Serrated polyps <10 mm cannot reliably be characterized by i-Scan without magnification at routine colonoscopy.

BACKGROUND: Colorectal lesions (CRLs) <10 mm found at colonoscopy tend towards "diagnose-and-leave" or "resect-and-discard" strategies based on real-time Kudo glandular pit-pattern's assessment using i-Scan. However, i-Scan has not yet been validated for Kudo's classification. We aimed to assess whether, in routine colonoscopy, i-Scan without magnification and optical enhancement (M-OE) reliably differentiates hyperplastic polyps (HPs) from other serrated lesions (SLs) and conventional adenomas (CAs), and, among SLs, HPs from sessile serrated lesions (SSLs) and traditional or unknown serrated adenomas (TSAs, USAs), in Kudo type II CRLs<10 mm, according to ASGE Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) recommended negative predictive value (NPV) threshold for adenomas. METHODS: Prospectively recorded CRLs over 12 months, classified according to Kudo pit-pattern using i-Scan, were retrospectively compared with histology. RESULTS: Overall, 898 ≤5-mm and 704 6- to 9-mm CRLs were included. Type II pit-pattern was found in 76.6% and 38.7% of HPs and SSLs-TSAs/CAs (P<0.000001), and in 84.1% and 26.6% of SLs and CAs (P<0.000001). Among SLs, it was found in 81.9% and 86.6% of HPs and SSLs-TSAs. In CRLs≤5 mm, HPs were prevalent over other SLs (P=0.00001); in CRLs 6-9 mm, CAs were prevalent (P<0.000001). About 77% of SLs in right colon were SSLs-TSAs; 82% in left colon were HPs. PIVI ≥90% NPV threshold for adenomas was reached for CRLs 6-9mm (92.1%), nearly achieved for CRLs≤5 mm (88.2%), and not reached for SLs independently on the size. CONCLUSIONS: A strategy of "diagnose-and-leave" or "resect-and-discard" cannot be recommended for SLs<10 mm with Kudo type II pit-pattern using i-Scan, especially in right colon, if M-OE unavailable.

Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk.

Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p<10-5) compared with the additive effects (p>10-3), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5×10-8). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores.

Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report.

PURPOSE: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants. METHODS: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years. RESULTS: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery. CONCLUSION: Uptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene- and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syndrome to improve outcomes.

The Management of Peutz-Jeghers Syndrome: European Hereditary Tumour Group (EHTG) Guideline.

The scientific data to guide the management of Peutz-Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients. Methods: Literature searches were performed using MEDLINE, Embase, and Cochrane. Evidence levels and recommendation strengths were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A Delphi process was followed, with consensus being reached when ≥80% of the voting guideline committee members agreed. Recommendations and statements: The only recent guidelines available were for gastrointestinal and pancreatic management. These were reviewed and endorsed after confirming that no more recent relevant papers had been published. Literature searches were performed for additional questions and yielded a variable number of relevant papers depending on the subject addressed. Additional recommendations and statements were formulated. Conclusions: A decade on, the evidence base for recommendations remains poor, and collaborative studies are required to provide better data about this rare condition. Within these restrictions, multisystem, clinical management recommendations for PJS have been formulated.

Risk factors and clinical characteristics of early-onset colorectal cancer vs. late-onset colorectal cancer: a case-case study.

BACKGROUND AND OBJECTIVES: Early-onset colorectal cancer (eoCRC), defined as colorectal cancer (CRC) before the age of 50 is increasing in incidence. We evaluated exogenous and endogenous risk factors, and clinical features of eoCRC, compared to late-onset CRC (loCRC). METHODS: In this retrospective case-case study, patients were prospectively enrolled from 2015 to 2018. We collected clinical features (age, sex, time from symptom onset to diagnosis, symptoms, family history, smoking and alcohol habits, diabetes, BMI, and genetic analysis) and tumor characteristics. Independent risk factors for eoCRC and odds ratios (ORs) were identified. RESULTS: Fifty-four eoCRCs and 494 loCRCs were enrolled. Patients with eoCRC experienced longer delay time from symptom onset to diagnosis: 40.7% were diagnosed within 6 months from symptoms onset, compared to 85.6% of patients with loCRC (P < 0.0001). They differed for sex, presence of symptoms, family history, smoking habit, alcohol intake, and BMI. Rectal localization was more closely associated with eoCRC (64.8%) than loCRC (34.5%, P < 0.0001). Family history of CRC was associated with eoCRC (OR = 8.8). When family history occurred with hereditary cancer syndromes, the OR for eoCRC increased to 21. CONCLUSION: In young adults with alarming symptoms, CRC must be suspected to avoid delay time from symptom onset to diagnosis and genetic risk assessment has to be evaluated. Smoking habits, alcohol intake, and BMI are not associated with eoCRC.

Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10(-14)), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10(-8)) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10(-8)). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10(-9)), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.

Quality of life in uncomplicated symptomatic diverticular disease: is it another good reason for treatment?

BACKGROUND: Quality of life (QoL) is becoming a major issue in the evaluation of any therapeutic intervention. AIMS: To assess the QoL in patients with uncomplicated symptomatic diverticular disease (DD) and to elucidate the influence of two different treatments either on symptoms or QoL. MATERIALS AND METHODS: 58 outpatients affected by uncomplicated symptomatic DD, admitted in our Gastroenterological Unit from October 2003 to March 2004, were enrolled. Patients were randomly assigned to two different treatments consisting of rifaximin or mesalazine for 10 days every month for a period of 6 months. QoL was evaluated by means of an SF-36 questionnaire and clinical evaluation was registered by means of a global symptomatic score (GSS) at baseline and after 6 months. RESULTS: At baseline, lower values in all SF-36 domains were confirmed in patients with DD. Both rifaximin and mesalazine groups showed a significant reduction of their mean GSS (p < 0.01 and p < 0.001, respectively) and improvement of SF-36 mean scores after therapy, even though treatment with mesalazine showed better results. CONCLUSIONS: DD has a negative impact on QoL. Cyclic treatment with poorly absorbable antibiotics or anti-inflammatory drugs relieves symptoms and improves QoL.

A curcumin-based 1-week triple therapy for eradication of Helicobacter pylori infection: something to learn from failure?

BACKGROUND: Curcumin is the principal element of turmeric powder extracted from the root of Curcuma longa. Studies on curcumin have demonstrated some anti-Helicobacter pylori activity as well as immunomodulating properties. N-acetylcysteine and lactoferrin with their respective mucolytic and antibacterial activities might also be effective in H. pylori eradication therapy. AIM: To determine if a 7-day non-antibiotic therapy comprised of curcumin, lactoferrin, N-acetylcysteine, and pantoprazole was effective for eradication of H. pylori infection and reduction of gastric inflammation, assessed by serum pepsinogens and relief of symptoms. SUBJECTS AND METHODS: Twenty-five consecutive H. pylori-positive patients (12 males, mean age 50 +/- 12 years, range 31-76) with functional dyspepsia were enrolled. Patients were administered for 7 days curcumin 30 mg b.i.d., bovine lactoferrin 100 mg b.i.d., N-acetylcysteine 600 mg b.i.d., and pantoprazole 20 mg b.i.d. H. pylori status and upper gastrointestinal symptoms were assessed by (13)C-urea breath test and a scale of upper gastrointestinal symptoms intensity (absent, mild, moderate, and severe), as well as a blood test for serum pepsinogens (sPGI, sPGII), gastrin-17 (G-17), and anti-H. pylori IgG (IgG-Hp) at baseline (T0) and after 2 months (T1). RESULTS: Three of 25 patients (12%) were cured of H. pylori infection. A significant decrease in the overall severity of symptoms (T0: 6, interquartile range [IQR]: 4.5-8; T1: 2, IQR: 2-3; p < or = .001), and sPGII (T0: 16 microg/L, IQR: 13-22; T1: 10 microg/L, IQR: 8-16; p < or = .001) and sPGI (T0: 82 microg/L, IQR: 67-97; T1: 74 microg/L, IQR: 62-94; p = .02) levels were observed after 2 months of the treatment. IgG and G-17 values did not significantly decrease after 2 months. CONCLUSIONS: This novel therapy was not effective for H. pylori eradication. However, despite the bacterium persistence, significant improvement of dyspeptic symptoms and reduction of serologic signs of gastric inflammation were observed after 2 months at the end of the 7-day treatment schedule.

Protective effects of proton pump inhibitors against indomethacin-induced lesions in the rat small intestine.

Proton pump inhibitors (PPIs) have been shown to be effective in preventing gastric and duodenal ulcers in high-risk patients taking nonsteroidal anti-inflammatory drugs (NSAIDs); by contrast, scarce information is available concerning the effects of PPIs on intestinal damage induced by NSAIDs in humans or in experimental animals. We examined the effects of lansoprazole and omeprazole on the intestinal injury induced by indomethacin in the conscious rat. PPIs were administered by the intragastric route at 30, 60 and 90 micromol/kg, 12 h and 30 min before and 6 h after indomethacin treatment. The effects of omeprazole and lansoprazole were evaluated on: (1) macroscopic and histologic damage; (2) mucosal polymorphonuclear cell infiltration; (3) oxidative tissue damage and (4) bacterial translocation from lumen into the intestinal mucosa. Lansoprazole and omeprazole (at 90 micromol/kg) significantly decreased (P<0.01) the macroscopic and histologic damage induced by indomethacin in the rat small intestine. Furthermore, both drugs greatly reduced (P<0.01) the associated increases in myeloperoxidase levels and lipid peroxidation induced by indomethacin, whereas they only moderately affected (P<0.05) the translocation of enterobacteria from lumen into the intestinal mucosa. These data demonstrate that omeprazole and lansoprazole can protect the small intestine from the damage induced by indomethacin in the conscious rat. The intestinal protection, possibly related to antioxidant and anti-inflammatory properties of these drugs, may suggest new therapeutic uses of PPIs in intestinal inflammatory diseases.

Use of mesalazine in diverticular disease.

Diverticular disease includes a spectrum of conditions sharing the underlying pathology of acquired diverticula of the colon: symptomatic uncomplicated diverticular disease, recurrent symptomatic uncomplicated diverticular disease, and complicated diverticular disease. Goals of therapy in diverticular disease should be to improve symptoms and to prevent recurrent attacks in symptomatic uncomplicated diverticular disease, and to prevent the complications of disease such as diverticulitis. Inflammation seems to play a key role in all forms of the disease. This is the rationale for the use of anti-inflammatory drugs such as mesalazine. Inflammation in such diseases seems to be generated by a heightened production of proinflammatory cytokines, reduced anti-inflammatory cytokines, and enhanced intramucosal synthesis of nitric oxide. The mechanisms of action of mesalazine are not yet well understood. It is an anti-inflammatory drug that inhibits factors of the inflammatory cascade (such as cyclooxygenase) and free radicals, and has an intrinsic antioxidant effect. Some recent studies confirm the efficacy of mesalazine in diverticular disease both in relief of symptoms in symptomatic uncomplicated forms and in prevention of recurrence of symptoms and main complications.