E. Guido

Barrett's esophagus and adenocarcinoma risk: the experience of the North-Eastern Italian Registry (EBRA).

Objective:To establish the incidence and risk factors for progression to high-grade intraepithelial neoplasia (HG-IEN) or Barretts esophageal adenocarcinoma (BAc) in a prospective cohort of patients with esophageal intestinal metaplasia [(BE)]. Background:BE is associated with an increased risk of BAc unless cases are detected early by surveillance. No consistent data are available on the prevalence of BE-related cancer, the ideal surveillance schedule, or the risk factors for cancer. Methods:In 2003, a regional registry of BE patients was created in north-east Italy, establishing the related diagnostic criteria (endoscopic landmarks, biopsy protocol, histological classification) and timing of follow-up (tailored to histology) and recording patient outcomes. Thirteen centers were involved and audited yearly. The probability of progression to HG-IEN/BAc was calculated using the Kaplan-Meier method; the Cox regression model was used to calculate the risk of progression. Results:HG-IEN (10 cases) and EAc (7 cases) detected at the index endoscopy or in the first year of follow-up were considered to be cases of preexisting disease and excluded; 841 patients with at least 2 endoscopies {median, 3 [interquartile range (IQR): 2–4); median follow-up = 44.6 [IQR: 24.7–60.5] months; total 3083 patient-years} formed the study group [male/female = 646/195; median age, 60 (IQR: 51–68) years]. Twenty-two patients progressed to HG-IEN or BAc (incidence: 0.72 per 100 patient-years) after a median of 40.2 (26.9–50.4) months. At multivariate analysis, endoscopic abnormalities, that is, ulceration or nodularity (P = 0.0002; relative risk [RR] = 7.6; 95% confidence interval, 2.63–21.9), LG-IEN (P = 0.02, RR = 3.7; 95% confidence interval, 1.22–11.43), and BE length (P = 0.01; RR = 1.16; 95% confidence interval, 1.03–1.30) were associated with BE progression. Among the LG-IEN patients, the incidence of HG-IEN/EAc was 3.17 patient-years, that is, 6 times higher than in BE patients without LG-IEN. Conclusions:These results suggest that in the absence of intraepithelial neoplastic changes, BE carries a low risk of progression to HG-IEN/BAc, and strict surveillance (or ablative therapy) is advisable in cases with endoscopic abnormalities, LG-IEN or long BE segments.

Detection of fluorescent organic nanoparticles by confocal laser endomicroscopy in a rat model of Barrett’s esophageal adenocarcinoma

For many years, novel strategies for cancer detection and treatment using nanoparticles (NPs) have been developed. Esophageal adenocarcinoma is the sixth leading cause of cancer-related deaths in Western countries, and despite recent advances in early detection and treatment, its prognosis is still very poor. This study investigated the use of fluorescent organic NPs as potential diagnostic tool in an experimental in vivo model of Barrett’s esophageal adenocarcinoma. NPs were made of modified polysaccharides loaded with [4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran] (DCM), a well-known fluorescent dye. The NP periphery might or might not be decorated with ASYNYDA peptide that has an affinity for esophageal cancer cells. Non-operated and operated rats in which gastroesophageal reflux was surgically induced received both types of NPs (NP-DCM and NP-DCM-ASYNYDA) by intravenous route. Localization of mucosal NPs was assessed in vivo by confocal laser endomicroscopy, a technique which enables a “real time” and in situ visualization of the tissue at a cellular level. After injection of NP-DCM and NP-DCM-ASYNYDA, fluorescence was observed in rats affected by esophageal cancer, whereas no signal was observed in control non-operated rats, or in rats with simple esophagitis or Barrett’s esophagus mucosa. Fluorescence was observable in vivo 30 minutes after the administration of NPs. Interestingly, NP-DCM-ASYNYDA induced strong fluorescence intensity 24 hours after administration. These observations suggested that NPs could reach the tumor cells, likely by enhanced permeability and retention effect, and the peptide ASYNYDA gave them high specificity for esophageal cancer cells. Thus, the combination of NP platform and confocal laser endomicroscopy could play an important role for highlighting esophageal cancer conditions. This result supports the potential of this strategy as a targeted carrier for photoactive and bioactive molecules in esophageal cancer diagnosis and treatment.

A new endoscopic technique for suspension of esophageal prosthesis for refractory caustic esophageal strictures.

There is no clear consensus concerning the best endoscopic treatment of benign refractory esophageal strictures due to caustic ingestion. Different procedures are currently used: frequent multiple dilations, retrievable self-expanding stent, nasogastric intubation and surgery. We describe a new technique to fix a suspended esophageal silicone prosthesis to the neck in benign esophageal strictures; this permits us to avoid the frequent risk of migration of the expandable metallic or plastic stents. Under general anesthesia a rigid esophagoscope was placed in the patients hypopharynx. Using transillumination from the optical device, the patients neck was pierced with a needle. A n.0 monofilament surgical wire was pushed into the needle, grasped by a standard foreign body forceps through the esophagoscope and pulled out of the mouth (as in percutaneous endoscopic gastrostomy procedure). After tying the proximal end of the silicone prosthesis with the wire, it was placed through the strictures under endoscopic view. This procedure was successfully utilized in four patients suffering from benign refractory esophageal strictures due to caustic ingestion. The prosthesis and its suspension from the neck were well-tolerated until removal (mean duration 4 months). A postoperative transitory myositis was diagnosed in only one patient. One of the most frequent complications of esophageal prostheses in refractory esophageal strictures due to caustic ingestion is distal migration. Different solutions were proposed. For example the suspension of a wire coming from the nose and then fixed behind the ear. This solution is not considered optimal because of patient complaints and moreover the aesthetic aspect is compromised. The procedure we utilized in four patients utilized the setting of a silicone tube hanging from the neck in a way similar to that of endoscopic pharyngostomy. This solution is a valid alternative both for quality of life and for functional results.

Tumor budding as a risk factor for nodal metastasis in pT1 colorectal cancers: a meta-analysis

Worldwide, colorectal cancer (CRC) screening programs have significantly increased the detection of submucosal (pT1) adenocarcinoma. Completion surgery may be indicated after endoscopic excision of these potentially metastasizing early cancers. However, the postsurgical prevalence of nodal implants does not exceed 15%, leading to questions concerning the clinical appropriateness of any post-endoscopy surgery. Eastern scientific societies (Japanese Society for Cancer of the Colon-Rectum, in particular) include tumor budding (TB), defined as the presence of isolated single cancer cells or clusters of fewer than 5 cancer cells at the tumor invasive front, among the variables that must be included in histologic reports. In Western countries, however, no authoritative endorsements recommend the inclusion of TB in the histology report because of the heterogeneity of definitions and measurement methods as well as its apparent poor reproducibility. To assess the prognostic value of TB in pT1 CRCs, this meta-analysis evaluated 41 studies involving a total of 10137 patients. We observed a strong association between the presence of TB and risk of nodal metastasis in pT1 CRC. In comparing TB-positive (684/2401; 28.5%) versus TB-negative (557/7736; 7.2%) patients, the prevalence of nodal disease resulted in an odds ratio value of 6.44 (95% confidence interval, 5.26-7.87; P<.0001; I2 = 30%). This increased risk of regional nodal metastasis was further confirmed after accounting for potential confounders. These results support the priority of histologically reporting TB in any endoscopically removed pT1 CRC to direct more appropriate patient management.

Clean Colon Software Program (CCSP), Proposal of a standardized Method to quantify Colon Cleansing During Colonoscopy: Preliminary Results

Background and study aims: Neoplastic lesions can be missed during colonoscopy, especially when cleansing is inadequate. Bowel preparation scales have significant limitations and no objective and standardized method currently exists to establish colon cleanliness during colonoscopy. The aims of our study are to create a software algorithm that is able to analyze bowel cleansing during colonoscopies and to compare it to a validate bowel preparation scale. Patients and methods: A software application (the Clean Colon Software Program, CCSP) was developed. Fifty colonoscopies were carried out and video-recorded. Each video was divided into 3 segments: cecum-hepatic flexure (1st Segment), hepatic flexure-descending colon (2nd Segment) and rectosigmoid segment (3rd Segment). Each segment was recorded twice, both before and after careful cleansing of the intestinal wall. A score from 0 (dirty) to 3 (clean) was then assigned by CCSP. All the videos were also viewed by four endoscopists and colon cleansing was established using the Boston Bowel Preparation Scale. Interclass correlation coefficient was then calculated between the endoscopists and the software. Results: The cleansing score of the prelavage colonoscopies was 1.56 ± 0.52 and the postlavage one was 2,08 ± 0,59 (P < 0.001) showing an approximate 33.3 % improvement in cleansing after lavage. Right colon segment prelavage (0.99 ± 0.69) was dirtier than left colon segment prelavage (2.07 ± 0.71). The overall interobserver agreement between the average cleansing score for the 4 endoscopists and the software pre-cleansing was 0.87 (95 % CI, 0.84 – 0.90) and post-cleansing was 0.86 (95 % CI, 0.83 – 0.89). Conclusions: The software is able to discriminate clean from non-clean colon tracts with high significance and is comparable to endoscopist evaluation.

PWE-008 Colorectal cancer screening programs and the rate of surgical oncology procedures in the veneto region (italy)

Introduction Colorectal cancer (CRC) is a leading cause of cancer mortality in the Veneto Region (North-east Italy). Population screening of adults between 50 and 75 for CRC was begun in 2002, and it became standard practice in all 21 local health units (LHU) of the region in 2008, 14 LHU provided in the program also follow-up colonoscopy and 7 LHU no. This study was carried out to evaluate the impact on surgery rates of CRC screening and follow-up programs. Method This is a retrospective cohort study on administrative data based on anonymous computerised database of Veneto Region hospital discharges between 2000 and 2015. All Veneto residents (in screening age) discharge records with principal diagnosis of CRC treated with surgery were included in the study. The number of patients studied rose approximately 18% reaching 1,547,097 for the last year (2015). The Standardised Hospitalisation Ratio (SHR) per five-year age group was calculated and expressed per 10 000 population. Results During the study period, 30 399 surgical procedures for colorectal cancer were performed (colon 63%, rectum 36%, secondary malignant neoplasm 1%) with a SHR of 139.1, higher in males (OR: 1.66; CI 95%: 1.62–1.7; p<0.05). An analysis of the annual SHR distribution uncovered two distinct phases: during the first phase there was a rising tendency that reached a maximum value in 2007 (166,9; X2 trend: 46.731; p<0.05) and during the second there was a falling tendency that reached its minimum value in 2015 (102.3; X2 trend: 429.791; p<0.05), with a total reduction of 28%. The cancer stratification by site shows that the rate of surgical procedures of the proximal colon during the last year was the same as the 2000 value (41.5), instead there was a significant decrease (−37,3%; X2 trend: 559.282; p<0.05) in the rate of procedures on the distal colon and rectum which fell from 94.4 to 59.2 (Figure1). The stratification of LHU in which the screening program included a follow-up colonoscopy and others didn’t show significant difference in the reduction in surgical procedures (Figure2). Abstract PWE008 Figure 1 Abstract PWE-008 Figure 2 Conclusion Study findings confirmed that CRC screening was effective in reducing the number of oncological surgical oncology procedures particularly with regard to the distal colon and rectum. Data analysis showed that the screening seemed to accelerate reaching the peak rate in surgical procedures that took place in 2007. After that time point the number of operations began to fall as far as the distal colon was concerned (it fell by 37.3%). Finally data suggest that the real benefit in reduction of oncological surgery procedures is due to the first screening colonoscopy. Disclosure of Interest None Declared

PTU-016 The Endoscopic Submucosal Dissection Learning Curve: The Experience of a Large Volume Italian Colorectal (CRC) Screening Centre

Introduction Endoscopic submucosal dissection (ESD) is an advanced endoscopic technique. In Eastern countries the learning curve is begun with gastric GI lesions carried out under expert supervision and then goes on to address esophageal and colon lesions. As Early Gastric Cancer (EGC) is a rare disease in Western countries, expert guidance is not commonly available. Methods All the ESD performed in our Endoscopy Unit in Padua from February 2012 to December 2015 including 12,552 colonoscopies were recruited retrospectively in this study. We considered the learning curve of a single endoscopist who performed 10 ESD on in vivo animal models under expert supervision before starting on human subjects. All the dissections were performed using a Hybridknife needle and ERBEJET2 (ERBE®). ESD was performed if the neoplastic lesion was considered susceptible to ESD regardless to the size. T tests for unpaired data and Pearson’s chi-test were used for statistical analysis. Results 49 ESD were performed, 28 M(57%), mean age 63 yr. The breadown was: 29 rectum (59%), 12 sigmoid tract (24%), 2 trasverse colon (4%), 4 ascending colon (8%), 2 stomach (4%). The neoplastic lesions were: 36 laterally spreading tumours (73%), 5 polypoid lesions 0 Is (10%), 4 recurrent ton scars (8%), 4 polypoid lesions 0 Isp(10%). Mean polyp area was 17.6 cm2 (range 1–70). Mean intervention time was 98 min (range 20–240). En-bloc dissection was successful in 34/49 (69%) and R0 was reached in 24/33 (72%). The histological features of the polyps were: 10 LGD (20%), 27 HGD (55%), 9 pT1 (18%), 3 pT2 (6%). The procedural complications that took place (14/49 = 28%) included: perforation during the procedure in 10/49 (20%), delayed bleeding in 3/49 (6%), rectal stenosis in 3/49 (6%). No deaths or surgical interventions followed the periprocedural complications. From the 12th procedure onwards the surgical performance became acceptable 22/27 (81%) vs 3/12 (25%) (p < 0.001). From the 30th procedure onwards the surgical performance became good 17/19 (90%, p < 0.05) and the mean execution time was significantly lower 55 vs 122 min (p < 0.0001) with no significant difference in the mean area of the lesions 15.6 vs 18.2 cm2 (p=ns). Only 3 complications occurred after the 30th procedure (p=ns). Conclusion Our findings demonstrate than an endoscopist can reach a satisfactory level of competence in ESD procedures by beginning training with in vivo animal models (at least 10 procedures) and then should go on to colo-rectal neoplasms (without size limits and no less than 12 procedures). Trainees have probably still not reached a learning curve plateau even after 40 procedures. Disclosure of Interest None Declared

OC.05.5 CANCER INVADING THE SUBMUCOSAL LAYER: IS IT TIME TO CHANGE SURGICAL INDICATIONS FOR SCREENING COLONOSCOPIES?

CANCER INVADING THE SUBMUCOSAL LAYER: IS IT TIME TO CHANGE SURGICAL INDICATIONS FOR SCREENING COLONOSCOPIES? E. Rosa-Rizzotto ∗ ,1, M. Lo Mele2, D. Caroli 3 , E. Guido1, F. Ancona1, L. Peraro1, R. Cappellesso2 , S. Cocchio4 , V. Baldo4, M. Rugge2, F. De Lazzari 1 1Dpt of Medicine, Gastroenterology Unit, St Anthony Hospital, Padova, Italy; 2Department of Diagnostic, Medical Sciences and Special Therapies, Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Padova, Italy; 3Dpt of Medicine, Chioggia Hospital, Venice, Italy; 4Dpt of Molecular Medicine, Laboratory of Public Health and Population Studies, University of Padua, Padova, Italy