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PubMed2006

Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms and risk of colorectal polyps.

Prostacyclin synthase (PGIS) and arachidonate 5-lipoxygenase (ALOX5) are enzymes relevant to prostaglandin and leukotriene synthesis, both important pathways for colon cancer risk. We hypothesized that genetic variation altering the function of these enzymes would modify risk of colorectal polyps. In a Minnesota-based case-control study of adenomatous (n = 517) or hyperplastic (n = 192) polyps versus polyp-free controls (n = 618), we investigated the role of promoter repeat polymorphisms in PGIS and ALOX5 as well as ALOX5 -1700 G>A. Having fewer than six repeats on both PGIS alleles (<6R/<6R) was associated with an increased risk of adenomas compared with the 6R/6R (wild-type) genotype (OR, 1.90; 95% CI, 1.09-3.30). Having more repeats (>6R/> or =6R) reduced risk (OR, 0.73; 95% CI, 0.40-1.35; P(trend) = 0.03). In allele-based analyses, fewer repeats were associated with a modestly increased risk of adenomas and perhaps hyperplastic polyps. There were no risk differences for either the ALOX5 VNTR or -1700 G>A polymorphisms. Associations with regular use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) differed by PGIS genotype. Among individuals with at least one wild-type allele, NSAID use was associated with a decreased risk; however, those with fewer PGIS repeats (<6R/<6R) did not benefit (P(interaction) = 0.06). There was also evidence of an interaction between the COX-2 -765 G>C and ALOX5 -1700 G>A genotypes (P(interaction) = 0.07). The PGIS promoter polymorphism may affect risk of colorectal polyps and modify the effects of NSAID use on polyp risk. A more comprehensive investigation of genetic variability in prostaglandin synthesis in relation to risk of colorectal neoplasia and NSAID pharmacogenetics is warranted.

Adenomatous Polyps↗
PubMed1998

Growth and recurrence of colorectal polyps: a double-blind 3-year intervention with calcium and antioxidants.

BACKGROUND: Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer. This has been supported by animal experimental studies, case control and cohort studies. MATERIALS AND METHODS: In a prospective intervention study of colorectal adenomas, and intermediary stage in colorectal carcinogenesis, 116 polyp-bearing patients received a placebo-controlled daily mixture of beta-carotene 15 mg, vitamin C 150 mg, vitamin E 75 mg, selenium 101 microg, and calcium (1.6 g daily) as carbonate for a period of 3 years with annual colonoscopic follow-up to test if the mixture was able to reduce polyp growth or recurrence. All polyps of < 10 mm at enrollment or follow-up were left unresected until the end of the study. RESULTS: 87-91% of the patients attended the annual endoscopic follow-up investigations, and 19% of the patients dropped out of the medical intervention. The rest consumed 85% of the total amount of tablets over the 3 years. The fecal calcium concentration was 2.3-2.7 times higher in patients taking active medication compared to the placebo group. Diet registration showed that, when adding the intake of antioxidants and calcium from diet and intervention, there was a significant difference between the intake of these substances in the active and the placebo group. No difference was detected in the growth of adenomas between the active and the placebo group from year to year and for the total study period. Moreover, there was no effect on polyps of < 5 or 5-9 mm, or on polyps in the different colonic segments analyzed separately. A reduced growth of adenomas was found in patients <60 years of age taking active medication (n = 8) compared to those taking placebo (n = 6; mean difference 2.3 mm; 95% CI 0.26-4.36). There was a significantly lower number of patients free of new adenomas in the placebo group compared to those taking active medication as tested by logistic regression and Kaplan-Meier analysis (log-rank test p value 0.035). Subgroup analysis showed that only the group of patients with no family history of colorectal cancer, those with only one adenoma at inclusion, and those <65 years benefitted from the intervention medication. CONCLUSION: The study did not find an overall effect on polyp growth. Our data, however, may support a protective role of calcium and antioxidants on new adenoma formation.

Adenoma↗
PubMed1987

Comparison of arachidonic acid metabolism in nasal polyps and eosinophils.

Nasal polyp tissue is characterized by its frequent infiltration by large numbers of eosinophils. We have studied the metabolism of 14C-labeled arachidonic acid by both nasal polyp tissue and by eosinophils. The major metabolite produced by both is 15-hydroxyeicosatetraenoic acid (HETE) with lesser amounts of 12-HETE. No cyclooxygenase pathway products were found. The 15-lipoxygenase activity of nasal polyps averages 30 times that of normal nasal mucosa or chronically inflamed sinus mucosa. Nasal polyps which contained significant numbers of eosinophils averaged 7 times the 15-lipoxygenase activity of nasal polyps without eosinophilia. Thus, eosinophils appear to be a major source of 15-lipoxygenase activity in nasal polyps.

Arachidonic Acid↗
PubMed1992

Evidence of platelet-activating factor in nasal polyps.

Platelet-activating factor (PAF) was measured in human nasal polyps obtained from patients with chronic sinusitis. PAF was quantitated by platelet-aggregating activity and was found to be 7.8 +/- 1.8 pg/micrograms phosphorus of polyp phospholipid (mean +/- SE; n = 23). In the polyps, phosphatidylcholine constituted 30% of the total phospholipids, of which 8.5% was the ether-linked type. Incubations of replicates of the fresh polyps in Tyrode's solution in the presence of calcium ionophore A23187 and antihuman immunoglobulin E resulted in 295 and 65% increases in the amount of PAF, respectively. Thus, nasal polyps in humans with chronic sinusitis possess PAF and have the potential to produce PAF upon stimulation. The participation of PAF in nasal polyp formation is discussed.

Adolescent↗
PubMed1992

Ear polyps in posterior superior retraction pockets, herodion. Histopathological and pathogenetic aspects.

Histopathological characteristics of 20 ear herodion polyps with a certain localisation and a well-known underlying pathological process were studied in order to elucidate the pathogenesis of ear mucosal polyp formation. Only 12 of the polyps were covered with epithelium; either a squamous keratinized epithelium or a cylindrical epithelium. Three polyps were covered with cylindrical and squamous keratinized epithelium. Incipient gland formation was seen and glands were only found in 35% of the polyps. It seems possible that the polyp is a local newly formed process and may have the aim of catching, eliminating and digesting bacteria and dead cells.

Adolescent↗
PubMedDate not supplied

Expression of vasoactive intestinal peptide, substance P and bombesin-flanking peptide in nasal polyps.

The presence of neuropeptide-containing sensory, parasympathetic and sympathetic nerves in human nasal mucosa is well established. However, information regarding the neuropeptide distribution in nasal polyps is still lacking. The aim of this study was to compare immunohistologically the presence and distribution of substance P (SP), vasoactive intestinal peptide (VIP) and bombesin-flanking peptide (BFP) in normal nasal mucosa and nasal polyps. The expression was studied using Formalin-fixed and paraffin-embedded biopsy sections from 20 patients with nasal polyps and 10 controls with normal nasal mucosa from the anterior part of the inferior turbinate. Indirect immunohistochemistry (APAAP method) with mono- and polyclonal antibodies was used. None of the control group but 5 patients of the nasal polyp group had an atopic disease. Comparing localization and intensity of the immunohistological reaction in nasal mucosa and nasal polyp tissue, there was no difference in the expression of the three neuroendocrine substances. There was no difference of expression in the polyposis group itself concerning allergic and nonallergic subjects. The results indicate that VIP, SP and BFP have an equal distribution in nasal polyps and normal nasal mucosa.

Adult↗
PubMed1994

Cervical polyp: evaluation of current treatment.

The removal of a cervical polyp is routinely accompanied by a fractionated dilatation and curettage (D&C) in various institutions. In order to assess the necessity of performing a D&C on all the patients admitted with the diagnosis of a cervical polyp, we reviewed the charts of 362 patients admitted for a cervical polypectomy and D&C during a 5-year period. The procedure was performed on a day clinic basis under general anesthesia. No serious complications were noted. In 218 women (60%) the discovery of the cervical polyp was incidental and in this group no malignant change was found in the polyp or in the endometrium. Six cases of atypical hyperplasia and 2 cases of adenocarcinoma of the endometrium were found in the symptomatic group of patients (40%). Removal of the polyp as an outpatient procedure is recommended of the asymptomatic patient. Hospitalization and removal of the polyp under general anesthesia, accompanied by D&C should be reserved for the symptomatic patients only, or even then, replaced by ambulatory polypectomy and endometrial sampling.

Adult↗
PubMed2001

Nasal polyp-derived superoxide anion: dose-dependent inhibition by nitric oxide and pathophysiological implications.

The epithelium of the paranasal sinuses produces nitric oxide (NO), which probably plays a major role in the nonspecific defense of these cavities through its bacteriostatic and cilia motility stimulation properties. Abundant eosinophils of nasal polyps potentially generate superoxide anion (O2-*), but NO and O2-* inactivate reciprocally. The purpose of the present work was to evaluate the relationship between NO concentrations and nasal polyp production of O2-*. Polyp fragments from 24 patients were studied using histological examination and lucigenin-enhanced chemiluminescence (to assess O2-* production). The effect of various concentrations of exogenous NO on chemiluminescent signals was assessed. Basal and phorbol ester-stimulated O2-* production varied largely among patients, but both were highly related to eosinophilic infiltration. A slow releasing NO donor DETA NONOate (DETA/NO NOC-18) dose dependently inhibited lucigenin-enhanced chemiluminescence from phorbol ester-stimulated polyp fragments, with an EC50 of 1.5 mM. The NO concentration in normal maxillary sinus was estimated about 10 ppm (i.e., 0.5 microM in aqueous phase) (Lundberg, et al. Nature Med 1995;1:370). Calculations revealed that the DETA NONOate 0.75 mM and 1.5 mM generate steady-state concentrations of NO of 0.5 microM and 2.5 microM, respectively. In conclusion, the NO concentration present in paranasal sinuses appears to partially suppress (approximately 20-40%) O2-* production from polyp eosinophils. Conversely, phagocytic-derived O2-* could contribute to decrease sinus NO concentration, further altering this natural local defense. Together, these events could participate in chronic inflammation and contribute to the pathophysiology of nasal polyps.

Acridines↗
PubMed2006

Human nasal polyp microenvironment maintained in viable and functional states as xenografts in SCID mice.

OBJECTIVES: We undertook to maintain human nasal polyp tissue in a viable and functional state in SCID (severe combined immunodeficiency) mice. METHODS: Small, nondisrupted pieces of human nasal polyp tissues were subcutaneously implanted into SCID mice depleted of natural killer cells. The resulting xenografts were examined histologically, and the sera were evaluated for the presence of human protein. RESULTS: The original histologic architecture of the polyp was maintained in the xenografts. The tissues, including pseudostratified columnar epithelial-lined polyps and subepithelial stroma, remained viable, and goblet cells continued to produce mucin for up to 26 weeks after engraftment. Human inflammatory leukocytes, including CD3+ T cells, CD20+ B cells, CD138+ plasma cells, and CD68+ monocytes and/or macrophages, were present. Identification of human immunoglobulin and human interferon-gamma in the sera of xenograft-bearing mice indicated that the B cells or plasma cells and T cells within the xenografts remained functional for 2 weeks after engraftment. CONCLUSIONS: The ability to engraft and maintain nasal polyps provides an in vivo human/mouse chimeric model with which to investigate the role of inflammatory leukocytes and stromal cells in the maintenance and progression of polyposis and to determine how exogenous cytokines may alter the interaction of inflammatory cells, stromal cells, and epithelial cells in the polyp.

Animals↗
PubMed1998

Keratinocyte growth factor and its receptor messenger RNA expression in nasal mucosa and nasal polyps.

To examine the potential biologic role of fibroblast growth factors (FGFs) in nasal polyps and nasal mucosa during chronic inflammatory conditions, we investigated messenger RNA (mRNA) expression of three members of the FGF family -- acidic FGF, basic FGF, and keratinocyte growth factor (KGF)-- in nasal polyp tissues, as well as in hyperplastic nasal mucosa. Using the sensitive method reverse transcription-polymerase chain reaction (RT-PCR), we demonstrated that of the examined FGFs, KGF had the most abundant mRNA expression in nasal polyps and nasal mucosa. We also found that significantly higher levels of KGF mRNA were expressed in nasal polyps than in nasal mucosa, whereas mRNA expression of acidic FGF and basic FGF was relatively low in these tissues. In addition, we showed that KGF receptor mRNA was present in most of the nasal mucosa; however, none or little was expressed in nasal polyps. These results suggest that KGF might play an important role in nasal epithelial proliferation and that excessive synthesis of KGF in nasal polyp stroma may contribute to hypertrophy of the nasal mucosa in patients with chronic sinusitis associated with nasal polyposis.

Adult↗
PubMed1989

Nasal polyps: a manifestation of allergy?

The cause of nasal polyps is speculative. In the 1930s nasal polyps were considered to be a manifestation of allergy. This theory was challenged in the 1970s. Many patients with nasal polyps have no identifiable allergic disease. The purpose of this study is to better define the relationship between allergy and nasal polyps. Twelve patients with nasal polyps were evaluated by history, physical examination, skin testing, nasal smear for eosinophils, specific IgE determination from serum, nasal secretions, and nasal polyp fluid. Similar data were collected from three control groups: (1) 10 patients with allergic rhinitis, (2) 10 patients with nonallergic rhinitis, and (3) 10 patients with no known nasal disease. By comparing the incidence of markers for allergic disease in patients with nasal polyposis to each of the three control groups, the role of allergic disease in nasal polyposis was delineated.

Adult↗
PubMed1995

Inflammatory bronchial polyps associated with asthma: resolution with inhaled corticosteroid.

In a 50 year old man who complained of cough and sputum, a small endobronchial tumour was found in the left main bronchus and was biopsied via bronchoscopy. The histological diagnosis was inflammatory polyp with marked infiltration of eosinophils. Six years later, the patient developed asthma. At the same time, another polyp was found in the posterior basal bronchus of the right lower lobe. The appearance of the first polyp was unchanged endoscopically and histologically. Inhalation of beclomethasone dipropionate, 200 micrograms b.i.d., was started and symptoms of asthma soon subsided. In addition, the two polyps regressed and eventually disappeared after one year of treatment. Inhaled corticosteroids, being noninvasive and relatively safe, appear to be a possible therapeutic option in inflammatory bronchial polyps, especially in cases where the patient has asthma as an underlying condition, or the polyps are small and their management is not urgent.

Administration, Inhalation↗
PubMed2003

Antral hyperplastic polyp causing intermittent gastric outlet obstruction: case report.

BACKGROUND: Hyperplastic polyps are the most common polypoid lesions of the stomach. Rarely, they cause gastric outlet obstruction by prolapsing through the pyloric channel, when they arise in the prepyloric antrum. CASE PRESENTATION: A 62-year-old woman presented with intermittent nausea and vomiting of 4 months duration. Upper gastrointestinal endoscopy revealed a 30 mm prepyloric sessile polyp causing intermittent gastric outlet obstruction. Following submucosal injection of diluted adrenaline solution, the polyp was removed with a snare. Multiple biopsies were taken from the greater curvature of the antrum and the corpus. Rapid urease test for Helicobacter pylori yielded a negative result. Histopathologic examination showed a hyperplastic polyp without any evidence of malignancy. Biopsies of the antrum and the corpus revealed gastritis with neither atrophic changes nor Helicobacter pylori infection. Follow-up endoscopy after a 12-week course of proton pomp inhibitor therapy showed a complete healing without any remnant tissue at the polypectomy site. The patient has been symptom-free during 8 months of follow-up. CONCLUSIONS: Symptomatic gastric polyps should be removed preferentially when they are detected at the initial diagnostic endoscopy. Polypectomy not only provides tissue to determine the exact histopathologic type of the polyp, but also achieves radical treatment.

Endoscopy, Gastrointestinal↗
PubMed2004

Nuclear accumulation of beta-catenin occurs commonly in the epithelial cells of juvenile polyps.

In the two conditions juvenile polyps (JPs) and juvenile polyposis coli (JPC), colonic polyps may have overlapping histologic and phenotypic appearance, but JPC confers a significant risk for colon adenocarcinoma. Although not thought to contain adenomatous polyposis coli (APC) mutations, the status of beta-catenin and full-length APC protein expression in JPs is not known. We evaluated beta-catenin and full-length APC protein expression in JPs from children with JPs and JPC. Cases were identified through endoscopic procedure records. Immunohistochemistry was performed for beta-catenin and full-length APC protein. Loss of heterozygosity at the APC gene locus on chromosome 5 was assessed using two APC-linked microsatellite markers. Polyp and normal colonic tissue were analyzed from 36 children with JPs and 9 with JPC. Both APC and beta-catenin immunoreactivity were present in epithelial cells from all samples but in different patterns. In all normal colon and polyp samples, APC expression was cytoplasmic with maximal immunoreactivity in the goblet cells. In contrast, beta-catenin immunoreactivity in epithelial cells was limited to the plasma membrane in normal colon but was both cytoplasmic and nuclear in all 45 JPs. No evidence of APC gene loss of heterozygosity was found. In polyps from children with JPs and JPC, nuclear beta-catenin accumulation is a consistent feature, and it is not due to APC gene mutation or loss of full-length APC protein expression. Thus, beta-catenin accumulation may be intrinsic to the formation of juvenile-type polyps through an as-yet-undefined mechanism.

Adenomatous Polyposis Coli Protein↗
PubMed2002

Surface structures of aural polyps: a scanning electron microscopic study.

Surfaces of aural polyps collected from 30 patients were examined by scanning electron microscopy. In the polyps not associated with cholesteatoma, the epithelial lining showed individually variable metaplasia towards cuboidal 'cobblestone'-type and squamous epithelium covered with microvilli of various shapes and sizes. Squamous epithelium was present on the surface of all polyps with underlying cholesteatoma, with superficial cells possessing elongated microvilli, microplicae of different sizes, grooves and pits. Such surface structures reflect different stages of the keratinization process that seems to be characteristic for the epithelial lining of polyps with underlying cholesteatoma. Incomplete epithelium accompanied by granulation tissue was found in several polyps; in two cholesteatoma-associated polyps plate-like cholesterol crystals were observed.

Adolescent↗
PubMed1979

Histamine, norepinephrine and serotonin content of nasal polyps.

Histamine, norepinephrine and serotonin were assayed and localized by fluorescence histochemistry in normal mucosa and nasal polyps because of their possible role in the development of inflammation and edema. Histamine was present in greater concentration in nasal polyps than in normal mucosa. Norepinephrine was present primarily in the base of nasal polyps and in greater concentration than in normal mucosa. Patients with aspirin sensitivity and asthma had much lower histamine concentrations in their nasal polyps than all other patients with nasal polyps. A proposal for a possible mechanism of formation of nasal polyps based on vascular and inflammatory mechanisms and incorporative roles for histamine and norepinephrine is presented.

Adolescent↗
PubMed2002

Nasal polyps in cystic fibrosis: clinical endoscopic study with nasal lavage fluid analysis.

STUDY OBJECTIVES: Nasal polyps frequently appear in patients with cystic fibrosis (CF). The aims of this study were to focus on what problems (symptoms, endoscopic findings, and laboratory correlates) nasal polyps cause the CF patient, and how these correlate to the total health situation of this patient group. PATIENTS AND STUDY DESIGN: The clinical histories, endoscopic investigations of the nasal cavity, and analyses of nasal lavage fluid of 44 patients with CF complicated with nasal polyposis have been compared with those of 67 CF control subjects. The patients were examined at annual control examinations (with pulmonary tests, working capacity, liver tests, and bacterial and blood tests) from 1995 to 1996 at Stockholm Cystic Fibrosis Center, Huddinge University Hospital. All patients were > 2 years of age. The endoscopic findings were related to the actual pulmonary function, inflammatory blood parameters, colonizing pathogens, antibodies (Staphylococcus aureus and Pseudomonas aeruginosa), and genotype. RESULTS: The patients with nasal polyps differed with respect to chronic colonization of P aeruginosa in sputum samples and had a higher occurrence of serum antibodies against the same species. The two groups did not differ in pulmonary functions, inflammatory parameters, or genotype. The polyps found were mainly small (within the meatus media) and gave no significant increase in ongoing clinical symptoms such as rhinorrhea, nasal obstruction, or hyposmia. Neither was any significantly marked finding concerning the nose (mucosal swellings, secretion, etc.) made in the polyp patients. The patients with CF scored slightly lower in a smell identification test in comparison with the healthy control group. The nasal lavage fluid was analyzed (in 93 of the 111 patients) for the occurrence of P aeruginosa (by polymerase-chain reaction [PCR]), interleukin [IL]-5, IL-8, and lysozyme. The lysozyme and IL-8 content was equal in the two CF groups but increased in comparison with the healthy control group. P aeruginosa was not detected with PCR in any nasal lavage fluid. No measurable levels of IL-5 in the nasal lavage were found. CONCLUSIONS: There was a higher frequency of chronic colonization of P aeruginosa in the lower respiratory tract in patients with nasal polyps. Otherwise, nonsevere nasal polyposis was not an indicator of lower respiratory tract morbidity in CF patients.

Adolescent↗
PubMed1976

Further studies on lipid-chemical differences between cancerous and adenomatous polypous tissues in the human large intestine.

17 cases of cancer and 18 cases of adenomatous polyp in the large intestine were subjected to lipid-chemical studies of their tissues in order to clarify the biochemical differences between malignant neoplastic growth and benign growth. Cancerous and adenomatous polypous tissues were collected by biopsy or surgical operation together with the respective control tissues. One part of the total lipid extracted from each tissue was separated into triglyceride and phospholipid fraction by a thin-layer chromatography (TLC). The fatty acid composition and content of each lipid fraction were measured by a gas-liquid chromatography (GLC). When the fatty acid composition of a phospholipid was expressed in terms of the deviation rate, that of C14:0 was remarkably increased and that of C20:4 was remarkably decreased in the cancerous cases as compared with the respective values of the cases of adenomatous polyp. More definite differences were recognized between the cancerous cases and the cases of adenomatous polyp, when the ratio of the deviation rate of C14:0 to that of C20:4 was calculated in each case. Namely, the ratios distributed between 2.064 and 4.125 in 10 cancerous cases, and between 0.393 and 1.856 in 16 cases of adenomatous polyp, indicating the biochemical differences between cancerous tissues and adenomatous polypous tissues.

Diagnosis, Differential↗