Colorectal cancer incidence and mortality in patients younger than 50 years are increasing, but screening before the age of 50 is not offered in Europe. Advanced-stage diagnosis and mortality from ...colorectal cancer before 50 years of age are increasing. This is not a detection-bias effect; it is a real issue affecting the entire population. Three independent computational models indicate that screening from 45 years of age would yield a better balance of benefits and risks than the current start at 50 years of age. Experimental data support these predictions in a sex- and race-independent manner. Earlier screening is seemingly affordable, with minimal impediments to providing younger adults with colonoscopy. Indeed, the American Cancer Society has already started to recommend screening from 45 years of age in the United States. Implementing early screening is a societal and public health problem. The three independent computational models that suggested earlier screening were criticized for assuming perfect compliance. Guidelines and recommendations should be derived from well-collected and reproducible data, and not from mathematical predictions. In the era of personalized medicine, screening decisions might not be based solely on age, and sophisticated prediction software may better guide screening. Moreover, early screening might divert resources away from older individuals with greater biological risks. Finally, it is still unknown whether early colorectal cancer is part of a continuum of disease or a biologically distinct disease and, as such, it might not benefit from screening at all. The increase in early-onset colorectal cancer incidence and mortality demonstrates an obligation to take actions. Earlier screening would save lives, and starting at the age of 45 years may be a robust screening option.
The diagnosis of coeliac disease (CD) in adult patients requires the simultaneous assessment of clinical presentation, serology, and typical histological picture of villous atrophy. However, several ...years ago, the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines approved new criteria for the diagnosis in children: Biopsy could be avoided when anti-transglutaminase antibody (TGA) values exceed the cut-off of × 10 upper limit of normal (ULN) and anti-endomysium antibodies are positive, independently from value. This “no biopsy” approach is a decisive need for pediatric population, allowing to avoid stressful endoscopic procedures in children, if unnecessary. This approach relies on the correlation existing in children between TGA levels and assessment of mucosal atrophy according to Marsh’s classification. Several lines of evidence have shown that patients with villous atrophy have markedly elevated TGA levels. Therefore, we aim to perform a narrative review on the topic in adults. Despite that some studies confirmed that the × 10 ULN threshold value has a very good diagnostic performance, several lines of evidence in adults suggest that TGA cut off should be different from that of pediatric population for reaching a good correlation with histological picture. In conclusion, the heterogeneity of study reports as well as some conditions, which may hamper the serological diagnosis of CD (such as seronegative CD and non-celiac villous atrophy) and are much more common in adults than in children, could represent a limitation for the “no biopsy” approach to CD diagnosis in patients outside the pediatric age.
One-fourth of colorectal neoplasias are missed during screening colonoscopies; these can develop into colorectal cancer (CRC). Deep learning systems allow for real-time computer-aided detection ...(CADe) of polyps with high accuracy. We performed a multicenter, randomized trial to assess the safety and efficacy of a CADe system in detection of colorectal neoplasias during real-time colonoscopy.
We analyzed data from 685 subjects (61.32 ± 10.2 years old; 337 men) undergoing screening colonoscopies for CRC, post-polypectomy surveillance, or workup due to positive results from a fecal immunochemical test or signs or symptoms of CRC, at 3 centers in Italy from September through November 2019. Patients were randomly assigned (1:1) to groups who underwent high-definition colonoscopies with the CADe system or without (controls). The CADe system included an artificial intelligence–based medical device (GI-Genius, Medtronic) trained to process colonoscopy images and superimpose them, in real time, on the endoscopy display a green box over suspected lesions. A minimum withdrawal time of 6 minutes was required. Lesions were collected and histopathology findings were used as the reference standard. The primary outcome was adenoma detection rate (ADR, the percentage of patients with at least 1 histologically proven adenoma or carcinoma). Secondary outcomes were adenomas detected per colonoscopy, non-neoplastic resection rate, and withdrawal time.
The ADR was significantly higher in the CADe group (54.8%) than in the control group (40.4%) (relative risk RR, 1.30; 95% confidence interval CI, 1.14–1.45). Adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07 ±1.54) than in the control group (mean 0.71 ± 1.20) (incidence rate ratio, 1.46; 95% CI, 1.15–1.86). Adenomas 5 mm or smaller were detected in a significantly higher proportion of subjects in the CADe group (33.7%) than in the control group (26.5%; RR, 1.26; 95% CI, 1.01–1.52), as were adenomas of 6 to 9 mm (detected in 10.6% of subjects in the CADe group vs 5.8% in the control group; RR, 1.78; 95% CI, 1.09–2.86), regardless of morphology or location. There was no significant difference between groups in withdrawal time (417 ± 101 seconds for the CADe group vs 435 ± 149 for controls; P = .1) or proportion of subjects with resection of non-neoplastic lesions (26.0% in the CADe group vs 28.7% of controls; RR, 1.00; 95% CI, 0.90–1.12).
In a multicenter, randomized trial, we found that including CADe in real-time colonoscopy significantly increases ADR and adenomas detected per colonoscopy without increasing withdrawal time. ClinicalTrials.gov no: 04079478
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One of the controversial issues in the diagnosis of pancreatic neuroendocrine tumours (pNETs) is the accurate prediction of their clinical behaviour.
The aim of the study was to evaluate the role of ...endoscopic ultrasound (EUS) biopsy in the diagnosis and grading of pNETs in a certified ENETS Center.
A prospectively maintained database of EUS biopsy procedures was retrospectively reviewed to identify all consecutive patients referred to a certified ENETS Center with a suspicion of pNET between June 2014 and April 2017. The cytological and/or histological specimens were stained and the Ki-67 labeling index was evaluated. In patients undergoing surgery, the grade obtained with EUS-guided biopsy was compared with the final histological grade. The grade was evaluated according to the 2017 WHO classifications and grading.
The study population included 59 patients. EUS biopsy material reached an adequacy of 98.3% and was adequate for Ki-67 evaluation in 84.7% of cases. Twenty-nine patients (49.2%) underwent surgery. Of these, 25 patients had Ki-67 evaluated on EUS biopsy: the agreement between EUS biopsy grading and surgical specimen grading was 84%.
EUS biopsy is an accurate method for the diagnosis and grading of pNETs based on the WHO 2017 Ki-67 labelling scheme.
Multiple therapeutic modalities including surgery and rigid and flexible endoscopy have been adopted to manage Zenker's diverticulum (ZD). Minimally invasive flexible endoscopic septotomy (FES) ...techniques have been increasingly favored over the past 20 years; however, long-term data are still scanty. The aim of this study is to evaluate early and long-term outcomes of FES for naive ZD in a single-center setting.
From 2010 to 2017, ZD patients treated with FES were included in a prospectively maintained database (NCT03948438). Those who had already been treated surgically or endoscopically were excluded from the analysis. The Dakkak and Bennett dysphagia scale was used to rate the dysphagia. Persistent complete or near-complete resolution of symptoms (Dakkak and Bennett 0 or 1) was defined as clinical success. Postprocedural adverse events were reported according to ASGE lexicon.
Overall, 256 consecutive patients were treated. Mean pouch size was 29.8 ± 11.3 mm. The procedure was successfully completed in all scheduled patients, with an early clinical success of 96.1%. Adverse events occurred in 3.5% (9/256) of patients. Eight of them were mild/moderate with no fatal events, whereas one patient required surgery. Recurrences occurred in 31.3% (80/256) of treated patients after a mean time of 9 ± 3 months and 95% of recurrences were treated by a second FES. At an average follow-up of 5.5 years, 95.3% of patients were asymptomatic after a mean number of 1.3 procedures.
FES is a safe and effective treatment modality for patients with ZD. Recurrence rate is significant; however, endoscopic reintervention is associated with long-term relief of dysphagia.
Endoscopic papillectomy (EP) is a viable therapy in ampullary lesions (AL). Many series have reported low morbidity and acceptable outcomes. We performed a systematic review with pooled analysis to ...assess the safety and efficacy of EP for AL. Electronic databases (Medline, Scopus and EMBASE) were searched up to September 2018. Studies that included patients with endoscopically resected AL were eligible. The rate of adverse events (AEs; primary outcome) and the rates of both technical and clinical efficacy outcomes were pooled by means of a random- or fixed-effects model to obtain a proportion with a 95% confidence interval (CI). Twenty-nine studies were included (1751 patients). The overall AE rate was 24.9%. The post-procedural pancreatitis rate was 11.9%, with the only factor affecting this outcome being prophylactic pancreatic stenting. The complete resection rate was 94.2%, with a rate of oncologically curative resection of 87.1%. The recurrence rate was 11.8% (follow-up: 9.6–84.5 months). EP is a relatively safe and effective option for AL. Our study might definitively suggest the protective role of prophylactic pancreatic stenting against post-procedural pancreatitis.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches ...an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P = 7.14 × 10−10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18, whose increased levels have been reported to correlate with various tumour cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P = 3.56 × 10–6). This single nucleotide polymorphism is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms.
For the first time, all pancreatic expression quantitative trait loci were analysed in relation to pancreatic cancer risk, in an association study with over 20 000 individuals. We identified a novel variant in the SRGAP1 gene associated with pancreatic cancer risk.
Background and Aim
Tissue acquisition in pancreatic cystic lesions (PCL) is the ideal method for diagnosis and risk stratification for malignancy of these lesions. Direct sampling from the walls of ...PCL with different devices has shown better results than cytology from cystic fluid. We carried out a retrospective, multicenter study to evaluate the feasibility, safety, and diagnostic yield of a micro‐forceps, specifically designed to be used through a 19‐gauge needle after endoscopic ultrasonography (EUS)‐guided puncture of PCL.
Methods
We retrospectively collected data from patients who underwent EUS‐through‐the‐needle biopsy (EUS‐TTNB) in PCL at six referral centers.
Results
The sampling procedure was carried out in 56 patients (mean age 57.5 ± 13.1 years, M:F 17:39), and was technically successful in all of them (100%; 95% confidence interval CI, 94–100%). Adverse events occurred in 9/56 (16.1%; 95% CI, 8–28%) patients, with self‐limited intracystic hemorrhage the most common (7/56, 12.5%; 95% CI, 5–24%). All adverse events were mild, and resolved without any specific intervention. Specimens were considered adequate for histological diagnosis in 47/56 (83.9%; 95% CI, 72–92%). In two of these patients, despite the histological adequacy, a diagnosis could not be reached. In two other cases, a specimen sufficient for a cytological diagnosis was obtained. Overall diagnostic yield by combining cytological and histological samples was 47/56 (83.9%; 95% CI, 72–92%).
Conclusion
EUS‐TTNB with micro‐forceps in PCL is feasible, safe, and has a high diagnostic yield. Future prospective studies are needed to better assess the clinical impact of EUS‐TTNB on the management of PCL.
Background Guidewire (GW) cannulation can reduce the risk of post-ERCP pancreatitis (PEP) by avoiding the opacification of the main pancreatic duct. Objective To compare the effects of conventional ...contrast ERCP and GW cannulation of the common bile duct on the rate of PEP in low- and high-risk patients. Design Prospective, comparative-intervention single-center study. Setting Tertiary referral center. Patients Patients with biliary disease with an intact papilla were prospectively examined by ERCP. Interventions Biliary cannulation using a sphincterotome with contrast injection (ConI) or a hydrophilic GW without contrast injection. Main Outcome Measurements Pancreatitis rate in the GW group and the contrast injection (ConI) group. Results PEP occurred in 60 of 1249 patients (4.8%), 35 of 678 (5.2%) in the GW group and 25 of 571 (4.4%) in the ConI group (not significant). The overall rate of PEP was significantly higher in high-risk patients (12.2%) than in low-risk patients (3.5%) ( P < .001), but was similar for the 2 techniques within each of these 2 groups. In patients with unintended main pancreatic duct (MPD) cannulation or opacification, the rate of PEP was not significantly different with the GW (15.2%) and ConI (8.4%) techniques but was associated with a significantly higher rate of pancreatitis (11.9%) than in patients in whom the contrast medium or GW did not enter the MPD (3.5%) ( P < .001). Multivariate analysis indicated that more than 10 papillary cannulation attempts, MPD cannulation or opacification, suspected sphincter of Oddi dysfunction, and precut methods were significant risk factors independently associated with PEP. Limitations Lack of randomization. Conclusions For selective cannulation of the CBD, the risk of inducing PEP is similar with the ConI and GW techniques in high-risk and low-risk patients. Any manipulation of the MPD must be considered a high-risk factor for PEP, such as multiple attempts on the papilla or use of the precut method.
To investigate if high-definition (HD) colonoscope with i-Scan gave a higher detection rate of mucosal lesions vs standard white-light instruments.
Data were collected from the computerized database ...of the endoscopy unit of our tertiary referral center. We retrospectively analyzed 1101 consecutive colonoscopies that were performed over 1 year with standard white-light (n = 849) or HD+ with i-Scan (n = 252) instruments by four endoscopists, in an outpatient setting. Colonoscopy records included patients' main details and family history for colorectal cancer, indication for colonoscopy (screening, diagnostic or surveillance), type of instrument used (standard white-light or HD+ plus i-Scan), name of endoscopist and bowel preparation. Records for each procedure included whether the cecum was reached or not and the reason for failure, complications during or immediately after the procedure, and number, size, location and characteristics of the lesions. Polyps or protruding lesions were defined as sessile or pedunculated, and nonprotruding lesions were defined according to Paris classification. For each lesion, histological diagnosis was recorded.
Eight hundred and forty-nine colonoscopies were carried with the standard white-light video colonoscope and 252 with the HD+ plus i-Scan video colonoscope. The four endoscopists did 264, 300, 276 and 261 procedures, respectively; 21.6%, 24.0%, 21.7% and 24.1% of them with the HD+ plus i-Scan technique. There were no significant differences between the four endoscopists in either the number of procedures done or the proportions of each imaging technique used. Both techniques detected one or more mucosal lesions in 522/1101 procedures (47.4%). The overall number of lesions recognized was 1266; 645 in the right colon and 621 in the left. A significantly higher number of colonoscopies recognized lesions in the HD+ plus i-Scan mode (171/252 = 67.9%) than with the standard white-light technique (408/849 = 48.1%) (P < 0.0001). HD+ with i-Scan colonoscopies identified more lesions than standard white-light imaging (459/252 and 807/849, P < 0.0001), in the right or left colon (mean ± SD, 1.62 ± 1.36 vs. 1.33 ± 0.73, P < 0.003 and 1.55 ± 0.98 vs. 1.17 ± 0.93, P = 0.033), more lesions < 10 mm (P < 0.0001) or nonprotruding (P < 0.022), and flat polyps (P = 0.04). The cumulative mean number of lesions per procedure detected by the four endoscopists was significantly higher with HD+ with i-Scan than with standard white-light imaging (1.82 ± 2.89 vs. 0.95 ± 1.35, P < 0.0001).
HD imaging with i-Scan during the withdrawal phase of colonoscopy significantly increased the detection of colonic mucosal lesions, particularly small and nonprotruding polyps.