Cristina Bellisario

Efficacy and safety of endoscopic resection of large colorectal polyps: a systematic review and meta-analysis

Objective To assess the efficacy and safety of endoscopic resection of large colorectal polyps. Design Relevant publications were identified in MEDLINE/EMBASE/Cochrane Central Register for the period 1966–2014. Studies in which ≥20 mm colorectal neoplastic lesions were treated with endoscopic resection were included. Rates of postendoscopic resection surgery due to non-curative resection or adverse events, as well as the rates of complete endoscopic removal, invasive cancer, adverse events, recurrence and mortality, were extracted. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was produced based on random effect models. I2 statistic was used to describe the variation across studies due to heterogeneity. Meta-regression analysis was also performed. Results 50 studies including 6442 patients and 6779 large polyps were included in the analyses. Overall, 503 out of 6442 patients (pooled rate: 8%, 95% CI 7% to 10%, I2=78.6%) underwent surgery due to non-curative endoscopic resection, and 31/6442 (pooled rate: 1%, 95% CI 0.7% to 1.4%, I2=0%) to adverse events. Invasive cancer at histology, non-curative endoscopic resection, synchronous lesions and recurrence accounted for 58%, 28%, 2.2% and 5.9% of all the surgeries, respectively. Endoscopic perforation occurred in 96/6595 (1.5%, 95% CI 1.2% to 1.7%) polyps, while bleeding in 423/6474 (6.5%, 95% CI 5.9% to 7.1%). Overall, 5334 patients entered in surveillance, 502/5836 (8.6%, 95% CI 7.9% to 9.3%) being lost at follow-up. Endoscopic recurrence was detected in 735/5334 patients (13.8%, 95% CI 12.9% to 14.7%), being an invasive cancer in 14/5334 (0.3%, 95% CI 0.1% to 0.4%). Endoscopic treatment was successful in 664/735 cases (90.3%, 95% CI 88.2% to 92.5%). Mortality related with management of large polyps was reported in 5/6278 cases (0.08%, 95% CI 0.01% to 0.15%). Conclusions Endoscopic resection of large polyps appeared to be an extremely effective and safe intervention. However, an adequate endoscopic surveillance is necessary for its long-term efficacy.

Clinical outcomes after endoscopic submucosal dissection for colorectal neoplasia: a systematic review and meta-analysis

BACKGROUND AND AIMS Endoscopic submucosal dissection (ESD) is an endoscopic resection technique for lesions suspicious of superficial malignancy. It is performed using an ESD knife on its own (standard technique) or by the sequential use of a knife and a snare (hybrid technique). The experience with these techniques is different in Asian and non-Asian countries. We performed a systematic review and meta-analysis of available evidence on colorectal ESD. METHODS Electronic databases were searched up to August 2016 for studies evaluating R0, en bloc resection, and adverse event rates of both techniques for the treatment of colorectal lesions. Proportions were pooled by a random effects model. RESULTS Ninety-seven studies (71 performed in Asia) evaluated the standard technique and 12 studies (7 in Asia) the hybrid technique. The R0 resection rate of the standard technique was 82.9%, and it was significantly lower in non-Asian versus Asian countries: 71.3% versus 85.6%. The en bloc resection rate was 91% and was significantly lower in non-Asian versus Asian countries (81.2% vs 93%, respectively). Surgery was needed in 1.1% of the ESD-related adverse events, with a significant difference between non-Asian and Asian countries (3.1% vs 0.8%). The R0 and en bloc resection rates with the hybrid technique were significantly lower than those achieved with the standard technique: 60.6% and 68.4%, respectively, with similar adverse event rates. CONCLUSIONS In non-Asian countries the standard ESD technique is still failing to achieve acceptable levels of performance. The hybrid technique showed low R0 resection rates and should not be considered as an adequate alternative to the standard technique.

Population Based Cancer Screening Programmes as a Teachable Moment for Primary Prevention Interventions. A Review of the Literature

Background and aim: Unhealthy diet, physical inactivity, and smoking are key risk factors for the major non-communicable diseases such as cancer, cardiovascular diseases, and diabetes. The screening procedure may represent an ideal setting for promoting healthy lifestyles as it represents a time when subjects are probably more inclined to consider a relationship between their own habits and their effects on health. The aim of this study is to review available evidence concerning interventions combining screening and primary prevention interventions, aimed at promoting the adoption of healthy lifestyles. Methods: We searched the MEDLINE and Cochrane library electronic databases for intervention studies of primary prevention interventions implemented in the context of established screening programmes, or of pilot screening projects, where the study design included a comparison group. Results: Comprehensive interventions are acceptable for asymptomatic subjects targeted for cancer screening, can result in improvements and may be cost–effective. A positive impact of these interventions in favoring the adoption of cancer protective dietary behaviors was observed in all studies. Conflicting results were instead reported with respect to physical activity, while no impact could be observed for interventions aimed to favor smoking cessation. Conclusions: The retrieved studies suggest that the screening setting may offer valuable opportunities to provide credible, potentially persuasive life style advice, reaching a wide audience. A multiple risk factor approach may maximize the benefit of behavioral change, as the same health related habits are associated not only with cancers targeted by screening interventions, but also with other cancers, coronary artery disease, and other chronic conditions, while unhealthy behaviors may be mutually reinforcing. In order to cover a maximum number of possibilities, health education programmes should include multiple strategies, integrating and combining models of individual, social, and environmental change.

The European Society of Gastrointestinal Endoscopy Quality Improvement Initiative: developing performance measures

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) have a vision to create a thriving community of endoscopy services across Europe, collaborating with each other to provide high quality, safe, accurate, patient-centered and accessible endoscopic care. Whilst the boundaries of what can be achieved by advanced endoscopy are continually expanding, we believe that one of the most fundamental steps to achieving our goal is to raise the quality of everyday endoscopy. The development of robust, consensus- and evidence-based key performance measures is the first step in this vision. ESGE and UEG have identified quality of endoscopy as a major priority. This paper explains the rationale behind the ESGE Quality Improvement Initiative and describes the processes that were followed. We recommend that all units develop mechanisms for audit and feedback of endoscopist and service performance using the ESGE performance measures that will be published in future issues of this journal over the next year. We urge all endoscopists and endoscopy services to prioritize quality and to ensure that these performance measures are implemented and monitored at a local level, so that we can provide the highest possible care for our patients.

Development of standardized image interpretation for 68Ga-PSMA PET/CT to detect prostate cancer recurrent lesions

MethodsAfter primary treatment, biochemical relapse (BCR) occurs in a substantial number of patients with prostate cancer (PCa). PET/CT imaging with prostate-specific membrane antigen based tracers (68Ga-PSMA) has shown promising results for BCR patients. However, a standardized image interpretation methodology has yet to be properly agreed. The aim of this study, which was promoted and funded by European Association of Nuclear Medicine (EANM), is to define standardized image interpretation criteria for 68Ga-PSMA PET/CT to detect recurrent PCa lesions in patients treated with primary curative intent therapy (radical prostatectomy or radiotherapy) who presented a biochemical recurrence. In the first phase inter-rater agreement between seven readers from seven international centers was calculated on the reading of 68Ga-PSMA PET/CT images of 49 patients with BCR. Each reader evaluated findings in five different sites of recurrence (local, loco-regional lymph nodes, distant lymph nodes, bone, and other). In the second phase the re-analysis was limited to cases with poor, slight, fair, or moderate agreement [Krippendorff’s (K) alpha<0.61]. Finally, on the basis of the consensus readings, we sought to define a list of revised consensus criteria for 68Ga-PSMA PET/CT interpretation.ResultsBetween-reader agreement for the presence of anomalous findings in any of the five sites was only moderate (K’s alpha: 0.47). The agreement improved and became substantial when readers had to judge whether the anomalous findings were suggestive for a pathologic, uncertain, or non-pathologic image (K’s alpha: 0.64). K’s alpha calculations for each of the five sites of recurrence were also performed and evaluated. First Delphi round was thus conducted. A more detailed definition of the criteria was proposed by the project coordinator, which was then discussed and finally agreed by the seven readers. After the second Delphi round only four cases of disagreement still remained. These were evaluated for a final round, allowing a final agreement table to be written.ConclusionWe hope that by developing these consensus guidelines on the interpretation of 68Ga-PSMA PET/CT, clinicians reporting these studies will be able to provide more consistent clinical reports and that within clinical trials, abnormality classifications will be harmonized, allowing more robust assessment of its diagnostic performance.

Gastroesophageal reflux disease after per-oral endoscopic myotomy as compared with Heller's myotomy with fundoplication: a systematic review with meta-analysis

BACKGROUND AND AIMS Per-oral endoscopic myotomy (POEM) represents a less invasive alternative to conventional laparoscopic Hellers myotomy (LHM) for patients with achalasia. It cannot be excluded, however, that the lack of fundoplication after POEM may result in a higher incidence of reflux disease, as compared with LHM. The aim of our study was to conduct a systematic review of prospective studies reporting the incidence of reflux disease developed after POEM and LHM. METHODS A literature search with electronic databases was performed (up to February 2017) to identify full articles on the incidence of gastroesophageal reflux symptoms and endoscopic monitoring and pH monitoring findings after POEM and LHM (with fundoplication). Proportions and rates were pooled by means of random or fixed-effects models, according to the level of heterogeneity between studies. RESULTS After we applied the selection criteria, 17 and 28 studies, including 1542 and 2581 participants who underwent POEM and LHM, respectively, were included. The pooled rate of postprocedural symptoms was 19.0% (95% confidence interval [CI], 15.7%-22.8%) after POEM and 8.8% (95% CI, 5.3%-14.1%) after LHM, respectively. The pooled rate estimate of abnormal acid exposure at pH monitoring was 39.0% (95% CI, 24.5%-55.8%) after POEM and 16.8% (95% CI, 10.2%-26.4%) after LHM, respectively. The rate of esophagitis after POEM was 29.4% (95% CI, 18.5%-43.3%) after POEM and 7.6% (95% CI, 4.1%-13.7%) after LHM. At meta-regression, heterogeneity was explained partly by the POEM approach and study population. CONCLUSION The incidence of reflux disease appears to be significantly more frequent after POEM than after LHM with fundoplication. Monitoring pH and ensuring appropriate treatment after POEM should be considered in order to prevent long-term reflux-related adverse events.

Epidemiologic evidence of slow growing, nonprogressive or regressive breast cancer: A systematic review

The general aim of this systematic review is to mitigate breast cancer (BC) overdiagnosis and overtreatment. The specific aim is to summarize available data on the occurrence and features of indolent invasive or in situ (DCIS) BC, and precisely survival of untreated cases, prevalence of occult cancers found in autopsies, frequency of regressive BC. PubMed, Embase and Cochrane Library were systematically searched up to 3/31/2014. Eligibility criteria were: cohort studies, case‐control studies, uncontrolled case series assessing survival in women with a diagnosis of BC who did not receive treatment compared to treated women; case series of autopsies estimating the prevalence of undiagnosed BC; cohort studies, case‐control studies, uncontrolled case series, case reports assessing the occurrence of spontaneous regression of BC in women with a confirmed histology diagnosis. Untreated BC: 8 cohort studies and 12 case series (3593 BC) were included. In three controlled cohort studies (diagnoses 1978–2006), the 5‐years overall survival was 19–43%. Occult BC: 8 case series (2279 autopsies) were included. The prevalence of invasive BC undiagnosed during lifetime range was 0–1.5%, while for DCIS the range was 0.2–14.7%. Spontaneous regression: 2 cohort studies, 3 case reports, 1 case series included. In the cohort studies the relative risk of regression for screen detected compared with nonscreened BC was estimated as 1.2 and 1.1. It seems plausible that around 10% of invasive BC are not symptomatic during life, and that one fith of BC patients if untreated would be alive after 5 years. Around 1 of 10 screen‐detected BC may regress according two studies.

Why attempt en bloc resection of non-pedunculated colorectal adenomas? A systematic review of the prevalence of superficial submucosal invasive cancer after endoscopic submucosal dissection

Objective Endoscopic submucosal dissection (ESD) aims to achieve en bloc resection of non-pedunculated colorectal adenomas which might be indicated in cases with superficial submucosal invasive cancers (SMIC), but the procedure is time consuming and complex. The prevalence of such cancers is not known but may determine the clinical necessity for ESD as opposed to the commonly used piecemeal mucosal resection (endoscopic mucosal resection) of colorectal adenomas. The main aim was to assess the prevalence of SMIC SM1 (ie, invasion ≤1000 µm or less than one-third of the submucosa) on colorectal lesions removed by ESD. Design A literature review was conducted using electronic databases (up to March 2017) for colorectal ESD series reporting the histology of the dissected lesions. Results 51 studies with data on 11 260 colorectal dissected lesions were included. Most resected lesions (82.2%; 95% CI 78.8% to 85.3%) were adenomas (low- and high-grade dysplasia, 26.8% and 55.4%, respectively). Overall, 15.7% were submucosal cancers, but only slightly more than half (8.0%; 95% CI 6.1% to 10.3%) had an infiltration depth of ≤1000 µm, providing a number needed to treat (NNT) to avoid one surgery of 12.5. Estimating an oncologically curative (R0; G1/2; L0/V0) resection rate of 75.3% (95% CI 52.2% to 89.4%) for malignant lesions, the prevalence of curative resection lowered to 6% (95% CI 4.2% to 7.2%) with an NNT of 16.7. Conclusion The low prevalence of SMIC SM1 in lesions selected for ESD as well as the even lower rate of curative resection limits the clinical applicability of endoscopic en bloc resection. This calls for caution over an indiscriminate use of this technique in the resection of colorectal neoplasia.

Distribution of colorectal polyps: implications for screening

BACKGROUND During the last decades data from different studies reported modifications of the topographic distribution of colorectal cancers (CRCs), with an increased frequency of tumours in proximal colonic segments. Given the documented link between adenomas and CRC, a proximal migration of adenomas over time could be expected as well. AIM To evaluate available evidence about the prevalence of adenomas and of sessile serrated polyps across colonic segments, the changing trends in their distribution across the colon and the diagnostic performance of screening tests currently adopted in population based screening programs for lesions located in different colonic segments. METHODS Literature search on PubMed, Embase, and Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects with reference to preferred reporting items for systematic reviews and meta-analysis (PRISMA), considering all adult human studies in English, published between January 2000 and February 2017. RESULTS Cross-sectional analysis of endoscopy and pathology data-bases are consistently showing a trend toward an increase with age of the proportion of adenomas located in the proximal colon. Several observational studies analysed the site distribution of adenomas, testing the hypothesis of a proximal shift of these lesions, and most of them reported an increase in the proportion of right-sided adenomas over time, although a similar trend was not confirmed by others. Also the quality of the retrieved evidence was low. Both endoscopy and FIT are showing a different level of sensitivity for lesions arising in different colonic segments, depending also on screenees characteristics. CONCLUSION Available evidence is supporting the hypothesis of an increase in the proportion of right-sided adenomas with age, while a similar increase has not been reported for SSP/A, at least among subjects aged 50 or older. The trend toward a proximalization of colorectal adenomas over time, reported by some authors, likely results from improved diagnostic performances and/or the process of population ageing.

Organization of surveillance in GI practice

BACKGROUND Several reports documented an inefficient utilisation of available resources, as well as a suboptimal compliance with surveillance recommendations. Although, evidence suggests that organisational issues can influence the quality of care delivered, surveillance protocols are usually based on non-organized approaches. METHODS We conducted a literature search (publication date: 01/2000-06/2016) on PubMed and Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Cochrane Central Register of Controlled Trials for guidelines, or consensus statements, for surveys of practice, reporting information about patients, or providers attitudes and behaviours, for intervention studies to enhance compliance with guidelines. Related articles were also scrutinised. Based on the clinical relevance and burden on endoscopy services this review was focused on surveillance for Barretts oesophagus, IBD and post-polypectomy surveillance of colonic adenomas. RESULTS Existing guidelines are generally recognising structure and process requirements influencing delivery of surveillance interventions, while less attention had been devoted to transitions and interfaces in the care process. Available evidence from practice surveys is suggesting the need to design organizational strategies aimed to enable patients to attend and providers to deliver timely and appropriate care. Well designed studies assessing the effectiveness of specific interventions in this setting are however lacking. Indirect evidence from screening settings would suggest that the implementation of automated standardized recall systems, utilisation of clinical registries, removing financial barriers, could improve appropriateness of use and compliance with recommendations. CONCLUSIONS Lack of sound evidence regarding utility and methodology of surveillance can contribute to explain the observed variability in providers and patients attitudes and in compliance with the recommended surveillance.