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Experimentally induced polyps in the sinus mucosa: a structural analysis of the initial stages.

To document polyp formation in the sinus mucosa, the authors of this study subjected New Zealand white rabbits to different modes of manipulation intended to induce inflammation of the maxillary sinus. These manipulations included a combination of bacterial infection and mechanical trauma, the deposition of agarose into the sinus cavity, and the deposition of N-formyl-methionyl-leucyl-phenylalanine, a chemotactic peptide, into the sinus cavity. A majority of animals developed polyps, which were examined by light and electron microscopy. Polyp formation appears to involve epithelial disruption and the migration of immature branching epithelium. While part of the migrating epithelium eventually covers the mucosal defect, other branches spread into the underlying connective tissue, where intraepithelial microcavities with a differentiated, ciliated lining are formed. Fusing cavities separate the developing polyp body from the adjacent mucosa. With the described method, mucosal polyps can be induced with high reproducibility.

Animals↗

Interaction between fibronectin and eosinophils in the growth of nasal polyps.

OBJECTIVES: The aim of this study was to determine roles of fibronectin and eosinophils in the etiology of nasal polyposis. STUDY DESIGN: We designed a cohort study of cases with nasal polyposis. Sampled nasal polyps were differentiated by their histopathologic characteristics, and compared by size and computed tomography (CT) stage. METHODS: The size of nasal polyps was determined on the basis of the endoscopic findings, and the extent of sinusitis was evaluated by CT staging. Nasal polyp samples were taken from 82 patients during ethmoidectomy and differentiated by morphologic characteristics, infiltration cell types, or fibronectin positivity. Then their sizes and CT stages were compared. In addition, correlation among these histological characteristics was analyzed. RESULTS: Nasal polyps showing edematous morphology, eosinophil infiltration, or fibronectin expression were significantly large in size. Concerning CT stages, only the infiltration cell type showed a significant difference. Significant correlation among edematous morphology, eosinophil infiltration, and fibronectin expression was also recognized. CONCLUSIONS: These findings suggest that interaction between eosinophils and fibronectin may play a role in edema formation, which contributes to the growth of nasal polyps.

Adolescent↗

Outcome analysis of endoscopic sinus surgery in patients with nasal polyps and asthma.

OBJECTIVE: To investigate the efficacy of endoscopic sinus surgery (ESS) in the management of chronic sinusitis and asthma in patients with nasal polyps and steroid-dependent asthma. STUDY DESIGN: Retrospective chart review. METHODS: The study included 17 patients who underwent ESS with nasal polyps, steroid-dependent asthma with or without aspirin sensitivity and a minimum of 1 year postoperative follow-up. Nine patients were ASA sensitive, and eight patients were ASA tolerant. Chronic sinusitis and asthma were evaluated using subjective (patient complaints) and objective (computed tomography scans, pulmonary function tests, steroid doses) criteria. Preoperative data were compared with data obtained 12 to 18 months postESS. Tissue samples were graded for degree of inflammation and edema. RESULTS: Thirteen of the 17 (76.5%) patients reported improved clinical symptoms postESS. The postoperative Lund-Mackay scores were statistically lower for the 17 patients (P <.0001). The group experienced improvement in postoperative forced expiratory volume at 1 second (FEV1) (P <.014). Twelve of 17 (70.6%) experienced reduction in systemic steroid usage (P <.048). The ASA sensitive patients did not have a statistical improvement in postoperative FEV1 (P >.08) and sinonasal symptoms (P >.16) compared with the ASA tolerant group. Polyp tissue from the ASA sensitive patients demonstrated more edema and more inflammation on average than ASA tolerant polyps, but the results were not statistically significant. CONCLUSION: ESS demonstrates a beneficial effect on the sinonasal and asthma symptomatology in patients with nasal polyps and asthma using objective measures. Subset of aspirin-tolerant patients have statistically better outcome for sinonasal symptoms and pulmonary function testing than aspirin-sensitive patients.

Adult↗

Lifestyle-related factors and colorectal polyps: preliminary results from a Norwegian follow-up and intervention study.

Lifestyle-related variables are suggested to play a major role in the development of colorectal cancer (CRC). Within a 3-year follow-up and intervention study with calcium and antioxidants against growth and recurrence of colorectal polyps, supplementary studies were performed in which different aspects of lifestyle were examined. Instead of polypectomy at diagnosis, polyps <9 mm were left in situ in 116 polyp patients (50-76 years, 50% men). After 3 years, all polyps were removed and subjected to histology. Two different sets of control groups were included (all controls were age- and sex-matched and proven to be free of polyps). We applied two different methods in order to assess most exposure variables. Generally, in case-control studies, the validity of the study outcomes is high if they are similar regardless of choice of controls and methods, since bias due to these choices may affect the risk estimates. In contrast, the validity of the study outcomes is low if dependent upon these choices. Our preliminary data support the theory that different factors may be of importance in different stages of the neoplastive formation, and that lifestyle-related factors are likely to play a major role in CRC development.

Adenoma↗

Tibolone and risk of endometrial polyps: a prospective, comparative study with hormone therapy.

OBJECTIVE: To assess the incidence of endometrial polyps during postmenopausal replacement therapy with tibolone, using an appropriate control group. DESIGN: A total of 485 postmenopausal women were included in this open, prospective, comparative study for a duration of 36 months. Of this group, 249 women received 2.5 mg/day of tibolone and 244 women served as controls, receiving continuous-combined estrogen-progestogen therapy (HT). Transvaginal ultrasound, hysteroscopy, and directed biopsies were performed before treatment was initiated and at the end of the study. RESULTS: Two hundred twenty-one of the women receiving tibolone and 203 receiving continuous-combined HT completed the study. Endometrial polyps were detected in 74 women (33.4%) from the tibolone group and in 22 women (10.8%) from the HT group (P < 0.01). The vaginal bleeding rate did not differ between the groups. The frequency of atrophic polyps was significantly higher in the tibolone group (P < 0.01). No difference was found in the size of the polyps. CONCLUSIONS: Tibolone increases by threefold the risk for endometrial polyps.

Adult↗

A short course of oral prednisone followed by intranasal budesonide is an effective treatment of severe nasal polyps.

BACKGROUND: Nasal polyposis is an inflammatory disease of unknown etiology. This study aimed to evaluate the effect of a short course of oral prednisone followed by intranasal budesonide on nasal symptoms, polyp size, nasal flow, and computed tomography scan. METHODS: Eighty-four patients with severe nasal polyps were included. After a steroid washout period, patients were randomized into two groups: group A (n = 63) received oral prednisone for 2 weeks and group B (n = 21) did not receive any steroid treatment. Patients from group A received intranasal budesonide for 12 weeks. RESULTS: Atopy was positive in 36.8% of patients. Blood eosinophilia was higher in asthmatic (7.2 +/- 0.7%, P < .05) than in nonasthmatic (3.0 +/- 0.4%) patients. Asthmatic patients showed higher scores on nasal obstruction and loss of smell than nonasthmatics. Oral steroids caused a significant improvement in all nasal symptoms and improved polyp size (2.1 +/- 0.1, P < .05) and nasal flow (560 +/- 35 cm/s, P < .05) compared with nontreated patients (2.8 +/- 0.1 and 270 +/- 34 cm/s, respectively). Intranasal budesonide maintained the improvement on nasal symptoms, polyp size, and nasal flow. Steroid treatment reduced the computed tomography scan score (15.4 +/- 1, P < .05) compared with before treatment (18.2 +/- 0.8). CONCLUSION: A short course of oral steroids improved all nasal symptoms, polyp size, and nasal flow, whereas intranasal steroid maintain this effect.

Administration, Intranasal↗

Do gastroenterologists notify polyp patients that family members should have screening?

OBJECTIVE: The objective of this study was to determine whether patients found to have adenomatous polyps or cancer were notified that their relatives should have screening, due to an increased risk of developing colorectal cancer. METHODS: Consecutive (n = 121) colonoscopy patients from December of 1999 to October of 2001 found to have adenomatous colon polyps or colon cancer formed the study group. Charts were reviewed for documentation of relative notification, and when documentation was not present, study subjects were contacted by telephone. RESULTS: Overall, 71% had data that were able to be evaluated; the remaining 29% were unable to be contacted because of changes of address or phone numbers. Adenomatous polyps were seen in 95%, and cancer seen in 5%. Overall, 30% of the patients were notified: 23 of 82 (28%) in the polyp group and 3 of 4 (75%) in the cancer group. Advanced adenomas or multiple adenomas were noted in 28 of the 82 (34%). Of those, 8 of 28 (29%) were notified. CONCLUSIONS: Gastroenterologists should be aware of the need for increased attention to family notification, especially in those with advanced adenomas or multiple adenomas. Template notification letters may complement the polyp surveillance programs that many colonoscopists use.

Adult↗

A statistical 3-D pattern processing method for computer-aided detection of polyps in CT colonography.

Adenomatous polyps in the colon are believed to be the precursor to colorectal carcinoma, the second leading cause of cancer deaths in United States. In this paper, we propose a new method for computer-aided detection of polyps in computed tomography (CT) colonography (virtual colonoscopy), a technique in which polyps are imaged along the wall of the air-inflated, cleansed colon with X-ray CT. Initial work with computer aided detection has shown high sensitivity, but at a cost of too many false positives. We present a statistical approach that uses support vector machines to distinguish the differentiating characteristics of polyps and healthy tissue, and uses this information for the classification of the new cases. One of the main contributions of the paper is the new three-dimensional pattern processing approach, called random orthogonal shape sections method, which combines the information from many random images to generate reliable signatures of shape. The input to the proposed system is a collection of volume data from candidate polyps obtained by a high-sensitivity, low-specificity system that we developed previously. The results of our ten-fold cross-validation experiments show that, on the average, the system increases the specificity from 0.19 (0.35) to 0.69 (0.74) at a sensitivity level of 1.0 (0.95).

Adult↗

A pipeline for computer aided polyp detection.

We present a novel pipeline for computer-aided detection (CAD) of colonic polyps by integrating texture and shape analysis with volume rendering and conformal colon flattening. Using our automatic method, the 3D polyp detection problem is converted into a 2D pattern recognition problem. The colon surface is first segmented and extracted from the CT data set of the patient's abdomen, which is then mapped to a 2D rectangle using conformal mapping. This flattened image is rendered using a direct volume rendering technique with a translucent electronic biopsy transfer function. The polyps are detected by a 2D clustering method on the flattened image. The false positives are further reduced by analyzing the volumetric shape and texture features. Compared with shape based methods, our method is much more efficient without the need of computing curvature and other shape parameters for the whole colon surface. The final detection results are stored in the 2D image, which can be easily incorporated into a virtual colonoscopy (VC) system to highlight the polyp locations. The extracted colon surface mesh can be used to accelerate the volumetric ray casting algorithm used to generate the VC endoscopic view. The proposed automatic CAD pipeline is incorporated into an interactive VC system, with a goal of helping radiologists detect polyps faster and with higher accuracy.

Algorithms↗

Food restriction inhibits the growth of intestinal polyps in multiple intestinal neoplasia mouse.

The effect of food restriction (FR) on spontaneous intestinal carcinogenesis in multiple intestinal neoplasia (Min) mice was examined. Thirty male Min mice were allotted to ad libitum feeding control and 20% FR groups from six weeks of age until the end of the 13-week experimental period. Although the total number of visible intestinal polyps in the FR group was not significantly different from the control group value, a significant decrease in large-sized polyps (>2 mm) and an increase in small-sized polyps (< or =2 mm) were observed in the distal small intestine. In this segment, the percentage of apoptotic cells counted in intestinal polyps in the FR group was significantly higher than in the control group, the percentage of proliferating cell nuclear antigen (PCNA)-positive cells not being significantly different. These results indicate that the FR may inhibit the growth of intestinal polyps in the Min mouse, and that apoptosis contributed in part to the inhibitory effect.

Animals↗

Dose-dependent suppression of hyperlipidemia and intestinal polyp formation in Min mice by pioglitazone, a PPAR gamma ligand.

In our previous study, a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, pioglitazone, suppressed both hyperlipidemia and intestinal polyp formation in Apc(1309) mice at doses of 100 and 200 ppm in the diet. In contrast, it has been reported that doses of 1500 or 2000 ppm of another PPAR gamma agonist, troglitazone, enhanced colon polyp development in Min mice. In the present study, we therefore investigated the effects of a wide range of pioglitazone doses on both hyperlipidemia and intestinal polyp formation in Min mice. Serum triglycerides and very low density lipoprotein (VLDL) cholesterol in the basal diet group were elevated to levels 13-15 times higher than those in the wild-type counterparts at 20 weeks of age. They were reduced dose-dependently by treatment with 100, 200, 400 and 1600 ppm pioglitazone from 6-20 weeks of age with suppression to almost the wild-type level at the highest dose. Moreover, up-regulation of the liver mRNA levels for lipoprotein lipase (LPL) was evident in the pioglitazone-treated animals. Dose-dependent reduction of intestinal polyps was observed in Min mice given 100-1600 ppm for 14 weeks, total numbers being decreased to 63-9% of the control value. A suppressive effect of pioglitazone on colon polyp formation was also found. The PPAR gamma agonist, pioglitazone, may thus be a promising candidate chemopreventive agent for colon cancer.

Animals↗

Nasal polyps: medical or surgical management?

Nasal polyposis is considered to be a non-IgE-mediated inflammatory condition of the nose and sinuses, often associated with chronic non-allergic rhinitis, aspirin intolerance and non-allergic asthma. The aetiology of nasal polyposis is unknown. The main symptoms are nasal obstruction and disturbance of the sense of smell. Occlusion of the nasal passage by a few large polyps could be treated by simple polypectomy to help the patient breathe through the nose. Polypectomy per se does not worsen asthma. Other surgical procedures can be performed, depending on the degree of the disease. The aim of surgery is to restore the physiological properties of the nose by making the nose as free from polyps as possible, and to allow drainage of infected sinuses. Complementary medical treatment of polyposis is always necessary, as surgery cannot treat the inflammatory component of the mucosal disease. In this respect, topical corticosteroids have long been the drugs of choice to reduce the size of polyps, to prevent recurrence after surgery, and are often the main treatment for the disease in many patients. Fluticasone propionate has now been shown to be at least as effective as beclomethasone dipropionate as a medical tool in the management of polyposis. Short-term treatment with systemic corticosteroids is an alternative method of inducing remission and controlling nasal polyps. However, in most patients with nasal polyps, treatment consists of both medical and surgical management.

Humans↗

Fluticasone propionate aqueous nasal spray does not influence the recurrence rate of chronic rhinosinusitis and nasal polyps 1 year after functional endoscopic sinus surgery.

BACKGROUND: Local corticosteroids are widely used in the treatment of nasal polyps and chronic rhinosinusitis both before and after nasal surgery. Their efficacy after functional endoscopic sinus surgery (FESS) has not been fully established by placebo-controlled trials. OBJECTIVE: This double-blind placebo-controlled randomized study was performed in order to investigate whether fluticasone propionate aqueous nasal spray (FPANS) reduces the recurrence rate of nasal polyps and chronic rhinosinusitis during the first year after FESS. PATIENTS AND METHODS: The trial looked at 162 patients aged 18 years and older requiring FESS for chronic rhinosinusitis or nasal polyps. After FESS combined with peri-operative systemic corticosteroids, patients were randomized and given FPANS 400 microg b.i.d., FPANS 800 microg b.i.d. or placebo b.i.d. for the duration of 1 year. Patients were withdrawn from the trial (but still included in the study for statistical purposes) if there were recurrent or persistent diseases, defined as progressive regrowth of nasal polyps, recurrent signs and symptoms of chronic sinusitis combined with abnormalities on computed tomography scan and persistent complaints for at least 2 months after FESS. RESULTS: A significant reduction of symptoms was seen after FESS. After 1 year, 46 patients had been withdrawn from the trial because of recurrent diseases and 32 patients because of persistent symptoms. No differences in the number of patients withdrawn because of recurrent or persistent diseases were found between the patients treated with FPANS and patients treated with placebo. We were also unable to find a positive effect of FPANS compared with placebo in several subgroups such as patients with nasal polyps, high score at FESS or no previous sinus surgery. CONCLUSION: This placebo-controlled study does not show that treatment with FPANS up to 1 year after FESS had a positive effect compared with placebo.

Administration, Intranasal↗

Specific immunoglobulin E for staphylococcal enterotoxins in nasal polyps from patients with aspirin-intolerant asthma.

BACKGROUND: Nasal polyps infiltrated with eosinophils are commonly found in chronic asthmatic patients, more frequently in those with aspirin-intolerant asthma (AIA) than aspirin-tolerant asthma (ATA). Some studies have suggested a contribution of superantigens derived from Staphylococcus sp to nasal polyposis and eosinophilia, but their relative importance in AIA and ATA subjects is unknown. OBJECTIVE: We investigated whether local production of specific IgE to staphylococcal enterotoxins A and B (SEA and SEB) and relationships with markers of eosinophilic inflammation differ in the nasal polyps of AIA and ATA subjects. METHODS: Fifteen AIA subjects with positive responses to lysine-aspirin bronchoprovocation and 15 ATA subjects underwent polypectomy. Immunoassays were used to quantify eosinophil cationic protein (ECP), IL-5, mast cell tryptase, soluble IL-2 receptors (sIL-2R), total IgE, and specific IgE for SEA and SEB. RESULTS: ECP levels in nasal polyp homogenates were higher in AIA subjects than in ATA subjects (P < 0.02), with no significant differences in tryptase, IL-5 or sIL-2R. Total IgE, and specific IgE to both SEA and SEB, were detectable in some nasal polyps from both subject groups, but median levels were markedly higher in AIA subjects than in ATA subjects (P = 0.04, 0.01, 0.05, respectively). Levels of specific IgE to SEA and SEB correlated significantly with levels of ECP and IL-5, but not those of tryptase or sIL-2R. CONCLUSION: These findings suggest that staphylococcal superantigens may drive local eosinophilic inflammation in nasal polyp tissue, and that this is exacerbated in subjects with AIA.

Adult↗

Is routine histological examination of nasal polyps justified?

This study aims to assess the indications for histological examination of polypoid lesions removed from the nose. To achieve this we have performed a national survey of consultant ENT surgeons and reviewed 2866 nasal polypectomy operations. The operations were performed between 1982 and 1988 in the Radcliffe Infirmary, Oxford and the Freeman Hospital, Newcastle. One hundred and fifty questionnaires were sent to randomly selected ENT consultants in the United Kingdom. One hundred and seventeen were returned completed (return rate 78%). The questionnaire asked whether or not the surgeon sent all polyps for examination and, if not, what his indications were for so doing. A retrospective review of all nasal polypectomy operations at the two hospitals was performed. The questionnaire revealed that 38% of the surgeons who replied sent all nasal polyps for examination and 62% did not. The commonest indications for requesting histology were unilateral polyps, abnormal appearance and a history of bleeding. The review of polypectomies showed that 74% of cases in Oxford were examined histologically and 33% in Newcastle. Two per cent of polyps were tumours, of which half were malignant. There were no cases in this study in which unsuspected malignancy was found. All cases of nasal tumours, benign or malignant, were diagnosed clinically either in the Outpatient clinic or in the operating theatre. The results of this survey suggest that it is unnecessary to send all nasal polyps for histological examination.

General Surgery↗

The effect of budesonide (Rhinocort) in the treatment of small and medium-sized nasal polyps.

The objectives of this study were to determine if the size of nasal polyps could be assessed in a reproducible way and to study the effect of budesonide in patients suffering from eosinophilic nasal polyposis with small and medium sized polyps. Ninety-one patients entered the study. Budesonide 200 micrograms b.i.d. (aerosol or aqua) and placebo (aerosol or aqua) were compared in a 3-month double-blind, multi-centre, randomized study. Efficacy was measured by an assessment of polyp size, nasal peak-flow index and the patient's assessment of nasal symptoms. The conclusions were that the size of polyps could be assessed in a reproducible way, and that budesonide delivered either as a water-based suspension or as an aerosol is effective in the treatment of patients with small and medium sized polyps.

Administration, Topical↗

Advances in the medical treatment of nasal polyps.

The objectives of the medical management of nasal polyposis are to eliminate or reduce the size of polyps, re-establish nasal breathing, reduce symptoms of rhinitis, restore the sense of smell and prevent the recurrence of nasal polyps. Corticosteroids have a proven therapeutic effect on the symptoms of nasal polyposis and may reduce one of the underlying causes of polyps, inflammation. The efficacy of topical corticosteroids such as beclomethasone dipropionate nasal spray and betamethasone nasal drops in reducing polyp size and rhinitis symptoms has been demonstrated in several randomized, placebo-controlled trials. Flunisolide and budesonide have also been shown to delay the recurrence of polyps after surgery. Topical corticosteroids can be used as long-term therapy either alone in mild cases, or combined with systemic corticosteroids and/or surgery in severe cases. Most patients will respond well to topical corticosteroid treatment of their nasal polyposis; consequently, the requirement for repetitive nasal surgery will be reduced.

Administration, Intranasal↗

Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine.

Nasal polyp tissue which contains mast cells and eosinophils is similar to the inflamed airway mucosa in cellular composition and mediator content. This investigation assessed the effect of desloratadine (DL), on activation of cells in nasal polyp tissue. Polyps were obtained from 22 patients with chronic rhinosinusitis [nine aspirin acetylosalitic acid (ASA)-sensitive and 13 ASA-tolerant]. Polyp tissue was dispersed by digestion, and preincubated with DL and incubated with anti-immunoglobulin E (IgE) or calcium ionophore. LTC4, eosinophil cationic protein (ECP) and tryptase concentrations in supernatants were measured by immunoassays. Desloratadine (1, 10 and 50 microM) inhibited calcium ionophore-induced LTC4 release by a mean of 29%, 50% and 63% respectively, and anti-IgE-induced LTC4 release by a mean of 27%, 35% and 39% respectively. Calcium ionophore-induced tryptase release was inhibited 60% and 69% by 10 and 50 microM of DL, respectively, and anti-IgE-induced tryptase release was inhibited 33%, 47% and 66% for 1, 10 and 50 microM of DL. Desloratadine 10 microM and 50 microM inhibited ECP release by and 45% and 48% respectively. Polyp tissue from ASA-sensitive patients when compared with ASA-tolerant patients released at baseline significantly more ECP (medians 120.0 microg/ml, range: 69.0-182.0 vs 63.4 microg/ml, range: 3.7-172.0; P <0.05), but similar amounts of tryptase and LTC4. This study demonstrated that DL inhibits activation of both eosinophils and mast cells derived from a site of airway mucosal inflammation.

Adult↗