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Polyps of colon and small intestine [keywords]
- Multitargeted low-dose GLAD combination chemoprevention: a novel and promising approach to combat colon carcinogenesis. [Journal Article, Research Support, N.I.H., Extramural]
- Neoplasia 2013 May; 15(5):481-90.
Preclinical studies have shown that gefitinib, licofelone, atorvastatin, and α-difluoromethylornithine (GLAD) are promising colon cancer chemopreventive agents. Because low-dose combination regimens can offer potential additive or synergistic effects without toxicity, GLAD combination was tested for toxicity and chemopreventive efficacy for suppression of intestinal tumorigenesis in adenomatous polyposis coli (APC)(Min/+) mice. Six-week-old wild-type and APC(Min/+) mice were fed modified American Institute of Nutrition 76A diets with or without GLAD (25 + 50 + 50 + 500 ppm) for 14 weeks. Dietary GLAD caused no signs of toxicity based on organ pathology and liver enzyme profiles. GLAD feeding strongly inhibited (80-83%, P < .0001) total intestinal tumor multiplicity and size in APC(Min/+) mice (means ± SEM tumors for control vs GLAD were 67.1 ± 5.4 vs. 11.3 ± 1.1 in males and 72.3 ± 8.9 vs 14.5 ± 2.8 in females). Mice fed GLAD had >95% fewer polyps with sizes of >2 mm compared with control mice and showed 75% and 85% inhibition of colonic tumors in males and females, respectively. Molecular analyses of polyps suggested that GLAD exerts efficacy by inhibiting cell proliferation, inducing apoptosis, decreasing β-catenin and caveolin-1 levels, increasing caspase-3 cleavage and p21, and modulating expression profile of inflammatory cytokines. These observations demonstrate that GLAD, a novel cocktail of chemopreventive agents at very low doses, suppresses intestinal tumorigenesis in APC(Min/+) mice with no toxicity. This novel strategy to prevent colorectal cancer is an important step in developing agents with high efficacy without unwanted side effects.
- Grape antioxidant dietary fiber inhibits intestinal polyposis in ApcMin/+ mice: relation to cell cycle and immune response. [Journal Article, Research Support, Non-U.S. Gov't]
- Carcinogenesis 2013 Aug; 34(8):1881-8.
Epidemiological and experimental studies suggest that fiber and phenolic compounds might have a protective effect on the development of colon cancer in humans. Accordingly, we assessed the chemopreventive efficacy and associated mechanisms of action of a lyophilized red grape pomace containing proanthocyanidin (PA)-rich dietary fiber [grape antioxidant dietary fiber (GADF)] on spontaneous intestinal tumorigenesis in the Apc(Min/+) mouse model. Mice were fed a standard diet (control group) or a 1% (w/w) GADF-supplemented diet (GADF group) for 6 weeks. GADF supplementation greatly reduced intestinal tumorigenesis, significantly decreasing the total number of polyps by 76%. Moreover, size distribution analysis showed a considerable reduction in all polyp size categories [diameter <1mm (65%), 1-2mm (67%) and >2mm (87%)]. In terms of polyp formation in the proximal, middle and distal portions of the small intestine, a decrease of 76, 81 and 73% was observed, respectively. Putative molecular mechanisms underlying the inhibition of intestinal tumorigenesis were investigated by comparison of microarray expression profiles of GADF-treated and non-treated mice. We observed that the effects of GADF are mainly associated with the induction of a G1 cell cycle arrest and the downregulation of genes related to the immune response and inflammation. Our findings show for the first time the efficacy and associated mechanisms of action of GADF against intestinal tumorigenesis in Apc(Min/+) mice, suggesting its potential for the prevention of colorectal cancer.
- Muco-submucosal elongated polyps of the gastrointestinal tract: a case series and a review of the literature. [Case Reports, Journal Article, Review]
- World J Gastroenterol 2013 Mar 21; 19(11):1845-9.
We present three cases of gastrointestinal muco-submucosal elongated polyps, two located in the duodenum and one in the descending colon. All three cases had a characteristic, "worm-like" endoscopic appearance and were lined by unremarkable mucosa. The vascular component was located in the submucosa and was composed of a mixture of variably dilated blood vessels (capillaries and veins) and lymphatics. The duodenal polyps displayed lipomatous metaplasia of the submucosal stroma. The dual vascular phenotype of the vascular component was confirmed by immunohistochemistry with D2-40 and CD31.
- Clinical usefulness of single-balloon endoscopy in patients with previously incomplete colonoscopy. [Journal Article]
- World J Gastrointest Endosc 2013 Mar 16; 5(3):117-21.
To evaluate the clinical usefulness of single-balloon endoscopy (SBE) in patients in whom a colonoscope was technically difficult to insert previously.The study group comprised 15 patients (8 men and 7 women) who underwent SBE for colonoscopy (30 sessions). The number of SBE sessions was 1 in 7 patients, 2 in 5 patients, 3 in 1 patient, 4 in 1 patient, and 6 in 1 patient. In all patients, total colonoscopy was previously unsuccessful. The reasons for difficulty in scope passage were an elongated colon in 6 patients, severe intestinal adhesions after open surgery in 4, an elongated colon and severe intestinal adhesions in 2, a left inguinal hernia in 2, and multiple diverticulosis of the sigmoid colon in 1. Three endoscopists were responsible for SBE. The technique for inserting SBE in the colon was basically similar to that in the small intestine. The effectiveness of SBE was assessed on the basis of the success rate of total colonoscopy and the presence or absence of complications. We also evaluated the diagnostic and treatment outcomes of colonoscopic examinations with SBE.Total colonoscopy was successfully accomplished in all sessions. The mean insertion time to the cecum was 22.9 ± 8.9 min (range 9 to 40). Abnormalities were found during 21 sessions of SBE. The most common abnormality was colorectal polyps (20 sessions), followed by radiation colitis (3 sessions) and diverticular disease of the colon (3 sessions). Colorectal polyps were resected endoscopically in 15 sessions. A total of 42 polyps were resected endoscopically, using snare polypectomy in 32 lesions, hot biopsy in 7 lesions, and endoscopic mucosal resection in 3 lesions. Fifty-six colorectal polyps were newly diagnosed on colonoscopic examination with SBE. Histopathologically, these lesions included 2 intramucosal cancers, 42 tubular adenomas, and 2 tubulovillous adenomas. The mean examination time was 48.2 ± 20.0 min (range 25 to 90). Colonoscopic examination or endoscopic treatment with SBE was not associated with any serious complications.SBE is a useful and safe procedure in patients in whom a colonoscope is technically difficult to insert.
- [Serrated polyps of the duodenum. Three cases with immunohistological and molecular pathological findings]. [English Abstract, Journal Article]
- Pathologe 2013 Jul; 34(4):347-51.
We report on three cases of serrated polyps of the duodenum which were incidental endoscopic findings in three male patients with a median age of 70 years (range 63-84 years). Architecturally the histological findings in cases 1 and 2 were similar to hyperplastic polyps of the colon. In case 3 there was a low grade intraepithelial neoplasia which covered the whole polyp. This polyp relapsed after 2 years with similar histological findings. Immunohistochemically an increased proliferative activity was found in case 3 as well as associated overexpression of p16 (INK4a) and p53. No abnormal expression of MLH1 and β-catenin was found in any of the polyps. Molecular pathological analysis showed a BRAF mutation (V600E) in case 3. A wild type sequence in the KRAS gene was found in all polyps. In conclusion, serrated polyps should be included in the diagnostic spectrum of benign duodenal polyps.
- Single-incision laparoscopic colectomy: training the next generation. [Journal Article]
- Surg Endosc 2013 May; 27(5):1784-90.
Single-incision laparoscopic colectomy (SILC) is touted to be an improved approach for minimally invasive surgery although no data currently exists regarding the acquisition of skills for the safe performance of this technique. The authors report their early experience with proctoring of surgical residents in SILC by experienced colorectal surgeons.Data regarding patient demographics, operative data, and short-term outcomes were prospectively collected at two surgical training hospitals. Residents and staff independently rated individual components of this technique to compare them with learning standard multiport colectomy (MP).A total of 31 SILC cases (15 men; mean age 53 years) were managed. The average BMI was 26.5 kg/m(2) (range 16-39 kg/m(2)). The surgical indications included cancer (n = 13), polyps (n = 8), diverticular disease (n = 4), Crohn's disease (n = 2), familial adenomatous polyposis (n = 2), volvulus (n = 1), and rectal prolapse (n = 1). The average operative time was 164 ± 86 min, and the mean blood loss was 80 ± 83 mL. The mean incision length was 4.1 ± 1.1 cm. One case required additional trocar placement (stoma creation), and three cases required conversion to open procedure because of failure to progress, difficult colorectal anastomosis, or poor visualization. The median hospital stay was 5.7 ± 1.3 days. The 30-day morbidity included minor wound infections (9.7 %), ileus (6.5 %), blood transfusion (3.2 %), and intraabdominal abscess (3.2 %). No deaths occurred. Residents rated vascular pedicle isolation, mobilization, critical structure exposure, instrument conflict/handling, and ergonomics as significantly more difficult with SILC.Senior-level residents can safely perform SILC under appropriate experienced supervision. The required advanced skills reflect complex laparoscopic training occurring during residency. Opportunities exist for better preparation and training of surgical residents to perform this complex surgery independently and safely at completion of residency.
- Peutz-Jegher syndrome in childhood: need for updated recommendations? [Journal Article]
- J Pediatr Gastroenterol Nutr 2013 Feb; 56(2):191-5.
We reviewed our institution's experience with Peutz-Jegher syndrome (PJS) in children to determine whether current recommendations on timing of screening and follow-up should be modified.We reviewed the charts of all of the children with a diagnosis of PJS at our institution from 2000 to 2011 abstracting data on intussusceptions events, polyp characteristics, Sertoli cell (SC) tumors, family history, imaging, and interventions.Of 14 children identified, 10 were boys. Median age at first clinical evaluation was 4.5 years, and family history and/or mucocutaneous pigmentation were the 2 most common factors stimulating screening. Median age at first screening test was 5 years (range 1-16), and at first polyp identification, 5 years (range 1 to 18). There were 7 intussusception events in 5 children, with median age of 10 and range 5 to 16 for first event. Two boys had SC tumors at 8 and 11 years. Polyps were identified during initial screening in 9 of 14 patients. Polyps were found in the stomach or duodenum in 5 (36%), small bowel in 7, (50%) and colon in 3 (21%) children. Large polyps were identified in 9 children at median age of 7 years.Polyps causing significant clinical consequences can occur frequently in children with PJS younger than 8 years. Revised guidelines should consider initial screening at age 4 to 5 with capsule endoscopy and upper and lower endoscopy as well as evaluation for SC tumors and re-evaluation whenever symptoms suggest polyp-associated complications.
- Suture marker lesion detection in the colon by self-stabilizing and unmodified capsule endoscopes: pilot study in acute canine models. [Evaluation Studies, Journal Article]
- Gastrointest Endosc 2013 Feb; 77(2):272-9.
Capsule endoscopy is a noninvasive method for examining the small intestine. Recently, this method has been used to visualize the colon. However, the capsule often tumbles in the wider colon lumen, resulting in potentially missed pathology. In addition, the capsule does not have the ability to distend collapsed segments of the organ. Self-stabilizing capsule endoscopy is a new method of visualizing the colon without tumbling and with the ability to passively distend colon walls.To quantitatively compare the detection rate of intraluminal suture marker lesions for colonoscopy by using a custom-modified, self-stabilizing capsule endoscope (SCE); an unmodified capsule endoscope (CE) of the same brand; and a standard colonoscope.Four mongrel dogs underwent laparotomy and the implantation of 5 to 8 suture markers to approximate colon lesions. Each dog had both capsule endoscopy and self-stabilizing capsule endoscopy, administered consecutively in random order. In each case, the capsule was inserted endoscopically into the proximal lumen of the colon followed by pharmacologically induced colon peristalsis to propel it distally through the colon. Blinded standard colonoscopy was performed by an experienced gastroenterologist after the capsule endoscopies.Experimental study in a live canine model.Four dogs.Laparotomy, capsule endoscopy, colonoscopy.Comparison of the marker detection rate of the SCE to that of the unmodified MiroCam CE and a colonoscope.The average percentages of the marker detection rate for unmodified capsule endoscopy, self-stabilizing capsule endoscopy, and colonoscopy, respectively, were 31.1%, 86%, and 100% (P < .01), with both self-stabilizing capsule endoscopy and colonoscopy performing significantly better than the unmodified capsule endoscopy.Acute canine model, suture markings poorly representative of epithelial polyps, limited number of animals.The proposed self-stabilizing capsule endoscope delivered a significant improvement in detection rates of colon suture markings when compared with the unmodified capsule endoscope.
- Localized ileal giant pseudopolyposis in Crohn's disease: a case report. [Case Reports, Journal Article]
- Pathologica 2012 Aug; 104(4):198-200.
Localized giant pseudopolyposis is a rare complication in inflammatory bowel disease defined as a pseudopolyp (isolated or clustered) larger than 1.5 cm in size. Giant pseudopolyps are more commonly found in ulcerative colitis compared to Crohn's disease and mainly involve the left colon. A 26-year-old male patient with a two-year history of Crohn's disease was admitted with increasing abdominal pain, vomiting, anorexia, weight loss and fever. On physical examination, the abdomen was diffusely tender. Computed tomography showed diffuse irregular thickening of the ileal wall and stenosis of the terminal ileum. The patient underwent ileo-cecal resection with re-anastomosis. The ileal portion of the resected specimen harboured multiple finger-like pedunculated polyps, with the smallest measuring 0.5 cm and the largest measuring 1.8 cm. Histologically, the polyps were consistent with granulation tissue. No evidence of dysplasia or malignancy was found. The post-operative course was uneventful considering one month follow-up. This report illustrates an unusual case of giant pseudopolyposis involving the ileum in a patient with Crohn's disease. The natural history of these lesions, as well as their optimal management, remain uncertain.
- Chemoprevention of intestinal adenomatous polyposis by acetyl-11-keto-beta-boswellic acid in APC(Min/+) mice. [Journal Article, Research Support, Non-U.S. Gov't]
- Int J Cancer 2013 Jun 1; 132(11):2667-81.
Acetyl-11-keto-beta-boswellic acid (AKBA) is a derivative of boswellic acid, which is an active component of the gum resin of Boswellia serrata. AKBA has been used as an adjuvant medication for treatment of inflammatory diseases. In this study, we aimed to evaluate the efficacy of AKBA as a chemopreventive agent against intestinal adenomatous polyposis in the adenomatous polyposis coli multiple intestinal neoplasia (APC(Min/+) ) mouse model. APC(Min/+) mice were administered AKBA by p.o. gavage for 8 consecutive weeks. The mice were sacrificed and the number, size and histopathology of intestinal polyps were examined by light microscopy. AKBA decreased polyp numbers by 48.9% in the small intestine and 60.4% in the colon. An even greater AKBA effect was observed in preventing the malignant progression of these polyps. The number of large (>3 cm) colonic polyposis was reduced by 77.8%. Histopathologic analysis demonstrated a significant reduction in the number of dysplastic cells and in the degree of dysplasia in each polyp after AKBA treatment. There was no evidence of high grade dysplasia or intramucosal carcinoma in any of the polyps examined within the treated group. More interestingly, interdigitated normal appearing intestinal villi were observed in the polyps of the treated group. During the course of the study, AKBA was well tolerated by the mice with no obvious signs of toxicity. Results from immunohistochemical staining, Western blotting and enzyme-linked immunosorbent assay indicated that the chemopreventive effect of AKBA was attributed to a collection of activities including antiproliferation, apoptosis induction, antiangiogenesis and anti-inflammation. AKBA was found to exert its chemopreventive action through the inhibition of the Wnt/β-catenin and NF-κB/cyclooxygenase-2 signaling pathways. Our findings suggest that AKBA could be a promising regimen in chemoprevention against intestinal tumorigenesis.