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Pathophysiological effects of glucocorticoids on nasal polyps: an update.

PURPOSE OF REVIEW: The exact mechanisms by which glucocorticoids exert their beneficial effects on nasal polyps are not clearly defined. Nasal polyps, asthma and allergic rhinitis share common features such as mucosal infiltration with eosinophils and mast cells as well as local IgE production. The present review is an update on the pathophysiological mechanisms of glucocorticoids on nasal polyps described during the last 2 years. RECENT FINDINGS: The reduction of leukocyte numbers in nasal polyps following glucocorticoid treatment depends on several mechanisms, for example altered balance between the two isoforms of the human glucocorticoid receptors, GRalpha and GRbeta. Another explanation may be inhibition of CD4+ T by CD8+ T cells. Increased expression of the antiinflammatory cytokine transforming growth factor beta may contribute to this. A DNA microarray study which examined the expression of some 22 000 genes showed increased expression of several antiinflammatory genes in nasal polyps after treatment with glucocorticoids. The antiinflammatory gene that increased most was uteroglobin (also known as Clara cell protein 16) which is abundantly expressed in airway secretions and thought to have an important role in regulating inflammation. SUMMARY: Glucocorticoids affect both pro and antiinflammatory pathways in nasal polyps. Upregulation of antiinflammatory genes such as transforming growth factor beta and uteroglobin may play an important role. Elucidation of these mechanisms may help us to understand not only the effects of glucocorticoids on nasal polyps, but also on related disorders such as allergic rhinitis and asthma.

Cytokines↗

Immunohistochemical expression of p63 in endometrial polyps: evidence that a basal cell immunophenotype is maintained.

OBJECTIVE: Although endometrial polyps likely originate from reserve cells in the basal layer, the underlying biology is not fully understood. One protein that plays an important role in regulating epithelial proliferation and differentiation is the 63-kd membrane protein (p63), which is also a marker of basal and reserve cells in the female genital tract. Our objective was to determine whether p63 is expressed differently in postmenopausal endometrial polyps than in the adjacent endometrium. DESIGN: In this study, 36 specimens of endometrial polyps and 36 samples of the adjacent endometrium were obtained from postmenopausal women through hysteroscopic surgery performed in a tertiary-care university hospital. Immunohistochemistry was used to evaluate the expression of p63 in all samples. RESULTS: The majority of endometrial polyp samples (94.4%) presented nuclear immunostaining for p63, whereas only 5.6% of adjacent endometrium samples were positive for p63 (P < 0.0001). Distribution of p63 immunostaining in the endometrial polyp samples was homogeneous. CONCLUSIONS: Our results provide evidence that a basal cell immunophenotype is maintained in the endometrial polyps seen in postmenopausal women, suggesting that p63 plays a role in the pathogenesis of such polyps.

Aged↗

Genetic alterations of mixed hyperplastic adenomatous polyps in the colon and rectum.

Some mixed hyperplastic adenomatous polyps (MHAPs) contain dysplastic lesions or even carcinomas. These polyps are considered to be different from ordinary hyperplastic polyps and may have a preneoplastic potential. We investigated APC and K-ras mutations in MHAPs of the colon and rectum, and also in colorectal adenomas and hyperplastic polyps to identify molecular differences between MHAPs, adenomas and hyperplastic polyps, using direct sequencing of mutation cluster regions (MCR) in APC and K-ras. No APC mutations were identified in 12 MHAPs and 8 hyperplastic polyps, whereas 10 of 27 (37.0%) adenomas showed somatic mutations. K-ras mutations were identified in one of 12 (8.3%) MHAPs, one of 8 (12.5%) hyperplastic polyps, and 10 of 27 (37.0%) adenomas. p53 mutation was found in a carcinoma arising in an MHAP. Mutations other than APC mutations may play a role in the development of MHAPs.

Adenoma↗

Juvenile and inflammatory polyps of the colon--a histological and histochemical study.

A light microscopy and histochemical study of 24 juvenile and 27 inflammatory polyps showed that both may derive from inflammatory processes. Granulation tissue, secondary to spontaneous local inflammation or due to surgical procedures may subsequently be covered by regenerating epithelium which lines haemorrhagic cavities and mucus lakes to form irregular, elongated and cystic glands, which are characteristic of juvenile polyps. Both juvenile and inflammatory polyps showed cystic, metaplastic and 'transitional-type' glands. The mucin distribution was identical in both types of polyps. All these findings suggest a common origin of the polyps. The presence of 'transitional-type' glands seems to confirm these as a secondary regenerative phenomenon rather than pre-neoplastic, although dysplastic changes in juvenile polyps have been described. It is suggested that both the juvenile and inflammatory polyps may undergo dysplasia only in genetically predisposed subjects. However, this event seems to be very rare.

Adolescent↗

Association of stem cell factor expression in nasal polyp epithelial cells with aspirin sensitivity and asthma.

Mast cells constitute a significant proportion of cells infiltrating nasal polyp tissue, and epithelial cells may release stem cell factor (SCF), a cytokine with chemotactic and survival activity for mast cells. We aimed to assess the expression of SCF in human nasal polyp epithelial cells (NPECs) as related to patients' clinical phenotypes. Nasal polyp tissues were obtained from 29 patients [including nine with aspirin (ASA)-hypersensitivity and 12 with bronchial asthma] undergoing polypectomy for nasal obstruction. Epithelial cells were obtained following 6-week culture of nasal polyps explants. The SCF released into the culture supernatant was assessed by enzyme-linked immunosorbent assay (ELISA) and total SCF mRNA in the polyp tissue was determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). For the whole group of patients, the number of polypectomies correlated with expression of SCF mRNA (r = 0.62; P < 0.005), SCF protein in the NPECs supernatants (r = 0.39; P < 0.05) and with density of mast cells in epithelial layer (r = 0.37; P < 0.05) and stromal layer (r = 0.5; P < 0.01) of nasal polyps. The SCF/beta-actin mRNA ratios were significantly higher in ASA-hypersensitive (AH) asthmatics (median 0.97, range: 0.8-1.5) when compared with ASA-tolerant (AT) patients (median 0.5, range: 0.1-0.7; P < 0.001). The SCF protein concentration in NPEC supernatants was also significantly higher in AH asthmatics (median 1.10 pg/microg DNA, range: 0.4-1.9) when compared with AT patients (median 0.1 pg/microg DNA, range: 0.02-1.2; P < 0.001). In the subpopulation of ASA-sensitive asthmatics the number of polypectomies correlated also with the density of mast cells and eosinophils in the polyp tissue.

Adult↗

Clinico-pathological study of juvenile polyp of large intestine.

Although the difference of juvenile polyps between the childhood and adult groups was investigated, no significant difference could be pointed out both clinically and histologically. Since the polyps showing similar pathological findings were examined in the present investigation, it should be considered as a matter of course that no significant difference by age was pointed out. In a sense, these facts revealed the existence of a juvenile polyp which occurs in adult patients. In fact, the incidence of juvenile polyp which occurs in adult patients beyond the age of 20 has been estimated as 0 to 44% in the literature. If the term of juvenile polyp is not preferable in the adult cases, the term adult juvenile type polyp may be useful. Although several theories like as hamartoma, inflammation, allergy, etc. have been discussed for its histogenesis, it may be difficult to understand the histogenesis of juvenile polyps by a single theory.

Adolescent↗

Ultrasonographic evidence of association of polyps and stones with gallbladder cancer.

OBJECTIVE: The purpose of this study was to evaluate the level of gallbladder cancer risk associated with polyps and stones of the gallbladder by ultrasound examinations. METHODS: We investigated abdominal ultrasonographic findings for gallstones and polyps of the gallbladder and the relationship of these findings to malignancy in 194,767 asymptomatic participants in health screening examinations. RESULTS: Gallstones were detected in 7,985 participants (4.1%), at a prevalence of 5.3% in male and 4.5% in female participants. The prevalence was highest in the participants' seventh decade, followed by the sixth and the fifth decades, in both male and female participants. Polyps were found in 10,926 (5.6%), at a prevalence of 6.9% in the male and 4.5% in the female participants. In the male participants, prevalence was highest in the fourth decade, followed by the third and the fifth decades, whereas in the female participants it was highest in the fifth decade, followed by the fourth and third. High prevalence of polyps > or = 10 mm in diameter was found in the fifth to seventh decades in both sexes. Nineteen participants (0.01%) were diagnosed as having gallbladder cancer, and many of them were in the sixth or seventh decade in both sexes. Patients with stones showed a higher prevalence of gallbladder cancer. This difference was shown to be statistically significant by age-adjusted analysis (p < 0.01). The age distribution of the participants with polyps > or = 10 mm in diameter was correlated with that of patients diagnosed with gallbladder cancer. Furthermore, polyp incidence was significantly related to cancer by statistical analysis (p < 0.01). CONCLUSION: These results suggest an association between gallstone or polyp of the gallbladder and increased risk of malignancy, implying that an etiological association may also exist.

Adult↗

Colonic inflammation found at diagnosis of juvenile retention polyps in pediatric patients.

OBJECTIVE: The finding of colonic inflammation concurrently with a juvenile retention polyp (JRP) may have prognostic value. However, the significance of abnormal mucosal histology with JRP has not been evaluated. We evaluated the significance of mucosal histology at the time of JRP removal with respect to future development of inflammatory bowel disease (IBD) and polyp recurrence. METHODS: The medical records of patients who had an endoscopic polypectomy performed at the Children's Hospital of Philadelphia (CHOP) from 1/1/87 through 4/30/98 were retrospectively reviewed. RESULTS: JRP was histologically identified in 96 patients. A total of 54 patients had colonic mucosal biopsies: 30 (55.6%) had normal histology and 24 (44.4%) had colitis. Of the 24 patients with colitis, 14 patients (58.3%) had inflammation at the polyp site. Twelve of these patients had additional inflammation elsewhere in the colon. Nine (37.5%) had inflammation elsewhere in the colon; however, biopsies around the polyp site were not obtained. One patient with inflammation did not have the location of the polyp documented. Four patients (16.7%) had IBD at the time of polypectomy; two were diagnosed prior and two coincident with JRP. None have subsequently been diagnosed with IBD. There was no difference in polyp recurrence between those with or without inflammation (16.7% [4/24] vs 10.0% [3/30]). The mean follow-up period was 72.4 months (range, 5-142 months). CONCLUSIONS: In our experience, histological mucosal inflammation is a common finding with JRP. This inflammation may be a precursor for the development of JRP but has no predictive value for polyp recurrence. This colitis does not seem to be associated with IBD.

Adolescent↗

Predictive value of rectal bleeding in screening for rectal and sigmoid polyps.

Overt rectal bleeding is a common symptom of colorectal cancer and polyps but also occurs in apparently healthy people. It is not known how often this represents bleeding from an undiagnosed rectal or sigmoid polyp or cancer. Three hundred and nineteen apparently healthy men aged over 50, selected by random sampling, were interviewed and underwent flexible sigmoidoscopy to at least 30 cm. Polyps of 10 mm or more in diameter were diagnosed in 12, one of whom also had an adenocarcinoma. Rectal bleeding during the previous six months was reported by 48, four of whom were found to have polyps; seven polyps and one cancer were diagnosed among the 271 who reported no rectal bleeding. Rectal bleeding had a specificity of 86%, a sensitivity of 33%, and a positive predictive value of 8% for rectal or sigmoid polyps or cancer. Restricting the analysis to those subjects who regularly inspected their stools did not improve the predictive value. Sigmoidoscopy in apparently healthy subjects with rectal bleeding will not result in the diagnosis of appreciable numbers of rectal and sigmoid polyps or cancers.

Gastrointestinal Hemorrhage↗

Multiple duodenal polyps in uraemia: a little known clinical entity.

Multiple duodenal polyps were found by endoscopy in five out of 33 patients with chronic renal failure and in one of 300 controls. In the uraemic cases the polyps were caused by circumscribed nodular hyperplasia of Brunner's glands. One of these five patients later underwent surgery for duodenal obstruction caused by the polyps; the other patients were asymptomatic. One of the controls had multiple duodenal polyps. The recorded incidence of multiple duodenal polyps was significantly higher among patients with chronic renal failure than in patients without renal disease. Patients with chronic renal failure and polyps did not differ significantly from the other renal patients in the comparison of variables such as gastric acid secretion, serum concentrations of gastrin and group I pepsinogens or mean length of dialysis treatment. The mean pH of gastric resting juice was significantly higher, however, in uraemic patients with polyps than in those without. Uraemic patients displayed a gastric acid secretion capacity within normal range, and significantly raised serum gastrin and group I pepsinogen concentrations.

Adolescent↗

Colonic polyps.

Carcinoma of the large bowel arises almost exclusively in neoplastic polyps, which are present in 5-10% of the population over age 40. These polyps may be of three histologic types: (a) tubular adenoma (adenomatous polyp), (b) tubulovillous adenoma (villoglandular polyp), and (c) villous adenoma. The tendency for malignant change is greatest in the villous adenoma (41%) and in tubulovillous (villoglandular polyps--23%). In tubular adenomas (simple adenomatous polyps), the incidence of malignancy is 5% over all. The tendency toward malignant change is determined by histologic type, size, and degree of atypicality of adenoma. Early detection and complete removal of neoplastic polyps of the colon are essential to the prevention of cancer of the large bowel, and this may usually be done in most cases with the colonoscope.

Adenoma↗

Polyp size at CT colonography after electronic subtraction cleansing in an anthropomorphic colon phantom.

PURPOSE: To evaluate the effect of various bowel contrast material concentrations and subtraction software on size measurements of well-defined polyp lesions in a colon phantom at CT colonography. MATERIALS AND METHODS: Repeated scanning and a precise reference standard required the use of a colon phantom in which 21 polyps were randomly distributed. Two readers who had each reviewed computed tomographic (CT) colonographic images from more than 100 cases evaluated polyp size on images obtained when the phantom was partially filled with varying concentrations of contrast material, scanned by using CT colonography, and subjected to electronic subtraction cleansing. The single largest dimension was recorded for each reader for a randomized series of polyps. These measurements were compared with a reference standard that was based on a combination of the manufacturer's polyp size specifications and the subsequent verification of these sizes by an independent consensus panel. Six weeks after initial observations, readers evaluated images of the phantom scanned without the presence of contrast material. Polyp size estimations for the two readers for each series were compared with the reference standard to obtain a mean absolute measurement error for each reader for each series. Data for each reader were compared by using a nonparametric Kruskal-Wallis analysis of variance test. A pair-wise comparison of the experimental and control series was then performed by using the Dunn post hoc test. RESULTS: Contrast material dilutions resulting in an average attenuation of less than 500 HU resulted in complete subtraction and the absence of streak artifacts. There was no statistically significant difference between the average measurement error for contrast attenuations between 300 and 500 HU when compared with that of control. Streak artifact was noticeable for the highest dilution (mean, 840 HU). No statistically significant differences were observed for series in which cleansing software was used in the absence of bowel contrast material. CONCLUSION: The combination of electronic cleansing and bowel contrast enhancement in the range of 300-500 HU results in no substantial change in readers' estimations of polyp size at CT colonography.

Analysis of Variance↗

CT colonography in the detection of colorectal polyps and cancer: systematic review, meta-analysis, and proposed minimum data set for study level reporting.

PURPOSE: To assess the methodologic quality of available data in published reports of computed tomographic (CT) colonography by performing systematic review and meta-analysis. MATERIALS AND METHODS: The MEDLINE database was searched for colonography reports published between 1994 and 2003, without language restriction. The terms colonography, colography, CT colonoscopy, CT pneumocolon, virtual colonoscopy, and virtual endoscopy were used. Studies were selected if the focus was detection of colorectal polyps verified with within-subject reference colonoscopy by using key methodologic criteria based on information presented at the Fourth International Symposium on Virtual Colonoscopy (Boston, Mass). Two reviewers independently abstracted methodologic characteristics. Per-patient and per-polyp detection rates were extracted, and authors were contacted, when necessary. Per-patient sensitivity and specificity were calculated for different lesion size categories, and Forest plots were produced. Meta-analysis of paired sensitivity and specificity was conducted by using a hierarchical model that enabled estimation of summary receiver operating characteristic curves allowing for variation in diagnostic threshold, and the average operating point was calculated. Per-polyp sensitivity was also calculated. RESULTS: Of 1398 studies considered for inclusion, 24 met our criteria. There were 4181 patients with a study prevalence of abnormality of 15%-72%. Meta-analysis of 2610 patients, 206 of whom had large polyps, showed high per-patient average sensitivity (93%; 95% confidence interval [CI]: 73%, 98%) and specificity (97%; 95% CI: 95%, 99%) for colonography; sensitivity and specificity decreased to 86% (95% CI: 75%, 93%) and 86% (95% CI: 76%, 93%), respectively, when the threshold was lowered to include medium polyps. When polyps of all sizes were included, studies were too heterogeneous in sensitivity (range, 45%-97%) and specificity (range, 26%-97%) to allow meaningful meta-analysis. Of 150 cancers, 144 were detected (sensitivity, 95.9%; 95% CI: 91.4%, 98.5%). Data reporting was frequently incomplete, with no generally accepted format. CONCLUSION: CT colonography seems sufficiently sensitive and specific in the detection of large and medium polyps; it is especially sensitive in the detection of symptomatic cancer. Studies are poorly reported, however, and the authors propose a minimum data set for study reporting.

Colonic Polyps↗

Sensitivity of double-contrast barium study for left-colon polyps.

A blinded, prospective study was conducted to determine the sensitivity of double-contrast barium enema examination (DCBE) in detecting left-colon polyps. Metal clips were endoscopically placed on normal mucosa either adjacent to polyps (in 65 study subjects with 92 polyps) or not adjacent to polyps (in 50 control subjects). DCBE had a high sensitivity for detection of polyps greater than or equal to 1 cm and 6-9 mm in size (100% and 83% detection, respectively) but was insensitive in detecting polyps in the 4 to 5-mm and 2 to 3-mm size ranges (56% and 22% detection, respectively). The factors contributing most commonly to false-negative interpretations were the presence of air bubbles, overlap of bowel loops, and luminal fecal debris. No error in radiographic technique was evident to account for false-negative interpretations in 14 (41%) of 34 polyps that were not detected by DCBE.

Barium Sulfate↗

Endometrial polyps, hyperplasia, and carcinoma in postmenopausal women: differentiation with endovaginal sonography.

PURPOSE: To characterize endometrial polyps, hyperplasia, and carcinoma with endovaginal ultrasound in postmenopausal women. MATERIALS AND METHODS: Seventy-three postmenopausal women with abnormally thick endometria on endovaginal sonograms were retrospectively identified. The endometrial appearance was characterized as hyperechoic, containing cystic spaces, or heterogeneous. The final study group consisted of 68 women, in whom the pathologic and sonographic findings were correlated. RESULTS: Thirty sonograms showed hyperechoic endometria in women with hyperplasia (n = 8), polyps (n = 4), polyps and hyperplasia (n = 2), or atrophy, proliferative change, mild atypia, or normal endometria (n = 16); 27 sonograms showed cystic spaces in women with polyps (n = 21), carcinoma (n = 1), polyps and hyperplasia (n = 2), or atrophy (n = 3); and 11 sonograms showed heterogeneous endometria in women with endometrial carcinoma (n = 7), atrophy (n = 2), proliferative endometrium (n = 1), or secretory endometrium (n = 1). Cystic spaces were predictive of polyps (P = 1.19 x 10(-10)). CONCLUSION: Endovaginal sonography may be useful for differentiation of endometrial polyps, hyperplasia, and carcinoma.

Aged↗

The so-called 'allergic' nasal polyp.

A series of 95 consecutive patients who have had a polypectomy was investigated with regard to clinical history and the morphology of the polyps. The results were compared with a series of 203 patients with allergy, of whom 12 had been polypectomized. The study revealed that a high percentage of the 95 patients had subjective complaints, particularly nasal congestion, nasal discharge, sneezing, headache, snoring and a loss of smell. The latter was present in nearly 58% of the patients, and persisted long after the operation in a third of the cases. More than 50% of the 95 patients had had 3 or more polypectomies. Rather few patients suffered from allergy-like conditions. Eighty-two of the 95 polyps were of the ordinary, oedematous, eosinophilic type; 7 were neutrophilic, fibro-inflammatory; 5 showed pronounced hyperplasia of the seromucinous glands, and 1 was a so-called polyp with atypical stroma. Only 6% of the 203 patients with allergy had had a polypectomy. Ten of the 12 polyps removed from the series of patients with allergy were of the ordinary type and 2 of the fibro-inflammatory type. A review of the literature is done concerning the association between nasal polyp and different diseases. The results of the present study support the concept that allergy is not the only cause for nasal polyps and that the accumulation of eosinophilic granulocytes observed in most polyps is often not related to allergy.

Adult↗

Overexpression of Fas-ligand in human nasal polyps.

Apoptosis mediated through the Fas/Fas-L system is essential in regulating immune function, developing organs, and conferring immune privilege. To illustrate the role of the Fas/Fas-L system in the pathogenesis of human nasal polyps, we investigated the transcripts and protein level of the Fas-L gene in 8 human nasal polyp tissues and 7 nasal turbinate mucosa specimens using reverse transcription-polymerase chain reaction and Western blotting. Localization of Fas-L was performed with immunohistochemistry. The transcripts of the Fas-L gene were detected at similar levels in both polyps and nasal mucosa. There was a significant overexpression of Fas-L protein on nasal polyps compared to nasal mucosa. Fas-L-positive cells were localized on the epithelial layers of cystically dilated glands and the down-growing epithelium of nasal polyps. Fas-L may play an important role in the pathogenesis of human nasal polyps, including cystic degeneration of submucosal glands and conferring of immune privilege to nasal polyp formation.

Blotting, Western↗

Expression of glucocorticoid receptors and cyclooxygenase-2 in nasal polyps from nonallergic patients.

Glucocorticoid treatment has been widely used to suppress inflammatory and immune responses. However, from a clinical point of view, its efficacy in the treatment of nasal polyposis seems to vary individually from patient to patient. In the present study, we examined the presence of glucocorticoid receptors (GRs) and cyclooxygenase-2 (COX-2) in the nasal polyps of nonallergic patients as compared with normal controls. Reverse transcription-polymerase chain reaction analyses revealed the presence of both GR messenger RNA and COX-2 messenger RNA expression in nasal polyps from nonallergic patients, as well as in normal nasal mucosa from controls. Consistent with this finding, immunohistochemical analysis demonstrated that GRs and COX-2 were labeled in both tissues. In nasal polyps, GR labeling was associated with the cytoplasm and nucleus of surface mucosa, submucosal glands, endothelial cells, and inflammatory cells. Importantly, COX-2 labeling was seen in the cytoplasm of surface mucosa, submucosal glands, and the vascular wall in nasal polyps. In contrast, in normal nasal tissues, COX-2 labeling was only found in the vascular wall, and the expression was weaker--a finding demonstrating that COX-2 is upregulated in nasal polyps. Therefore, 1) the presence of GRs and COX-2 in nasal polyps from nonallergic patients, as well as upregulation of COX-2 expression, suggests that inflammation may play an important role in the pathophysiology of nasal polyps; and 2) glucocorticoid could be a potential treatment method for suppressing inflammatory processes.

Adolescent↗