In the human gastrointestinal tract, the functional mucosa of the small intestine has the highest capacity for absorption of nutrients and rapid proliferation rates, making it vulnerable to chemoradiotherapy. Recent understanding of the protective role of p53-mediated cell cycle arrest in the small intestinal mucosa has led researchers to explore new avenues to mitigate mucosal injury during cancer treatment. A traditional p53 inhibitor and two other molecules that exhibit strong protective effects on normal small intestinal epithelium during anticancer drug treatment and radiation therapy are introduced in this work. The objective of this review was to update current knowledge regarding potential mechanisms and targets that inhibit the side effects induced by chemoradiotherapy.

Barrett's esophagus (BE) is characterized by intestinal metaplasia with the differentiated epithelium replaced by another type of epithelium morphologically similar to normal intestinal epithelium. The metaplasia is preceded by bile and acid reflux into the esophagus. BE is a premalignant condition associated with increased risk of esophageal cancer, especially esophageal adenocarcinoma. The Caudal-related homeodomain transcription factors Caudal-related homeodomain transcription factor CDX1 and CDX2 are expressed exclusively in the small and large intestine, playing important roles in proliferation and differentiation of intestinal epithelial cells. Ectopic expression of CDX1 and CDX2 occurs in BE. The apical sodium-dependent bile acid transporter (ASBT) is expressed primarily in terminal ileum where it is a key factor for intestinal reabsorption of bile salts. In addition to upregulation of CDX1 and CDX2, ASBT expression is up-regulated in BE. Furthermore, both CDX1/CDX2 and ASBT expressions are down-regulated in high-grade esophageal dysplasia. The alteration of the above-mentioned factors calls for attention: what is the relationship between CDXs and ASBT aberrant expression in BE? In this commentary, we discuss this issue on basis of the recent study done by Ma et al.

A 56-year-old woman with a history of gynecological surgery for cervical cancer 18 years previously was referred to our hospital for colicky abdominal pain, nausea and vomiting. Intestinal obstruction was diagnosed by contrast-enhanced computed tomography (CT) which showed dilation of the small intestine and suggested obstruction in the terminal ileum. In addition, CT showed a thick-walled cavitary lesion communicating with the proximal jejunum. (18)F-fluorodeoxyglucose positron emission tomography showed abnormal uptake at the same location as the cavitary lesion revealed by CT. The patient underwent laparotomy for the ileus and resection of the cavitary lesion. At laparotomy, we found a retained surgical sponge in the ileum 60 cm from the ileocecal valve. The cavitary tumor had two fistulae communicating with the proximal jejunum. The tumor was resected en bloc together with the transverse colon, part of the jejunum and the duodenum. Microscopic examination revealed fibrous encapsulation and foreign body giant cell reaction. Since a retained surgical sponge without radiopaque markers is extremely difficult to diagnose, retained surgical sponge should be considered in the differential diagnosis of intestinal obstruction in patients who have undergone previous abdominal surgery.

Cadherins constitute a superfamily of Ca(2+)-dependent cell adhesion molecules that play critical roles in the maintenance of tissue structure and morphogenesis. Their dysregulation is commonly observed in a variety of cancers. Liver-intestine cadherin (LI-cadherin), which was so named in view of its sole expression in the liver and intestine of the rat, is a structurally unique member of the cadherin superfamily, possessing seven cadherin repeats within the extracellular cadherin domain and only 25 amino acids in the cytoplasmic domain. Its adhesive property does not require any interaction with cytoplasmic components such as catenins, and it responds to small changes in extracellular Ca(2+) below the physiological plasma concentration. In humans, the distribution of LI-cadherin is limited to the duodenum, jejunum, ileum, colon, and part of the pancreatic duct. Data accumulated from studies of the biological characteristics of LI-cadherin have shown that it plays an important role in the pathophysiology of human cancers. Here, we review recent information about LI-cadherin and its implications for cancer progression.

The prognosis of metastatic or recurrent gastrointestinal stromal tumors (GISTs) accompanied by multiple hepatic metastases and peritoneal dissemination is very poor. We encountered a case of stage IV small intestinal GIST with multiple hepatic metastases and peritoneal dissemination that were observed after resection of the primary lesion. Multidisciplinary treatments were performed over time, including hepatic resection, radiotherapy, imatinib therapy, sunitinib therapy, and transcatheter arterial chemoembolization, and the disease had been brought under control following resection of a primary lesion 14 years ago. The patient was a 49-year-old woman diagnosed with hemorrhagic stool in July 1998, when a computed tomography scan revealed an 8-cm-diameter tumor in her small bowel. Partial resection of her small bowel was performed and the pathological diagnosis was a high-risk GIST showing 15 mitoses per 50 high power fields. Several metastases developed in the S4 and S5 segments of the patient's liver 3 years after resection of the primary lesion, and a central two-segmental resection of the liver was performed. Furthermore, 1 year after this procedure, peritoneal dissemination developed near the pancreas, for which radiotherapy was performed. Four months later, the patient again developed multiple liver metastases and was started on treatment with 400 mg imatinib per day, achieving a partial response(PR). Five years and 6 months after imatinib initiation, resistance emerged in one of the liver metastases. The patient was switched to sunitinib(50 mg per day), but was diagnosed with progressive disease at the end of the second course and the procedure was discontinued. Treatment with 400 mg of imatinib per day was resumed, and transcatheter arterial chemoembolization was performed twice over a 17-month period for the resistant hepatic region and a PR was achieved each time. We were able to maintain a PR in this patient; other metastases indicated the effectiveness of imatinib therapy. Therefore, a multidisciplinary team approach can be effective in achieving long-term disease control in patients with metastatic or recurrent GIST.

The existence of slowly cycling, adult stem cells has been challenged by the identification of actively cycling cells. We investigated the existence of uncommitted, slowly cycling cells by tracking 5-iodo-2'-deoxyuridine (IdU) label-retaining cells (LRCs) in normal esophagus, Barrett's esophagus (BE), esophageal dysplasia, adenocarcinoma, and healthy stomach tissues from patients.Four patients (3 undergoing esophagectomy, 1 undergoing esophageal endoscopic mucosal resection for dysplasia and an esophagectomy for esophageal adenocarcinoma) received intravenous infusion of IdU (200 mg/m(2) body surface area; maximum dose, 400 mg) over a 30-minute period; the IdU had a circulation half-life of 8 hours. Tissues were collected at 7, 11, 29, and 67 days after infusion, from regions of healthy esophagus, BE, dysplasia, adenocarcinoma, and healthy stomach; they were analyzed by in situ hybridization, flow cytometry, and immunohistochemical analyses.No LRCs were found in dysplasias or adenocarcinomas, but there were significant numbers of LRCs in the base of glands from BE tissue, in the papillae of the basal layer of the esophageal squamous epithelium, and in the neck/isthmus region of healthy stomach. These cells cycled slowly because IdU was retained for at least 67 days and co-labeling with Ki-67 was infrequent. In glands from BE tissues, most cells did not express defensin-5, Muc-2, or chromogranin A, indicating that they were not lineage committed. Some cells labeled for endocrine markers and IdU at 67 days; these cells represented a small population (<0.1%) of epithelial cells at this time point. The epithelial turnover time of the healthy esophageal mucosa was approximately 11 days (twice that of the intestine).LRCs of human esophagus and stomach have many features of stem cells (long lived, slow cycling, uncommitted, and multipotent), and can be found in a recognized stem cell niche. Further analyses of these cells, in healthy and metaplastic epithelia, is required.

The small and large intestines are tubular organs composed of several tissue types. The columnar epithelium that lines the inner surface of the intestines distinguishes the digestive physiology of each region of the intestine and consists of several distinct cell types that are rapidly and continually renewed by intestinal stem cells that reside near the base of the crypts of Lieberkühn. Notch signaling controls the fate of intestinal stem cells by regulating the expression of Hes genes and by repressing Atoh1. Alternate models of Notch pathway control of cell fate determination are presented. Roles for Notch signaling in development of the intestine, including mesenchymal and neural cells, are discussed. The oncogenic activities of Notch in colorectal cancer, as well as the tumor suppressive activities of Atoh1, are reviewed. Therapeutic targeting of the Notch pathway in colorectal cancers is discussed, along with potential caveats.

Peutz-Jeghers syndrome is a rare hereditary syndrome characterized by mucocutaneous pigmentation and hamartomatous polyps of the gastrointestinal tract, especially in the small intestine. Double-balloon endoscopy is a new endoscopic technique that enables both endoscopic visualization of the entire small bowel and therapeutic interventions in a single procedure. In this study, we evaluate the efficacy and safety of double-balloon endoscopy for both treatment and surveillance of patients with Peutz-Jeghers syndrome.We retrospectively evaluated 7 consecutive patients who were referred to Dokuz Eylül University, Gastroenterology Department, with the diagnosis of Peutz-Jeghers syndrome between 2007 and 2010.Patients with Peutz-Jeghers syndrome (M/F: 5/2) underwent a total 31 double-balloon endoscopy procedures: 21 by the oral route, 9 by the anal route, and 1 intraoperatively. All of the patients had a history of laparotomy and small bowel resection due to complications such as invagination and ileus. In 7 patients, we found a total of 110 polyps ≥10 mm in diameter (10-100 mm) and polypectomies were performed in all of them. The only complication was a bleeding after polypectomy, which was controlled by sclerotherapy. In 1 patient, because of the intraabdominal adhesions due to past laparotomies, polypectomy was done by intraoperative endoscopy. In 2 of our patients, we made surveillance colonoscopies, found new polyps in the small intestine, and performed polypectomies.Double-balloon endoscopy is an effective and safe endoscopic technique, and represents a milestone for both treatment and surveillance of patients with Peutz-Jeghers syndrome. Polypectomies made in the small intestine might decrease the complication rate due to these polyps and the need for surgery.

The aim of this study was to estimate the efficacy of flexible spectral imaging color enhancement (FICE) on the detection of small intestinal diseases by capsule endoscopy (CE).Six individuals without significant lesions and 18 patients with following diseases were selected: four tumors, five angioectasias, seven ulcerative diseases, one ulcerative lesion and tumor and one ulcerative lesion and angioectasia. Three endoscopists reviewed all CE videos on standard and three types of FICE modes and compared their sensitivity and specificity for detection of small intestinal diseases.The overall sensitivity of CE was 94.4% at standard mode, 90.7% at FICE channel (Ch) 1, 87.0% at FICE Ch 2 and 87.0% at FICE Ch 3 and the overall specificity of CE was 66.7%, 55.6%, 77.8% and 66.7%, respectively, per patient. There was no significant difference between the standard and each FICE mode. In per-lesion analysis, FICE Ch 1 detected more angioectasias and ulcerative lesions than the standard mode (angioectasia, 25.7 vs 21.0, P = 0.005; ulcerative lesions, 19.3 vs 14.0, P = 0.06). However, FICE Ch 1 missed more tumors than the standard mode (4.3 vs 10.0, P = 0.003).Although FICE Ch 1 is better in detecting angioectasias and ulcerative lesions and worse in tumors or polyps than the standard mode, the patient-based sensitivity and specificity of small intestinal diseases are not different between standard and each FICE mode. Further experiences with and improvement of FICE are required.

This study aimed to evaluate the performance, diagnostic yield, and safety of single-balloon enteroscopy (SBE) at a Chinese tertiary-care center.A total of 67 patients with suspected small bowel diseases who underwent SBE via the oral and/or anal routes from January 2009 to August 2011 were retrospectively analyzed. Data were extracted from electronic clinical and endoscopy records. The indications, SBE procedure time, diagnostic yield and complications were summarized and evaluated.A total of 42 SBE procedures through the oral route and 38 via the anal route were performed in these 67 patients. Patients were referred mainly for obscure gastrointestinal bleeding (OGIB) (40.3%) and abdominal pain (29.8%). The mean procedure duration was 68.1 min from the oral cavity and 77.5 min from the anus. The estimated depth of insertion was 247.6 ± 80.3 cm from the oral cavity and 131.1 ± 68.7 cm from the anus. The overall significant diagnostic yield was 68.7%. In patients with OGIB and unexplained chronic abdominal pain, the diagnostic yield was 74.1% and 50.0%, respectively. There were no significant complications.SBE appears to be a safe and effective method for the diagnosis and treatment of deep small bowel disease.