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Polyps of colon and small intestine [keywords]
- 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.
- 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. [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.
- Cronkhite-Canada syndrome complicated with multiple gastric cancers and multiple colon adenomas. [Journal Article]
- Am J Case Rep 2013.:120-8.
We experienced a case in which Cronkhite-Canada Syndrome presented with complications of multiple gastric cancers and multiple colon adenomas.Our case is a 64-year-old male who visited a nearby hospital with diarrhea and weight loss. The patient was anemic and hypoproteinemic, with multiple polyps in the stomach, duodenum, and large intestine. He also presented with alopecia, onychatrophia, cutaneous pigmentation, and dysgeusia, and was diagnosed with Cronkhite-Canada Syndrome. Follow-up examinations found multiple gastric cancers and colon adenomas. We performed a total gastrectomy and a polypectomy of the large intestine lesions, revealing 4 well-differentiated adenocarcinomas in the resected stomach, and tubular adenomas in the large intestine lesions. Intraoperative findings included scattered melanoid pigmentation on the mesentery and the small intestinal wall. Tumor cells were positive for p53 and Ki67 and partially positive for MUC5AC and MUC2. Cronkhite-Canada Syndrome polyps are generally classified as juvenile type polyps, and these polyps rarely become cancerous. However, of the 383 cases of Cronkhite-Canada Syndrome reported in Japan, complications of gastric cancer were found in 39 cases (10.2%), and only 8 cases with multiple gastric cancer were reported in Japan. including the cases we have personally experienced. There were only two English literatures on Cronkhite-Canada Syndrome complicated with gastric cancer. So it is necessary to notify this information of Cronkhite-Canada Syndrome to the world.Close gastrointestinal examination and strict follow-up are believed to be essential for Cronkhite-Canada Syndrome patients.
- [A case of Peutz-Jeghers syndrome with repeated small intestinal intussusception successfully treated by intraoperative endoscopic polypectomy]. [Case Reports, English Abstract, Journal Article]
- Nihon Shokakibyo Gakkai Zasshi 2013 Jun; 110(6):1014-21.
Intestinal polyps are a distinctive feature of Peutz-Jeghers syndrome (PJS). These hamartomas can lead to significant complications such as intussusception or gastrointestinal bleeding which necessitate multiple laparotomies and bowel resections. In an operation for intestinal intussusception, it is preferable to simultaneously resect as many polyps as possible to prevent recurrence of complications caused by intestinal polyps. We report a case of a woman in her twenties with PJS, diagnosed as small intestinal intussusception caused by an intestinal polyp. We performed not only repair of the intussusception but also endoscopic polypectomy without resection of the small intestine. We successfully resected all polyps larger than 10mm from the duodenum to the ascending colon during the operation.
- Investigation of the atypical FBXW7 mutation spectrum in human tumours by conditional expression of a heterozygous propellor tip missense allele in the mouse intestines. [Journal Article, Research Support, Non-U.S. Gov't]
- Gut 2014 May; 63(5):792-9.
FBXW7 encodes the substrate recognition component of a ubiquitin ligase that degrades targets such as Notch1, c-Jun, c-Myc and cyclin E. FBXW7 mutations occur in several tumour types, including colorectal cancers. The FBXW7 mutation spectrum in cancers is unusual. Some tumours have biallelic loss of function mutations but most have monoallelic missense mutations involving specific arginine residues at β-propellor tips involved in substrate recognition.FBXW7 functional studies have generally used null systems. In order to analyse the most common mutations in human tumours, we created a Fbxw7(fl(R482Q))(/+) mouse and conditionally expressed this mutation in the intestines using Vill-Cre. We compared these mice with heterozygous null (Fbxw7(+/-)) mutants.A few sizeable intestinal adenomas occurred in approximately 30% of R482Q/+ and Fbxw7(+/-) mice at age >300 days. Breeding the R482Q allele onto Apc mutant backgrounds led to accelerated morbidity and increased polyp numbers and size. Within the small bowel, polyp distribution was shifted proximally. Elevated levels of two particular Fbxw7 substrates, Klf5 and Tgif1, were found in normal intestine and adenomas of R482Q/+, R482Q/R482Q and Fbxw7(-/-) mice, but not Fbxw7(+/-) animals. On the Apc mutant background, Fbxw7(+/-) mutants had a phenotype intermediate between Fbxw7 wild-type and R482Q/+ mice.Heterozygous Fbxw7 propellor tip (R482Q) mutations promote intestinal tumorigenesis on an Apc mutant background. Klf5 and Tgif1 are strong candidates for mediating this effect. Although heterozygous null Fbxw7 mutations also promote tumour growth, these have a weaker effect than R482Q. These findings explain the FBXW7 mutation spectrum found in human cancers, and emphasise the need for animal models faithfully to reflect human disease.
- 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.