Prediction of metachronous advanced colorectal neoplasia by KRAS mutation in polyps.

BACKGROUND: The potential of molecular markers in the removed polys as reliable predictors of metachronous lesions is still uncertain. AIM: Our aim was to evaluate the role of somatic mutations in KRAS in polyps of patients with high-risk adenomas to predict the risk of advanced polyps or colorectal cancer (CRC) within 3 years. METHODS: A total of 518 patients were prospectively enrolled. The included patients had adenomas ≥10 mm, high-grade dysplasia, villous component or ≥3 more adenomas at baseline and were scheduled to undergo surveillance colonoscopy at 3 years ± 6 months. Somatic KRAS mutation was performed on 1189 polyps collected from these patients. At surveillance, advanced lesions were defined as adenomas with a size of ≥10 mm. High-grade dysplasia or villous component, serrated polyps ≥10 mm or with dysplasia or CRC. RESULTS: At baseline, 81 patients (15.6%) had KRAS mutations in at least one polyp. Patients with KRAS mutated polyps had more frequent villous histological lesions and size ≥20 mm. In the multivariate analysis, adjusted for age and sex, only age (odds ratios [OR], 1.06; 95% confidence interval [CI], 1.02-1.09; p < 0.001), ≥5 adenomas (OR, 3.92; 95% CI, 1.96-7.82), and KRAS mutation (OR, 2.54; 95% CI, 1.48-4.34; p < 0.01) were independently associated with the development of advanced lesions at surveillance. CONCLUSIONS: Our results show that, in patients with high-risk adenomas, the presence of somatic mutations in KRAS is an independent risk factor for the development of advanced metachronous polyps.

Tobacco is a Leading Risk Factor for Liver and Extrahepatic Cancers in Patients With Liver Cirrhosis: A Prospective Cohort Study.

Background & aims: This study aims to assess the incidence and characteristics of all cancers, hepatocellular carcinoma (HCC), and extrahepatic cancers in patients with cirrhosis of various etiologies. Methods: Prospective cohort study in patients with cirrhosis but no cancer, followed every 6-9 months through the HCC early detection program. Cancer incidence was compared with Spanish population data to calculate standardized incidence ratios (SIR), and cumulative incidence was calculated separately for cancer and competing events. Longitudinal outcomes were assessed with multivariate Fine-Gray and Cox regression models. Results: A total of 215 patients (68.4% male, median age 61 years) were included. Cirrhotic etiology was alcohol (38%), hepatitis B or C virus infection (36%), alcohol plus hepatitis B or C virus infection (9%), and other causes (17%). Sixty percent were current or former smokers. Thirty-nine cancers were observed (56% liver cancer), while 3.3 were expected (SIR 11.7; 95% confidence interval [CI] 8.6-16.1). Ten (4.6%) patients were censored for liver transplantation and 34 (15.8%) for death, constituting relevant competing risks. Smoking was significantly associated with overall cancer incidence (smokers: subdistribution hazard ratio [SHR] 3.14, 95% CI 1.33-7.38; former smokers: SHR 2.54, 95% CI 1.08-5.98). In the multivariable regression analysis, viral etiology, Child-Pugh score (B or C versus A), and smoking were associated with liver cancer, and smoking with extrahepatic cancer. Conclusions: Patients with cirrhosis have an 11-fold risk of cancer compared to the general population. Risk is increased in liver and non-liver cancers. Active surveillance of any type of cancer and smoking cessation interventions are needed in these patients.

Risk factors for metachronous colorectal cancer or advanced lesions after endoscopic resection of serrated polyps: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Serrated polyps (SPs) are precursors to 15% to 20% of colorectal cancers (CRCs). However, there are uncertainties regarding which SPs require surveillance and at what intervals, with recommendations adapted from those for adenomas in the absence of solid evidence. Our aim was to assess which SP risk characteristics relate to a higher risk of metachronous CRC or advanced polyps. METHODS: We systematically searched PubMed, Embase, and Cochrane for cohort studies, case-control studies, and clinical trials from inception to December 31, 2023, of CRC or advanced polyps (advanced adenoma [AA] or advanced SP) incidence at surveillance stratified by baseline SP size, dysplasia, location, and multiplicity. We defined advanced SPs as those ≥10 mm or with dysplasia. CRC and advanced polyp incidence per 1000 person-years were estimated. We performed a meta-analysis by calculating pooled relative risks (RRs) using a random-effects model. RESULTS: A total of 5903 studies were reviewed, and 14 were included with 493,949 patients (mean age, 59.5 years; 55% men). The mean follow-up was 4.9 years. CRC incidence per 1000 person-years was 2.09 (95% confidence interval [CI], 1.29-2.90) for advanced SPs, 1.52 (95% CI, 0.78-2.25) for SPs of ≥10 mm, 5.86 (95% CI, 2.16-9.56) for SPs with dysplasia, 1.18 (95% CI, 0.77-1.60) for proximal SPs, 0.52 (95% CI, 0.08-1.12) for ≥3 SPs, 0.50 (95% CI, 0.35-0.66) for nonadvanced SPs, and 0.44 (95% CI, 0.41-0.46) for normal colonoscopy findings. Metachronous CRC risk was higher in advanced SPs versus nonadvanced SPs (RR, 1.84; 95% CI, 1.11-3.04) and versus normal colonoscopy findings (RR, 2.92; 95% CI, 2.26-3.77), in SPs of ≥10 mm versus <10 mm (RR, 2.61; 95% CI, 1.43-4.77) and versus normal colonoscopy findings (RR: 3.52; 95% CI, 2.17-5.69); and in SPs with dysplasia versus normal colonoscopy findings (RR: 2.71; 95% CI, 2.00-3.67). No increase in CRC or advanced polyp risk was found in patients with proximal versus distal SPs, nor in ≥3 SPs versus 1 or 2 SPs. CONCLUSIONS: CRC risk is significantly higher in patients with baseline advanced SPs after 4.9 years of follow-up, with risk magnitudes similar to those described for AA, supporting the current recommendation for 3-year surveillance in patients with advanced SPs.

Effect of the SARS-CoV-2 pandemic on colorectal cancer diagnosis and prognosis.

BACKGROUND AND STUDY AIMS: Our aim was to determine the impact of the SARS-CoV-2 pandemic on the diagnosis and prognosis of colorectal cancer (CRC). PATIENTS AND METHODS: This prospective cohort study included individuals diagnosed with CRC between March 13, 2019 and June 20, 2021 across 21 Spanish hospitals. Two time periods were compared: prepandemic (from March 13, 2019 to March 13, 2020) and pandemic (from March 14, 2020 to June 20, 2021, lockdown period and 1 year after lockdown). RESULTS: We observed a 46.9% decrease in the number of CRC diagnoses (95% confidence interval (CI): 45.1%-48.7%) during the lockdown and 29.7% decrease (95% CI: 28.1%-31.4%) in the year after the lockdown. The proportion of patients diagnosed at stage I significantly decreased during the pandemic (21.7% vs. 19.0%; p = 0.025). Centers that applied universal preprocedure SARS-CoV-2 PCR testing experienced a higher reduction in the number of colonoscopies performed during the pandemic post-lockdown (34.0% reduction; 95% CI: 33.6%-34.4% vs. 13.7; 95% CI: 13.4%-13.9%) and in the number of CRCs diagnosed (34.1% reduction; 95% CI: 31.4%-36.8% vs. 26.7%; 95% CI: 24.6%-28.8%). Curative treatment was received by 87.5% of patients diagnosed with rectal cancer prepandemic and 80.7% of patients during the pandemic post-lockdown period (p = 0.002). CONCLUSIONS: The COVID-19 pandemic has led to a decrease in the number of diagnosed CRC cases and in the proportion of stage I CRC. The reduction in the number of colonoscopies and CRC diagnoses was higher in centers that applied universal SARS-CoV-2 PCR screening before colonoscopy. In addition, the COVID-19 pandemic has affected curative treatment of rectal cancers.

Incidence, characteristics, and predictive factors of post-colonoscopy colorectal cancer.

BACKGROUND: Post-colonoscopy colorectal cancer (PCCRC) is colorectal cancer (CRC) diagnosed after a colonoscopy in which no cancer is found. OBJECTIVE: As PCCRC has become an important quality indicator, we determined its rates, characteristics, and index colonoscopy-related predictive factors. METHODS: We carried out a multicenter, observational, retrospective study between 2015 and 2018. Rates were calculated for PCCRC developing up to 10 years after colonoscopy. PCCRC was categorized according to the most plausible explanation using World Endoscopy Organization methodology. Our PCCRC population was compared to a control cohort without CRC matched 1:4 by sex, age, index colonoscopy date, indication, endoscopist, and hospital. RESULTS: One hundred seven PCCRC and 2508 detected CRC were diagnosed among 101,524 colonoscopy (0.1%), leading to rates of 0.4%, 2.2%, 3.1%, and 4.1% at 1, 3, 5, and 10 years, respectively. PCCRC was in right (42.4%), left (41.4%), and transverse (16.4%) colon with 31.5% at stage I, 24.7% stage II, 32.6% stage III, and 11.2% stage IV. Twenty point three percent were classified as incomplete resection, 5.4% as unresected lesions, 48.6% as missed lesions with adequate colonoscopy, and 25.7% as missed lesions with inadequate colonoscopy. The median time from colonoscopy to PCCRC was 42 months. Previous inadequate preparation (OR 3.05, 95%CI 1.73-5.36) and piecemeal polypectomy (OR 19.89, 95%CI 8.67-45.61) were independently associated with PCCRC. CONCLUSIONS: In our population, 4.1% of CRC cases were PCCRC. Most of these lesions were in right colon and attributable to lesions not visualized despite adequate bowel cleansing. Previous inadequate cleansing and piecemeal polypectomy were associated with PCCRC.

Cirrhosis-downregulated LSECtin can be retrieved by cytokines, shifts the TLR-induced LSECs secretome and correlates with the hepatic Th response.

BACKGROUND AND AIMS: We evaluated tolerogenic C-type lectin LSECtin loss in cirrhosis and its potential regulation by cytokines. METHODS: Liver tissue from patients with cirrhosis and healthy controls, immortalised and generated LSECtin-CRISPR immortalised LSECs, and murine primary LSECs from the CCl4 model were handled. RESULTS: LSECtin expression was reduced in liver tissue from cirrhotic patients, and it decreased from compensated to decompensated disease. Increased phosphorylation of MAPK, Akt and NFkB was observed upon LSECtin stimulation in LSEC murine cell line, showing a pattern of inflammatory and chemotactic cytokines either restrained (IL-10, CCL4) or unrestrained (TNF-α, IL-1ß, IL-6, CCL2). CD44 attenuated whereas LAG-3 increased all substrates phosphorylation in combination with TLR4 and TLR2 ligands except for NFkB. TNF-α, IL-1 ß, IL-6 and CCL2 were restrained by LSECtin crosslinking on TLRs studied. Conversely, IL-10 and CCL4 were upregulated, suggesting a LSECtin-TLRs synergistic effect. Also, LSECtin was significantly induced after IL-13 stimulation or combined with anti-inflammatory cytokines in cirrhotic and immortalised LSECs. Th17 and regulatory T cells were progressively increased in the hepatic tissue from compensated to decompensated patients. A significant inverse correlation was present between gene expression levels of CLEC4G/LSECtin and RORγT and FOXP3 in liver tissues. CONCLUSION: LSECtin restrains TLR proinflammatory secretome induced on LSECs by interfering immune response control, survival and MAPKs signalling pathways. The cytokine-dependent induction of LSECtin and the association between LSECtin loss and Th17 cell subset expansion in the liver, provides a solid background for exploring LSECtin retrieval as a mechanism to reprogram LSEC homeostatic function hampered during cirrhosis.

Role of Artificial Intelligence in Colonoscopy Detection of Advanced Neoplasias : A Randomized Trial.

BACKGROUND: The role of computer-aided detection in identifying advanced colorectal neoplasia is unknown. OBJECTIVE: To evaluate the contribution of computer-aided detection to colonoscopic detection of advanced colorectal neoplasias as well as adenomas, serrated polyps, and nonpolypoid and right-sided lesions. DESIGN: Multicenter, parallel, randomized controlled trial. (ClinicalTrials.gov: NCT04673136). SETTING: Spanish colorectal cancer screening program. PARTICIPANTS: 3213 persons with a positive fecal immunochemical test. INTERVENTION: Enrollees were randomly assigned to colonoscopy with or without computer-aided detection. MEASUREMENTS: Advanced colorectal neoplasia was defined as advanced adenoma and/or advanced serrated polyp. RESULTS: The 2 comparison groups showed no significant difference in advanced colorectal neoplasia detection rate (34.8% with intervention vs. 34.6% for controls; adjusted risk ratio [aRR], 1.01 [95% CI, 0.92 to 1.10]) or the mean number of advanced colorectal neoplasias detected per colonoscopy (0.54 [SD, 0.95] with intervention vs. 0.52 [SD, 0.95] for controls; adjusted rate ratio, 1.04 [99.9% CI, 0.88 to 1.22]). Adenoma detection rate also did not differ (64.2% with intervention vs. 62.0% for controls; aRR, 1.06 [99.9% CI, 0.91 to 1.23]). Computer-aided detection increased the mean number of nonpolypoid lesions (0.56 [SD, 1.25] vs. 0.47 [SD, 1.18] for controls; adjusted rate ratio, 1.19 [99.9% CI, 1.01 to 1.41]), proximal adenomas (0.94 [SD, 1.62] vs. 0.81 [SD, 1.52] for controls; adjusted rate ratio, 1.17 [99.9% CI, 1.03 to 1.33]), and lesions of 5 mm or smaller (polyps in general and adenomas and serrated lesions in particular) detected per colonoscopy. LIMITATIONS: The high adenoma detection rate in the control group may limit the generalizability of the findings to endoscopists with low detection rates. CONCLUSION: Computer-aided detection did not improve colonoscopic identification of advanced colorectal neoplasias. PRIMARY FUNDING SOURCE: Medtronic.

Immune changes over time and survival in patients with cirrhosis treated with non-selective beta-blockers: A prospective longitudinal study.

BACKGROUND: Treatment with non-selective beta-blockers (NSBB) has been associated with anti-inflammatory and anti-cancer effects in patients with cirrhosis. This study aims to analyze the impact of chronic NSBB treatment on immune activation and disease progression in stable outpatients with cirrhosis. METHODS: In this prospective follow-up of 150 patients with cirrhosis, 39 received treatment with NSBB. Blood samples were taken every 6-9 months, and immune and adrenergic variables were measured. Mixed linear models were used to assess the effect of NSBB on these variables over time. Multivariate Cox regression was used to study associations with adverse clinical events (hepatocellular carcinoma, death, or liver transplant). RESULTS: Median follow-up was 1635 days. NSBB treatment was associated with significantly lower levels of IL-6 (ß - 4.7; 95% confidence interval [CI] -6.9, -2.6) throughout the study. During follow-up, 11 patients developed hepatocellular carcinoma, 32 died, and 4 underwent liver transplant. Patients with higher concentrations of IL-10, IL-6 and IFN-γ developed more clinical events. Event-free survival was significantly better in patients treated with NSBB (hazard ratio 0.36, 95% CI 0.18, 0.71) in a multivariate Cox regression adjusted for Child-Pugh-Score, esophageal varices, and platelets. CONCLUSION: Chronic treatment with NSBB in patients with stable cirrhosis gives rise to a different state of immune activation, characterized by lower concentrations of IL-6 over time, and it is associated with a reduced risk of adverse event (death, hepatocellular carcinoma, or transplant), after controlling for disease severity.

Propensity score matching analysis of laparoscopic surgery vs. open approach in 4 297 adult patients with acute appendicitis, acute cholecystitis or gastrointestinal tract perforation: a prospective multicentre study of nationwide outcomes.

BACKGROUND AND AIMS: Previous studies indicated that laparoscopic surgery could improve postoperative outcomes in acute appendicitis, acute cholecystitis, perforated gastroduodenal ulcer, or acute diverticulitis, but some reported opposite results or differences in the magnitude of improvement. A contemporary analysis using propensity score matching that compares outcomes is lacking. METHODS: Over a 6-month period, 38 centres (5% of all public hospitals) attending emergency general surgery patients on a 24 h, 7 days a week basis, enroled all consecutive adult patients who underwent laparoscopic surgery or open approach. RESULTS: The study included 2 645 patients with acute appendicitis [32 years (22-51), 44.3% women], 1 182 with acute cholecystitis [65 years (48-76); 46.7% women], and 470 with gastrointestinal tract perforation [65 years (50-76); 34% women]. After propensity score matching, hospital stays decreased in acute appendicitis [open, 2 days (2-4); lap, 2 days (1-4); P <0.001], acute cholecystitis [open, 7 days (4-12); lap, 4 days (3-6); P <0.001], and gastrointestinal tract perforation [open, 11 days (7-17); lap, 6 days (5-8.5); P <0.001]. A decrease in 30-day morbidity was observed in acute appendicitis (open, 15.7%; lap, 9.7%; P <0.001), acute cholecystitis (open, 41%; lap, 21.7%; P <0.001), and gastrointestinal tract perforation (open, 45.2%; lap, 23.5%; P <0.001). A decrease in 30-day mortality was found in acute cholecystitis (open, 8.8%; lap, 2.8%; P =0.013) and gastrointestinal tract perforation (open, 10.4%; lap, 1.7%; P =0.013). CONCLUSIONS: This clinically based, multicentre study suggests that an initial laparoscopic approach could be considered not only in patients with acute appendicitis or acute cholecystitis but also in patients with a perforation of the gastrointestinal tract.

Gender Biases and Diagnostic Delay in Inflammatory Bowel Disease: Multicenter Observational Study.

BACKGROUND: Female gender could be a cause of diagnostic delay in inflammatory bowel disease (IBD). The aim of this study was to investigate the diagnostic delay in women vs men and potential causes. METHODS: This multicenter cohort study included 190 patients with recent diagnosis of IBD (disease duration <7 months). Reconstruction of the clinical presentation and diagnostic process was carried out in conjunction with the semistructured patient interview, review, and electronic medical records. RESULTS: The median time from symptom onset to IBD diagnosis was longer in women than in men: 12.6 (interquartile range, 3.7-31) vs 4.5 (2.2-9.8) months for Crohn's disease (CD; P = .008) and 6.1 (3-11.2) vs 2.7 (1.5-5.6) months for ulcerative colitis (UC; P = .008). Sex was an independent variable related to the time to IBD diagnosis in Cox regression analysis. The clinical presentation of IBD was similar in both sexes. Women had a higher percentage of misdiagnosis than men (CD, odds ratio [OR], 3.9; 95% confidence [CI], 1.5-9.9; UC, OR 3.0; 95% CI, 1.2-7.4). Gender inequities in misdiagnosis were found at all levels of the health system (emergency department, OR 2.4; 95% CI, 1.1-5.1; primary care, OR 2.5; 95% CI, 1.3-4.7; gastroenterology secondary care, OR 3.2; 95% CI, 1.2-8.4; and hospital admission, OR 4.3; 95% CI, 1.1-16.9). CONCLUSIONS: There is a longer diagnostic delay in women than in men for both CD and UC due to a drawn-out evaluation of women, with a higher number of misdiagnoses at all levels of the health care system.

This paper shows a longer delay in the diagnosis of inflammatory bowel disease in women compared with men for both Crohn's disease and ulcerative colitis. These differences are present at all levels of the health care system, and misdiagnosis is also more common in women.

Risk Factors for Metachronous Colorectal Cancer or Advanced Adenomas After Endoscopic Resection of High-risk Adenomas.

BACKGROUND & AIMS: Among the characteristics of high-risk adenomas (HRAs), some may predict a higher risk of metachronous advanced lesions. Our aim was to assess which HRA characteristics are associated with high risk of metachronous colorectal cancer (CRC) or advanced adenomas (AAs). METHODS: We systematically searched Pubmed, EMBASE, and Cochrane for cohort studies and clinical trials of CRC or AA incidence at surveillance stratified by baseline lesion size, histology, and multiplicity. We calculated pooled relative risks (RRs) using a random-effects model. Heterogeneity was assessed with the I2 statistic. RESULTS: Fifty-five studies were included, with 936,540 patients with mean follow-up 5.4 ± 2.9 years. CRC incidence per 1000 person-years was 2.6 (2.1-3.0) for adenomas ≥20 mm, 2.7 (2.2-3.2) for high-grade dysplasia (HGD), 2.0 (1.8-2.3) for villous component, 0.8 (0.1-1.4) for ≥5 adenomas, 1.0 (0.7-1.2) for ≥3 adenomas. Metachronous CRC risk was higher in adenomas ≥20 mm vs 10 to 19 mm (RR, 2.08; 95% confidence interval [CI], 1.20-3.61), HGD vs low-grade dysplasia (RR, 2.89; 95% CI, 1.88-4.44), villous vs tubular (RR, 1.75; 95% CI, 1.33-2.31). No significant differences in CRC risk were found in ≥3 adenomas vs 1 to 2 (RR, 1.24; 95% CI, 0.84-1.83), nor in ≥5 adenomas vs 3 to 4 (RR, 0.79; 95% CI, 0.30-2.11). Compared with normal colonoscopy, RR for CRC risk was 2.61 (95% CI, 2.06-3.32) for ≥10mm, 6.62 (95% CI, 4.60-9.52) for HGD, 3.58 (95% CI, 2.24-5.73) for villous component, and 2.03 (95% CI, 1.40-2.94) for ≥3 adenomas. Similar trends were seen for metachronous AAs. CONCLUSION: Metachronous CRC risk is highest in patients with baseline adenomas with ≥20 mm or HGD. Multiplicity does not seem to be associated with substantially higher CRC risk in the near term.

Factors associated with lesion detection in colonoscopy among different indications.

BACKGROUND AND OBJECTIVE: Different factors may influence colonoscopy performance measures. We aimed to analyze procedure- and endoscopist-related factors associated with detection of colorectal lesions and whether these factors have a similar influence in the context of different colonoscopy indications: positive fecal immunochemical test (+FIT) and post-polypectomy surveillance colonoscopies. METHODS: This multicenter cross-sectional study included adults aged 40-80 years. Endoscopists (N = 96) who had performed ≥50 examinations were assessed for physician-related factors. Adenoma detection rate (ADR), adenomas per colonoscopy rate (APCR), advanced ADR, serrated polyp detection (SDR), and serrated polyps per colonoscopy rate (SPPCR) were calculated. RESULTS: We included 12,932 procedures, with 4810 carried out after a positive FIT and 1967 for surveillance. Of the 96 endoscopists evaluated, 43.8% were women, and the mean age was 41.9 years. The ADR, advanced ADR, and SDR were 39.7%, 17.7%, and 12.8%, respectively. Adenoma detection rate was higher in colonoscopies after a +FIT (50.3%) with a more than doubled advanced ADR compared to non-FIT procedures (27.6% vs. 13.0%) and similar results in serrated lesions (14.7% vs. 13.5%). Among all the detection indicators analyzed, withdrawal time was the only factor independently related to improvement (p < 0.001). Regarding FIT-positive and surveillance procedures, for both indications, withdrawal time was also the only factor associated with a higher detection of adenomas and serrated polyps (p < 0.001). Endoscopist-related factors (i.e., weekly hours dedicated to endoscopy, annual colonoscopy volume and lifetime number of colonoscopies performed) had also impact on lesion detection (APCR, advanced ADR and SPPCR). CONCLUSIONS: Withdrawal time was the factor most commonly associated with improved detection of colonic lesions globally and in endoscopies for + FIT and post-polypectomy surveillance. Physician-related factors may help to address strategies to support training and service provision. Our results can be used for establishing future benchmarking and quality improvement in different colonoscopy indications.

Identification of Leukemia-Associated Immunophenotypes by Databaseguided Flow Cytometry Provides a Highly Sensitive and Reproducible Strategy for the Study of Measurable Residual Disease in Acute Myeloblastic Leukemia.

Background: Multiparametric Flow Cytometry (MFC) is an essential tool to study the involved cell lineages, the aberrant differentiation/maturation patterns and the expression of aberrant antigens in acute myeloid leukemia (AML). The characterization of leukemia-associated immunophenotypes (LAIPs) at the moment of diagnosis is critical to establish reproducible strategies for the study of measurable residual disease using MFC (MFC-MRD). Methods: In this study, we identify and characterize LAIPs by comparing the leukemic populations of 145 AML patients, using the EuroFlow AML/ MDS MFC panel, with six databases of normal myeloid progenitors (MPCs). Principal component analysis was used to identify and characterize the LAIPs, which were then used to generate individual profiles for MFC-MRD monitoring. Furthermore, we investigated the relationship between the expression patterns of LAIPs and the different subtypes of AML. The MFC-MRD study was performed by identifying residual AML populations that matched with the LAIPs at diagnosis. To further validate this approach, the presence of MRD was also assessed by qPCR (qPCR-MRD). Finally, we studied the association between MFC-MRD and progression-free survival (PFS). Results: The strategy used in this study allowed us to describe more than 300 different LAIPs and facilitated the association of specific phenotypes with certain subtypes of AML. The MFC-MRD monitoring based on LAIPs with good/strong specificity was applicable to virtually all patients and showed a good correlation with qPCR-MRD and PFS. Conclusions: The described methodology provides an objective method to identify and characterize LAIPs. Furthermore, it provides a theoretical basis to develop highly sensitive MFC-MRD strategies.

Early postoperative complications after gastric bypass revisional surgery in patients with previous sleeve gastrectomy versus primary gastric bypass.

BACKGROUND: Revisional bariatric surgery (RS) is indicated if there is weight regain or insufficient weight loss, no improvement or reappearance of co-morbidities, or previous bariatric surgery complications. It has been associated with higher postoperative morbidity. OBJECTIVE: To evaluate the early postoperative complications (<30 d) of Roux-en-Y gastric bypass RS (RYGB-RS) after primary sleeve gastrectomy (SG-1) compared with primary RYGB (RYGB-1) at a bariatric surgery referral center. SETTING: Department of General and Digestive Surgery of General Universitary Hospital of Alicante, Spain. METHODS: Retrospective cohort study comparing RYGB-RS after SG-1 and RYGB-1 between January 2008 and March 2021. Postoperative complications, hospital stay, mortality, and readmissions were analyzed. RESULTS: Six hundred and twenty-eight RYGB surgeries (48 RYGB-RS, 580 RYGB-1) were studied. The mean age of patients undergoing RYGB-RS was 50 years, compared with 46 years in the RYGB-1 group (P = .017). Mean initial body mass index was 44.2 kg/m2 (RYGB-RS) versus 47.6 kg/m2 (RYGB-1; P = .004). Cardiovascular risk factors were higher in the RYGB-1 group (P < .05). Indications for RS were weight regain or insufficient weight loss (72.9%), weight regain or insufficient weight loss plus gastroesophageal reflux disease (14.6%), and gastroesophageal reflux disease (12.5%). There were no differences in the frequency of complications (RYGB-RS 22.9% vs RYGB-1 20.5%) or in their severity (Clavien-Dindo ≥IIIa; RYGB-RS 10.4% vs RYGB-1 6.4%; P > .05). There were no differences in emergency room visits (RYGB-RS at 12.5% vs RYGB-1 at 14.9%) or in readmissions (RYGB-RS at 12.5% vs RYGB-1 at 9.4%). CONCLUSION: No differences were observed between primary RYGB and revisional RYGB in early morbidity, mortality, emergencies, or readmissions. Revisional bariatric surgery is a safe procedure at referral centers and must be done by expert hands.

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients.

BACKGROUND: Previous studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. METHODS: Prospective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. RESULTS: We included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. CONCLUSIONS: Compared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.

Textbook outcome among patients undergoing enhanced recovery after liver transplantation stratified by risk. A single-center retrospective observational cohort study.

BACKGROUND & AIMS: Liver transplantation (LT) is one of the most complex surgical procedures. Enhanced recovery after surgery (ERAS) aims to reduce the risk of postoperative complications. When patients achieve all desirable outcomes after a procedure, they are considered to have experienced a textbook outcome (TO). METHODS: Two cohorts of patients undergoing low (n = 101) or medium risk (n = 15) LT were identified. The remaining patients (n = 65) were grouped separately. The ERAS protocol included pre-, intra-, and post-operative steps. TO was defined as the absence of complications, prolonged length of hospital stays, readmission and mortality during the first 90 days. RESULTS: One third of patients who underwent ERAS after LT experienced a TO. On multivariable analysis, age (OR, 1.05 [95% CI, 1.01-1.09]; P = .02), and having hepatocellular carcinoma (OR, 2.83 [95% CI, 1.37-6.03]; P = .005) were individually associated with a greater probability of achieving a TO. Belonging to the cohorts of medium risk or outside the selection criteria was associated with a lower probability of achieving a TO (OR, 0.46 [96% CI, 0.22-0.93]; P = .03). Patients less likely to experience TO required more hospital resources. Patients who achieved TO were more likely to remain free of chronic kidney disease (achieved TO, 83.8% [82.7-85.6]; failed TO, 67.9% [66.9-70.2]; P < .05). Tacrolimus dose and trough levels were similar. CONCLUSIONS: A novel finding of our study is that short and medium-term kidney function is better preserved in patients who experience a TO. Better kidney function of patients who achieve TO is not due to lower tacrolimus dosage.

Absent in Melanoma 2 (AIM2) Regulates the Stability of Regulatory T Cells.

Absent in melanoma 2 (AIM2) is a cytosolic dsDNA sensor that has been broadly studied for its role in inflammasome assembly. However, little is known about the function of AIM2 in adaptive immune cells. The purpose of this study was to investigate whether AIM2 has a cell-intrinsic role in CD4+ T cell differentiation or function. We found that AIM2 is expressed in both human and mouse CD4+ T cells and that its expression is affected by T cell receptor (TCR) activation. Naïve CD4+ T cells from AIM2-deficient (Aim2-/-) mice showed higher ability to maintain forkhead box P3 (FOXP3) expression in vitro, while their capacity to differentiate into T helper (Th)1, Th2 or Th17 cells remained unaltered. Transcriptional profiling by RNA sequencing showed that AIM2 might affect regulatory T cell (Treg) stability not by controlling the expression of Treg signature genes, but through the regulation of the cell's metabolism. In addition, in a T cell transfer model of colitis, Aim2-/--naïve T cells induced less severe body weight loss and displayed a higher ability to differentiate into FOXP3+ cells in vivo. In conclusion, we show that AIM2 function is not confined to innate immune cells but is also important in CD4+ T cells. Our data identify AIM2 as a regulator of FOXP3+ Treg cell differentiation and as a potential intervention target for restoring T cell homeostasis.

Risk of Colorectal Cancer and Advanced Polyps One Year After Excision of High-Risk Adenomas.

BACKGROUND: Patients with multiple or large adenomas are considered to be high-risk for metachronous colorectal cancer. OBJECTIVE: Evaluate the risks of detecting colorectal cancer, advanced adenoma, and advanced serrated polyps at 1-year surveillance colonoscopy in patients with >5 adenomas or adenomas >20 mm. DESIGN: Descriptive, retrospective, multicentric, cohort study. We calculated the absolute risk of developing colorectal cancer, advanced adenomas, and advanced serrated polyps at the 1-year surveillance colonoscopy. Potential risk factors for advanced neoplasia at follow-up were evaluated with univariable and multivariable logistic regression analyses. SETTINGS: This study included data from a multicenter cohort colorectal cancer screening program, conducted from January 2014 to December 2015, based on fecal immunochemical tests in Spain. PATIENTS: We included 2119 participants with at least 1 adenoma ≥20 mm or ≥5 adenomas of any size. MAIN OUTCOME MEASURES: We calculated the absolute risk of developing colorectal cancer, advanced adenomas, and advanced serrated polyps at the 1-year surveillance colonoscopy. Potential risk factors for advanced neoplasia at follow-up were evaluated with univariable and multivariable logistic regression analyses. RESULTS: At 1 year, participants displayed 6 colorectal cancers (0.3%), 228 advanced adenomas (10.5%), and 58 advanced serrated polyps (2.7%). The adjusted analysis identified 2 factors associated with advanced neoplasia: >5 adenomas (odds ratio 1.53; 95% CI: 1.15-2.03; p = 0.004) and polyps in a proximal location (OR 1.52; 95% CI: 1.15-2.02; p = 0.004). LIMITATIONS: First, the sample size was relatively small compared to other studies with similar aims. Another limitation was the lack of a comparison group, which could have provided more practical results in terms of surveillance recommendations. CONCLUSIONS: The colorectal cancer detection rate at a 1-year colonoscopy surveillance was low among patients classified at high risk of advanced neoplasia. The risk factors for advanced neoplasia were ≥5 adenomas and proximal polyps at baseline. See Video Abstract at http://links.lww.com/DCR/B820 . RIESGO DE CNCER COLORRECTAL Y DE PLIPOS AVANZADOS UN AO DESPUS DE LA RESECCIN DE ADENOMAS DE ALTO RIESGO: ANTECEDENTES:Los pacientes con adenomas múltiples o grandes se consideran de alto riesgo para desarrollar cáncer colorrectal metacrónico.OBJETIVO:Evaluar los riesgos de detectar cáncer colorrectal, adenoma avanzado y pólipos serrados avanzados en la colonoscopia de seguimiento al año, en pacientes con un número mayor o igual a 5 adenomas o adenomas de 20 mm o más.DISEÑO:Estudio descriptivo, retrospectivo, multicéntrico, de cohortes. Calculamos el riesgo absoluto de desarrollar cáncer colorrectal, adenomas avanzados y pólipos serrados avanzados en la colonoscopia de vigilancia al año. Los factores de riesgo potenciales para el desarrollo de una neoplasia avanzada en el seguimiento, fueron evaluados mediante un análisis de regresión logística univariable y multivariable.AJUSTES:Este estudio incluyó datos de un programa de cribado de cáncer colorrectal de cohorte multicéntrico, realizado entre enero de 2014 y diciembre de 2015, con base en pruebas inmunoquímicas de materia fecal, en España.PACIENTES:Incluimos 2119 participantes con al menos un adenoma ≥20 mm o con cinco o más adenomas de cualquier tamaño.PRINCIPALES MEDIDAS DE RESULTADO:Calculamos el riesgo absoluto de desarrollar cáncer colorrectal, adenomas avanzados y pólipos serrados avanzados en la colonoscopia de vigilancia al año. Los potenciales factores de riesgo para desarrollar una neoplasia avanzada en el seguimiento, se evaluaron mediante un análisis de regresión logística univariable y multivariable.RESULTADOS:Al año se encontraron en los pacientes participantes, 6 cánceres colorrectales (0,3%), 228 adenomas avanzados (10,5%) y 58 pólipos serrados avanzados (2,7%). Mediante el análisis ajustado se identificaron dos factores asociados con el desarrollo de neoplasia avanzada: un número igual o mayor a 5 adenomas (razón de probabilidades 1,53; IC del 95%: 1,15-2,03; p = 0,004) y la presencia de pólipos en una ubicación proximal (razón de probabilidades 1,52; IC del 95%: 1,15-2,02; p = 0,004).LIMITACIONES:Primero, el tamaño de la muestra fue relativamente pequeño en comparación con otros estudios con objetivos similares. Otra limitación fue la falta de un grupo comparativo, que podría haber proporcionado resultados más prácticos, en términos de recomendaciones de vigilancia.CONCLUSIÓNES:La tasa de detección de cáncer colorrectal mediante una colonoscopia de vigilancia al año, fue baja entre los pacientes clasificados como de alto riesgo de neoplasia avanzada. Los factores de riesgo para desarrollar una neoplasia avanzada fueron; un número igual o mayor a 5 adenomas y la presencia de pólipos proximales en la colonoscopia inicial de base. Consulte Video Resumen en http://links.lww.com/DCR/B820 . ( Traducción-Eduardo Londoño-Schimmer ).

Endocrine disruption in Crohn's disease: Bisphenol A enhances systemic inflammatory response in patients with gut barrier translocation of dysbiotic microbiota products.

The relevance of environmental triggers in Crohn's disease remains poorly explored, despite the well-known association between industrialization and disease onset/progression. We have aimed at evaluating the influence of endocrine disrupting chemicals in CD patients. We performed a prospective observational study on consecutive patients diagnosed of CD. Serum levels of endocrine disruptors, short-chain fatty acids, tryptophan and cytokines were measured. Bacterial-DNA and serum endotoxin levels were also evaluated. Gene expression of ER-α, ER-ß and GPER was measured in PBMCs. All patients were genotyped for NOD2 and ATG16L1 polymorphisms. A series of 200 CD patients (140 in remission, 60 with active disease) was included in the study. Bisphenol A was significantly higher in patients with active disease versus remission and in colonic versus ileal disease. GPER was significantly increased in active patients and correlated with BPA levels. BPA was significantly increased in patients with bacterial-DNA and correlated with serum endotoxin levels, (r = 0.417; P = .003). Serum butyrate and tryptophan levels were significantly lower in patients with bacterial-DNA and an inverse relationship was present between them and BPA levels (r = -0.491; P = .001) (r = -0.611; P = .001). Serum BPA levels correlated with IL-23 (r = 0.807; P = .001) and IL-17A (r = 0.743; P = .001). The multivariate analysis revealed an independent significant contribution of BPA and bacterial-DNA to serum levels of IL-23 and IL-17A. In conclusion, bisphenol A significantly affects systemic inflammatory response in CD patients with gut barrier disruption and dysbiotic microbiota secretory products in blood. These results provide evidence of an endocrine disruptor playing an actual pathogenic role on CD.

Effects of Somatic Methylation in Colonic Polyps on Risk of Developing Metachronous Advanced Colorectal Lesions.

The utility of molecular markers for predicting the risk of metachronous advanced colorectal lesions (MACLs) remains poorly investigated. We examined the relationship between somatic hypermethylation in polyps at baseline and the risk of developing MACL. This retrospective cohort study included 281 consecutive patients with colonic polyps who were enrolled between 2007 and 2009 and followed-up until 2014. MACLs were defined as adenomas of ≥10 mm, high-grade dysplasia, or with a villous component; and serrated lesions of ≥10 mm or with dysplasia. In total, 595 polyps were removed at baseline colonoscopy and analyzed for pathological characteristics and CpG island methylator phenotype (CIMP) using the MS-MLPA (Methylation-Specific -- Multiplex Ligation-dependent Probe Amplification) technique. Forty-five patients (16.0%) showed at least one CIMP+ polyp. MACL risk was higher in patients with CIMP+ polyps (odds ratio (OR), 4.50; 95% CI, 1.78-11.4; p = 0.002). Patients with CIMP+ polyps also exhibited shorter time to MACL development (33.8 months vs. 50.1 months; p < 0.001), even with adjustment for polyp size and number (OR, 2.40; 95% CI, 1.33-4.34). Adding CIMP analysis improved the sensitivity (57.0% to 70.9%), negative predictive value (71.1% to 77.3%), and overall accuracy (49.8% to 52.0%) for MACL risk estimation. These results highlight that CIMP may be a useful marker for endoscopic surveillance.