The role of wireless capsule endoscopy (WCE) in the detection of occult primary neuroendocrine tumors.

BACKGROUND AND AIMS: Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with unclear etiology that may show functioning or non-functioning features. Primary tumor localization often requires integrated imaging. The European Neuroendocrine Tumors Society (ENETS) guidelines proposed wireless-capsule endoscopy (WCE) as a possible diagnostic tool for NETs, if intestinal origin is suspected. However, its impact on therapeutic management is debated. We aimed to evaluate the yield of WCE in detecting intestinal primary tumors in patients showing liver NET metastases when first-line investigations are inconclusive. METHOD: Twenty-four patients with a histological diagnosis of metastatic NET from liver biopsy and no evidence of primary lesions at first-line investigations were prospectively studied in an ENETS-certified tertiary care center. Wireless-capsule endoscopy was requested before explorative laparotomy and intra-operative ultrasound. The diagnostic yield of WCE was compared to the surgical exploration. RESULTS: Sixteen subjects underwent surgery; 11/16 had positive WCE identifying 16 bulging lesions. Mini-laparotomy found 13 NETs in 11/16 patients (9 small bowel, 3 pancreas, 1 bile ducts). Agreement between WCE and laparotomy was recorded in 9 patients (Sensitivity=75%; Specificity=37.5%; PPV=55%; NPV=60%). Correspondence assessed per-lesions produced similar results (Sensitivity=70%; Specificity=25%; PPV=44%; NPV=50%). No capsule retentions were recorded. CONCLUSIONS: Wireless-capsule endoscopy is not indicated as second-line investigation for patients with gastro-entero-pancreatic NETs. In the setting of a referral center, it might provide additional information when conventional investigations are inconclusive about the primary site.

Wireless capsule endoscopy in adolescents with familial adenomatous polyposis.

AIMS AND BACKGROUND: Guidelines for surveillance in patients with familial adenomatous polyposis (FAP) recommend mutation carriers to undergo periodic colorectal examination starting in the early teens. Performing colonoscopy in children may lead to complications. Wireless capsule endoscopy (WCE) has been introduced recently to evaluate both the upper and lower gastrointestinal tract, and seems suitable as a first screening examination for adolescents. The aim of this study was to evaluate the pros and cons of WCE. METHODS: This was a retrospective review of a single institution database of adolescent patients with FAP identified through the Hereditary Colorectal Tumor Registry between 2007 and 2013. The main outcomes were identification of upper and lower gastrointestinal tract polyps, tolerance of the examination, and number and size of polyps. RESULTS: Of 46 adolescent patients with FAP, 14 (30.4%) patients carrying adenomatous polyposis coli gene (APC) mutation, 6 male and 8 female, age (median, range) 12 (10-17) years, body mass index 19 (13-24), underwent WCE as first screening examination. The examination was completed in 13 patients (93.3%). Wireless capsule endoscopy identified the duodenal papilla in 4 patients and colonic and rectal polyps in all 13 patients. In 7 patients, fewer than 25 polyps were identified. No complications were recorded related to the use of the video capsule. CONCLUSIONS: Wireless capsule endoscopy is feasible and well-tolerated as a first screening examination in adolescent patients. It cannot be used as alternative to the colonoscopy, but could improve compliance with colonoscopy, and increase early adherence to a surveillance program.

Can we improve the detection rate and interobserver agreement in capsule endoscopy?

BACKGROUND: Data about strategies for improving the diagnostic ability of capsule endoscopy readers are lacking. AIM: (1) To evaluate the detection rate and the interobserver agreement among readers with different experience; (2) to verify the impact of a specific training (hands-on training plus expert tutorial) on these parameters. METHODS: 17 readers reviewed 12 videos twice; between the two readings they underwent the training. The identified small bowel findings were described by a simplified version of Structured Terminology and classifies as clinically significant/non-significant. Findings identified by the readers were compared with those identified by three experts (Reference Standard). RESULTS: The Reference Standard identified 26 clinically significant findings. The mean detection rate of overall readers for significant findings was low (about 50%) and did not change after the training (46.2% and 46.4%, respectively). There was no difference in the detection rate among readers with different experience. The interobserver agreement with the Reference Standard in describing significant findings was moderate (k = 0.44; CI95%: 0.39-0.50) and did not change after the training (k = 0.44; CI95%: 0.38-0.49) or stratifying readers according to their experience. CONCLUSIONS: Both the interobserver agreement and the detection rate of significant findings are low, regardless of the readers' experience. Our training did not significantly increase the performance of readers with different experience.

Small bowel capsule endoscopy in clinical practice: a multicenter 7-year survey.

BACKGROUND AND AIM: Data about small bowel capsule endoscopy (SBCE) come from studies involving small and highly selected populations. The study aim was to describe extent of use, indications, results, complications, and practical issues of SBCE in clinical practice in a Northern Italian Region (Lombardia). MATERIALS AND METHODS: Twenty-three out of 29 invited centers fulfilled a specific questionnaire. RESULTS: Between 2001 and 2008, 2921 procedures were performed and both the number of centers performing SBCE (from 5 to 29) and the number of SBCE (from 7.2 to 69.2 per month) increased steadily. The main indications for SBCE were: obscure gastrointestinal bleeding (OGIB) (43.4%), unexplained anemia (23.9%), suspected Crohn's disease (7.8%) and abdominal pain (5.3%). Overall, SBCE was positive in 50% of cases, negative in 36% and undefined in 14%. The highest diagnostic yields were observed in patients with OGIB (62.5%), polypoid syndromes (74.1%), known (54.8%) or suspected (47.3%) inflammatory bowel disease, while the yields were low in patients examined for chronic diarrhea (27.4%) and abdominal pain (14.9%), 61 patients (2.1%) experienced capsule retention. Thirty-two of them eventually excreted the capsule naturally while endoscopic or surgical retrieval was necessary in 29 (1%) (in two because of obstruction). CONCLUSION: Over a period of 7 years the use of SBCE in Lombardia increased steadily confirming, in clinical practice, a high diagnostic yield and an acceptable safety profile.

Cyclooxygenase-2 expression in FAP patients carrying germ line MYH mutations.

Familial adenomatous polyposis (FAP) is an autosomal condition caused by inherited mutations in the adenomatous polyposis coli (APC) or in the MYH genes. Clinical trials have established that nonsteroidal anti-inflammatory drugs (NSAID) are effective in preventing the development as well as reducing the size and decreasing the number of adenomas in FAP patients. Our aim was to evaluate the cyclooxygenase-2 (COX-2) expression in surgical specimens from patients with no evidence of germ line APC mutations but carrying germ line MYH mutations. COX-2 expression was evaluated through immunohistochemical and mRNA analysis in carcinomas, adenomas, and healthy mucosa from six patients carrying germ line biallelic MYH mutations. A modulation of COX-2 expression from adenoma (lower level) to carcinoma (higher level) was observed in all patients by both immunohistochemical and mRNA analysis. Moreover, patients with MYH mutations showed a weak COX-2 expression in the whole colorectal mucosa, as for classic FAP patients carrying germ line APC mutations. All together, our data suggest that biallelic MYH patients might benefit from NSAID treatment, because in these patients COX-2 is overexpressed in the whole colorectal mucosa, a finding possibly related to the interplay between COX-2 and APC protein being the APC gene a common target of mutations in MYH patients.

Predictors of metachronous colorectal neoplasms in sporadic adenoma patients.

Our objective was to assess the overall risk of subsequent colorectal neoplasms (cancer or adenoma) in relation with the various characteristics of the index lesion in a cohort of patients who underwent endoscopic polypectomies of colorectal adenomas. A total of 1086 patients with adenomas of the large bowel were reported between 1979 and 1999 at the National Cancer Institute of Milan during a screening program for colorectal carcinoma. Data on patients who had colonoscopic examinations and treatments were collected prospectively. The relation between colorectal cancer (CRC) and adenoma features was assessed by computing the hazard ratio (HR) values and corresponding confidence intervals (95% CI) according to Cox proportional hazard models. Of the 1086 eligible patients (487 females, 579 males), 736 had single adenomas (67.7%) and 350 had multiple adenomas (32.3%). Histologic examination revealed 772 cases of tubular adenoma (73%), 205 cases of tubulovillous adenoma and 80 cases of villous adenoma (7.5%). Severe dysplasia was found in 3.3% of the cases. During the 11393 person-years of follow-up, with an average time of surveillance of 10.5 years, colorectal carcinomas developed in 10 patients (0.8%) and a new adenoma in 323 patients (29%). Multivariate analysis showed that male gender (HR 1.6; 95% CI 1.3-2.0), multiple polyps (HR 1.6; 95% CI 1.3-2.0), polyps larger than 2 cm (HR 1.5; 95% CI 1.1-2.1), tubulovillous and villous histology (HR 1.3; 95% CI 1.0-1.6 and HR 1.8; 95% CI 1.2-2.6, respectively) at index polypectomy were statistically significant risk factors for developing metachronous adenomatous polyps. The standardized incidence rates (SIR) for CRC was 0.52 (95% CI 0.25-0.95). The SIR was increased in subjects with severe dysplasia (2.8; 95% CI 0.34-1.02). Some features of large bowel adenomas are strongly correlated with an increased risk of metachronous adenomas and colorectal cancer. However, the endoscopic polypectomy is able to reduce by 50% the incidence of CRC in patients with large bowel adenomas.