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PubMed1998

Expression and localization of the inducible isoform of nitric oxide synthase in nasal polyp epithelium.

BACKGROUND: The pathogenesis of nasal polyp disease is poorly understood. Recent evidence has suggested that nitric oxide (NO), an endogenous soluble gas vasodilator and inflammatory mediator, may be synthesised within the nasal cavity. Three nitric oxide synthase isoforms have been identified in humans, with the inducible isoform (iNOS) generally expressed in the setting of inflammation. OBJECTIVE: The aim of this study was to detect and localize iNOS expression in nasal polyp tissue, and compare these findings with normal nasal turbinate tissue. METHODS: We examined the expression and localisation of inducible nitric oxide synthase (iNOS) in human nasal airway specimens from patients undergoing elective nasal turbinectomy (n = 5) or nasal polypectomy (n = 5). iNOS mRNA expression was determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis and localised by in situ hybridization. Densitometric data were analysed using Student's unpaired t-test. Adjacent sections were also examined for iNOS protein expression by immunohistochemistry. RESULTS: Semi-quantitative RT-PCR/Southern analysis of RNA obtained from the 10 surgical specimens demonstrated that iNOS mRNA expression was significantly increased in the five nasal polyps (P < 0.05). In situ hybridization studies revealed strong iNOS mRNA signal localized to the respiratory epithelium of nasal polyps, but not nasal turbinates. This pattern was confirmed by immunohistochemistry. Localization to inflammatory cells or other subepithelial structures was not seen. CONCLUSIONS: We conclude that iNOS expression is upregulated in nasal polyp disease, and is localized to the polyp epithelial layer. These data reinforce the concept that the epithelial layer may be important in the pathogenesis of nasal disease, and suggest a potential role for NO in the formation of nasal polyps.

Epithelium↗
PubMed1997

Multiple hyperplastic polyps in the stomach: evidence for clonality and neoplastic potential.

The origin and neoplastic potential of gastric epithelial polyps remains an area of great interest, and treatment choices are a topic of controversy. This report describes a patient diagnosed with three concurrent hyperplastic gastric polyps that were studied for genetic alterations. The polyps were investigated for alterations in the K-ras oncogene and the p53 tumor suppressor gene and for p21WAF1/Cip1 and MDM2 protein overexpression. In addition, loss of heterozygosity at several loci that are frequently involved in human cancer was analyzed, microsatellite instability, a hallmark of the "mutator" phenotype, was determined, and Epstein-Barr virus infection was investigated. All separate areas from the three independent polyps harbored the same activating point mutation in codon 12 of the K-ras oncogene, indicating a clonal origin. DNA sequence alterations in p53 were not found, although high p53 protein levels could be shown by immunohistochemistry in areas of carcinoma within the largest polyp. No alterations in any of the other molecular markers were observed. The results strongly favor a clonal origin of the three independent gastric polyps and support the notion that these hyperplastic polyps may carry a risk for malignancy.

Aged↗
PubMed1999

Accuracy of polyp detection by gastroenterologists and nurse endoscopists during flexible sigmoidoscopy: a randomized trial.

BACKGROUND & AIMS: The use of nurse endoscopists to perform flexible sigmoidoscopy is expanding, increasing the availability of colorectal cancer screening. However, the effectiveness of this practice has not been studied in randomized trials. The aim of this trial was to examine the miss rate of polyps, the depth of sigmoidoscope insertion, and the incidence of complications during flexible sigmoidoscopy performed by nurse endoscopists and by gastroenterologists. METHODS: Three hundred twenty-eight patients were randomized to undergo screening flexible sigmoidoscopy performed by a nurse endoscopist or by a gastroenterologist. Frequency of missed polyps was determined by repeat sigmoidoscopy, performed by a gastroenterologist blinded to the identity of the first endoscopist. Multiple logistic regression analysis identified characteristics associated with missed polyps. RESULTS: Gastroenterologists and nurse endoscopists had equivalent miss rates for adenomatous polyps (20% vs. 21%, respectively; P = 0.91). No complications occurred in any patient. Gastroenterologists inserted the sigmoidoscope further than nurse endoscopists (61 vs. 55 cm, respectively; P < 0.00001). Polyp location in the descending colon (odds ratio, 4.1; 95% confidence interval, 1.7-10.3) was highly associated with missed polyps. CONCLUSIONS: No differences in detection of adenomatous polyps or frequency of complications were found. These data suggest that experienced nurse endoscopists may perform screening flexible sigmoidoscopy as safely and as effectively as gastroenterologists.

Adult↗
PubMed2006

Yield of advanced adenoma and cancer based on polyp size detected at screening flexible sigmoidoscopy.

BACKGROUND & AIMS: Observational screening of the colon with subsequent referral for colonoscopy raises questions about the threshold of polyp size that necessitates referral. To examine the yield at colonoscopy when a given size lesion is observed, we assessed the yield of advanced adenoma and cancer at colonoscopy based on the size of the abnormality detected at flexible sigmoidoscopy (FSG). METHODS: We used data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a randomized, controlled, community-based study of FSG. RESULTS: Subsequent colonoscopy was performed on 10,850 subjects (60.4% male; mean age, 62.9 years) with a polyp visualized on screening FSG. For women with a polyp 0.5-0.9 cm on FSG (n = 1426), the yield in the distal colon on colonoscopy was 0.6% for cancer (number needed to screen [NNS] = 166) and 14.5% for advanced adenoma (NNS = 7). In men (n = 2183), the yield was 0.7% (NNS = 142) for cancer and 15.9% (NNS = 6) for advanced adenoma. Among persons with polyps 0.5-0.9 cm identified on FSG, 5.5% (198/3609) had distal advanced adenomas that measured <1.0 cm but had villous histology or high-grade dysplasia, and 9.9% (357/3609) had adenomas > or =1 cm. CONCLUSIONS: The yield for a distal advanced adenomatous lesion when a polyp 0.5-0.9 cm is observed at FSG is substantial and is due to the presence of advanced histology in polyps <1 cm and to detection of polyps that measure > or =1.0 cm on colonoscopy. Establishing thresholds for observation versus evaluation will require careful assessment of the overall yield.

Adenoma↗
PubMed2001

Colorectal polyps: Detection with multi-slice CT colonography.

PURPOSE: To compare the performance of virtual and conventional colonoscopy for the detection of colorectal polyps using a multislice spiral CT scanner (MSCT). MATERIALS AND METHODS: 48 patients (20 women, 28 men, mean age 61.5 years) with clinical indication for conventional colonoscopy were prospectively studied using a MSCT (Somatom Volume Zoom, Siemens, Forchheim). Examination was performed after standard oral preparation for colonoscopy and colonic distension with room air and i. v. butylscopolamin. Images were obtained in prone and supine position using a detector configuration of 4 x 1 mm, a table feed of 5 mm/rotation at 140 mAs and 120 kV. Slice thickness and reconstruction increment were 3 and 1.5 mm, respectively. CT data were assessed by two blinded radiologists on a Vitrea workstation (Vital Images, USA) using a software with multiplanar and volume-rendering capabilities. RESULTS: 33 patients had normal findings on conventional colonoscopy. In 15 patients a total of 30 polyps and one carcinoma with stenosis were identified. MSCT-colonography identified the carcinoma and 23 polyps (77 %). 3 of 3 polyps were 10 mm or more (100 %), 6 of 7 were 5.1 to 9.9 mm (86 %) and 14 of 20 were 5 mm or smaller (70 %). There were 13 false positive findings for polyps (10 lesions < 6 mm in 5 patients) and no false positive finding of carcinoma. CONCLUSIONS: MSCT colonography allows accurate detection of polyps larger than 10 mm. Compared to published results of single-slice CT, multislice CT colonography increases the rate of detection of small colorectal polyps in particular. However, false positive results still remain a problem.

Colonic Diseases↗
PubMed2003

A gastric hyperplastic polyp observed endoscopically before and after autoamputation.

Autoamputation of a gastric polyp is a relatively rare phenomenon and its precise mechanism is unclear. To learn more about the mechanism(s) involved, it is important to observe a polyp just before and just after its disappearance. We report a case of a gastric polyp that was observed endoscopically just before and then just after autoamputation. A 61-year-old woman with a thumb-sized, pedunculated hyperplastic polyp in the gastric antrum visited our institution for investigation of hematemesis. She was being treated with oral hypoglycaemic drugs for diabetes mellitus but was not taking any other medicine around that time. Emergency gastroscopy revealed a bleeding point near the polyp; gastroscopy the next day revealed that the polyp had disappeared. It was concluded that autoamputation of a gastric polyp may follow gastric injury induced by diabetes mellitus or oral antidiabetic drugs.

Diabetes Mellitus↗
PubMed1987

Geographic differences in the prevalence and distribution of large-bowel polyps--colonoscopic findings.

The large-bowel polyp pattern in two widely separated geographic regions of Sweden, Bollnäs in the central part and Trelleborg in the south, was studied prospectively by colonoscopic polypectomy. In Bollnäs 11.8% of 1,153 patients had neoplastic, and 3.8% hyperplastic, polyps. In Trelleborg 29% of 1,040 patients had neoplastic, and 17.3% hyperplastic, polyps. Furthermore, the Trelleborg patients had, on average, more polyps per patients than their Bollnäs counterparts: 2.0 versus 1.5 neoplastic, and 2.1 versus 1.7 hyperplastic, polyps. There was a marked difference in the anatomic location of the polyps between the two regions: in Trelleborg 55.4% of the neoplastic, and 40.5% of the hyperplastic polyps were distributed above the rectosigmoid, compared with 20.9% and 26.4%, respectively, in Bollnäs. The findings offer an explanation of the fact that the incidence of colorectal carcinoma in the Malmö region, close to the Trelleborg area, is the highest in Sweden.

Adult↗
PubMed1989

[Gallbladder polyps and gallbladder stones].

Over a period of 32 years 689 patients with upper abdominal symptoms were examined radiologically at least twice for gall-bladder polyps and stones. All were without evidence of stones initially, but 181 had gall-bladder polyps on first examination. During a mean observation period of 9 1/2 years gall-bladder stones occurred in 18% (pigment stones in about 24%, solitary cholesterol stones in 30% and multiple ones in 46%), regardless of the presence or absence of gall-bladder polyps. There was no evidence for a change from polyps to stones. Cholesterolosis runs through four stages in the course of decades; accumulation of cholesterol esters in subepithelial foam-cell nests is characteristic. 95% of gall-bladder polyps are cholesterol polyps which gradually empty. Prophylactic cholecystectomy for gall-bladder polyps is justified only if they are more than 10 mm in diameter.

Adolescent↗
PubMed1985

Dominant inheritance of adenomatous colonic polyps and colorectal cancer.

Except in the rare polyposis syndromes, the contribution of heritable factors to the genesis of colorectal cancer and adenomatous polyps is not well understood. We examined the inheritance of susceptibility to colonic polyps and cancer in a large Utah pedigree with multiple cases of common colorectal cancer but no recognizable inheritance pattern among them. Inheritance was clarified, however, by systematic screening for colonic polyps in pedigree members and spouse controls, using flexible proctosigmoidoscopy. One or more adenomatous polyps were found in 21 per cent of family members (41 of 191) but in only 9 per cent of controls (12 of 132) (P less than 0.005). Pedigree analysis was performed with likelihood methods that compared random occurrence of cancer and polyps with autosomal recessive and autosomal dominant patterns of inheritance. The analysis suggested that the observed excess of discrete adenomatous polyps and colorectal cancers was the result of an inherited autosomal dominant gene for susceptibility, rather than an inherited recessive gene for susceptibility or a chance occurrence. This type of inheritance of colorectal polyps and cancer may be more common than previously recognized.

Adult↗
PubMed2001

Free radical damage in nasal polyp tissue.

OBJECTIVE: To investigate whether the free radical injury in nasal polyp tissue exists or not. STUDY DESIGN: A prospective study in patients with nasal polyps. METHODS: Polyp specimens were obtained from 19 patients. Control specimens were acquired from 16 patients who underwent partial turbinectomy with concha bullosa free of rhinitis, sinusitis, and allergy, confirmed by endoscopic nasal examination, coronal paranasal sinus CT scan, and prick test. MDA levels of nasal polyps and control specimens were measured by using the method of Knudsen et al. RESULTS: The mean MDA levels of nasal polyps and control specimens were 38.2 +/- 5.1 (33.3-52.2) and 33.9 +/- 1.6 (32.6-37.4), respectively. MDA levels in NP were significantly higher compared with control specimens (P < 0.01). CONCLUSION: High level of MDA in nasal polyp tissue that represents FR increase supports the existence of cell injury in nasal polyp tissue. FRs should be considered in the development and life cycles of NP which is thought to have multifactorial pathogenesis.

Adult↗
PubMed2000

Polyp and fibrous adhesion formation in acute otitis media caused by non-typeable or type b Haemophilus influenzae or Moraxella catarrhalis.

Among a variety of other histopathologic changes, polyps and fibrous adhesions are readily formed in the middle ear mucosa during experimental acute otitis media (AOM) caused by Streptococcus pneumoniae. Quantitative studies on experimental AOM caused by other bacteria have shown that some of these histopathologic changes, such as adaptive bone modeling and increase in goblet cell density, differ according to the type of bacteria. This investigation surveys polyp and fibrous adhesion formation in experimental AOM caused by either non-typeable or type b Haemophilus influenzae, or Moraxella catarrhalis. Seventy-five rats were inoculated with 1 of these 3 bacteria (25 rats in each of 3 groups). Five rats from each group were sacrificed on days 4, 8, 16, 60 and 180 post-inoculation. The middle ear mucosae were dissected and histopathologic changes in whole-mount and section preparations were studied using light microscopy. Polyps were found in most ears and in the greatest numbers on the early days; fewer polyps were found on the later days, regardless of the type of bacteria. However, non-typeable and type b H. influenzae induced formation of significantly more polyps than M. catarrhalis. The polyps were primarily located in the epitympanum. Fibrous adhesions were primarily located in the hypotympanum and formed in almost all ears, on all days post-inoculation, regardless of the type of bacteria. Numbers increased to a peak on day 16 and then decreased. Non-typeable and type b H. influenzae induced formation of significantly more adhesions than M. catarrhalis, and the middle ears displayed a higher number of persisting adhesions in the animals inoculated with non-typeable H. influenzae. We conclude that polyps and adhesions are formed in experimental AOM regardless of bacterial type, confirming a pathogenesis based on inflammation. Both types of H. influenzae induce formation of greater numbers of polyps/adhesions than M. catarrhalis, and the non-typeable form causes more adhesive sequelae in the mucosa than the encapsulated type b.

Acute Disease↗
PubMed2002

Upregulation of MUC8 and downregulation of MUC5AC by inflammatory mediators in human nasal polyps and cultured nasal epithelium.

Polyps are believed to be the source of mucus hypersecretion in chronic inflammation of the sinus. However, it is not clear which mucins are responsible for the hypersecretion of mucus by nasal polyps. We describe the over-expression of MUC8 mRNA in nasal polyps and the upregulation of MUC8 mRNA expression and downregulation of MUC5AC mRNA expression by inflammatory mediators. We found that the level of MUC8 mRNA, but not the level of MUC5AC mRNA, increased in nasal polyps. We also found that there was an increase in intracellular mucin in nasal polyps, compared to the normal nasal inferior turbinate. A mixture of inflammatory mediators increased MUC8 mRNA expression and decreased MUC5AC mRNA expression in cultured normal human nasal epithelial cells. Among inflammatory mediators, IL-4 is responsible for the decrease in MUC5AC mRNA and MUC5AC mucin secretion. These results indicate that MUC8 may be one of the major mucins secreted from the polyp epithelium and that it may play an important role in the pathogenesis of mucus hypersecretion in chronic sinusitis with polyps.

Cells, Cultured↗
PubMed2002

Laparoscopic "radical appendectomy" is an effective alternative to endoscopic removal of cecal polyps.

BACKGROUND: The endoscopic removal of cecal polyps can be complicated by hemorrhage, perforation, or incomplete resection. Laparoscopic radical appendectomy represents a safe alternative for the definitive resection and accurate pathologic evaluation of selected cecal polyps. METHODS: Patients with cecal cap polyps not involving the ileocecal valve were candidates for laparoscopic radical appendectomy. Intraoperative colonoscopy and resection of the appendix and cecum to the level of the ileocecal valve were accomplished via three midline ports. For each patient, histologic evaluation by frozen section ruled out malignancy and ensured complete resection. RESULTS: Five patients, four of whom had significant medical comorbidities, presented with large adenomatous polyps contained within the cecum. Each polyp was determined to be unresectable endoscopically; therefore, a laparoscopic radical appendectomy was performed. One patient with cirrhosis also underwent intraoperative liver ultrasonography and biopsies, which contributed to the longest operative time and hospital stay. The histologic diagnosis by frozen section was benign for each patient. The mean operative time was 95 minutes, and the mean length of hospital stay was 1.8 days. No postoperative complications were observed during a mean follow-up of 6 months. CONCLUSION: Laparoscopic "radical appendectomy" is an effective treatment for selected cecal adenomatous polyps. Our ability to resect the polyps completely and avoid a standard right hemicolectomy supports this approach.

Adenomatous Polyps↗
PubMed1997

Suppression of intestinal polyp development by low-fat and high-fiber diet in Apc(delta716) knockout mice.

Most epidemiological and animal studies show a positive correlation of the dietary intake of fat with the incidence of colon cancer, whereas an inverse correlation of the dietary intake of fiber. In rats fed a diet low in fat and high in wheat bran fiber and calcium, a significant decrease was reported in the number of azoxymethane-induced aberrant crypt foci compared with those fed a high-fat, low-fiber and low-calcium diet. Mutations in the human APC gene play a key role, not only in familial adenomatous polyposis, but also in many sporadic cancers of the entire digestive tract. We previously constructed a mouse strain Apc(delta716), carrying a truncation mutation at codon 716 of the Apc gene, the homolog of human APC (10). The heterozygous mice developed numerous intestinal polyps, and all microadenomas dissected from the earliest polyps had already lost the wild-type allele, indicating the loss of heterozygosity. Using these Apc(delta716) knockout mice, we have investigated the effect of a low-fat and high-fiber diet (LRD for 'low-risk' diet) on intestinal polyposis, and compared it with that of a high-fat and low-fiber diet (HRD for 'high-risk' diet). The mice were fed either diet for 7 weeks, and the number and size of intestinal polyps were scored. The LRD-fed mice had fewer polyps than the HRD-fed mice, by 36% in the small intestine and by 64% in the colon. As for the polyp size distribution, there was no significant difference between the HRD- and LRD-fed mice. These results indicate that LRD can suppress intestinal polyposis compared with HRD which does not, and suggest that its suppression is at the initiation of polyp formation. This is likely to be due to a decreased frequency of loss of heterozygosity, rather than a retarded growth of the polyp adenomas.

Animals↗
PubMed1982

Gastric polyps.

We suggest an approach to patients with gastric polyps, based on a study of 73 patients seen at this institution over a 5-year period. There were 40 cases of adenomatous and 20 cases of hamartomatous polyps. Differentiation between these two groups of polyps was not possible on the basis of clinical presentation, laboratory data, radiological, or endoscopic appearance. Differentiation was possible only on histologic examination of a totally resected specimen. In this series, only the adenomatous polyps were associated with gastric cancers in five patients. Since the malignancy either preceded or followed the recognition of adenomatous polyps, it is important to establish an early definite histological diagnosis. Patients with known adenomatous polyps should be followed closely for the development of gastric carcinoma, even after the polyps have been removed.

Adenoma↗
PubMed2000

Regulation of immunoglobulin secretion by plasma cells infiltrating nasal polyps.

OBJECTIVE/HYPOTHESIS: To learn more about the role of plasma cells infiltrating nasal polyps in the pathogenesis of nasal polyposis, we examined their function by analyzing immunoglobulin (Ig) production and the factors implicated in the secretion. STUDY DESIGN: A series of 19 consecutive nasal polyp tissue samples and, as a control, peripheral blood samples from the same patients, were studied by histopathological and immunological examination. METHODS: Hematoxylin-eosin and immunohistochemical staining was carried out to identify plasma cells infiltrating nasal polyps. Nasal polyp mononuclear cells (NPMNCs) were purified from nasal polyp tissue samples, and Ig-secreting cells were identified in cytospin preparations stained with fluorescein isothiocyanate-conjugated antibodies against IgA, IgG, IgM, and IgE. Purified NPMNCs were cultured in basal conditions and after the addition of several stimuli. Ig secreted into the culture supernatants was evaluated by an enzyme-linked immunosorbent assay. RESULTS: Plasma cells accounted for an important fraction of the inflammatory infiltrate. The main Ig isotype synthesized by these cells was IgA, whereas little IgE was detected. In vitro cultures demonstrated that the plasma cells actively secreted Ig for a short period. When cytokine dependence was analyzed, interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) were shown to be partially responsible for the Ig production. Dependence on CD95-mediated apoptosis was not observed. CONCLUSIONS: Nasal polyp-infiltrating plasma cells are mainly IgA-secreting cells, the latter property being related to the mucosal immune system. The IgA production is partly dependent on IL-10 and TNF-alpha. The absence of IgE-secreting cells in most of the samples suggests that a type I hypersensitivity reaction is not essential for the development of nasal polyp.

Adolescent↗
PubMed2002

HLA-DR and ICAM-1 expression and modulation in epithelial cells from nasal polyps.

OBJECTIVE/HYPOTHESIS: Through human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1) expression, nasal epithelial cells could actively participate in the chronic inflammation and eosinophil infiltration observed in nasal polyps. The objective of the study was to evaluate HLA-DR and ICAM-1 expression in polyp epithelium and in a culture model of polyp epithelial cells allowing ciliated and secretory differentiation. STUDY DESIGN: Prospective non-randomized controlled in vitro study. METHODS: The in vitro HLA-DR and ICAM-1 expression was studied under basal conditions or after exposure to interferon-gamma, transforming growth factor-beta1, lipopolysaccharide, dexamethasone, or cetirizine. HLA-DR and ICAM-1 expression was investigated in situ by immunohistochemical staining of polyps and in vitro by immunofluorescent staining of cell cultures. HLA-DR and ICAM-1 were localized in cultured cells by confocal microscopy. Cultured cells expressing HLA-DR and ICAM-1 were quantified by flow cytometry. RESULTS: Both HLA-DR and ICAM-1 showed significant immunostaining of nasal polyp epithelium. In nasal polyp epithelial cell cultures, less than 5% of cells were positive for HLA-DR whereas 40% were positive for ICAM-1 at day 3. In vitro, HLA-DR was mainly located in the cytoplasm and ICAM-1 predominated on the apicolateral cytoplasmic membrane. Comparison of in situ and in vitro results showed that well-differentiated and poorly differentiated cells predominantly expressed HLA-DR and ICAM-1, respectively. Interferon-gamma significantly increased HLA-DR and ICAM-1 expression, whereas transforming growth factor-beta1 significantly decreased HLA-DR expression and lipopolysaccharide significantly increased ICAM-1 expression. CONCLUSION: HLA-DR and ICAM-1 epithelial expression in nasal polyps in situ and in vitro and their in vitro modulation reinforce the active role of epithelial cells in chronic inflammatory diseases of the upper airways.

Analysis of Variance↗
PubMed2004

Regression of a sphenochoanal polyp in a child.

OBJECTIVES: To present an unusual case of a sphenochoanal polyp that regressed and review the etiology of such polyps in comparison to the commoner antrochoanal polyp. STUDY DESIGN: Case study. METHODS: One was incidentally discovered in a girl aged 3 years, 8 months at postnasal mirror examination after adenotonsillectomy. RESULTS: Computed tomography scans 1 month later confirmed the polyp, but three months later, MRI scans only revealed sphenoid sinus opacification. Sphenoidotomy revealed normal sinuses implying inflammation had resolved. CONCLUSION: This patient is believed to be the youngest reported to have sphenochoanal polyp, and the only one where the polyp had completely regressed. This regression suggests that sphenochoanal polyps may be more common than is thought but are mostly asymptomatic.

Adenoidectomy↗