Long-Term Follow-up of the Italian Flexible Sigmoidoscopy Screening Trial.

BACKGROUND: Recent reports showed that the protective effect of flexible sigmoidoscopy (FS) screening was maintained up to17 years, although differences were reported by sex. OBJECTIVE: To assess long-term reduction of colorectal cancer (CRC) incidence and mortality after a single FS screening. DESIGN: Parallel randomized controlled trial. (ISRCTN registry number: 27814061). SETTING: 6 centers in Italy. PARTICIPANTS: Persons aged 55 to 64 years expressing interest in having FS screening if invited, recruited from 1995 to 1999 and followed until 2012 (incidence) and 2014 to 2016 (mortality). INTERVENTION: Eligible persons were randomly assigned (1:1 ratio) to either the once-only FS screening group or control (usual care) group. MEASUREMENTS: Incidence and mortality rate ratios (RRs) and rate differences. RESULTS: A total of 34 272 persons (17 136 in each group) were included in the analysis; 9911 participants had screening in the intervention group. Median follow-up was 15.4 years for incidence and 18.8 years for mortality. Incidence of CRC was reduced by 19% (RR, 0.81 [95% CI, 0.71 to 0.93]) in the intention-to-treat (ITT) analysis, comparing the intervention with the control group, and by 33% (RR, 0.67 [CI, 0.56 to 0.81]) in the per protocol (PP) analysis, comparing participants screened in the intervention group with the control persons. Colorectal cancer mortality was reduced by 22% (RR, 0.78 [CI, 0.61 to 0.98]) in the ITT analysis and by 39% (RR, 0.61 [CI, 0.44 to 0.84]) in the PP analysis. Incidence of CRC was statistically significantly reduced among both men and women. Colorectal cancer mortality was statistically significantly reduced among men (ITT RR, 0.73 [CI, 0.54 to 0.97]) but not among women (ITT RR, 0.90 [CI, 0.59 to 1.37]). LIMITATION: Self-selection of volunteers from the general population sample targeted for recruitment may limit generalizability. CONCLUSION: The strong protective effect of a single FS screening for CRC incidence and mortality was maintained up to 15 and 19 years, respectively. PRIMARY FUNDING SOURCE: Italian Association for Cancer Research, Italian National Research Council, Istituto Oncologico Romagnolo, Fondo "E. Tempia," University of Milan, and Local Health Unit ASL-Torino.

Plasma miRNA-based signatures in CRC screening programs.

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607-0.682), 0.670 (0.626-0.714) and 0.682 (0.580-0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.

Endoscopic submucosal dissection: Italian national survey on current practices, training and outcomes.

BACKGROUND AND AIMS: Most of the evidence supporting endoscopic submucosal dissection (ESD) comes from Asia. European data are primarily reported by specialized referral centers and thus may not be representative of common European ESD practice. The aim of this study is to understand the current state of ESD practice across Italian endoscopy centers. METHODS: All Italian endoscopists who were known to perform ESD were invited to complete a structured questionnaire including: operator features and competencies, ESD training details and clinical outcomes over a 2-year period. RESULTS: Twenty-nine operators from 23 centers (69% response rate) completed the questionnaire: 18 (62%) were <50 years old; 7 (24%) were female; 16 (70%) were located in Northern Italy. Overall ESD volume was <40 cases in 9 (31%) operators, 40-80 in 8 (27.5%), 80-150 in 4 (13.8%) and >150 in 8 (27.5%). Colorectal ESD was predominant for operators with an experience >80 cases. En-bloc resection rates ranged from 77.2 to 97.2% depending on the anatomic location with an R0 resection rate range of 75.3-93.6%. ESD perforation rates in the colon and rectum were significantly lower when experience was >150 compared to 80-150 cases (p < 0.0001 and p = 0.006 for colon and rectum, respectively). CONCLUSION: ESD in Italy is performed by a significant number of operators. Overall, Italian endoscopists performing ESD have achieved a good competence level. However, there is much variability in training protocols, initial supervision of procedures, practice settings, case mix and procedural volume/year that are likely responsible for some of the suboptimal resectional outcomes and increased perforation risk, mainly in the colon. Standardized training programs, practice parameters and auditing of outcomes are required.

Double indocyanine green technique of robotic right colectomy: Introduction of a new technique.

In robotic right hemicolectomy for colorectal cancer (CRC), appropriate lymphadenectomy and anastomotic leak prevention are critical. Visualisation of lymph nodes and blood flow with near-infrared (NIR) fluorescence DaVinci® imaging system is a recent development. Herein, we present an improved robotic modified complete mesocolic excision (mCME) technique using indocyanine green (ICG) fluorescence. Before surgery, ICG is injected into the submucosa around the tumour with endoscopy for intraoperative detection of lymph nodes. Robotic mCME with central vascular ligation is performed, supplemented in most of the cases with selective extended lymphadenectomy. Intestinal blood flow before anastomosis is evaluated by administering ICG intravenously and NIR visualisation. Visualisation of the lymph nodes with ICG facilitates standard mCME lymphadenectomy and enables extended lymphadenectomy. Blood flow of the intestinal walls of the anastomotic site can be assessed and determines the extent of intestinal resection. Robotic double ICG technique for robotic right hemicolectomy enables improved lymphadenectomy and warrants the extent of intestinal resection; thus, becoming a strong candidate for gold standard in robotic resections of the right colon for CRC.

A rationale multidisciplinary approach for treatment of esophageal and gastroesophageal junction cancer: Accurate review of management and perspectives.

Cancer of the esophagus and of gastroesophageal junction can be cured, even if with lacking cure rate. Different approaches have been developed, mostly when carcinoma has loco-regional pattern. Multimodality therapy showed a survival rate superior than 10% if compared to a single approach. This is a systematic review, carried to assess the following matters: Which therapeutic opportunities are available? Who could benefit of them? Which adverse reactions could possibly verify? How can physicians definitely choose the proper strategy? Which is the role of surgery? We mean to give either General Practitioner or specialists clear and efficient updates about current treatment of this tumour, starting from physical examination. Four eminent guidelines were consulted for our study: Cancer Care Ontario's Program in Evidence-Based Care, NCCN, Belgian Health Care Knowledge Centre and Esmo.

Aggressive Surgical Approach for Treatment of Primary and Recurrent Retroperitoneal Soft Tissue Sarcoma.

To analyze treatment and survival in a series of resected patients with primary or recurrent retroperitoneal sarcoma (RPS) treated and prospectively followed at a single institution. Between July 1994 and December 2015, 89 patients (36 M, 53 F; mean age 60 years, range 25-79) were evaluated. For the purpose of analysis, complete resection was defined as removal of gross tumor with histologically confirmed clear resection margins. Eighty-three out of the 89 patients (93%), 46 of whom affected by primary RPS, and 37 by recurrent RPS, underwent surgical exploration. Sixty-two had a grossly and microscopically complete resection. Fifty-three out of 83 patients (64%) underwent removal of contiguous intra-abdominal organs. Preoperative mortality was nil and significant preoperative complications occurred in six cases only (7%). High-grade tumor pointed out to be a significant variable for a worse survival in all 83 patients amenable to undergo surgical resection (57% 5 years survival for low grade vs 14% for high grade; P = 0.0004). Among completely resected patients, only histologic grade clearly affected disease-free survival (72% 5 years survival for low grade vs 50% for high grade; P = 0.04), while the role of preoperative blood transfusions (67% 5 years survival for non-transfused patients vs 29% for transfused patients; P = 0.05) has to be evaluated in connection to patient complexity. Histological grade and recurrence are the most valuable prognostic predictors; in this clinical subset, an aggressive surgical approach in both primary and recurrent RPS is associated with a best long-term survival and disease-free survival.

Evaluation of Clensia®, a new low-volume PEG bowel preparation in colonoscopy: Multicentre randomized controlled trial versus 4L PEG.

BACKGROUND: Success of colonoscopy is linked to the adequacy of bowel cleansing. Polyethylene glycol 4L (PEG 4L) solutions are widely used for colonic cleansing but with limitations concerning tolerability and acceptability. AIM: To demonstrate the equivalence of a new low-volume PEG containing citrates and simeticone (Clensia) versus a standard PEG 4L. METHODS: In this, multicentre, randomised, observer-blind trial, patients received either Clensia 2L or PEG 4L solution. Primary endpoint was the proportion of patients with colon cleansing evaluated as excellent or good. RESULTS: 422 patients received Clensia (n=213) or PEG 4L (n=209). Rate of excellent/good bowel cleansing was 73.6% and 72.3% in Clensia and PEG 4L group respectively. Clensia was demonstrated to be equivalent to PEG 4L. No SAEs were observed. Clensia showed better gastrointestinal tolerability (37.0% vs 25.4%). The acceptability was significantly better with Clensia in terms of proportion of subjects who felt no distress (Clensia 72.8% vs PEG 4L 63%, P=0.0314) and willingness-to-repeat (93.9% vs 82.2%, P=0.0002). The rate of optimal compliance was similar with both formulations (91.1% for Clensia vs 90.9% for PEG 4L, P=0.9388). CONCLUSIONS: The low-volume Clensia is equally effective and safe in bowel cleansing compared to the standard PEG 4L, with better gastrointestinal tolerability and acceptability.

Predictors of advanced colorectal neoplasia at initial and surveillance colonoscopy after positive screening immunochemical faecal occult blood test.

BACKGROUND: Characteristics such as gender and lifestyle are not taken in account in colorectal cancer screening and surveillance recommendations. AIMS: To identify factors associated with advanced neoplasia at initial and surveillance colonoscopy. METHODS: In this observational study, 750 individuals with positive faecal occult blood test, aged 50-74 years, underwent a first screening colonoscopy in 2007-2009. We collected anthropometric data as well as data on physical activity, smoking and drinking habits, fruit and vegetable consumption and low-dose aspirin use through a questionnaire. RESULTS: At initial colonoscopy advanced neoplasia (n=399, 53.2%) was positively associated with age, male gender, smoking and alcohol drinking, and inversely associated with physical activity, fruit and vegetables consumption and long-term use of aspirin. These 7 factors were used to calculate a risk score, ranging from 0 (no unfavourable characteristics) to 7 (all unfavourable characteristics present), which was significantly associated with advanced neoplasia (odds ratio 1.55 for one point increase, P<0.01). Among the 372 adenoma patients who returned for follow-up surveillance colonoscopy, the score remained associated with advanced neoplasia (odds ratio 1.28 for one point increase, P=0.01). CONCLUSION: Besides age and gender, modifiable factors such as lifestyle and aspirin use were associated with the risk of advanced neoplasia at initial and surveillance colonoscopy.

Endoscopic electrocautery dilation of benign anastomotic colonic strictures: a single-center experience.

BACKGROUND: Benign anastomotic colonic stenosis sometimes occur after surgery and usually require surgical or endoscopic dilation. Endoscopic dilation of anastomotic colonic strictures by using balloon or bougie-type dilators has been demonstrated to be safe and effective in multiple uncontrolled series. However, few data are available on safety and efficacy of endoscopic electrocautery dilation. The aim of our study was to retrospectively investigate safety and efficacy of endoscopic electrocautery dilation of postsurgical benign anastomotic colonic strictures. METHODS: Sixty patients (37 women; median age 63.6 years, range 22.6-81.7) with benign anastomotic colonic or rectal strictures treated with endoscopic electrocautery dilation between June 2001 and February 2013 were included in the study. Anastomotic stricture was defined as a narrowed anastomosis through which a standard colonoscope could not be passed. Only annular anastomotic strictures were considered suitable for electrocautery dilation which consisted of radial incisions performed with a precut sphincterotome. Treatment was considered successful if the colonic anastomosis could be passed by a standard colonoscope immediately after dilation. Recurrence was defined as anastomotic stricture reappearance during follow-up. RESULTS: The time interval between colorectal surgery and the first endoscopic evaluation or symptoms development was 7.3 months (1.3-60.7). Electrocautery dilation was successful in all the patients. There were no procedure-related complications. Median follow-up was 35.5 months (2.0-144.0). Anastomotic stricture recurrence was observed in three patients who were successfully treated with electrocautery dilation and Savary dilation. CONCLUSIONS: Endoscopic electrocautery dilation is a safe and effective treatment for annular benign anastomotic postsurgical colonic strictures.

Early and delayed complications of polypectomy in a community setting: The SPoC prospective multicentre trial.

BACKGROUND: Colonoscopic polypectomy is effective in reducing the incidence of and mortality from colorectal cancer, but is not complication-free. AIMS: To evaluate the incidence of early and delayed polypectomy complications and factors associated with their occurrence in a community setting. METHODS: Web-database collection of patients' and polyp's features in consecutive colonic polypectomies during a 3-month period in 18 endoscopy centres. RESULTS: Data on 5178 polypectomies in 2692 patients (54.3% males, mean age 59 years) were collected. The majority of the polyps were <10mm (83.5%). Antithrombotic agents were taken by 22.7% of patients, 57.3% of which withheld them before the procedure. Overall, 5 patients experienced perforations (0.2%) and 114 had bleeding (4.2%); the overall complication rate was 4.4%. Early complications were observed in 87 (3.2%); delayed complications (all major bleedings) occurred in 32 (1.2%). At multivariate analysis polyp size (size >10mm: OR 4.35, 95% CI 5.53-7.48) and, inversely, right-sided location (OR 0.58, 95% CI 0.36-0.94) were correlated with bleeding events. The use of antithrombotics was associated with 5-fold increased risk of delayed bleeding. CONCLUSIONS: In the community setting, polypectomy was associated with a 1.4% risk of major complications. Polyp size and, inversely, right-sided location were associated with early bleeding; the use of antithrombotics increased the risk of delayed events.

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 ±â€Š0.52 and the postlavage one was 2,08 ±â€Š0,59 (P < 0.001) showing an approximate 33.3 % improvement in cleansing after lavage. Right colon segment prelavage (0.99 ±â€Š0.69) was dirtier than left colon segment prelavage (2.07 ±â€Š0.71). 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.

Overall acceptability and efficacy of commonly used bowel preparations for colonoscopy in Italian clinical practice. A multicentre prospective study.

BACKGROUND & AIMS: The recent enormous increase in colonoscopy demand prompted this multicentre observational study assessing overall acceptability and efficacy of commonly used bowel preparations in Italian clinical practice. METHODS: Consecutive outpatients undergoing colonoscopy were recruited from 9 major gastroenterological centres in Italy. Each patient evaluated overall acceptability of the bowel cleansing preparation through a 0-100mm Visual Analogue Scale. The Visual Analogue Scale score was dichotomized by a median split: 80-100 (high acceptability) vs. 0-79 (low acceptability). Bowel cleansing was assessed through a validated scale. The influence of potential individual determinants on patients' acceptability and cleansing efficacy of the bowel preparations was determined by multivariate analyses. RESULTS: 599 evaluable patients were enrolled; 57.3% received 4L-PEG preparations, 29.5% 2L-PEG preparations and 13.2% 2-glasses-solutions (Na-phosphate/Mg-citrate/Na-picosulphate-containing preparations). Overall acceptability was significantly higher for 2L-PEG and 2-glasses solutions than 4L-PEG (adjusted odds ratio, 4.72; and adjusted odds ratio 2.07, respectively). Successful bowel cleansing achieved with 4L-PEG (85.9%) was similar to 2L-PEG (85.3%; adjusted odds ratio 0.82) and significantly higher than 2-glasses solutions (69.6%; adjusted odds ratio 0.34 vs. 4L-PEG). Split regimen, lower total preparation volume and colonoscopy reason (periodical control vs. 1st procedure) were significantly associated with high acceptability. Age ≥60 years, dissatisfaction with the preparation taken, and ≤4/week bowel movements were major determinants of a poor bowel cleansing. CONCLUSIONS: 2L-PEG and 4L-PEG preparations provide the most effective bowel cleansing for colonoscopy in clinical practice, with a significantly higher acceptability for 2L-PEG preparations.

Efficacy of 9°Yttrium-ibritumomab tiuxetan in relapsed/refractory extranodal marginal-zone lymphoma.

We evaluated clinical activity of 9°Yttrium-ibritumomab (9°Y-ibritumomab) tiuxetan in extranodal marginal-zone lymphoma. From May 2004 to April 2011, 30 patients affected by relapsed/refractory marginal-zone lymphoma--arisen at any extranodal site--received 9°Y-ibritumomab tiuxetan at the activity of 0.4 mCi/kg. Median age was 57 years. At time of treatment, 13 out of 30 patients had disseminated disease (stage III/IV). All patients had received a previous treatment with a maximum of 7. Overall response rate was 90%: 23 patients achieved a complete response (77%); partial response occurred in 4 patients (13%), stable disease in 2 patients (7%) and 1 progression (3%). With a median follow-up of 5.3 years, median time to relapse was not reached; 2 patients relapsed after complete response; 18 out of 23 complete responses are still responders after >3 years, 12 of them after >5 years. 9°Y-ibritumomab tiuxetan seems to be active in patients with extranodal marginal-zone lymphoma relapsed/refractory to conventional treatment including radiotherapy. These results suggest that radioimmunotherapy could represent a possible option for the treatment in this subset of patients.

Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy.

AIM: To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy. METHODS: Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure. RESULTS: A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes. CONCLUSION: Same-day PEG-CS is feasible, effective as split-dose 4-L PEG for late morning colonoscopy and does not interfere with work and daily activities the day before colonoscopy.

Consensus guidelines for the use of bowel preparation prior to colonic diagnostic procedures: colonoscopy and small bowel video capsule endoscopy.

BACKGROUND: Adequate bowel preparation prior to colonic diagnostic procedures is essential to ensure adequate visualisation. SCOPE: This consensus aims to provide guidance as to the appropriate use of bowel preparation for a range of defined clinical circumstances. A consensus group from across Europe was convened and met to discuss appropriate bowel preparation. The use of polyethylene glycol (PEG), sodium picosulphate and sodium phosphate (NaP), together with other agents, prokinetics and simethicone, in colonoscopy and small bowel video capsule endoscopy were considered. A systematic review of the literature was carried out and additional unpublished data was obtained from the members of the consensus group where required. Recommendations were graded according to the level of evidence. FINDINGS: PEG-based regimens are recommended first line for both procedures, since their use is supported by good efficacy and safety data. Sodium-picosulphate-based regimens are recommended second line as their cleansing efficacy appears less than PEG-based regimens. NaP is not recommended for bowel cleansing due to the potential for renal damage and other adverse events. However, the use of NaP is acceptable in patients in whom PEG or sodium picosulphate is ineffective or not tolerated. NaP should not be used in patients with chronic kidney disease, pre-existing electrolyte disturbances, congestive heart failure, cirrhosis or a history of hypertension. The timing of the dose, dietary restrictions, use in special patient groups and recording of the quality of bowel preparation are also considered for patients undergoing colonoscopy. During the development of the guidelines the European Society of Gastrointestinal Endoscopy (ESGE) issued guidance on bowel preparation for colonoscopy. The ESGE guidelines and these consensus guidelines share many recommendations; differences between the guidelines are reviewed. CONCLUSION: The use of bowel preparation should be tailored to the individual patient and their specific clinical circumstances.

Confocal laser endomicroscopy for in vivo diagnosis of Barrett's oesophagus and associated neoplasia: a pilot study conducted in a single Italian centre.

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.

Interobserver agreement among endoscopists on evaluation of polypoid colorectal lesions visualized with the Pentax i-Scan technique.

BACKGROUND AND AIMS: Advances in colonoscopy, such as the Pentax i-Scan electronic technique, have the potential to improve the early detection of colorectal cancer. The aim of this multicentre study was to assess the interobserver agreement in the visualization of the surface and margins of colorectal polyps and in distinguishing neoplastic from non-neoplastic polyps. PATIENTS AND METHODS: Eight expert endoscopists examined 400 mixed previously recorded images of polyps taken with different Pentax i-Scan settings in order to give an evaluation of the surface of the polyp and regular colonic mucosa, the pit-pattern and the nature of the lesion. RESULTS: A total of 400 mixed images of polyps with a diameter >5mm and <10mm were stored for analysis. Overall, there was a Kf agreement of 0.370 (p<0.001) and 0.306 (p<0.001) regarding pit-pattern and margins, respectively. The Kf agreement for the difference between neoplastic and non-neoplastic lesions was of 0.446 (p<0.001). CONCLUSIONS: We observed good interobserver agreement in the evaluation of neoplastic and non-neoplastic lesions and poor agreement in the evaluation of pit-pattern and margins. Adequate training is required in order to interpret images acquired with the i-Scan technique.

A randomized, placebo-controlled, preoperative trial of allopurinol in subjects with colorectal adenoma.

Inflammation and oxidative stress play a crucial role in the development of colorectal cancer (CRC) and interference with these mechanisms represents a strategy in CRC chemoprevention. Allopurinol, a safe molecular scavenger largely used as antigout agent, has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic studies. We conducted a randomized, double-blind, placebo-controlled preoperative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis. After complete colonoscopy and biopsy of the index polyp, 73 subjects with colorectal adenomas were assigned to either placebo or one of two doses of allopurinol (100 mg or 300 mg) and treated for four weeks before polyp removal. Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint. Secondary endpoints were the immunohistochemical (IHC) expression of NF-κB, ß-catenin, topoisomerase-II-α, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in adenomatous polyps and normal adjacent colonic tissue. Compared with placebo, Ki-67 levels were not significantly modulated by allopurinol, whereas ß-catenin and NF-κB expression levels decreased significantly in adenomatous tissue, with a mean change from baseline of -10.6%, 95% confidence interval (CI), -20.5 to -0.7, and -8.1%, 95% CI, -22.7 to 6.5, respectively. NF-κB also decreased significantly in normal adjacent tissue (-16.4%; 95% CI, -29.0 to -3.8). No dose-response relationship was noted, except for NF-κB expression in normal tissue. Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue. Further studies should define its potential chemopreventive activity.

Meta-analysis: efficacy of small bowel preparation for small bowel video capsule endoscopy.

OBJECTIVE: It is unclear whether small bowel visibility in video capsule endoscopy (VCE) is enhanced by the use of bowel preparation in addition to pre-procedural fasting. The objective of this study was to clarify this issue by means of a systematic review of the literature and meta-analysis. METHODS: Randomised controlled trials comparing the use of laxative bowel preparation with fasting alone were identified using a literature search. Categorical measures of treatment efficacy were extracted from qualifying studies and pooled using random-effects meta-analyses. Primary analysis compared any bowel preparation with fasting alone; subsidiary analyses assessed diagnostic yield and results for each regimen. RESULTS: Eight studies were identified, using either polyethylene glycol (PEG) or sodium phosphate (NaP) based regimens. No qualifying studies were identified using other laxatives. Study quality was sufficiently high to warrant meta-analysis. Use of any form of bowel preparation yielded significantly better visibility than fasting alone (OR = 2.31; 95% CI = 1.46-3.63; p < 0.0001). Similar results were seen for diagnostic yield (OR = 1.88; 95% CI = 1.24-2.84; p = 0.023). When sub-analysed according to the treatment used, PEG-based regimens showed benefit (OR = 3.11; 95% CI = 1.96-4.94; p < 0.0001), while NaP-based regimens yielded no significant difference from fasting alone (OR = 1.32; 95% CI = 0.59-2.96; p < 0.0001). LIMITATIONS: The study did not consider results from retrospective studies, nor those which did not give a categorical measure of efficacy. The impact of prokinetic and other adjunctive treatments was not considered. The results are only relevant to the most commonly used video capsule, as data for newer alternative devices have not yet been published. CONCLUSION: Based on the results of this analysis, the use of bowel preparation alongside fasting is recommended for VCE. PEG-based regimens offer a clear advantage in these patients, while the currently available evidence base does not support the use of NaP. For VCE, lower volume PEG appears to be as efficacious as higher volumes traditionally used for colonoscopy preparation.

Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial--SCORE.

BACKGROUND: A single flexible sigmoidoscopy at around the age of 60 years has been proposed as an effective strategy for colorectal cancer (CRC) screening. METHODS: We conducted a randomized controlled trial to evaluate the effect of flexible sigmoidoscopy screening on CRC incidence and mortality. A questionnaire to assess the eligibility and interest in screening was mailed to 236,568 men and women, aged 55-64 years, who were randomly selected from six trial centers in Italy. Of the 56,532 respondents, interested and eligible subjects were randomly assigned to the intervention group (invitation for flexible sigmoidoscopy; n = 17,148) or the control group (no further contact; n = 17,144), between June 14, 1995, and May 10, 1999. Flexible sigmoidoscopy was performed on 9911 subjects. Intention-to-treat and per-protocol analyses were performed to compare the CRC incidence and mortality rates in the intervention and control groups. Per-protocol analysis was adjusted for noncompliance. RESULTS: A total of 34,272 subjects (17,136 in each group) were included in the follow-up analysis. The median follow-up period was 10.5 years for incidence and 11.4 years for mortality; 251 subjects were diagnosed with CRC in the intervention group and 306 in the control group. Overall incidence rates in the intervention and control groups were 144.11 and 176.43, respectively, per 100,000 person-years. CRC-related death was noted in 65 subjects in the intervention group and 83 subjects in the control group. Mortality rates in the intervention and control groups were 34.66 and 44.45, respectively, per 100,000 person-years. In the intention-to-treat analysis, the rate of CRC incidence was statistically significantly reduced in the intervention group by 18% (rate ratio [RR] = 0.82, 95% confidence interval [CI] = 0.69 to 0.96), and the mortality rate was non-statistically significantly reduced by 22% (RR = 0.78; 95% CI = 0.56 to 1.08) compared with the control group. In the per-protocol analysis, both CRC incidence and mortality rates were statistically significantly reduced among the screened subjects; CRC incidence was reduced by 31% (RR = 0.69; 95% CI = 0.56 to 0.86) and mortality was reduced by 38% (RR = 0.62; 95% CI = 0.40 to 0.96) compared with the control group. CONCLUSION: A single flexible sigmoidoscopy screening between ages 55 and 64 years was associated with a substantial reduction of CRC incidence and mortality.