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Negative energy balance induced by voluntary wheel running inhibits polyp development in APCMin mice.

Treadmill running of approximately 0.9 km/day has had inconsistent effects on spontaneous intestinal polyp development in C57BL/6J-Apc(Min)/J (Min) mice; the amount of energy expenditure and/or a lack of hormonal changes could account for this variability. The purpose of this study was to examine the effects of a negative energy balance induced by voluntary wheel running on polyps, insulin-like growth factor-1 (IGF-1) and corticosterone in Min mice. Seven-week-old male Min mice were randomly assigned to control (CON, n = 23) or wheel running (EX, n = 24) conditions for a 10-week study period. All mice had water and AIN-76A diet ad libitum for the first approximately 3 weeks on study, after which the EX group was pair-fed to the CON group to maintain a negative energy balance due to the exercise. EX mice voluntarily ran 3.8 km/day (2.7-6.0 km/day) (median, interquartile range) and weighed less than CON mice throughout the study. More CON mice died before the end of the study versus EX mice (26 versus 0%, P < 0.01). CON mice had significantly more polyps versus EX mice (21.6 +/- 1.5 versus 16.9 +/- 2.0, P < 0.01; mean +/- SE), and daily running distance in EX was inversely correlated with total polyp number (r = -0.70, P < 0.01). Urinary corticosterone output (P < 0.01) and serum IGF-1 were significantly higher in EX than CON (P < 0.001); however, total polyp number was unrelated to corticosterone (r = 0.05, P = 0.84) and IGF-1 (r = -0.01, P = 0.93). In this study, a negative energy balance produced by wheel running exercise and restricted feeding decreased polyp burden in male Min mice and appeared to have a dose-response effect on polyp number. Although EX affected IGF-1 and corticosterone, neither marker was related to total polyp number.

Animals↗

Inherited variation in carcinogen-metabolizing enzymes and risk of colorectal polyps.

Exposures such as cigarette smoke and meat contain a variety of procarcinogens, which are thought to play a role in elevation of risk for colorectal polyps and/or cancer. These procarcinogens (including heterocyclic amines and polycyclic aromatic hydrocarbons) are metabolized by a variety of polymorphic enzymes including N-acetyltransferases, sulfotransferases, cytochrome P450 enzymes and epoxide hydrolase. We hypothesized that genetic variation in the encoding genes NAT1, NAT2, SULT1A1, SULT1A2, CYP1A1 or EPHX1 is associated with risk of colorectal polyps and interacts with cigarette use or meat intake to modify risk of colorectal polyps. We examined the role of these genes in a clinic-based study of 651 Caucasian cases with hyperplastic polyps, adenomatous polyps or both types of polyps and 556 polyp-free controls. We found evidence for interaction between NAT acetylator status and SULT1A1 genotype in risk of hyperplastic polyps: individuals with SULT1A1 638AA genotype and NAT1 and NAT2 intermediate/fast phenotypes had 3.5-fold increased risk (95% CI 1.2-10.3) compared with individuals with SULT1A1 638GG genotype and NAT1 and NAT2 slow phenotypes. Data were also consistent with interactions between smoking and variation in SULT1A1, CYP1A1 and EPHX1 and between meat intake and variation in CYP1A1 and EPHX1. No interactions were statistically significant. Although results should be interpreted with caution considering sample size and the number of hypotheses examined, our study suggests future avenues of investigation in larger investigations of genetic and lifestyle factors in the pathway to colorectal cancer.

Adult↗

Unusual adenomatous polyps in juvenile polyposis coli.

A 14-year-old boy had an ileocolectomy for juvenile polyposis coli. Twenty-five years later he developed peculiar adenomatous polyps in his rectum. The polyps had irregularly shaped glands lined by cells with stratified, atypical nuclei. Some glands were distended with mucus, but otherwise the polyps did not resemble juvenile polyps. Two other types of polyps associated with juvenile polyposis coli and often designated as adenomatous polyps are illustrated. A solitary juvenile polyp with foci of hyperplastic and adenomatous change is also depicted, and the association of juvenile polyps with colonic neoplasia is reviewed.

Adolescent↗

Hyperplastic (metaplastic) polyps of the colon. A histologic and histochemical study.

One hundred seventy-three hyperplastic polyps removed from the colon of 146 patients were carefully examined by light microscopy in order to evaluate the histologic variants. Seventy polyps were also studied histochemically in order to assess the mucin distribution. Seven polyps measured greater than 1 cm. The frequency of hyperplastic foci has been assessed in a review of 1000 colonic adenomas, 50 juvenile, 30 inflammatory, and six Peutz-Jeghers polyps. The vast majority of the hyperplastic polyps showed features similar to those of inflammatory and ischemic bowel mucosa, leading to the suggestion of an inflammatory-ischemic origin of the polyps. The frequent finding of dysplastic features within hyperplastic polyps greater than 1 cm suggests that at least the large polyps are dysplasia-prone.

Adenoma↗

Giant and symptomatic inflammatory polyps of the colon in idiopathic inflammatory bowel disease.

Four cases of giant inflammatory polyps were found in a series of 86 consecutive colectomies for inflammatory bowel disease. Two presented a distinctive clinical syndrome of abdominal pain and chronic iron-deficiency anemia due to blood loss. Secondary ulceration of the heads of the polyps accounted for the bleeding and anemia, and the size of the polyps accounted for the abdominal pain. In both cases unusually long portions of colon were involved by the giant polyps. The third and fourth cases had rare complications--reactivation of an enterocutaneous fistula and perforation of an acquired diverticulum. These cases demonstrate that giant inflammatory polyps may produce symptoms independently of the underlying inflammatory bowel disease. In reported cases of giant inflammatory polyps, approximately two-thirds had Crohn's disease and one-third had ulcerative colitis. The transverse colon was the commonest location, pain was the commonest symptom, and the polyps were localized to a short segment of colon in the majority of cases. More than 50% of cases mimicked neoplasm on barium enema. Giant inflammatory polyps may produce a variety of distinctive signs and symptoms and deserve independent recognition.

Adult↗

Hyperplastic polyps of the stomach: associations with histologic patterns of gastritis and gastric atrophy.

Hyperplastic polyps are common gastric lesions characterized by hyperplastic foveolae with variable amounts of inflamed stroma. Their pathogenesis is unknown, but they have been reported to occur in association with various forms of chronic gastritis, particularly autoimmune gastritis and Helicobacter pylori gastritis. Comprehensive histologic evaluation of the background mucosal pathology in patients with hyperplastic polyps has not been previously performed. We studied 160 patients with gastric hyperplastic polyps and characterized endoscopic and histologic features of the polyps (i.e., location, multiplicity, and presence of dysplasia and adenocarcinoma) and the background gastric mucosa (i.e., intestinal metaplasia, dysplasia, carcinoma, and presence and classification of gastritis). Hyperplastic polyps were most common in the antrum (60%) and were multiple in 20% of patients. Focal intestinal metaplasia of the polyp was present in 16% and dysplasia in 4% of patients. Only one patient (0.6%) had adenocarcinoma within the polyp. Evaluation of the surrounding gastric mucosa showed at least focal intestinal metaplasia in 37% of patients, adenoma or low-grade flat epithelial dysplasia in 2%, and synchronous or metachronous adenocarcinoma in 6%. Eighty-five percent of patients had inflammatory mucosal pathology, most commonly active chronic H. pylori gastritis (25%), reactive or chemical gastropathy (21%), and metaplastic atrophic gastritis of the autoimmune (12%) or environmental (8%) type. These results indicate a strong association between various forms of gastritis and the development of hyperplastic polyps and further emphasize the importance of biopsy of the nonpolypoid gastric mucosa during endoscopic examination.

Adenocarcinoma↗

Alcohol and smoking in relation to the prevalence of adenomatous colorectal polyps detected at sigmoidoscopy.

Cigarette smoking has been associated with adenomatous polyps of the large bowel but not with increased risk of colorectal cancer. Giovannucci et al recently proposed a hypothesis to explain this inconsistency. A key testable aspect of the hypothesis is that smoking in the distant past increases the risk of large polyps. Questions also remain about the association between colorectal polyps and consumption of alcohol. To address these issues, we examined data from 488 cases with adenomatous polyps and 488 controls. Subjects were members of a prepaid health plan in Los Angeles who had a sigmoidoscopy in 1991-1993. As expected, the adjusted odds of polyps in current smokers compared with never-smokers was increased [odds ratio = 2.43; 95% confidence interval (CI) = 1.56-3.79]. For those who had smoked in the distant past (for example, 30 or more pack-years before 20 years ago), the adjusted odds of an adenoma > or = 1 cm, relative to nonsmokers, was 0.88 (95% CI = 0.23-3.42). The adjusted odds of polyps in those consuming > or = 46 gm per day of alcohol compared with nondrinkers was 1.50 (95% CI = 0.72-3.13). Although imprecise, these data do not support the hypothesis that past smoking increases the risk of large polyps, but our results indicate a weak association between alcohol use and risk of adenomatous polyps.

Adenomatous Polyps↗

Duodenal polyps: diagnosis and management.

Forty-five polyps were encountered at duodenoscopy between 1973 and 1978. Upper gastrointestinal x-rays were helpful in 25 patients, 13 of whom had duodenal polyps and 12 duodenal deformity or mass lesions. Polyps in 23 patients were larger than 1 cm in size. Biopsies were done in 38 patients; in 19 there was only normal duodenal mucosa or chronic inflammation. Eight adenomatous polyps, six villous adenomas, two Brunner's gland hyperplasia, two lipomas, and one carcinoid tumor were found. Surgery was performed in eight patients and endoscopic polypectomy in four. We conclude that 1) small duodenal polyps are frequently missed on upper gastrointestinal x-rays, but these are submucosal polyps of little significance; 2) in general, polyps cannot be differentiated endoscopically into tissue categories, but villous adenomas show some characteristic features which allow a dependable endoscopic diagnosis; 3) a villous adenoma warrants excision because of the high incidence of malignancy; and 4) pedunculated duodenal polyps can be removed safely with endoscopic snare excision.

Adult↗

The clinical spectrum of duodenal polyps in pediatrics.

OBJECTIVES: The aim of this retrospective study was to determine the prevalence, clinical presentation, and histologic subclassification of duodenal polyps identified on endoscopy (EGD) in pediatric patients. METHODS: We performed an 18-year retrospective study of all pediatric patients (< 21 years) with duodenal polyps diagnosed between 1983 and 2001 at The Johns Hopkins Children's Center. Our analysis includes a formal histologic evaluation of duodenal polyps either biopsied using cold-forceps or removed by snare cautery. RESULTS: Duodenal polyps were reported in 22 of 5766 EGDs (0.4%) performed in 16 (M:F; 1:1) patients with a mean (SD) age of 14.1 (5.1) years. Polyps were equal in both the Caucasian and African American population (adjusted ratio 1.2:1). The histologic subtypes included Adenomatous (42%), Brunner's gland hyperplastic (33%), hamartomatous (17%), and heterotopic gastric gland polyps (8%). The most frequent indication for EGD was surveillance in patients with polyposis syndromes; most of these patients were asymptomatic at the time of their EGD. In comparison, the most frequent indication for an EGD in patients without polyposis syndromes was abdominal pain and vomiting. CONCLUSIONS: Duodenal polyps are most frequently encountered in children with polyposis syndromes, most of whom are asymptomatic. In nonsyndromic patients, the most common histologic subtype is Brunner's gland hyperplastic polyp and presenting symptoms include abdominal pain and vomiting.

Adolescent↗

Levels of intracellular protein and messenger RNA of mucin and lysozyme in normal human nasal and polyp epithelium.

OBJECTIVES: Mucus hypersecretion is a characteristic feature in chronic sinusitis with nasal polyps. The objective of this study is to examine whether the polyp epithelium itself contributes to a certain extent to the increased mucous secretions in chronic sinusitis with nasal polyps, and if it does, to determine which mucin genes are responsible for the increased mucin secretion. METHODS: Three pooled samples of normal nasal epithelial cells from each subject were obtained by scrapings from the inferior turbinates of 30 healthy adult volunteers and nasal polyps from 6 patients who underwent intranasal ethmoidectomy and polypectomy. Isolated epithelial cells were used for total RNA isolation for reverse transcriptase polymerase chain reaction and cell lysates for immunoblotting. RESULTS: The intracellular level of mucin from polyp epithelium was 2.9 times higher than that of normal nasal epithelium (P < .05). Interestingly, MUC2 and MUC8 messenger RNA (mRNA) levels were clearly upregulated in polyp epithelium compared with those of normal turbinate epithelium. CONCLUSIONS: Polyp epithelium can be considered to contribute in part to increased secretion in chronic sinusitis with polyps, and increased mucous secretion might be related to the increased mRNA level of MUC2 or MUC8 or both.

Adult↗

Quantitative analysis of eotaxin and RANTES messenger RNA in nasal polyps: association of tissue and nasal eosinophils.

OBJECTIVES/HYPOTHESIS: Nasal polyps develop in the ethmoidal and middle turbinate area, often in relation to inflammatory conditions. Their exact etiology and pathogenesis are still under debate. Histologically, the polyps are infiltrated by a number of inflammatory cells, with eosinophil predominating in most specimens. This finding suggests that the nasal polyp is an inflammatory growth that is controlled by the local environment. The chemokines eotaxin and RANTES (regulated on activation normal T cell expressed and secreted) have been postulated to be involved in the recruitment and activation of eosinophils to certain inflamed tissues. The purpose of this study was to investigate eotaxin and RANTES mRNA expression in nasal polyps and its effect on tissue and nasal eosinophils. METHODS: Nasal polyps (917 allergic and 30 nonallergic cases) were obtained from endoscopic sinus surgery, and 15 normal inferior turbinates also were taken. Immunohistochemical staining for eosinophils and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) tests for eotaxin and RANTES mRNA expression were performed, and the concentration of nasal eosinophil cationic protein (ECP) was measured. RESULTS: The amounts of eotaxin mRNA in the allergic nasal polyps were 11.4 times higher and the levels in the nonallergic polyps were 6.4 times higher than in the normal inferior turbinate. However, the RANTES mRNA expression did not show any differences among the three groups. Tissue eosinophilia and nasal ECP levels were significantly correlated with eotaxin mRNA level but not with RANTES mRNA expression. CONCLUSION: Nasal polyp eosinophilic infiltration and activation correlate mainly with increased eotaxin gene expression rather than with RANTES expression.

Adolescent↗

Prevalence of Helicobacter pylori in patients with nasal polyps: a preliminary report.

OBJECTIVES: The aim of the study is to determine the presence of H. pylori in nasal polyps by both immunohistochemical staining with H. pylori antibody of biopsy specimens and enzyme-linked immunoadsorbent assay (ELISA) of sera. STUDY DESIGN: A prospective, controlled, clinical trial. METHODS: We enrolled 30 patients with nasal polyps and 20 controls with middle concha bullosa undergoing endoscopic sinus surgery (ESS). Blood samples of both the study and control groups were evaluated for anti-H. pylori specific immunoglobulin (Ig)G antibodies by ELISA. In addition, biopsy specimens of the removed polyps and the mucosal part of middle conchas were examined by the immunohistochemical analysis with H. pylori antibody. RESULTS: In the blood samples, specific IgG antibodies to H. pylori were found in 26 (86.7%) of 30 polyp patients and 17 (85%) of 20 controls. In 6 (20%) of the 30 patients, H. pylori was identified in the nasal polyp tissue, but it was not detected in the mucosal part of the middle concha specimens. No significant statistical difference was observed for H. pylori antibodies by ELISA among the patients with nasal polyps and the control group (Fisher's exact test, P = .59). However, there was a statistical difference between the polyp biopsy specimens and the control biopsy specimens by immunohistochemical staining (Fisher's exact test, P = .037). CONCLUSIONS: This study indicates that H. pylori was found in increased prevalence in the nasal polyps. However, further controlled epidemiologic studies would be necessary to confirm our results and clarify the potential underlying pathogenetic mechanisms.

Adolescent↗

Superantigens and chronic rhinosinusitis: detection of staphylococcal exotoxins in nasal polyps.

OBJECTIVE/HYPOTHESIS: The role of infectious agents in the etiology of chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unclear. Recent studies have provided indirect evidence of exposure to staphylococcal exotoxins in the blood and polyp tissue of patients with CRSwNP. These exotoxins have the capacity to act as superantigens, bypassing normal antigen processing and directly stimulating a massive inflammatory response. The objective of the study was to analyze mucus and polyp tissue samples from patients with CRSwNP for the presence of staphylococcal exotoxins. STUDY DESIGN: Prospective study. METHODS: Tissue and mucus samples were obtained from 42 patients undergoing endoscopic sinus surgery for chronic rhinosinusitis and 11 normal control patients. Twenty-nine of 42 patients had chronic rhinosinusitis with bilateral nasal polyposis, 2 had antrochoanal polyps, and 11 had chronic rhinosinusitis without nasal polyps. Eleven patients without chronic rhinosinusitis or polyps served as normal control patients. Specimens were analyzed for the presence of five staphylococcal exotoxins (SEA, SEB, SEC, SED, and toxic shock syndrome toxin type 1 [TSST-1]) using enzyme-linked immunosorbent assay (ELISA). Histological analysis of specimens and mean eosinophil counts were correlated with the presence of toxin. RESULTS: At least one toxin was detected in 14 of 29 patients with bilateral nasal polyposis. Nine of the 14 patients also had positive findings for additional toxins. The dominant histological pattern in the CRSwNP patient group was polypoid mucosa with edema, which was found in both ELISA-positive and ELISA-negative patients. Mean eosinophil counts tended to be higher in ELISA-positive patients with polyps compared with patients without toxin detection. No toxin was detected in the 11 specimens taken from normal control patients. Only 1 of the 13 patients with CRS without polyps had positive ELISA results for toxin. CONCLUSION: The current study demonstrates the presence of superantigen toxins in 14 of 29 patients with CRSwNP, with SEB and TSST-1 being the most common. Further studies are necessary to correlate the presence of toxin with the pathological changes present in polyp tissue.

Adult↗

Colonic chicken-skin mucosa in children with polyps is not a preneoplastic lesion.

Colonic polyps are common both in adults and children; however, the malignant potential varies according to the type of polyp. Most childhood polyps are solitary juvenile polyps, which have negligible malignant potential. Chicken-skin mucosa (CSM) is an endoscopic finding initially described associated with adenomatous polyps and adenocarcinoma, suggesting a preneoplastic lesion. Subsequently, CSM was described in association with juvenile polyps, suggesting that this mucosal finding is not a precursor to dysplasia. To determine whether CSM represents a preneoplastic lesion, we studied endoscopic colonic mucosal biopsies for markers of cell replication (Ki-67) and malignant transformation (p53) in mucosal biopsies of CSM, normal colonic tissue, tubular adenomas, and adenocarcinomas. Samples were subjected to immunostaining for the presence of Ki-67 and p53. The degree of Ki-67-positive staining cells was similar for CSM and normal colonic tissue, whereas there was significantly increased staining for both tubular adenomas and adenocarcinomas. There was no evidence of p53 staining in CSM and normal colonic mucosa, whereas there was varying degrees of staining in tubular adenomas and adenocarcinomas. The association of CSM with benign juvenile polyps and the absence of histologic markers for increased replication and malignant transformation support the notion that this endoscopic finding is not preneoplastic. Rather, CSM arises in proximity to polyps of all histologic types because of local mucosal damage.

Adenocarcinoma↗

Three-dimensional computer-aided diagnosis scheme for detection of colonic polyps.

We have developed a three-dimensional (3-D) computer-aided diagnosis scheme for automated detection of colonic polyps in computed tomography (CT) colonographic data sets, and assessed its performance based on colonoscopy as the gold standard. In this scheme, a thick region encompassing the entire colonic wall is extracted from an isotropic volume reconstructed from the CT images in CT colonography. Polyp candidates are detected by first computing of 3-D geometric features that characterize polyps, folds, and colonic walls at each voxel in the extracted colon, and then segmenting of connected components corresponding to suspicious regions by hysteresis thresholding based on these geometric features. We apply fuzzy clustering to these connected components to obtain the polyp candidates. False-positive (FP) detections are then reduced by computation of several 3-D volumetric features characterizing the internal structures of the polyp candidates, followed by the application of discriminant analysis to the feature space generated by these volumetric features. The locations of the polyps detected by our computerized method were compared to the gold standard of conventional colonoscopy. The performance was evaluated based on 43 clinical cases, including 12 polyps determined by colonoscopy. Our computerized scheme was shown to have the potential to detect polyps in CT colonography with a clinically acceptable high sensitivity and a low FP rate.

Algorithms↗

Lines of curvature for polyp detection in virtual colonoscopy.

Computer-aided diagnosis (CAD) is a helpful addition to laborious visual inspection for preselection of suspected colonic polyps in virtual colonoscopy. Most of the previous work on automatic polyp detection makes use of indicators based on the scalar curvature of the colon wall and can result in many false-positive detections. Our work tries to reduce the number of false-positive detections in the preselection of polyp candidates. Polyp surface shape can be characterized and visualized using lines of curvature. In this paper, we describe techniques for generating and rendering lines of curvature on surfaces and we show that these lines can be used as part of a polyp detection approach. We have adapted existing approaches on explicit triangular surface meshes, and developed a new algorithm on implicit surfaces embedded in 3D volume data. The visualization of shaded colonic surfaces can be enhanced by rendering the derived lines of curvature on these surfaces. Features strongly correlated with true-positive detections were calculated on lines of curvature and used for the polyp candidate selection. We studied the performance of these features on 5 data sets that included 331 pre-detected candidates, of which 50 sites were true polyps. The winding angle had a significant discriminating power for true-positive detections, which was demonstrated by a Wilcoxon rank sum test with p < 0.001. The median winding angle and inter-quartile range (IQR) for true polyps were 7.817 and 6.770 - 9.288 compared to 2.954 and 1.995 - 3.749 for false-positive detections.

Algorithms↗

Epithelial damage in nasal polyps.

Bronchial epithelial damage occurs regularly in bronchial asthma, but it is not known whether such damage occurs in the mucosa of nasal polyps. We obtained nasal polyp tissues from thirty patients and we examined these tissues for evidence of epithelial damage. Immediately after resection, polyp tissue was fixed in Karnovsky's fixative, embedded in methacrylate and stained with Giemsa pH 6 X 5. Normal nasal tissue from eight patients undergoing nasal septal reconstruction was similarly processed. As a disease control, we examined tissue from eight patients with nasal polyps associated with cystic fibrosis. Tissues were viewed by microscopy and epithelial damage was expressed as the percent of surface involved. Twenty-eight of the thirty patients with idiopathic nasal polyps (93%) showed complete loss of nasal mucosa in varying degrees (range 3-81% of surface; mean, 29%). All patients showed evidence of some epithelial damage, either complete loss or marked desquamation (range 9-99% of surface; mean 54%). In contrast, six of eight biopsies from patients undergoing septal reconstruction and five of eight nasal polyps from patients with cystic fibrosis showed little or no evidence of epithelial damage. The results indicate that nasal polyps regularly show evidence of epithelial damage similar to that seen in bronchial asthma, and this abnormality may partly explain the rhinorrhea which is prominently associated with nasal polyps.

Adult↗

Activated eosinophils in nasal polyps: a comparison of asthmatic and non-asthmatic patients.

OBJECTIVES: There is a recognized clinical association between nasal polyps and asthma. Nasal polyps and the airways of asthmatic patients demonstrate marked eosinophilia suggesting that this inflammatory cell may have a key role to play in both conditions. The objective of this study was to determine whether nasal polyps from patients with asthma had a greater density of activated eosinophils than patients with no associated respiratory disease. DESIGN: Archived specimens were retrieved from patients who had undergone nasal polyp surgery and their case notes reviewed. Activated eosinophils were identified using immunohistochemistry for a monoclonal antibody to secreted eosinophil cationic protein (EG2). SETTING: Teaching hospital otolaryngology unit. PARTICIPANTS: Consecutive patients who had undergone nasal polyp surgery in 1994 were recruited. The diagnosis of asthma was based on a documented physician diagnosis and appropriate drug treatment. Twenty-four asthmatic and 35 non-asthmatic patients were studied. MAIN OUTCOME MEASURES: Eosinophil density was measured using a standardized counting technique. RESULTS: Asthmatic patients were significantly more likely to have had previous polyp surgery (chi-square test: P < 0.05). Areas of intense eosinophilia were identified in all samples. There was a significant greater degree of activated eosinophilia in the asthmatic patients (t-test: P < 0.05). CONCLUSIONS: We have demonstrated a higher number of previous operations in asthmatic patients, and also a greater degree of activated eosinophilia in asthmatic polyps compared with non-asthmatics. This would suggest that eosinophil activity has a role to play in the pathogenesis of nasal polyps.

Adult↗