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Effect of calcium supplementation on the risk of large bowel polyps.

BACKGROUND: Clinical trials have shown that calcium supplementation modestly decreases the risk of colorectal adenomas. However, few studies have examined the effect of calcium on the risk of different types of colorectal lesions or dietary determinants of this effect. METHODS: Our analysis used patients from the Calcium Polyp Prevention Study, a randomized, double-blind, placebo-controlled chemoprevention trial among patients with a recent colorectal adenoma. Nine hundred thirty patients were randomly assigned to calcium carbonate (1200 mg/day) or placebo. Follow-up colonoscopies were conducted approximately 1 and 4 years after the qualifying examination. We used general estimating equation (GEE) and generalized linear regression analyses to compute risk ratios and 95% confidence intervals (CIs) to assess the effect of calcium treatment versus placebo on the risk of hyperplastic polyps, tubular adenomas, and more advanced lesions. Additionally, we used GEE analyses to compare the calcium treatment effects for various types of polyps with that for tubular adenomas. We also examined the interaction between calcium treatment and baseline intake of dietary calcium, fat, and fiber. All P values were obtained using Wald tests based on the corresponding models. All tests of statistical significance were two-sided. RESULTS: The calcium risk ratio for hyperplastic polyps was 0.82 (95% CI = 0.67 to 1.00), that for tubular adenomas was 0.89 (95% CI = 0.77 to 1.03), and that for histologically advanced neoplasms was 0.65 (95% CI = 0.46 to 0.93) compared with patients assigned to placebo. There were no statistically significant differences between the risk ratio for tubular adenomas and that for other types of polyps. The effect of calcium supplementation on adenoma risk was most pronounced among individuals with high dietary intakes of calcium and fiber and with low intake of fat, but the interactions were not statistically significant. CONCLUSION: Our results suggest that calcium supplementation may have a more pronounced antineoplastic effect on advanced colorectal lesions than on other types of polyps.

Adenomatous Polyposis Coli↗

Tubo-cornual polyps: their relevance in subfertility.

One-hundred-and-seventy-four patients having hysterosalpingographs during the investigation of infertility have been reviewed to assess the incidence of tubo-cornual polyps and their relation to subsequent pregnancy. Definite polyps were present in 31 (18%) of the patients. There was no significant difference in age or parity in women with and without polyps, nor in associated infertility factors such as tubal occlusion or oligospermia. None of the patients with polyps had endometriosis. Conception rates in the two groups were not significantly different. The cumulative rates at 18 months with and without polyps were 34.5 +/- 13.7% (SE) and 43.6% +/- 3.9% respectively in the overall groups, and 36.9% +/- 24.1% and 59.0% +/- 9.1% in the couples with otherwise unexplained infertility. It is concluded that tubo-cornual polyps are not related to infertility and that they should not be treated.

Adult↗

Hyperplastic polyps of the large bowel.

One hundred seventy-one hyperplastic colonic polyps were examined and found to be less homogenous histologically than has been generally considered. For example, 13% exhibited adenomatous changes, 7.6% contained Paneth cells, and 3% had distinct stalks. They are at times pedunculated and relatively large; some cannot be distinguished grossly from small sessile polyps of other histological patterns and removal is required for proper identification. Other epithelial polyps of equivalent size were compared with the hyperplastic polyps to determine the frequency of the various types. Hyperplastic polyps comprised 43.5% of all surgically removed epithelial polyps of the colon measuring 5 mm or less.

Adult↗

Mucosal ganglioneuromatosis associated with multiple colonic polyps.

Two unusual cases of colonic ganglioneuromatosis are described. One case was associated with multiple adenomatous polyps in a 74-year-old man and the second case was associated with juvenile polyps in a 16-year-old boy. To our knowledge this is the first report of colonic mucosal ganglioneuromatosis associated with multiple adenomatous polyps and the second report associated with multiple juvenile polyps. In the first case the ganglioneuromatosis was found in colonic mucosa without adenomatous changes, while in the second case ganglioneuromatosis was found both within normal mucosa and within juvenile polyps. The relationship between mucosal ganglioneuromatosis and multiple colonic polyps remains unclear. Neither patient has yet developed features to suggest either multiple endocrine neoplasia type 2b or von Recklinghausen's disease.

Adolescent↗

Risk of recurrence of colon polyps.

At Wood Veterans Administration Center, 268 patients who had a polypectomy have been followed up to 20 years with semiannual proctosigmoidoscopic and barium enema examinations. For the present review of benign polyp disease, patients having coexisting carcinoma, chronic inflammatory disease, and those lost to followup have been excluded; 154 patients followed for a mean of 7 years comprise the study group. Thirty per cent of patients developed recurrent polyps. The risk of recurrence during the first year was 16 times that expected in a population of similar age and sex, but thereafter diminished steadily. After 48 months risk of polyp recurrence was little higher than the incidence expected in a normal population. Neither patient age, presenting symptoms nor the site or size of the initial polyp(s) were of any prognostic value regarding recurrence. Patients presenting with a villous adenoma or with more than 3 polyps had a significantly increased risk of recurrence may persist indefinitely. The overall incidence of colonic carcinoma may have been increased, but the location of subsequent cancer was not related to the site of a previously excised polyp.

Adult↗

Endometrial polyps in postmenopausal patients receiving tamoxifen.

The histologic features of an endometrial polyp include irregular, often dilated glands, thick-walled blood vessels, and a fibrotic stroma. Such polyps may be responsive to some chemotherapeutic drugs that can exert hormonal effects. We report on endometrial polyps detected in three postmenopausal patients who were receiving tamoxifen for treatment of metastatic breast carcinoma. The clinical presentation in all cases was vaginal bleeding and all had documented uterine enlargement suggestive of an intrauterine malignancy. The polyps were large, measuring up to 9 cm in largest diameter. On histologic examination each polyp had extensive cystic glandular hyperplasia. In one case foci of atypical epithelial proliferation and predecidualization were noted. The atypical proliferation suggested a borderline neoplastic process and was strongly positive for carcinoembryonic antigen. These findings underscore the marked proliferative changes that can be induced in endometrial polyps in postmenopausal women receiving hormonally active chemotherapeutic agents.

Aged↗

Computed tomography colonography: feasibility of computer-aided polyp detection in a "first reader" paradigm.

OBJECTIVE: : To determine the feasibility of a computer-aided detection (CAD) algorithm as the "first reader" in computed tomography colonography (CTC). METHODS: : In phase 1 of a 2-part blind trial, we measured the performance of 3 radiologists reading 41 CTC studies without CAD. In phase 2, readers interpreted the same cases using a CAD list of 30 potential polyps. RESULTS: : Unassisted readers detected, on average, 63% of polyps > or =10 mm in diameter. Using CAD, the sensitivity was 74% (not statistically different). Per-patient analysis showed a trend toward increased sensitivity for polyps > or =10 mm in diameter, from 73% to 90% with CAD (not significant) without decreasing specificity. Computer-aided detection significantly decreased interobserver variability (P = 0.017). Average time to detection of the first polyp decreased significantly with CAD, whereas total reading case reading time was unchanged. CONCLUSION: : Computer-aided detection as a first reader in CTC was associated with similar per-polyp and per-patient detection sensitivity to unassisted reading. Computer-aided detection decreased interobserver variability and reduced the time required to detect the first polyp.

Adult↗

Resolution of a metaplastic duodenal polyp after cure of Helicobacter pylori infection.

Although there have been several reports of hyperplastic gastric polyps associated with persistent Helicobacter pylori gastritis, the association of H. pylori infection with metaplastic polyps in the duodenum has not hitherto been described. After a 52-year-old man had a single episode of hematemesis, endoscopy showed a smooth polyp 1 cm in greatest dimension formed by a proliferation of gastric epithelial cells of fundic and antral type found in the duodenal bulb. The outer surface was entirely covered with a single layer of hyperplastic columnar epithelium with many H. pylori organisms. After administration of metronidazole 500 mg, omeprazole 20 mg for 4 weeks, and clarithromycin 250 mg twice a day for 2 weeks, endoscopy showed a decrease in size of the duodenal polyp. At 12 weeks there was complete regression of the polyp. This report documents a new and unusual finding: resolution of a gastric metaplastic polyp in the duodenum associated with cure of H. pylori.

Anti-Bacterial Agents↗

Effect of systemic pretreatment with betamethasone on the bacterial flora, inflammatory response, and polyp formation in experimentally infected rabbit maxillary sinus mucosa.

To investigate possible effects of corticosteroids on polyp formation and local bacterial colonization, pneumococcal sinusitis was experimentally induced in rabbits pretreated with betamethasone or saline. After 7 days, macroscopic polyps were counted post-mortem and on histologic slides after serial sectioning. Histologic sections were also examined with light microscopy. Macroscopic polyps were significantly fewer in animals given betamethasone, while there was no difference regarding the number of microscopic polyps. Ingrowth of pathogenic microorganisms was found in five of eight rabbits given placebo but in none of the animals treated with corticosteroids (P < 0.05). The reduced number of pathogenic strains in these animals may be explained by a better-preserved local host defense. The lower number of macroscopic polyps in the same animals could be because of a delayed mucosal repair and subsequent polyp formation.

Animals↗

Nasal polyps in the olfactory cleft.

OBJECTIVES: Nasal polyps frequently arise from the middle meatus in patients with nasal polyposis, but caution is required when polyps are seen protruding from the olfactory cleft. The purpose of this study was to evaluate a method to achieve effective and safe access to the olfactory cleft, and to determine the actual incidence of polyps arising from the olfactory cleft in patients with nasal polyposis. PATIENTS: Eighty-four patients with bilateral or unilateral nasal polyps (n = 143) ranging in age from 16 to 72 years underwent endoscopic sinus surgery in the period from January 1994 to December 1996. METHODS: To observe and gain access to the olfactory cleft, septoplasty combined with endoscopic sinus surgery was needed in patients with nasal polyposis. RESULTS: The endoscopy during the combined septoplasty and endoscopic sinus surgery revealed that 36.4% (n = 52) of bilateral or unilateral nasal polyps (n = 143) arose from the olfactory cleft. Of 52 polyps of olfactory cleft origin, 45 (86.5%) arose from the superior turbinate and/or superior meatus, 32 (67.3%) from the medial side of the middle turbinate, 24 (46.2%) from the anterior face of the sphenoid sinus, and 17 (32.7%) from the mucosa of the nasal septum. CONCLUSIONS: These findings suggest that for surgeries of nasal polyposis an approach to the olfactory cleft as well as to the middle meatus is required.

Adolescent↗

Nuclear factor-kappa B activation in the nasal polyp epithelium: relationship to local cytokine gene expression.

OBJECTIVES: A panel of cytokines has been found to be important for eosinophil accumulation and activation in nasal polyps. The aims of this study were to ascertain whether the activation of nuclear factor-kappa B (NF-kappaB) occurred in the polyp epithelium, and to examine the relationship between the degree of activation and local cytokine gene expression. STUDY DESIGN/METHODS: Nasal polyp specimens were obtained from 26 untreated patients. The proportion of nuclear translocation of the NF-kappaB p50 subunit in the polyp epithelium was quantitatively analyzed by a combination of fluorescent immunohistochemistry and a laser scanning confocal microscope image system. The levels of GM-CSF, IL-5, IL-8, IL-16, and eotaxin mRNA expression in the same speci-mens were measured using reverse transcription-polymerase chain reaction. RESULTS: Both cytoplasmic and nuclear localization of the p50 subunit was observed mainly in the epithelial layer in all specimens. The percentages of epithelial cells with nuclear translocation ranged from 4.5% to 40.5% (median, 18%). Significant correlations were observed between the degree of epithelial NF-kappaB activation and the levels of IL-8, IL-16, and eotaxin mRNA expression (r = 0.468, 0.47, and 0.739, respectively). CONCLUSION: The activation of NF-kappaB in the nasal polyp epithelium is responsible for the recruitment of inflammatory cells, particularly eosinophils, through the initiation of the transcriptional pathway of the related cytokines. The increased NF-kappaB activity in the polyp epithelium may reflect hypersensitivity to unknown stimuli.

Chronic Disease↗

Distribution of 3-nitrotyrosine in the nasal polyps of atopic patients.

OBJECTIVE: To investigate whether formation of nitrotyrosine in the nasal polyps of atopic patients occurs. STUDY DESIGN: A nonrandomized, retrospective, controlled qualitative and quantitative study. METHODS: Nasal polyp tissue samples were acquired from 12 atopic patients. Control fragments of nasal mucosa were taken from 10 patients undergoing corrective surgery of the nasal septum. For routine histologic examinations, hematoxylin-eosin staining was used. Low-magnification microscopy was designed to yield pathologic characteristics and high magnification to quantify the number of eosinophils in the subepithelial connective tissue. Presence of nitrotyrosine was assessed by immunohistochemical method. RESULTS: Hematoxylin-eosin staining revealed presence of numerous eosinophils in the epithelium and in the subepithelial connective tissue. All polyps were characterized by epithelial damage. Nitrotyrosine was present in the eosinophils, in the ciliated cell, and in cells of the damaged epithelium. Goblet cells, glands, and vessels were found to be negative. No significant differences concerning the localization of nitrotyrosine were recognized among the examined nasal polyps. CONCLUSIONS: Nitrotyrosine immunohistochemical staining in nasal-polyp tissues suggested the existence of progressive epithelium injury caused by peroxynitrite. Consequences of peroxynitrite formation in eosinophils remain to be precisely established. The lack of nitrotyrosine in glands and blood vessels indicated that peroxynitrite does not have a significant role in the vascular and glandular dysfunction of nasal polyps.

Adult↗

Nature and significance of colonic polyps.

The concept of inevitable premalignancy in all adenomatous polyps of the colon was challenged as early as 1958, and since that time much debate has centered about the malignant potential of adenomatous polyps of the colon. Current thinking indicates that the majority of colonic polyps fall into one of four categories: hyperplastic, villous adenoma, adenomatous, and villoglandular. Analysis of the present series of 387 colonic polyps removed endoscopically indicates that the villoglandular group has a notable malignant potential, and that the pure adenomatous polyp probably carries a minimal malignant threat. The present series does not challenge the accepted concept that hyperplastic polyps are of no malignant potential, and that villous adenomas are quite frequently malignant at the time of diagnosis.

Colonic Neoplasms↗

Incidence of adenomatous colorectal polyps in cardiac transplant recipients.

BACKGROUND: The present study evaluates the effects of long-term immunosuppression after cardiac transplantation on the risk for adenomatous polyps. METHODS: The endoscopic procedures performed at LDS and University Hospitals in cardiac transplant recipients were reviewed and compared with results from a previously studied control group. RESULTS: A total of 123 endoscopic procedures were performed in 98 heart transplant patients (59% for cancer screening and 41% for gastrointestinal complaints). Eighty-five percent of patients were male and 15% were female; their mean age was 57 years. In the group <3 years posttransplant, adenomatous polyps were present in 25%, hyperplastic polyps were present in 10%, and synchronous lesions in 3 patients. In the group >3 years posttransplant, adenomatous polyps were present in 16%, hyperplastic polyps were present in 22%, and synchronous lesions in were evident in 3 patients. No significant difference with results from a previously studied control group. CONCLUSIONS: Long-term immunosuppression does not increase the risk for adenomatous polyps of the colon.

Adenomatous Polyps↗

Fibroepithelial polyps causing ureteropelvic junction obstruction in children.

PURPOSE: Fibroepithelial polyps are benign mucosal projections that can be found throughout the urinary system. We review our experience with fibroepithelial polyps of the ureteropelvic junction in children to define more clearly this entity and its outcome following treatment. METHODS: We reviewed the records of all children with fibroepithelial polyps causing ureteropelvic junction obstruction treated at our institution between December 1967 and February 2002. RESULTS: Nine patients 6 weeks to 9 years old had 11 ureteropelvic junction obstructions secondary to fibroepithelial polyps, representing a 0.5% incidence of all ureteropelvic junction obstructions seen during that period. The majority of the patients were male (89%) and had obstruction on the left side (78%). Only 22% of the patients had a diagnosis of obstructing polyps suggested preoperatively. All patients underwent dismembered pyeloplasty but 1 required subsequent nephrectomy due to progressive loss of renal function. All lesions were characterized microscopically by polypoid projections of fibrous tissue covered by epithelium and demonstrating varying degrees of inflammation. No recurrences were seen during a mean followup of 44 months. CONCLUSIONS: Fibroepithelial polyps are rare lesions that cause ureteropelvic junction obstruction in children, primarily in males and on the left side. Filling defects were diagnosed preoperatively in 22% of the patients in this series. Excision and dismembered pyeloplasty were curative, and recurrences were not observed. The etiology of this disease remains obscure.

Child↗

Altered expression profile of superoxide dismutase isoforms in nasal polyps from nonallergic patients.

OBJECTIVE/HYPOTHESIS: Nasal polyposis (NP) is a chronic inflammatory disease of the upper respiratory tract. The pathophysiology is unknown but has been shown to be multifactorial. Free radical-mediated damage has been implicated in the pathogenesis of NP. Superoxide dismutases (SODs) are the first and the most important line of antioxidant enzyme defense against reactive oxygen species. Moreover, isozymes of the SOD family are critical for modulating the activity of nitric oxide, a gaseous free radical that is believed to play roles in the physiology and pathology of respiratory tracts. However, the expression profile of SOD isoforms in NP remains unclear. We aimed to investigate the expression profile of the SOD isoforms in nasal polyps from nonallergic patients. STUDY DESIGN: Prospective study. METHODS: Nasal polyp tissues were obtained from eight nonallergic patients who underwent elective polypectomy; mucosal specimens from the middle turbinates were acquired from eight subjects without NP as control tissues. The expression profile of SOD isoenzymes, SOD1, SOD2, and SOD3, in the nasal tissues was determined by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting (WB). RESULTS: NP in all eight of the NP patients manifested as severe or recurrent sinonasal polyposis clinically. The expression pattern of SOD isoenzymes evaluated by RT-PCR analysis indicated that the mean levels of SOD1 mRNA and, to a greater extent, SOD3 mRNA were higher in polyp tissues than in control tissues. There was no significant difference in the expression levels of SOD2 mRNA between the two groups. The data from ELISA and WB analysis showed that there were increased expressions of SOD1 and SOD3 protein in polyp tissues compared with the control tissues, but there was no difference in the expression of SOD2 protein between the two groups. The results from RT-PCR, ELISA, and WB were paralleled and revealed that the expressions of SOD1 and, to a greater extent, SOD3 were higher in polyp tissues than in the control group. CONCLUSIONS: The expressions of SOD3 and SOD1 were higher in polyp tissues. These results are consistent with previously reported data and support the hypothesis that there is increased oxidative stress in NP. Our data also suggest that the SODs might be important in the pathogenesis of NP; however, the roles these SOD isoforms, especially SOD3, play in both normal nasal mucosa and NP require further clarification.

Adult↗

Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points.

The aim of this study was to compare BRAF and KRAS, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status in each of the histologic categories, including end-point carcinomas with residual adenoma, of the serrated polyp neoplasia pathway and the traditional (nonserrated) adenoma-carcinoma sequence. Deoxyribonucleic acid (DNA) was extracted from the selected samples and assayed for BRAF, KRAS2 codon12, 13, CIMP using markers hMLH1, MGMT, MINT1, MINT2, p16, and MSI using an assay for BAT25 and BAT26. A BRAF mutation was present in 82% of serrated carcinomas (SCas), 62% of serrated adenomas (SAs), 83% of serrated polyps with abnormal proliferation (SPAPs-syn. sessile serrated adenoma [SSA]), 76% of microvesicular serrated polyps (MVSPs), and was not found in any of the histologic categories of the traditional adenoma-carcinoma sequence. KRAS2 mutations were found in 43% of the goblet cell serrated polyp (GCSP) category, 13% of MVSPs, 7% of SPAPs, and 24% of SAs; in 26% of large traditional adenoma (lTAs) compared with small traditional adenomas (sTAs) (0/30; P<0.005) and in 37.3% of traditional carcinomas (TCa). CIMP-H (>1 marker positive) was significantly more frequent in SPAP, SA, and SCa compared with MVSP (P<0.05); CIMP-H was present in 10% of sTAs but was found more frequently in lTA (44.4%; OR 7.2; P=0.007) and TCa (38.9%; OR 5.8; P=0.007). Higher CIMP levels (4 or more markers positive) were significantly more frequent in advanced categories of the serrated pathway (SAs [31%] and SCas [30%]) compared with lTAs [0%] and TCAs [3.4%] (OR 12.2; P=0.02). MSI-H was identified only in the adenocarcinoma component of SCas (9/11) or in the contiguous SAs (3/7). The findings indicate that a BRAF mutation is a specific marker for a serrated polyp pathway that has its origin in a hyperplastic polyp (MVSP) and a potential end point as MSI carcinoma. CIMP-High (CIMP-H) develops early in this sequence and MSI-H develops late. The data provided a less complete picture of a second serrated pathway, identified by a KRAS2 mutation in SAs, but showed that the progressive stages of both iterations of the serrated neoplasia pathway are separate and distinct from those of the traditional adenoma-carcinoma sequence.

Adenocarcinoma↗

Primary diffuse large B-cell lymphoma of the uterus presenting solely as an endometrial polyp.

We report a primary diffuse large B-cell lymphoma of endometrial polyp in a 44-year-old woman who presented with irregular vaginal spotting and was found to have a polyp protruding from the cervical os. Histology of the polyp showed an atypical diffuse infiltration by large, mononuclear cells within the stroma and between endometrial glands in one of the polypoid fragments. Immunohistochemistry and testing for immunoglobulin heavy chain gene rearrangement showed a B-cell lineage, consistent with diffuse large B-cell lymphoma. Staging procedures including detailed gynecology examination, body computed tomography scan, and bone marrow examination, as well as total hysterectomy, showed no evidence of lymphoma outside of the polyp. To our knowledge, this represents the first well-documented instance of primary lymphoma of the uterus presenting as an endometrial polyp. The differential diagnosis of endometrial biopsies containing an atypical lymphoid infiltrate should include the rather rare possibility of primary uterine lymphoma arising in an endometrial polyp. Immunohistochemistry and/or molecular analysis for antigen receptor gene rearrangements are critical in arriving at the correct diagnosis.

Adult↗