Causal association of nonalcoholic fatty liver disease with 22 extrahepatic cancers: A Mendelian randomization study.

AIM: It is unclear whether nonalcoholic fatty liver disease (NAFLD) acts as a direct contributing factor to multiple extrahepatic cancers. We aimed to systematically investigate the causal relationships of NAFLD with extrahepatic cancers. METHODS: We conducted a two-sample Mendelian randomization analysis to assess the causal effects of NAFLD on 22 extrahepatic cancers. We examined the association of NAFLD with extrahepatic cancers using multiple methods in the largest genome-wide association study meta-analysis to date. We also replicated the analyses and performed two independent sensitivity analysis in the largest genome-wide association study of UK Biobank. RESULTS: Using the weighted median method, genetically predicted NAFLD was significantly associated with female breast cancer risk (odds ratio [OR] 15.99; 95% confidence interval [CI] 9.58-26.69). Genetically predicted NAFLD is associated with cervical and laryngeal cancers using the inverse variance weighting method, and the ORs were 2.44 (95% CI 1.43-4.14) and 1.94 (95% CI 1.35-2.78), respectively. We observed that patatin-like phospholipase domain-containing protein 3-driven and transmembrane 6 superfamily member 2-driven NAFLD were associated with increased risks of leukemia, lung cancer, and prostate cancers (all with p < 0.05). Furthermore, we confirmed the causal association between NAFLD and breast cancer using five known single-nucleotide polymorphisms of NAFLD and six genome-wide association study-identified variants. The ORs of the weighted median estimator was 10.76 (95% CI 8.27-13.98) and 10.76 (95% CI 8.25-14.04), respectively (p < 0.001). CONCLUSION: Genetically predicted NAFLD is associated with an increased risk of female breast cancer, as well as cervical, laryngeal, leukemia, lung, and prostate cancers.

Minimal water exchange by the air-water valve versus left colon water exchange in unsedated colonoscopy: a randomized controlled trial.

BACKGROUND: Water exchange colonoscopy is the least painful method for unsedated colonoscopies. Simplified left colon water exchange (LWE) reduces the cecal intubation time but it is difficult to avoid the use of an additional pump. Minimal water exchange (MWE) is an improved novel method that eliminates the need for pumps, but it is not clear whether MWE has the same efficiency as LWE. METHODS: This was a prospective, randomized, controlled, noninferiority trial conducted in a tertiary hospital. Enrolled patients were randomized 1:1 to the LWE group or MWE group. The primary outcome was recalled insertion pain measured by a 4-point verbal rating scale. Secondary outcomes included adenoma detection rate (ADR), cecal intubation time, volume of water used, and patient willingness to repeat unsedated colonoscopy. RESULTS: 226 patients were included (LWE n = 113, MWE n = 113). The MWE method showed noninferior moderate/severe pain rates compared with the LWE method (10.6 % vs. 9.7 %), with a difference of 0.9 percentage points (99 % confidence interval [CI] -9.5 to 11.3; threshold, 15 %). ADR, cecal intubation time, and willingness to repeat unsedated colonoscopy were not significantly different between the two groups, but the mean volume of water used was significantly less with MWE than with LWE (163.7 mL vs. 407.2 mL; 99 %CI -298.28 to -188.69). CONCLUSION: Compared with LWE, MWE demonstrated a noninferior outcome for insertion pain, and comparable cecal intubation time and ADR, but reduced the volume of water used and eliminated the need for a water pump.

Causal relationship of sugar-sweetened and sweet beverages with colorectal cancer: a Mendelian randomization study.

BACKGROUND AND AIM: Prospective cohort studies have suggested that sugar-sweetened beverages (SSBs) intake is significantly associated with the risk of colorectal cancer (CRC). However, it remains unclear whether this observed association was susceptible to potential confounding factors due to the long-term development process of CRC, and the risk of CRC associated with sweet beverages has rarely been reported. We aimed to investigate the association between SSBs/sweet beverages and CRC risk. METHODS: We performed two-sample Mendelian randomization (MR) analysis using independent genetic variants for SSBs and sweet beverages from a published genome-wide association study (GWAS). Summary statistics for instrument-outcome associations from two databases for malignant neoplasms of the colon and the rectum (FinnGen and UK Biobank). The inverse weighted method (IVW) meta-analysis was the main method used to estimate the relationship, and sensitivity analyses were performed with Cochran's Q test, leave-one-out analysis, MR-Egger regression, Steiger filtering, and the MR PRESSO test. RESULTS: Genetically predicted SSBs intake was associated with a higher colonic malignant neoplasms risk (odds ratio (OR): 1.013; 95% confidence interval (CI) 1.001, 1.026; P = 0.036) in a combined sample size of 579,986 individuals (4029 cases). Such a significant causal effect of SSBs on rectal malignant neoplasms or sweet beverages on CRC was not observed. CONCLUSION: Our findings corroborated a causal association between SSBs and colonic malignant neoplasms risk but did not support such a relationship in the analysis of the rectal malignant neoplasms nor the sweet beverage intake, which might be interpreted with caution and further confirmed.

Iron Status and NAFLD among European Populations: A Bidirectional Two-Sample Mendelian Randomization Study.

Background and aim: Previous observational studies have suggested a paradoxical relationship between iron status and the risk of non-alcoholic fatty liver disease (NAFLD). Observed associations in these epidemiological studies fail to show sequential temporality and suffer from problems of confounding. Therefore, we performed a bidirectional two-sample Mendelian randomization (MR) to evaluate the relationship between serum iron status and NAFLD. Methods: The inverse weighted method (IVW) meta-analysis with the fixed-effect model was the main method to estimate the relationship between iron status, including serum ferritin, iron, transferrin saturation (TSAT) and total iron-binding capacity (TIBC), and NAFLD. Weighted median, penalized weighted median, and MR Robust Adjusted Profile Score (MR RAPS) methods were used as additional analyses. Sensitivity analyses were performed with Cochran's Q test, MR-Egger regression, Steiger filtering, and the MR PRESSO test. Results: Iron status, including serum ferritin, iron, and TSAT, was associated with an increased risk of NAFLD (odds ratio (OR) (95% confidence interval (CI)): 1.25 (1.06, 1.48); 1.24 (1.05, 1.46), 1.16 (1.02, 1.31), respectively). In contrast, minimal effects of NAFLD on serum ferritin, iron, TSAT, and TIBC were observed (OR (95% CI): 1.01 (1.00, 1.02), 1.01 (1.00, 1.02), 1.03 (1.01, 1.05), 1.03 (1.01, 1.05), respectively). Conclusions: Our findings corroborated the causal associations between serum ferritin, iron, TSAT, and NAFLD, which might suggest the potential benefits of iron-related therapy. In addition, NAFLD might, in turn, slightly affect iron homeostasis indicated as serum ferritin, iron, TSAT, and TIBC, but this needs to be further confirmed.

The efficacy and tolerability of sports drink versus water in bowel preparations: a randomised controlled study.

BACKGROUND: An optimal bowel preparation can result in an improved colonoscopy. This study was to compare the effectiveness and safety of the use of a sports drink (Mizone) plus polyethylene glycol (PEG) solution with a water plus PEG solution in bowel preparations. METHODS: This was a randomised controlled study. All of the included patients were randomly divided into the following two groups: the PEG + Mizone group and the PEG + water group. The palatability of the solution was measured through the use of questionnaires. Additionally, bowel cleanliness was evaluated according to the Ottawa Bowel Preparation Scale (OBPS, 0-14, with higher values indicating worse cleanliness), as well as with the aid of colonoscopy videos. RESULTS: A total of 270 patients were enrolled. The rate of adequate bowel preparation was 74.8% in the PEG + Mizone group and 68.9% in the PEG + water group, with a risk difference of 5.9% (95% CI: - 4.8-16.6%), which indicated noninferiority (noninferiority margin: - 9.5% < - 4.8%). However, patients rated the palatability (65.9% vs 44.4%, P < 0.001) and willingness to recommend or repeat (88.9% vs 75.6%, P = 0.004) the administration of the PEG + Mizone preparation as being better than those of the PEG + water preparation. The rates of adverse events during the bowel preparations were not significantly different between the two groups, except for bloating (PEG + Mizone vs PEG + water, 4.4% vs 13.3%, P = 0.010). CONCLUSION: The concomitant use of PEG + Mizone was a well tolerated and effective bowel preparation, compared with the PEG + water treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04247386 . Registered on 30 Jan 2020.

External validation of two prediction models for adequate bowel preparation in Asia: a prospective study.

BACKGROUND: Several models for predicting adequate bowel preparation are available but have never been externally validated. The aim of this study is to compare the available models in an independent population. METHODS: This study prospectively recruited 500 consecutive patients from August to December 2020 from the Endoscopy Center of a tertiary hospital. All patients underwent the same bowel preparation regimen. The discrimination of the prediction models was quantified with the area under the receiver operating characteristic curve (AUC), and the 95% confidence interval (CI) was calculated for each AUC. RESULTS: Finally, 461 patients were eligible for this study. A total of 110 (23.9%) patients were deemed to show inadequate bowel preparation during colonoscopy. There were significant differences between patients with and without adequate bowel preparation in terms of current hospitalization, procedure time, comorbidities (including diabetes and constipation), American Society of Anesthesiologists Physical Status Classification System score (ASA) ≥ 3, medication usage, and abdominal/pelvic surgery. The prediction models performed as follows: the Dik ≥ 2 model, the Dik ≥ 3 model, and the Antonio > 1.225 model had AUCs of 0.660 (95% CI = 0.604-0.717), 0.691 (95% CI = 0.646-0.733), and 0.645 (95% CI = 0.615-0.704), respectively. Comparison of the two prediction models showed no significant improvement (Antonio > 1.225 vs. Dik ≥ 3, 1.801, 95% CI = -0.004-0.096, P = 0.072). CONCLUSIONS: Both models are potentially helpful. However, it is necessary to develop or improve a prediction model to obtain a more suitable and detailed model. TRIAL REGISTRATION: ClinicalTrials.gov, Number NCT04607161.

Face-to-Face Instruction and Personalized Regimens Improve the Quality of Inpatient Bowel Preparation for Colonoscopy.

BACKGROUND: Poor bowel preparation is commonly observed in inpatients undergoing colonoscopy, particularly those with higher risks for inadequate bowel preparation. AIMS: The objective of this study was to determine whether personalized bowel preparation regimens combined with face-to-face instruction (FFI) could improve the quality of bowel preparation for inpatient. METHODS: In this endoscopist-blinded, randomized controlled trial, 320 inpatients were enrolled and randomly allocated (1:1) to the control and intervention groups. The intervention group received FFI and personalized bowel preparation regimens, while the control group received the routine bowel preparation regimen and education. The primary outcome was adequate bowel preparation rate. Secondary outcomes included rates of procedure-related adverse events, incorrect diet restriction and laxative intake, etc. RESULTS: The adequate bowel preparation rate in the intervention group was significantly higher compared to control group [intention-to-treat (ITT) analysis: 70.0% vs 51.3%, P < 0.001; per-protocol (PP) analysis: 79.4% vs 58.6%, P < 0.001]. Bowel cleanliness was significantly improved in high-risk inpatients (ITT analysis: 65% vs 44.6%, P = 0.004; PP analysis: 73.0% vs 51.7%, P = 0.004) and in low-risk inpatients (ITT analysis: 80% vs 62.7%, P = 0.037; PP analysis: 92.3% vs 69.8%, P = 0.003). There were no significant differences between two groups regarding procedure-related adverse events. CONCLUSIONS: Personalized bowel preparation regimens combined with FFI improve the rate of adequate bowel preparation, especially for patients with high-risk factors. As such, inpatients could benefit from this novel approach for better bowel preparation to ultimately improve the quality of colonoscopies.

Effectiveness and safety of the different endoscopic resection methods for 10- to 20-mm nonpedunculated colorectal polyps: A systematic review and pooled analysis.

BACKGROUND: We performed a systematic review and pooled analysis to assess the effectiveness and safety of different endoscopic resection methods for 10- to 20-mm nonpedunculated colorectal polyps. METHODS: Articles in PubMed, EMBASE, and the Cochrane Library related to the common endoscopic treatment of 10- to 20-mm nonpedunculated polyps published as of April 2020 were searched. Primary outcomes were the R0 resection rate and en bloc resection rate. Secondary outcomes were safety and the recurrence rate. Meta-regression and subgroup analysis were also performed. RESULTS: A total of 36 studies involving 3212 polyps were included in the final analysis. Overall, the effectiveness of resection methods with a submucosal uplifting effect, including endoscopic mucosal resection (EMR), cold EMR and underwater EMR (UEMR), was better than that of methods without a nonsubmucosal uplifting effect [R0 resection rate, 90% (95% confidence interval (CI) 0.81-0.94, I2 = 84%) vs 82% (95% CI 0.78-0.85, I2 = 0%); en bloc resection rate 85% (95% CI 0.79-0.91, I2 = 83%) vs 74% (95% CI 0.47-0.94, I2 = 94%)]. Regarding safety, the pooled data showed that hot resection [hot snare polypectomy, UEMR and EMR] had a higher risk of intraprocedural bleeding than cold resection [3% (95% CI 0.01-0.05, I2 = 68%) vs 0% (95% CI 0-0.01, I2 = 0%)], while the incidences of delayed bleeding, perforation and post-polypectomy syndrome were all low. CONCLUSIONS: Methods with submucosal uplifting effects are more effective than those without for resecting 10- to 20-mm nonpedunculated colorectal polyps, and cold EMR is associated with a lower risk of intraprocedural bleeding than other methods. Additional research is needed to verify the advantages of these methods, especially cold EMR.