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The estimated annual incidence of R-NENs is 1.04 per 100,000 persons although the real incidence may be underestimated, as not all R-NEN are systematically reported in registers. Also the prevalence has increased substantially, reflecting the rising incidence and indolent nature of R-NENs, showing the highest prevalence increase among all site of origin of NENs. The size of the tumor reveals the behavior of R-NENs where the risk for metastatic spread increases for lesions > 10 mm. Applying the WHO 2010 grading system to whole NENs originating in the gastroenteropancreatic system, R-NENs are classified as Well-Differentiated Neuroendocrine Tumors (WD-NET), which contain NET G1 and NET G2, and Poorly-Differentiated Carcinomas (PD-NEC) enclosing only G3 neoplasms for which the term carcinoma is applied. The treatment is endoscopic resection in most cases: conventional polypectomy or endoscopic mucosal resection (EMR) for smaller lesions or endoscopic submucosal resection with a ligation device (ESMR-L), cap-assisted EMR (EMR-C) and endoscopic submucosal dissection (ESD). However it is important to know when the endoscopic treatment is not enough, and surgical treatment is indicated, or when the latter could be unnecessary. For PD-NECs, it has recently been demonstrated that chemoradiotherapy is associated with a similar long-term survival to that obtained with surgery. As well, new targeted-agents chemotherapy may be indicated for metastatic WD-NETs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Metronomic therapy is characterized by the administration of regular low doses of certain drugs with very low toxicity. There have been numerous debates over the empirical approach of this regimen, but fewest side effects are always something to consider in order to improve patients' quality of life. Neuroendocrine tumors (NETs) are rare malignancies relatively slow-growing; therefore their treatment is often chronic, involving several different therapies for tumor growth control. Knowing that these tumors are highly vascularized, the anti-angiogenic aspect is highly regarded as something to be targeted in all patients harboring NETs. Additionally the metronomic schedule has proved to be effective on an immunological level, rendering this approach as a multi-targeted therapy. Rationalizing that advanced NETs are in many cases a chronic disease, with which patients can live for as long as possible, a systemic therapy with regular low doses and a very low toxicity is in many cases a judicious manner of pursuing stabilization. Metronomic schedule is usually correlated with chemotherapy in oncology, but other therapies, such as radiotherapy and biotherapy can be delivered in a metronomic like manner. This review describes clinical trials and case series involving metronomic therapies alone or in combination in patients with advanced NETs. Nowadays level of evidence about metronomic therapy in NETs is quite low, therefore future prospective clinical studies are needed to validate the metronomic approach in specific clinical settings., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Diagnosis and management of Barrett's oesophagus are controversial. Technical improvements in real-time recognition of intestinal metaplasia and neoplastic foci provide the chance for more effective target biopsies. Confocal laser endomicroscopy allows to analyze living cells during endoscopy., Aims: To assess the diagnostic accuracy, inter- and intra-observer variability of endomicroscopy for detecting in vivo neoplasia (dysplasia and/or early neoplasia) in Barrett's oesophagus., Methods: Prospective pilot study. Patients referred for known Barrett's oesophagus were screened. Endomicroscopy was carried out in a circular fashion, every 1-2 cm, on the whole columnar-lined distal oesophagus. Visible lesions, when present, were analyzed first. Targeted biopsies were taken. Confocal images were classified according to confocal Barrett classification. Endomicroscopic and histological findings were compared., Results: Forty-eight out of 50 screened patients underwent endomicroscopy. Visible lesions were observed in 3 patients. In a per-biopsy analysis, Barrett's-oesophagus-associated neoplasia could be predicted with an accuracy of 98.1%. The agreement between endomicroscopic and histological results was substantial (κ=0.76)., Conclusions: This study suggests that endomicroscopy can provide in vivo diagnosis of Barrett's oesophagus-associated neoplasia. Because it allows for the study of larger surface areas of the mucosa, endomicroscopy may lead to significant improvements in the in vivo screening and surveillance of Barrett's oesophagus., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Because of the many therapeutic options available, a reliable staging is crucial for rectal neoplasia management. Adenomas and cancers limited to the submucosa without lymph node involvement may be treated locally., Aims: The aim of this study is to evaluate the diagnostic accuracy of endorectal ultrasonography in the staging of neoplasias suitable for local treatment., Methods: We considered all patients who underwent endorectal ultrasonography between 2001 and 2010. The study population consisted of 92 patients with 92 neoplasias (68 adenocarcinomas and 24 adenomas). A 5 and 7.5MHz linear array echoendoscope was used. The postoperative histopathologic result was compared with the preoperative staging defined by endorectal ultrasonography. Adenomas and cancers limited to the submucosa were considered together (pT0-1)., Results: The sensitivity, specificity, overall accuracy rate, positive predictive value, and negative predictive value of endorectal ultrasonography for pT0-1 were 86%, 95.6%, 91.3%, 94.9% and 88.7%. Those for nodal involvement were 45.4%, 95.5%, 83%, 76.9% and 84%, with 3 false positive results and 12 false negative. For combined pT0-1 and pN0, endorectal ultrasonography showed an 87.5% sensitivity, 95.9% specificity, 92% overall accuracy rate, 94.9% positive predictive value and 90.2% negative predictive value., Conclusion: Endorectal linear array ultrasonography is a reliable tool to detect rectal neoplasias suitable for local treatment., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) has been reported to detect colorectal adenomas., Aims: This study aimed at evaluating the sensitivity of (18)F-FDG PET with computed tomography image fusion (PET/CT) for detecting colorectal adenomas., Methods: We retrospectively compared the results of 92 (18)F-FDG PET/CT studies followed by colonoscopy. Colonoscopy and histology were considered as the gold standard., Results: One hundred fifty-seven lesions were observed. All the 12 malignancies were identified by (18)F-FDG PET/CT but only 27 out of 119 resected adenomas (sensitivity 22.7%) and none of the hyperplastic polyps were detected. At the univariate and multivariate analyses there was a significant statistical association between adenomas sized more than 10mm, presence of villous component and high-grade dysplasia and the ability of (18)F-FDG PET/CT to detect adenomas. (18)F-FDG PET/CT showed an overall sensitivity of 29.8%, a specificity of 81.1%, a positive predictive value (PPV) of 84.8% and a negative predictive value (NPV) of 24.6% for the neoplastic colorectal lesions globally considered., Conclusion: (18)F-FDG PET/CT has a low sensitivity for detecting adenomas. However, because of the specificity and PPV of the technique for neoplastic colorectal lesions, the presence of a focal colorectal FDG uptake justifies the patient undergoing colonoscopy., (2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Pouchitis and dysplasia may affect the reservoir after restorative proctocolectomy., Aims: To assess the suitability of confocal laser endomicroscopy for the in vivo diagnosis of mucosal changes in ileal pouch for ulcerative colitis and familial adenomatous polyposis., Methods: Standard endoscopy and endomicroscopy were performed in 18 pouches. Confocal images were scored for the presence of villous atrophy, inflammation, ulceration, colonic metaplasia and dysplasia. Targeted biopsies were taken. Endomicroscopic and histological findings were compared., Results: At standard endoscopy, the signs of pouchitis were recorded in 7/18 (38.9%) patients. At endomicroscopy, pathological features were found in 16/18 (88.9%), villous atrophy in 15/18 (83.3%), inflammation in 13/18 (72.2%), ulceration in 3/18 (16.7%), and colonic metaplasia in 12/18 (67.7%). No dysplasia was observed. At histology, abnormalities were present in 17/18 (94.4%): villous atrophy in 15/18 (83.3%), inflammation in 17/18 (94.4%), ulceration in 6/18 (33.3%), colonic metaplasia in 15/18 (83.3%). Morphological changes of the ileal pouch could be predicted with an accuracy of 94.4% (95% CI: 74.2-99.0). The k-value for intra- and interobserver agreement was 0.93 and 0.78, respectively., Conclusions: Endomicroscopy may be helpful in the evaluation of morphologic changes in ileal pouch. The small size of the population sample requires further studies for the results to be confirmed.

The association between gastric carcinoma and lymphoma is rare. Confocal laser endomicroscopy is a new diagnostic tool that allows the identification of cellular and vascular architecture during endoscopy. This is the first report of an in vivo early gastric carcinoma diagnosis by confocal laser endomicroscopy in a patient successfully treated for a primary gastric diffuse large-B-cell lymphoma.

Background and Aims: Type 1 gastric neuroendocrine tumour surveillance and treatment are a matter of debate. Endoscopic, or surgical, resection and chronic somatostatin analog therapy have been proposed. Based on the favourable behaviour of this neoplasm, we performed an endoscopic and clinical follow-up in 11 patients affected by type 1 gastric neuroendocrine tumours, avoiding any specific treatment., Methods: Between 1994 and 2006, we prospectively recorded the data of 11 untreated patients with type 1 gastric neuroendocrine tumours who underwent an endoscopic and clinical follow-up. All the patients were also evaluated by means of an abdominal computed tomography scan, somatostatin receptor scintigraphy and blood tests., Results: During the follow-up (median 54 months, range 9-136), the endoscopic picture of 4 (36%) out of 11 patients changed in terms of increased number of lesions. In none of the cases were detected any lesions that exceeded 10mm in diameter, and none of the patients demonstrated any evidence of local or distant metastases., Conclusions: Our data confirm the literature data of the indolent behaviour of type 1 gastric neuroendocrine tumours and suggest that a careful endoscopic follow-up, without any treatment, might represent a reasonable and safe option in selected patients.

Background: Obstruction is a common complication of advanced colorectal cancer. Stent insertion can reduce the need for emergency surgery and allows chemotherapy to begin immediately., Aims: To evaluate the technical and clinical success and long-term outcome of stent placement in the management of acute malignant colorectal obstruction., Methods: From July 2002 to April 2005, 29 self-expanding metal stents were placed in 24 patients (13 men, mean age 67 years, range 36-83). Stents were inserted under endoscopic and fluoroscopic control. Patients were clinically and endoscopically followed up., Results: Twenty-eight out of 29 stents were successfully placed (96.5%) in 23 out of 24 patients with 25 strictures. The clinical success rate was 95.8% (23/24). Two early stent migrations were observed in two patients (8.3%). Late complications developed in eight patients (33.3%) after a median of 3.8 months (range <1-8.6): two migrations and six occlusions. The median survival was 9.8 months (range <1-27). Eleven patients (45.8%) died from progressive disease without any clinical evidence of recurrent obstruction., Conclusion: Stent placement is safe and effective. Stent complications are frequent but not life-threatening, and are easy to manage. An improvement in stent design and well-scheduled follow-up are needed in order to prevent such complications.

Background: During ovarian cancer surgery, colorectal resection may be required. In our institution, preoperative colonoscopy is performed in order to assess visceral involvement., Aims: The aim of this study was to evaluate the utility of preoperative colonoscopy in ovarian cancer patients and the prevalence of adenomas in this population., Patients: This retrospective study involved 144 consecutive patients with a supposed primary ovarian cancer., Methods: Mucosal infiltration, bowel wall elasticity and bowel fixation were used to predict colorectal infiltration. Endoscopic and pathological findings were compared. All the polyps observed were removed., Results: Six patients (4.2%) were excluded because of a misdiagnosed colorectal cancer metastatic to the ovary. Eight (6%) patients were considered, at endoscopy, to have a bowel infiltration and eight (6%), an uncertain infiltration. In 116 (88%), no signs of bowel infiltration were observed. The pathological analysis showed that colonoscopy had a low sensitivity (44%) in identifying bowel infiltration. Specificity was 100%, positive predictive value 100% and negative predictive value 92%. The overall accuracy was about 90%. Thirty-six adenomas were removed in 26 (20%) women., Conclusions: Colonoscopy identifies a not insignificant number of ovarian cancer patients requiring colorectal surgery. An increased prevalence of adenomas was not observed in this population.