Recurrence Pattern Is an Independent Surgical Prognostic Factor for Long-Term Oncological Outcomes in Patients with Hepatocellular Carcinoma.

BACKGROUND: The perioperative outcomes of a partial hepatectomy for hepatocellular carcinoma (HCC) have improved. However, high recurrence rates after a curative hepatectomy for HCC is still an issue. This study aimed to analyze the difference between various recurrence patterns. METHODS: We retrospectively reviewed 754 patients with HCC who underwent a curative hepatectomy between January 2012 and March 2021. Patients with recurrent events were categorized into three types: regional recurrence (type I), multiple intrahepatic recurrence (type II), or presence of any distant metastasis (type III). RESULTS: The median follow-up period was 51.2 months. Regarding recurrence, 375 (49.7%) patients developed recurrence, with 244 (32.4%), 51 (6.8%), and 80 (10.6%) patients having type I, II, and III recurrence, respectively. Type III recurrence appeared to be more common in male patients and those with major liver resection, vascular invasion, a large tumor size (>5 cm), a higher tumor grade, and higher levels of AST and AFP (p < 0.05). Patients who had distant metastasis at recurrence had the shortest recurrence time and the worst overall survival (p < 0.001 and p < 0.001). CONCLUSIONS: our study demonstrated that recurrence with distant metastasis occurred earliest and had the worst outcome compared to regional or multiple intrahepatic recurrences.

Risk of Metachronous Advanced Colorectal Neoplasia After Removal of Diminutive Versus Small Nonadvanced Adenomas: A Multicenter Study.

BACKGROUND: Current postpolypectomy guidelines treat 1-9 mm nonadvanced adenomas (NAAs) as carrying the same level of risk for metachronous advanced colorectal neoplasia (ACRN). AIMS: To evaluate whether small (6-9 mm) NAAs are associated with a greater risk of metachronous ACRN than diminutive (1-5 mm) NAAs. METHODS: We retrospectively evaluated 10,060 index colonoscopies performed from July 2011 to June 2019. A total of 1369 patients aged ≥ 40 years with index NAAs and having follow-up examinations were categorized into 5 groups based on size and number of index findings: Group 1, ≤ 2 diminutive NAAs (n = 655); Group 2, ≤ 2 small NAAs (n = 529); Group 3, 3-4 diminutive NAAs (n = 78); Group 4, 3-4 small NAAs (n = 65); and Group 5, 5-10 NAAs (n = 42). Size was classified based on the largest NAA. ACRN was defined as finding an advanced adenoma or colorectal cancer at follow-up. RESULTS: The absolute risk of metachronous ACRN increased from 7.2% in patients with all diminutive NAAs to 12.2% in patients with at least 1 small NAA (P = 0.002). Patients in Group 2 (adjusted odds ratio [AOR] 1.89; 95% confidence interval [CI], 1.21-2.95), Group 3 (AOR 2.40; 95% CI 1.78-4.90), Group 4 (AOR 2.77; 95% CI 1.35-5.66), and Group 5 (AOR 3.71; 95% CI 1.65-8.37) were associated with an increased risk of metachronous ACRN compared with Group 1. CONCLUSIONS: Patients with small NAAs have an increased risk of metachronous ACRN. Postpolypectomy guidelines should consider including risk stratification between small and diminutive adenomas.

The Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Poor Prognosis Factor in Patients with Hepatocellular Carcinoma: An Analysis of Microvessel Density.

The outcomes of patients with hepatocellular carcinoma (HCC) are unsatisfactory because of its high recurrence rate. The Vessels that encapsulate tumor clusters (VETC) pattern is a unique vascular structure. In this study, we investigated the clinical−pathological features of HCC patients with the VETC pattern. We retrospectively reviewed patients with HCC who underwent curative hepatectomy at Chang Gung Memorial Hospital between 2007 and 2013. The form of the VETC pattern was established using an anti-CD31 stain. The results were classified into positive (VETC+) and negative (VETC−) patterns. We investigated and compared demographic data between these two groups. Overall, 174 patients were classified into either the VETC+ or VETC− groups. The median followed-up period was 80.5 months. There were significant differences in the number of hepatitis B carriers, the occurrence of vascular invasion, tumor size, TNM staging, microvessel density, and recurrence (all p < 0.05). Regarding the prediction of disease-free survival, after COX regression multivariate analysis, VETC+ remained independently associated with recurrent episodes (p = 0.003). The intra-tumoral microvessel density, demonstrated by CD-31, was the only clinical−pathological feature independently associated with VETC+. Our study demonstrated that the VETC pattern is an independent factor of poor prognosis for DFS. Higher intra-tumoral microvessel density was significantly associated with the VETC pattern. Further studies are needed to validate our findings.

Rapid Polyp Classification in Colonoscopy Using Textural and Convolutional Features.

Colorectal cancer is the leading cause of cancer-associated morbidity and mortality worldwide. One of the causes of developing colorectal cancer is untreated colon adenomatous polyps. Clinically, polyps are detected in colonoscopy and the malignancies are determined according to the biopsy. To provide a quick and objective assessment to gastroenterologists, this study proposed a quantitative polyp classification via various image features in colonoscopy. The collected image database was composed of 1991 images including 1053 hyperplastic polyps and 938 adenomatous polyps and adenocarcinomas. From each image, textural features were extracted and combined in machine learning classifiers and machine-generated features were automatically selected in deep convolutional neural networks (DCNN). The DCNNs included AlexNet, Inception-V3, ResNet-101, and DenseNet-201. AlexNet trained from scratch achieved the best performance of 96.4% accuracy which is better than transfer learning and textural features. Using the prediction models, the malignancy level of polyps can be evaluated during a colonoscopy to provide a rapid treatment plan.

Correlation between drug sensitivity profiles of circulating tumour cell-derived organoids and clinical treatment response in patients with pancreatic ductal adenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumour samples for testing is challenging. METHODS: Circulating tumour cells (CTCs) from patients with PDAC liquid biopsies were expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. The correlation between CTS and clinical response was then assessed. RESULTS: A total of 41 liquid biopsies (87.8% from patients with Stage 4 disease) were collected from 31 patients. The CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in the surface marker analysis. All patients had received a median of two lines of treatment prior to enrolment and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts. CONCLUSIONS: CTCs were expanded from patients with PDAC liquid biopsies with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach.

Lightweight deep neural networks for cholelithiasis and cholecystitis detection by point-of-care ultrasound.

BACKGROUND AND OBJECTIVE: Emergency physicians (EPs) frequently deal with abdominal pain, including that is caused by either gallstones or acute cholecystitis. Easy access and low cost justify point-of-care ultrasound (POCUS) use as a first-line test to detect these diseases; yet, the detection performance of POCUS by EPs is unreliable, causing misdiagnoses with serious impacts. This study aimed to develop a machine learning system to detect and localize gallstones and to detect acute cholecystitis by ultrasound (US) still images taken by physicians or technicians for preliminary diagnoses. METHODS: Abdominal US images (> 89,000) were collected from 2386 patients in a hospital database. We constructed training sets for gallstones with or without cholecystitis (N = 10,971) and cholecystitis with or without gallstones (N = 7348) as positives. Validation sets were also constructed for gallstones (N = 2664) and cholecystitis (N = 1919). We applied a single-shot multibox detector (SSD) and a feature pyramid network (FPN) to classify and localize objects using image features extracted by ResNet-50 for gallstones, and MobileNet V2 to classify cholecystitis. The deep learning models were pretrained using the COCO-2017 and ILSVRC-2012 datasets. RESULTS: Using the validation sets, the SSD-FPN-ResNet-50 and MobileNet V2 achieved areas under the receiver operating characteristics curve of 0.92 and 0.94, respectively. The inference speeds were 21 (47.6 frames per second, fps) and 7 ms (142.9 fps). CONCLUSIONS: A machine learning system was developed to detect and localize gallstones, and to detect cholecystitis, with acceptable discrimination and speed. This is the first study to develop this system for either gallstone or cholecystitis detection with absence or presence of each one. After clinical trials, this system may be used to assist EPs, including those in remote areas, for detecting these diseases.

Deep learning for abdominal ultrasound: A computer-aided diagnostic system for the severity of fatty liver.

BACKGROUND: The prevalence of nonalcoholic fatty liver disease is increasing over time worldwide, with similar trends to those of diabetes and obesity. A liver biopsy, the gold standard of diagnosis, is not favored due to its invasiveness. Meanwhile, noninvasive evaluation methods of fatty liver are still either very expensive or demonstrate poor diagnostic performances, thus, limiting their applications. We developed neural network-based models to assess fatty liver and classify the severity using B-mode ultrasound (US) images. METHODS: We followed standards for reporting of diagnostic accuracy guidelines to report this study. In this retrospective study, we utilized B-mode US images from a consecutive series of patients to develop four-class, two-class, and three-class diagnostic prediction models. The images were eligible if confirmed by at least two gastroenterologists. We compared pretrained convolutional neural network models, consisting of visual geometry group (VGG)19, ResNet-50 v2, MobileNet v2, Xception, and Inception v2. For validation, we utilized 20% of the dataset resulting in >100 images for each severity category. RESULTS: There were 21,855 images from 2,070 patients classified as normal (N = 11,307), mild (N = 4,467), moderate (N = 3,155), or severe steatosis (N = 2,926). We used ResNet-50 v2 for the final model as the best ones. The areas under the receiver operating characteristic curves were 0.974 (mild steatosis vs others), 0.971 (moderate steatosis vs others), 0.981 (severe steatosis vs others), 0.985 (any severity vs normal), and 0.996 (moderate-to-severe steatosis/clinically abnormal vs normal-to-mild steatosis/clinically normal). CONCLUSION: Our deep learning models achieved comparable predictive performances to the most accurate, yet expensive, noninvasive diagnostic methods for fatty liver. Because of the discriminative ability, including for mild steatosis, significant impacts on clinical applications for fatty liver are expected. However, we need to overcome machine-dependent variation, motion artifacts, lacking of second confirmation from any other tools, and hospital-dependent regional bias.

Exploring and predicting mortality among patients with end-stage liver disease without cancer: a machine learning approach.

OBJECTIVE: End-stage liver disease is a global public health problem with a high mortality rate. Early identification of people at risk of poor prognosis is fundamental for decision-making in clinical settings. This study created a machine learning prediction system that provides several related models with visualized graphs, including decision trees, ensemble learning and clustering, to predict mortality in patients with end-stage liver disease. METHODS: A retrospective cohort study was conducted: the training data were from patients enrolled from January 2009 to December 2010 and followed up to December 2014; validation data were from patients enrolled from January 2015 to December 2016 and followed up to January 2019. Hospitalized patients with noncancer-related chronic liver disease were identified from the hospital's electrical medical records. RESULTS: In traditional multivariable logistic regression and Cox proportional hazard model, prothrombin time of international normalized ratio, which was significant with P value = 0.002, odds ratio = 2.790 and hazard ratio 1.363. Besides, blood urea nitrogen and C-reactive protein were also significant, with P value <0.001 and 0.026. The area under the curve was 0.771 in the receiver operating characteristic curve. In machine learning, blood urea nitrogen and age were regarded as the primary factors for predicting mortality. Creatinine, prothrombin time of international normalized ratio and bilirubin were also significant mortality predictors. The area under the curve of the random forest and AdaBoost was 0.838 and 0.792. CONCLUSION: The machine learning techniques provided a comprehensive assessment of patient conditions; it could help physicians make an accurate diagnosis of chronic liver disease and improve healthcare management.

Comparison of Right Colon Adenoma Miss Rates Between Water Exchange and Carbon Dioxide Insufflation: A Prospective Randomized Controlled Trial.

GOALS: To test the hypothesis that water exchange (WE), when compared with carbon dioxide (CO2) insufflation, significantly reduces the right colon adenoma miss rate (rAMR) in a blinded randomized controlled trial with cap-assisted colonoscopy. BACKGROUND: The unblinded consecutive group observational data showed that WE significantly decreased rAMR. The unblinded data are limited by potential bias. STUDY: Consecutive patients aged 45 years or more were randomized to undergo insertion with WE or CO2. Withdrawal and polypectomy were performed with CO2 in both groups to the hepatic flexure. The colonoscope was reinserted to the cecum. A second colonoscopist re-examined the right colon. The second colonoscopist was unaware, but made a guess, of the initial insertion method. The number of additional adenomas divided by the total number detected in both examinations equaled rAMR. RESULTS: Among 262 patients (131/group), demographic variables were similar. The body mass index was significantly higher in the WE group. Compared with CO2, WE significantly decreased rAMR [18.0% (33/183) vs. 34.6% (62/179), P=0.0025] and right colon serrated polyp miss rate [17.4% (27/155) vs. 39.3% (33/84), P=0.002]. Multivariate logistic regression analysis showed that WE was an independent predictor of rAMR (odds ratio, 0.42; 95% confidence interval, 0.21-0.86), and so was ≥2 adenomas in the right colon (odds ratio, 2.35; 95% confidence interval, 1.17-4.76). Whether the second colonoscopist guessed the insertion method correctly or not, and demographic and procedure variables were not associated with rAMR. CONCLUSIONS: The randomized controlled trial validated unblinded observational data showing that WE significantly decreased rAMR and right colon serrated polyp miss rate (clinical trial registration number: NCT03845933).

Interleukin-2 receptor alpha as a biomarker for nonalcoholic fatty liver disease diagnosis.

BACKGROUND: Two recent studies in the adult and pediatric Nonalcoholic Steatohepatitis-Clinical Research Network (NASH-CRN) cohorts have shown that soluble interleukin-2 receptor alpha (IL2RA) levels increased with fibrosis severity. However, no hepatic study has been conducted in Asian morbidly obese patients who underwent bariatric surgery. In this study, we proposed IL2RA as a biomarker for nonalcoholic fatty liver disease (NAFLD) diagnosis and performed immunohistochemistry (IHC) staining of IL2RA. METHODS: This prospective cohort study enrolled 123 morbidly obese patients who underwent bariatric surgery at Taipei Medical University Hospital from October 2016 to June 2018. During bariatric surgery, all patients underwent a wedge liver biopsy under laparoscopic guidance. The diagnoses of NASH and liver fibrosis were made histologically. In IHC of IL2RA, the number of lymphocytes with IL2RA immunoreactivity was counted in five high-power fields (×400, total: 1.19 mm2). RESULTS: Among the 123 patients, the mean age was 35.5 years, mean body mass index (BMI) was 40.6 kg/m2, 87 (70.7%) were female, 25 (20.7%) had diabetes mellitus, and 57 (46.3%; 11 with non-NAFLD and 46 with steatosis) and 66 (53.7%) were included in the non-NASH and NASH groups, respectively. The NASH group had higher IHC of IL2RA than the non-NASH group. In multivariate analysis, IHC of IL2RA (odds ratio, 1.025; 95% confidence interval, 1.006-1.045; p = 0.011) and alanine aminotransferase (ALT; odds ratio, 1.045; 95% confidence interval, 1.018-1.073; p = 0.001) were the independent factors associated with NASH. The area under the receiver operating curve of IL2RA IHC for NASH was 0.627 at the cutoff value of 82 (p = 0.0113). CONCLUSION: IL2RA is significantly associated with NASH in morbidly obese patients and would be a useful biomarker for NASH diagnosis.

Machine-Learning Monitoring System for Predicting Mortality Among Patients With Noncancer End-Stage Liver Disease: Retrospective Study.

BACKGROUND: Patients with end-stage liver disease (ESLD) have limited treatment options and have a deteriorated quality of life with an uncertain prognosis. Early identification of ESLD patients with a poor prognosis is valuable, especially for palliative care. However, it is difficult to predict ESLD patients that require either acute care or palliative care. OBJECTIVE: We sought to create a machine-learning monitoring system that can predict mortality or classify ESLD patients. Several machine-learning models with visualized graphs, decision trees, ensemble learning, and clustering were assessed. METHODS: A retrospective cohort study was conducted using electronic medical records of patients from Wan Fang Hospital and Taipei Medical University Hospital. A total of 1214 patients from Wan Fang Hospital were used to establish a dataset for training and 689 patients from Taipei Medical University Hospital were used as a validation set. RESULTS: The overall mortality rate of patients in the training set and validation set was 28.3% (257/907) and 22.6% (145/643), respectively. In traditional clinical scoring models, prothrombin time-international normalized ratio, which was significant in the Cox regression (P<.001, hazard ratio 1.288), had a prominent influence on predicting mortality, and the area under the receiver operating characteristic (ROC) curve reached approximately 0.75. In supervised machine-learning models, the concordance statistic of ROC curves reached 0.852 for the random forest model and reached 0.833 for the adaptive boosting model. Blood urea nitrogen, bilirubin, and sodium were regarded as critical factors for predicting mortality. Creatinine, hemoglobin, and albumin were also significant mortality predictors. In unsupervised learning models, hierarchical clustering analysis could accurately group acute death patients and palliative care patients into different clusters from patients in the survival group. CONCLUSIONS: Medical artificial intelligence has become a cutting-edge tool in clinical medicine, as it has been found to have predictive ability in several diseases. The machine-learning monitoring system developed in this study involves multifaceted analyses, which include various aspects for evaluation and diagnosis. This strength makes the clinical results more objective and reliable. Moreover, the visualized interface in this system offers more intelligible outcomes. Therefore, this machine-learning monitoring system provides a comprehensive approach for assessing patient condition, and may help to classify acute death patients and palliative care patients. Upon further validation and improvement, the system may be used to help physicians in the management of ESLD patients.

Fibroscan-Based Score to Predict Significant Liver Fibrosis in Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: The prevalence rate of nonalcoholic fatty liver disease (NAFLD) has been reported in 74 to 90% of morbidly obese patients. This study aims to develop a scoring system that predicts significant liver fibrosis in morbidly obese patients. METHODS: This prospective cohort study involved 123 morbidly obese patients who underwent metabolic surgery at Taipei Medical University Hospital between October 2016 and June 2018. Wedge liver biopsy was performed during surgery, and significant liver fibrosis was defined as a fibrosis score â‰§ 2. Ultrasonography and transient elastography were performed prior to surgery to assess the risk factors associated with significant liver fibrosis. RESULTS: Mean patient age was 35.5 years, mean body mass index (BMI) was 40.6 kg/m2, and 87 (70.7%) were female. Fibrosis staging revealed 28 (22.8%) at stage 2, 14 (11.4%) at stage 3, and 2 (1.6%) at stage 4. Patients were then separated into training (n = 73) and validation (n = 50) cohorts. Multivariate analysis revealed a liver stiffness measurement (LSM) > 7 kPa and aspartate aminotransferase/platelet ratio index (APRI) > 0.40 as independent factors associated with significant liver fibrosis among the training cohort. Fibroscan-base score weighted sum of (1 for presence of APRI > 0.40) + (2 for presence of LSM > 7 kPa) yielded the highest area under receiver operating curve (0.854, P = 0.0001; 0.785, P = 0.0002) compared with other non-invasive markers in the training and validation cohorts, respectively. CONCLUSION: We developed a simple, clinical scoring system incorporating Fibroscan and APRI to predict significant liver fibrosis in morbidly obese patients.

Effectiveness of stereotactic ablative radiotherapy in patients with advanced hepatocellular carcinoma unsuitable for transarterial chemoembolization.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) can deliver tumoricidal doses and achieve long-term control in early hepatocellular carcinoma (HCC). However, limited studies have investigated the safety and effectiveness of SABR in patients with advanced diseases that is unsuitable for transarterial chemoembolization (TACE). METHODS: In this observational study, we reviewed the medical records of patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease treated with linear accelerator-based SABR between 2008 and 2016. Their tumors were either refractory to TACE or TACE was contraindicated. Overall survival (OS), in-field progression-free survival (IFPFS), and out-field progression-free survival were calculated using Kaplan-Meier analysis. The Cox regression model was used to examine the effects of variables. Treatment-related toxicities were scored according to the Common Terminology Criteria for Adverse Events (version 4.03) and whether patients developed radiation-induced liver disease (RILD) after SABR. RESULTS: This study included 32 patients. The mean maximal tumor diameter and tumor volumes were 4.7 cm and 135.9 ml, respectively. Patients received linear accelerator-based SABR with a median prescribed dose of 48 Gy (30-60 Gy) in three to six fractions. Based on the assessment of treatment response by using the Response Evaluation Criteria in Solid Tumors (version 1.1), 19% of patients achieved a complete response and 53% achieved a partial response. After a median follow-up of 18.1 months (4.0-65.9 months), 10, 19, and 9 patients experienced in-field failure, out-field hepatic recurrence, and extrahepatic metastases, respectively. The estimated 2-year OS and IFPFS rates were 54.4% and 62.7%, respectively. In a multivariate analysis, a pretreatment Cancer of the Liver Italian Program (CLIP) score of ⩾2 (p = 0.01) was a prognostic factor for shorter OS, and a biologically effective dose (BED) of < 85 Gy10 (p = 0.011) and a Child-Pugh score of ⩾6 (p = 0.014) were prognostic factors for inferior IFPFS. In this study five and eight patients developed classic and nonclassic RILD, respectively. CONCLUSIONS: SABR can serve as a salvage treatment for patients with HCC with BCLC stage C disease unsuitable for TACE, in particular, in those with a baseline CLIP score of ⩽1. A BED10 of ⩾85 Gy is an appropriate prescribed dose for tumor control. Because out-field relapse is the major cause of treatment failure, SABR in combination with novel systemic modalities should be investigated in future studies.

Water exchange colonoscopy decreased adenoma miss rates compared with literature data and local data with CO2 insufflation: an observational study.

BACKGROUND: Reports showed adenoma miss rates (AMRs) of 22.5-27% in the right colon and 23.4-33.3% in the proximal colon. Missed lesions could contribute to postcolonoscopy cancers. Water exchange (WE) with near-complete removal of infused water during insertion increased adenoma detection rate but the impact on AMR had not been reported. We hypothesized that WE could reduce AMRs. Study 1 compared the AMRs of WE with literature data. Study 2 developed local AMR data with CO2 insufflation. METHODS: The lead author attended a research seminar in 2017 on WE colonoscopy. For performance improvement, study 1 was undertaken. When data in study 1 confirmed WE produced a considerably lower AMRs in the right and proximal colon, study 2 with CO2 insufflation was performed. RESULTS: Eighty-six patients completed each study. In study 1, WE removed 89% of infused water upon arrival to the cecum. The AMRs of right colon (17.5%) and proximal colon (15.5%) were considerably lower than those in the literature. Upon completion of study 2, compared with local data of CO2 insufflation, WE showed a significantly lower AMR in the right (17.5% vs. 33.8%, P = 0.034) and proximal (15.5% vs. 30.4%, P = 0.018) colon, respectively. The major limitation was that the investigation consisted of two consecutive observational studies, not a randomized controlled trial (RCT). CONCLUSIONS: WE with near-complete (89%) removal of infused water during insertion significantly decreased AMRs in the right and proximal colon compared with literature data and those of CO2 insufflation in our hands. The provocative data warrant confirmation in a RCT. TRIAL REGISTRATION: NCT03832322 (Retrospectively registered on February 2, 2019).

Comparison of polyp detection during both insertion and withdrawal versus only withdrawal of colonoscopy: A prospective randomized trial.

BACKGROUND AND AIMS: Polyps seen and not removed during colonoscope insertion are sometimes unable to be found during withdrawal. We aimed to evaluate whether additional inspection and polypectomy during insertion increases adenoma detection rate (ADR) compared with inspection and polypectomy entirely during withdrawal. METHODS: A total of 421 patients aged ≥ 45 years and undergoing colonoscopy were prospectively randomized to receive inspection and polypectomy during both insertion and withdrawal (study group) or inspection and polypectomy entirely during withdrawal (control group). The primary outcome was the ADR. Secondary outcomes included other adenoma-related parameters and procedure-related measures. RESULTS: Baseline demographics, procedure indications, preparation quality, total procedure time, sedative doses, colonoscopy difficulty, and patient discomfort were similar between the groups. The insertion time was significantly longer in the study group (11.1 ± 4.8 vs 6.2 ± 4.7 min, P < 0.0001). The withdrawal time was significantly longer in the control group (29.2 ± 9.8 vs 23.1 ± 7.9 min, P < 0.0001). There was no significant difference in the ADR (63.5% [study group] vs 68.1% [control group]), the mean adenoma per procedure (1.6 ± 2.0 vs 1.9 ± 2.4), or the mean adenoma per positive procedure (2.5 ± 2.0 vs 2.7 ± 2.5) between groups. The proximal colon ADR was significantly higher in the control group compared with the study group (56.2% vs 46.0%, P = 0.041). CONCLUSIONS: Additional inspection and polypectomy during colonoscope insertion did not improve ADR compared with inspection and polypectomy entirely during withdrawal. These results do not support an additional role for routine inspection during insertion (clinical trial registration number: NCT03444090).

Risk of Renal Injury After the Use of Polyethylene Glycol for Outpatient Colonoscopy: A Prospective Observational Study.

GOAL: The goal of this study was to estimate the risk of renal injury after the use of 3-L polyethylene glycol (PEG) before outpatient colonoscopy. BACKGROUND: Population-based studies showed that the use of PEG was associated with renal injury, but this association has not been confirmed by prospective study. STUDY: Patients ≥40 years of age with an estimated glomerular filtration rate ≥30 mL/min were screened for enrollment. Laboratory data were collected before, during, and after the colonoscopies. Patients with a ≥30% increase in baseline serum creatinine levels were followed until a peak level was detected. Renal injury included acute renal dysfunction (ARD) and acute kidney injury (AKI), defined as a 30% to 49% increase and ≥50% increase in creatinine levels compared with the baseline, respectively. RESULTS: A total of 1163 patients (mean age, 55.7 y) completed the study. Baseline and first postcolonoscopy laboratory data were obtained an average of 17.0 days before and 17.3 days after the colonoscopies were performed, respectively. Renal injury was identified in 32 patients; 26 patients (2.2%) had ARD, and 6 patients (0.5%) had AKI. All patients with renal injury recovered fully during follow-up. In the subgroup analysis, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) before colonoscopy was statistically associated with the development of AKI (odds ratio, 6.5; 95% confidence interval, 1.2-35.5; P=0.03). CONCLUSIONS: This prospective study showed that the use of PEG was associated with a small risk of renal injury. NSAIDs use was statistically associated with AKI in the context of colonoscopy for which PEG was used for bowel preparation.

Proton Pump Inhibitors and Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B or C.

Researchers have hypothesized that the long-term use of proton pump inhibitors (PPIs) can increase the risk of developing cancer. However, the association between PPI use and hepatocellular carcinoma (HCC) risk is unclear. Using data from the Taiwan National Health Insurance Research Database for the period between 2003 and 2013, we identified 35,356 patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. One-to-one propensity score matching by gender, age, cohort entry year, comorbidity, and medication resulted in the inclusion of 7,492 pairs of patients (PPI users and non-PPI users) for analyses. We performed multivariate and stratified analysis using the Kaplan-Meier method and Cox proportional hazards models in order to estimate the association between PPI use and the risk of developing HCC. In the HBV cohort, 237 patients developed HCC during a median follow-up of 53 months. However, PPI use was not associated with an increased risk of developing HCC (adjusted hazard ratio [aHR], 1.25; 95% confidence interval [CI], 0.90-1.73; P = 0.18). In the HCV cohort, 211 patients developed HCC; but again, PPI use was not associated with an increase in the risk of developing HCC (aHR, 1.19; 95% CI, 0.88-1.61; P = 0.25). We observed no relationship between a dose-dependent effect of PPI use and HCC risk. Subgroup analysis also confirmed that PPI use was not correlated to an increased HCC risk. Conclusion: Based on a retrospective population-based cohort study throughout Taiwan, where the prescription of PPI is tightly regulated, PPI use is not associated with the risk of developing HCC among patients with chronic HBV or HCV infections.

Red Blood Cell Aggregation-Associated Dietary Pattern Predicts Hyperlipidemia and Metabolic Syndrome.

Red blood cell (RBC) aggregation and iron status are interrelated and strongly influenced by dietary factors, and their alterations pose a great risk of dyslipidemia and metabolic syndrome (MetS). Currently, RBC aggregation-related dietary patterns remain unclear. This study investigated the dietary patterns that were associated with RBC aggregation and their predictive effects on hyperlipidemia and MetS. Anthropometric and blood biochemical data and food frequency questionnaires were collected from 212 adults. Dietary patterns were derived using reduced rank regression from 32 food groups. Adjusted linear regression showed that hepcidin, soluble CD163, and serum transferrin saturation (%TS) independently predicted RBC aggregation (all p < 0.01). Age-, sex-, and log-transformed body mass index (BMI)-adjusted prevalence rate ratio (PRR) showed a significant positive correlation between RBC aggregation and hyperlipidemia (p-trend < 0.05). RBC aggregation and iron-related dietary pattern scores (high consumption of noodles and deep-fried foods and low intake of steamed, boiled, and raw food, dairy products, orange, red, and purple vegetables, white and light-green vegetables, seafood, and rice) were also significantly associated with hyperlipidemia (p-trend < 0.05) and MetS (p-trend = 0.01) after adjusting for age, sex, and log-transformed BMI. Our results may help dieticians develop dietary strategies for preventing dyslipidemia and MetS.

Preoperative staging of cholangiocarcinoma and biliary carcinoma using 18F-fluorodeoxyglucose positron emission tomography: a meta-analysis.

This meta-analysis was performed to determine the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) in assessing primary cholangiocarcinoma (CCA) and CCA with lymph node and distant metastasis. A literature search for studies reporting the use of 18F-FDG-PET for preoperative work-up/staging in patients with CCA was performed. Diagnostic OR (DOR) was used as an index of diagnostic performance of FDG-PET/CT in predicting primary CCA, lymph node metastases, and distant metastases. The pooled DOR was 9.34 (95% CI 4.27 to 20.42) and the area under the summary receiver operating characteristic (SROC) curve was 0.8643 (SE=0.0362), indicating overall good discriminatory test performance in predicting primary CCA. Subgroup analyses based on the primary tumor site showed better diagnostic performance for intrahepatic CCA (DOR=54.44, 95% CI 13.44 to 220.49), both intrahepatic and extrahepatic CCA (DOR=32.96, 95% CI 1.41 to 768.80) and gallbladder cancer (DOR=12.93, 95% CI 1.97 to 84.80), than for extrahepatic CCA (DOR=2.55, 95% CI 0.71 to 9.20) and hilar CCA (DOR=2.75, 95% CI 0.17 to 43.72). The pooled DOR for the prediction of lymph nodes metastases in 10 studies was 11.34 (95% CI 4.79 to 26.80), with moderate heterogeneity (Cochran Q=15.14, p=0.0872, I2=40.5%). The area under the SROC curve was 0.8584 (SE=0.0729). In conclusion, 18F-FDG-PET and PET/CT were found to be accurate in the evaluation of primary tumors, lymph node metastasis, and distant metastasis in patients with CCA.

Optimal procedural sequence for same-day bidirectional endoscopy with moderate sedation: A prospective randomized study.

BACKGROUND AND AIM: Same-day bidirectional endoscopy (BDE) is a commonly performed procedure, but the optimal sequence for the procedure with moderate conscious sedation is not well established. This study investigated the optimal sequence for same-day BDE under moderate conscious sedation and carbon dioxide insufflation in terms of sedation doses, patient discomfort, and colonoscopy performance. METHODS: A prospective randomized controlled study of 120 patients who were scheduled for BDE examination was performed. Colonoscopy followed by esophagogastroduodenoscopy (EGD) examination was performed in 60 patients (colonoscopy-EGD group), and EGD followed by colonoscopy examination was performed in another 60 patients (EGD-colonoscopy group). Endoscopists and patients completed a questionnaire to assess objective and subjective discomfort. RESULTS: Baseline demographics, procedure indications, bowel preparation quality, cecal intubation rate/time, colonoscopy withdrawal time, endoscopic interventions, BDE procedure time, colon polyp/adenoma detection rates, patient discomfort, and adverse events were similar between the two study groups. The total doses of fentanyl and midazolam were significantly higher for the colonoscopy-EGD group than for the EGD-colonoscopy group (83.4 ± 17.7 vs 68.7 ± 18.6 µg and 6.3 ± 1.4 vs 5.2 ± 1.3 mg, P < 0.0001 and P < 0.0001, respectively). The recovery time to discharge was significantly longer for the colonoscopy-EGD group than for the EGD-colonoscopy group (43.5 ± 16.2 vs 34.5 ± 8.9 min, P = 0.0003). CONCLUSIONS: Esophagogastroduodenoscopy followed by colonoscopy is the optimal sequence for same-day BDE under moderate conscious sedation and carbon dioxide insufflation. Following this order allows for a reduction of sedation doses and for shorter recovery times.