (4, 8, and 12 cm from the anal verge) in 20 infants with clinically confirmed allergic proctocolitis to validate this morphologic feature, to characterize its distribution, and to correlate these data with the clinical information. The patients (age range, 4 to 304 days) were fed breast milk or a variety of formulas and all presented with rectal bleeding. Sigmoidoscopic examination was abnormal in 19 cases, typically characterized by focal areas of mucosal erythema. The major histologic finding was a strikingly focal increase in the number of eosinophils in all mucosal compartments, with a predilection to aggregate in close association with lymphoid nodules. Eosinophilic infiltration varied not only between biopsies at different sites, but also within individual biopsy specimens. Only 12 of 20 patients (60%) had all three of their biopsy specimens categorized as abnormal; in the remainder, only one (four patients) or two (four patients) of the three biopsy specimens were abnormal. The average number of eosinophils per high-power field of lamina propria for all cases was 15.6. No significant correlation was identified between the number of eosinophils in the mucosa and the patient's age, length of illness, endoscopic appearance, or type of inciting formula. In summary, eosinophils appear to be an excellent marker for infantile allergic proctocolitis. Given the focal distribution of the eosinophils, multiple mucosal biopsy specimens should be obtained and several levels of each examined to confirm the diagnosis.

Biopsy↗
PubMed1991

Peptic-ulcer-induced aortoenteric fistula. Report of a case and review of the literature.

A 71-year-old woman with a remote history of esophagogastric resection for malignancy developed abdominal pain, nausea and vomiting. She died of shock 15 days after admission, during which time clinical investigation failed to reveal recurrent tumor or an ulcer. The autopsy revealed massive exsanguination secondary to a peptic-ulcer-induced aortoenteric fistula (AEF). The ulcer involved the third portion of the duodenum, was chronic, and complicated by growth of fungus. We review the literature on peptic-ulcer-related AEF.

Aged↗