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Polyps of colon and small intestine [keywords]
- Sesamol suppresses cyclooxygenase-2 transcriptional activity in colon cancer cells and modifies intestinal polyp development in Apc (Min/+) mice. [Journal Article]
- J Clin Biochem Nutr 2014 Mar; 54(2):95-101.
Excessive prostaglandin production by cyclooxygenase-2 in stromal and epithelial cells is a causative factor of colorectal carcinogenesis. Thus, compounds which inhibit cyclooxygenase-2 transcriptional activity in colon epithelial cells could be candidates for anti-carcinogenic agents. A cyclooxygenase-2 transcriptional activity in the human colon cancer cell line DLD-1 has been measured using a β-galactosidase reporter gene system. Using this system, we demonstrated that the decrease in basal cyclooxygenase-2 transcriptional activities at 100 µM sesamol, one of the lignans in sesame seeds, was 50%. Other compounds in sesame seeds such as sesamin, sesamolin, ferulic acid, and syringic acid did not exhibit significant suppression of cyclooxygenase-2 transcriptional activity at up to 100 µM. In a following experiment, 6-week-old male Min mice, Apc-deficient mice, were divided into a non-treated and 500 ppm sesamol groups. At the age of 15 weeks, it was found that treatment with sesamol decreased the number of polyps in the middle part of small intestine to 66.1% of the untreated value. Moreover, sesamol suppressed cyclooxygenase-2 and cytosolic prostaglandin E2 synthase mRNA in the polyp parts. The present findings may demonstrate the novel anti-carcinogenetic property of sesamol, and imply that agents that can suppress cyclooxygenase-2 expression may be useful cancer chemopreventive agents.
- The comparative study of acetyl-11-keto-beta-boswellic acid (AKBA) and aspirin in the prevention of intestinal adenomatous polyposis in APC(Min/+) mice. [Comparative Study, Journal Article, Research Support, Non-U.S. Gov't]
- Drug Discov Ther 2014 Feb; 8(1):25-32.
Acetyl-11-keto-beta-BA (AKBA), a component of the gum resin of Boswellia serrata, has been recognized as a promising agent for the prevention of intestinal tumorigenesis. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), has also been considered to have the activity against intestinal tumorigenesis. However, the prevention of colonic cancer is insufficient and no definitive recommendation has been made for clinic use. Herein, we compared the efficacy of AKBA with that of aspirin in an adenomatous polyposis coli intestinal neoplasia consecutive weeks. Mice were sacrificed by anesthetizing. The whole intestine was removed from each mouse. The number, size and histopathology of intestinal adenomatous polyps were examined under microscopy. The adenomatous polyps were removed for further analysis by the assays of western blotting and immunohistochemical staining. AKBA significantly prevented the formation of intestinal adenomatous polyps without toxicity to mice. Statistical analysis indicated that AKBA's activity both in the prevention of small intestinal and colonic polyps was more potently than aspirin. Histopathologic examination revealed that AKBA's effect, that is the reduction of polyp size and degree of dysplasia, was more prominent in larger sized polyps, especially those originating in colon. These effects of AKBA were associated with its role in the induction of apoptosis in carcinomas. The assays of western blotting and immunohistochemistry staining indicated that the efficacy of AKBA might arise from its activity in the modulation of the Wnt/β-catenin pathway and NF-κB/COX-2 pathway in adenomatous polyps. Conclusion, AKBA by oral application prevented intestinal tumorigenesis more potential than aspirin.
- Colon capsule endoscopy: detection of colonic polyps compared with conventional colonoscopy and visualization of extracolonic pathologies. [Comparative Study, Journal Article]
- Can J Gastroenterol Hepatol 2014 Feb; 28(2):77-82.
Conventional colonoscopy (CC) is the gold standard for diagnostic examination of the colon. However, the overall acceptance of this procedure is low due to patient fears of complications or embarrassment. Colon capsule endoscopy (CCE) represents a minimally invasive, patient-friendly procedure that offers complete visualization of the entire intestine.To assess the PillCam Colon 2 (Given Imaging Ltd, Israel) capsule with regard to feasibility, sensitivity and specificity for the detection of colonic pathologies and additional recorded extracolonic findings.CCE was performed before CC in patients indicated for CC for known or suspected colonic disease. The results of both techniques were compared with regard to polyp detection. Additionally, bowel preparation and extracolonic pathologies were analyzed.Twenty-four patients (mean age 51.1 years) were included in the analysis. Visualization of the colon was complete in 23 CCs and 17 CCEs. No adverse events or major technical failures occurred. CC detected 47 polyps and CCE detected 43 polyps of any size (per-finding sensitivity 90.9%, specificity 67.6%). The accuracy of CCE in detecting polyp carriers was 81.5% (per-patient analysis). On average, the colon was adequately cleansed in 90.1% of patients. CCE identified esophageal, gastric and small bowel pathologies in seven (24%), nine (38%) and 14 (58%) patients, respectively.CCE proved to be technically feasible and safe. Acceptable sensitivity and moderate specificity levels in polyp detection were recorded. Bowel preparation was adequate in most patients. Because extracolonic pathologies were effectively visualized, new indications for the PillCam Colon 2 may be defined.
- Histomorphological profile of colonoscopic biopsies and pattern of colorectal carcinoma in Kavre district. [Journal Article]
- Kathmandu Univ Med J (KUMJ) 2013 Jul-Sep; 11(43):196-200.
Colonoscopy is the method to visualize the mucosa of the entire colon and terminal ileum to detect the intestinal abnormalities and obtain biopsy for definitive diagnosis. For clinical decisions in the diagnosis of various colonic lesions unambiguous interpretation of colorectal biopsies is necessary.To assess the prevalence pattern of colonic diseases and to correlate the incidence of colorectal carcinoma with age, sex, site and symptoms presented at Dhulikhel Hospital.The materials consisted of 126 biopsies which were submitted to the Department of Pathology, Kathmandu University School of Medical Sciences, Dhulikhel, during the period of July 2011-July 2012. Data collected and entered in MS-Excel and were analyzed using SPSS-16.Out of 126 colonoscopic biopsies 34(27%) showed chronic nonspecific inflammation, followed by carcinoma 25(19.8%), non-neoplastic polyps 21(16.7%), granulomatous inflammation 14(11.1%), neoplastic polyps 8(6.3%), ulcerative colitis 4(3.2%). Miscellaneous lesions; acute focal colitis, eosinophilic colitis were also observed in 19 (15.1%). A higher frequency of colonic diseases in males with a male to female ratio of 1.4:1 and age range of two years to 84 years was observed. Out of 25 patients diagnosed with colorectal carcinoma,48% (n=12) were males and 52% (n=13) were females with a mean age of 55.17 years in men and 59.46 years in females. Male and female ratio among cancer groups was 1:1.08. Total 36% (n=9) were diagnosed with cancer before the age of 50. Out of these nine cases, 6( 66.7%) were males and 3(33.3%) were females. The male and female ratio in younger and older age groups were 2:1 and 1:1.7 . 17( 68%) of the lesions were left sided and 8(32%) were right sided. Below age 50 , left to Right sided lesions in males were 2:1 and in females 1:2. However, above 50 years the ratio among proximal and distal lesions were 5:1 in males and 2.3:1 in females. A statistically significant association was seen between the growth (p=0.000) and per rectal bleeding (p= 0.006) with carcinoma.The most prevalent lesion in colorectal biopsies was non-specific colitis followed by carcinoma colon. The incidence of colorectal carcinoma is on rise in Nepalese society. Although colorectal carcinoma is more common in older age group the incidence are also increasing among young especially among women.
- Small bowel tumors detected and missed during capsule endoscopy: single center experience. [Journal Article, Research Support, Non-U.S. Gov't]
- World J Gastroenterol 2013 Dec 21; 19(47):9043-8.
To characterize small bowel (SB) tumors detected by capsule endoscopy (CE), and identify missed tumors.The study included 145 consecutive patients in whom 150 CEs were performed. Following CE, the medical records of the study population were reviewed. Results of double- or single-balloon enteroscopy performed after CE and the results of surgery in all patients operated on were retrieved. The patients were contacted through telephone interviews or postal mail. In addition, the national cancer registry and the polish clinical gastrointestinal stromal tumor (GIST) Registry were searched to identify missed neoplasms.Indications for CE included overt and occult obscure gastrointestinal bleeding (n = 81, 53.7%), anemia (n = 19, 12.7%), malabsorption (n = 18, 12%), abnormal CB follow through (n = 9, 6%), abdominal pain (n = 7, 5%), celiac disease (n = 5, 3%), neuroendocrine tumor (n = 3, 2%), Crohn's disease (n = 2, < 2%), Peutz-Jeghers syndrome (n = 2, < 2%), other polyposes (n = 2, < 2%), and diarrhea (n = 2, < 2%). The capsule reached the colon in 115 (76.6%) examinations. In 150 investigations, CE identified 15 SB tumors (10%), 14 of which were operated on or treated endoscopically. Malignancies included metastatic melanoma (n = 1), adenocarcinoma (n = 2), and GIST (n = 3). Benign neoplasms included dysplastic Peutz-Jeghers polyps (n = 4). Non-neoplastic masses included venous malformation (n = 1), inflammatory tumors (n = 2), and a mass of unknown histology (n = 1). During the follow-up period, three additional SB tumors were found (2 GISTs and one mesenteric tumor of undefined nature). The National Cancer Registry and Polish Clinical GIST Registry revealed no additional SB neoplasms in the post-examination period (follow-up: range 4.2-102.5 mo, median 39 mo). The sensitivity of CE for tumor detection was 83.3%, and the negative predictive value was 97.6%. The specificity and positive predictive value were both 100%.Neoplasms may be missed by CE, especially in the proximal SB. In overt obscure gastrointestinal bleeding, complementary endoscopic and/or radiologic diagnostic tests are indicated.
- Wireless capsule endoscopy. [Journal Article, Review]
- Gastrointest Endosc 2013 Dec; 78(6):805-15.
Over the last decade, WCE has established itself as a valuable test for imaging the small intestine. It is a safe and relatively easy procedure to perform that can provide valuable information in the diagnosis of small-bowel conditions. Its applications still remain limited within the esophagus and colon. Future developments may include improving visualization within the esophagus and developing technologies that may allow manipulation of the capsule within the GI tract and biopsy capabilities.
- Surgical alternatives in the treatment of intestinal intussusceptions resulting from polyps in adults. [Comparative Study, Journal Article]
- Am Surg 2013 Sep; 79(9):933-8.
Adult intussusception is an uncommon disease requiring surgical intervention. The aim of this study is to discuss the surgical alternatives and share our experience in the treatment of adult patients with intussusceptions formed as a result of polyps. The retrospective study included 16 adult patients who underwent surgery after the diagnosis of intestinal invaginations resulting from polyps between the years 2000 and 2011. Sixteen patients (seven males and nine females; mean age, 48.18 years; range, 18 to 76 years) presented with intestinal intussusceptions. Although a preoperative diagnosis was carried out in 11 (68.75%) patients, the diagnosis was made intraoperatively in five patients (31.25%). Among the patients, seven (43.8%) had undergone emergency surgeries and nine (52.8) had elective surgery. The invagination in 12 patients (75%) was located in the small intestine, in two patients (12.5%) in the colon, and in a further two patients (12.5%), it was ileocecally located. Ten patients (62.5%) had segmental resection + anastomosis; three patients underwent (18.8%) segmental resection + enterostomy, and three (18.8%) received hemicolectomies. In adults, surgical treatment is always the primary option in intussusceptions resulting from polyps. Although the surgical method of choice in colonically located ones is en bloc resection without reduction, because the polyps located in the small intestine are usually of a benign nature, segmental resection with reduction should be performed in elective surgery and segmental resection without reduction should be performed in emergency cases.
- Rectal carcinoma in a young female patient with Peutz-Jeghers syndrome: a case report. [Case Reports, Journal Article, Research Support, Non-U.S. Gov't]
- Med Princ Pract 2014; 23(1):89-91.
To report a case of rectal cancer in a patient with Peutz-Jeghers syndrome (PJS).A 20-year-old woman with intermittent bloody stool of 4 months was admitted for examination. Gastroendoscopy revealed multiple polyps involving the stomach, small intestine, colon and a rectal adenocarcinoma. A diagnosis of PJS was made based on intestinal polyps with characteristic pathology and melanotic macules on the lips. After surgery and chemotherapy upon follow-up at 8 months, the patient did not have any signs of recurrence.This case showed that rectal carcinoma should be considered for young patients with PJS.
- Epimorphin deletion inhibits polyposis in the Apcmin/+ mouse model of colon carcinogenesis via decreased myofibroblast HGF secretion. [Journal Article, Research Support, N.I.H., Extramural]
- Am J Physiol Gastrointest Liver Physiol 2013 Oct 15; 305(8):G564-72.
Interactions between the epithelium and surrounding mesenchyme/stroma play an important role in normal gut morphogenesis, the epithelial response to injury, and epithelial carcinogenesis. The tumor microenvironment, composed of stromal cells including myofibroblasts and immune cells, regulates tumor growth and the cancer stem cell niche. Deletion of epimorphin (Epim), a syntaxin family member expressed in myofibroblasts and macrophages, results in partial protection from colitis and from inflammation-induced colon cancer in mice. We sought to determine whether epimorphin deletion protects from polyposis in the Apcmin/+ mouse model of intestinal carcinogenesis. Epim-/- mice were crossed to Apcmin/+ mice; Apcmin/+ and Apcmin/+/Epim-/- mice were killed at 3 mo of age. Polyp numbers and sizes were quantified in small intestine and colon, and gene expression analyses for pathways relevant to epithelial carcinogenesis were performed. Primary myofibroblast cultures were isolated, and expression and secretion of selected growth factors from Apcmin/+ and Apcmin/+/Epim-/- myofibroblasts were examined by ELISA. Small bowel polyposis was significantly inhibited in Apcmin/+/Epim-/- compared with Apcmin/+ mice. Apcmin/+/Epim-/- compared with Apcmin/+ polyps and adjacent uninvolved intestinal mucosa had increased transforming growth factor-β (TGF-β) expression and signaling with increased P-Smad2/3 expression. Myofibroblasts isolated from Apcmin/+/Epim-/- vs. Apcmin/+ mice had markedly decreased hepatocyte growth factor (HGF) expression and secretion. We concluded that Epim deletion inhibits polyposis in Apcmin/+ mice, associated with increased mucosal TGF-β signaling and decreased myofibroblast HGF expression and secretion. Our data suggest that Epim deletion reduces tumorigenicity of the stromal microenvironment.
- Chemoprevention of colon and small intestinal tumorigenesis in APC(min/+) mice by SHetA2 (NSC721689) without toxicity. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- Cancer Prev Res (Phila) 2013 Sep; 6(9):908-16.
The occurrence of intestinal polyps in people at high risk for developing colorectal cancer provides an opportunity to test the efficacy of chemoprevention agents. In this situation of treating otherwise healthy people, the potential for toxicity must be minimal. The small-molecule flexible heteroarotinoid (Flex-Het), called SHetA2, has chemoprevention activity in organotypic cultures in vitro and lack of toxicity at doses capable of inhibiting xenograft tumor growth in vivo. The objective of this study was to evaluate SHetA2 chemoprevention activity and toxicity in the APC(min/+) murine model. Oral administration of SHetA2 at 30 and 60 mg/kg five days per week for 12 weeks significantly reduced development of intestinal polyps by 40% to 60% depending on the dose and sex of the treatment group. Immunohistochemical and Western blot analysis of polyps showed reduced levels of cyclin D1 and proliferating cell nuclear antigen in both SHetA2 treatment groups. Western blot analysis also showed SHetA2 induction of E-cadherin, Bax, and caspase-3 cleavage along with reduction in Bcl-2, COX-2, and VEGF, consistent with SHetA2 regulation of apoptosis, inflammation, and angiogenesis. Neither dose caused weight loss nor gross toxicity in APC(min/+) or wild-type littermates. Magnetic resonance imaging (MRI) of cardiac function showed no evidence of SHetA2 toxicity. SHetA2 did not alter left ventricular wall thickness. In summary, SHetA2 exerts chemoprevention activity without overt or cardiac toxicity in the APC(min/+) model. SHetA2 modulation of biomarkers in colon polyps identifies potential pharmacodynamic endpoints for SHetA2 clinical trials.