Single-center experience with intraprocedural cleansing system to improve inadequate bowel preparation during colonoscopy.

Inadequate bowel preparation is common despite various preprocedure interventions. There is a need for an intervention at the time of colonoscopy to combat poor preparation. In this retrospective, observational study of 46 patients, we evaluated the clinical efficacy and feasibility of implementing the third generation of the Pure-Vu EVS System, a US Food and Drug Administration-cleared over-the-scope-based intraprocedural cleansing device, into our practice at the Minneapolis VA Medical Center (Minneapolis, Minnesota, United States). To study clinical efficacy, we measured bowel preparation adequacy before and after using the device, as measured by the Boston Bowel Preparation Score, and reviewed colonoscopy surveillance interval recommendations. Technical success and feasibility of using the device were measured by procedure success rates and duration. We found that BBPS scores increased from 4.4 to 7.9 when using the device. Technical success was achieved 78.3% of the time (36/46 cases). Median colonoscopy duration was 46 minutes, although there was a trend toward shorter procedures over time. This is the first clinical evaluation of the third generation of an intraprocedural cleansing device. We found the device efficacious and easy to use with low procedure failure rates, but it does come with a learning curve. We suspect that adoption of this device mutually will benefit patients and health systems with the potential to improve resource utilization.

Incidental Finding of Hepatic Inflammatory Pseudotumor Immunoglobulin G4-Related Disease With Underlying Chronic Hepatitis C.

Immunoglobulin G4-related disease (IgG4-RD) is a unique immunological disease that can impact multiple organs including a formation of a hepatic inflammatory pseudotumor (IPT). We present a case of a 67-year-old male with a history of chronic viral hepatitis C infection who had an accidental finding on magnetic resonance imaging (MRI) of a liver arterially enhancing lesion. With an extensive work-up, immunohistochemical stains for immunoglobulin G of the liver lesion was performed and showed markedly increased IgG4-positive plasma cells (> 50/HPF), which was consistent with hepatic inflammatory pseudotumor related to IgG4-RD. The patient was treated with prednisone with a complete resolution of the hepatic lesion. The diagnosis of hepatic IPT and IgG4-RD requires a high degree of clinical suspicion and coordination with a multi-disciplinary team, including pathologists. Early tissue acquisition and staining for IgG4 was essential for the early diagnosis and treatment in this case. We also provide a comprehensive summary of published reports of IgG4-RD presenting with IPT.

CS-iCCA, A New Clinically Based Staging System for Intrahepatic Cholangiocarcinoma: Establishment and External Validation.

INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is a primary liver malignancy with poor prognosis. Current prognostic methods are most accurate for patients with surgically resectable disease. However, a significant proportion of patients with iCCA are not surgical candidates. We aimed to develop a generalizable staging system based on clinical variables to determine prognosis of all patients with iCCA. METHODS: The derivation cohort included 436 patients with iCCA seen between 2000 and 2011. For external validation, 249 patients with iCCA seen from 2000 to 2014 were enrolled. Survival analysis was performed to identify prognostic predictors. All-cause mortality was the primary end point. RESULTS: Eastern Cooperative Oncology Group status, tumor number, tumor size, metastasis, albumin, and carbohydrate antigen 19-9 were incorporated into a 4-stage algorithm. Kaplan-Meier estimates for 1-year survival were 87.1% (95% confidence interval [CI] 76.1-99.7), 72.7% (95% CI 63.4-83.4), 48.0% (95% CI 41.2-56.0), and 16% (95% CI 11-23.5), respectively, for stages I, II, III, and IV. Univariate analysis yielded significant differences in risk of death for stages II (hazard ratio [HR] 1.71; 95% CI 1.0-2.8), III (HR 3.32; 95% CI 2.07-5.31), and IV (HR 7.44; 95% CI 4.61-12.01) compared with stage I (reference). Concordance indices showed the new staging system was superior to the TNM staging for predicting mortality in the derivation cohort, P < 0.0001. In the validation cohort, however, the difference between the 2 staging systems was not significant. DISCUSSION: The proposed independently validated staging system uses nonhistopathologic data to successfully stratify patients into 4 stages. This staging system has better prognostic accuracy compared with the TNM staging and can assist physicians and patients in treatment of iCCA.

Potential Role of Inflammation-Promoting Biliary Microbiome in Primary Sclerosing Cholangitis and Cholangiocarcinoma.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a major risk factor for cholangiocarcinoma (CCA). We investigated biliary and fecal microbiota to determine whether specific microbes in the bile or stool are associated with PSC or CCA. METHODS: Bile was obtained from 32 patients with PSC, 23 with CCA with PSC, 26 with CCA without PSC, and 17 controls. Over 90% of bile samples were from patients with perihilar CCA. Stool was obtained from 31 patients with PSC (11 were matched to bile), 16 with CCA with PSC (10 matched to bile), and 11 with CCA without PSC (6 matched to bile). Microbiota composition was assessed using 16SrRNA-marker-based sequencing and was compared between groups. RESULTS: Bile has a unique microbiota distinguished from negative DNA controls and stool. Increased species richness and abundance of Fusobacteria correlated with duration of PSC and characterized the biliary microbiota in CCA. Stool microbiota composition showed no significant differences between groups. CONCLUSIONS: We identified a unique microbial signature in the bile of patients with increased duration of PSC or with CCA, suggesting a role for microbiota-driven inflammation in the pathogenesis and or progression to perihilar CCA. Further studies are needed to test this hypothesis.

A Novel Text Message Protocol to Improve Bowel Preparation for Outpatient Colonoscopies in Veterans.

Background: The current gold standard for screening for colorectal cancer is colonoscopy, a procedure that depends on the quality of bowel preparation. In 2016, the Veterans Health Administration introduced Annie, a text message service to improve health care communication with patients. The Minneapolis Veterans Affairs Medical Center conducted a prospective, single center study to measure the impact of Annie text messaging on patient satisfaction and quality of bowel preparation for patients undergoing outpatient colonoscopy. Methods: Patients undergoing colonoscopy were divided into 2 groups. The control group received standardized patient education and a phone call prior to procedure. The intervention group, consisting of all patients who agreed to enroll, received a 6-day Annie text messaging protocol consisting of key bowel preparation steps that started 5 days prior to their scheduled procedure. Bowel preparation quality was measured using the Boston Bowel Preparation Scale (BBPS) score. Results: During the study period, 688 veterans were scheduled for outpatient colonoscopy: 484 veterans were in the control group, 204 veterans were in the intervention group, and 126 were surveyed. Annie text messaging instructions were associated with a higher BBPS score (8.2) compared with usual care (7.8); P = .007 using independent t test, and P = .002 using parametric independent t test. Patients also reported satisfaction with the Annie text messaging service. Conclusions: There was a statistically significant improvement in the average BBPS score in veterans receiving Annie text messages compared with the routine care control group for outpatient colonoscopies.

Non-invasive tests for predicting liver outcomes in chronic hepatitis C patients: A systematic review and meta-analysis.

BACKGROUND: Liver fibrosis leads to liver-related events in patients with chronic hepatitis C (CHC) infection. Although non-invasive tests (NITs) are critical to early detection of the development of liver fibrosis, the prognostic role of NITs remains unclear due to the limited types of NITs and liver outcomes explored in previous studies. AIM: To determine the prognostic value of NITs for risk stratification in CHC patients. METHODS: The protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42019128176). The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search was performed using MEDLINE and EMBASE databases under a timeframe from the inception of the databases through February 25, 2020. We restricted our search to CHC cohort studies reporting an association between liver fibrosis assessed by NITs and the development of hepatocellular carcinoma, decompensation, or mortality. Pooled hazard ratios (HR) and area under the receiver operating characteristic (AUROC) for each NIT were estimated using a random effects model. Subgroup analyses were performed for NITs assessed at pre-treatment or post-treatment with sustained virologic response (SVR), treatment with either pegylated interferon and ribavirin or direct acting antiviral, Eastern or Western countries, and different cutoff points. RESULTS: The present meta-analysis included 29 cohort studies, enrolling 69339 CHC patients. Fibrosis-4 (FIB-4) index, aspartate aminotransferase to platelet ratio (APRI) score, and liver stiffness measurement (LSM) were found to have hepatocellular carcinoma predictive potential with pooled adjusted HRs of 2.48 [95% confidence interval (CI): 1.91-3.23, I 2 = 96%], 4.24 (95%CI: 2.15-8.38, I 2 = 20%) and 7.90 (95%CI: 3.98-15.68, I 2 = 52%) and AUROCs of 0.81 (95%CI: 0.73-0.89, I 2 = 77%), 0.81 (95%CI: 0.75-0.87, I 2 = 68%), and 0.79 (95%CI: 0.63-0.96, I 2 = 90%), respectively. Pooled adjusted HR with a pre-treatment FIB-4 cutoff of 3.25 was 3.22 (95%CI: 2.32-4.47, I 2 = 80%). Pooled adjusted HRs for post-treatment with SVR FIB-4, APRI, and LSM were 3.01 (95%CI: 0.32-28.61, I 2 = 89%), 9.88 (95%CI: 2.21-44.17, I 2 = 24%), and 6.33 (95%CI: 2.57-15.59, I 2 = 17%), respectively. Pooled adjusted HRs for LSM in patients with SVR following direct acting antiviral therapy was 5.55 (95%CI: 1.47-21.02, I 2 = 36%). Pooled AUROCs for post-treatment with SVR FIB-4 and LSM were 0.75 (95%CI: 0.55-0.95, I 2 = 88%) and 0.84 (95%CI: 0.66-1.03, I 2 = 88%), respectively. Additionally, FIB-4 and LSM were associated with overall mortality, with pooled adjusted HRs of 2.07 (95%CI: 1.49-2.88, I 2 = 27%) and 4.04 (95%CI: 2.40-6.80, I 2 = 63%), respectively. CONCLUSION: FIB-4, APRI, and LSM showed potential for risk stratification in CHC patients. Cutoff levels need further validation.

Aspirin and Statin Use and the Risk of Gallbladder Cancer.

Aspirin and statin drugs have been associated with reduced risk of several gastrointestinal cancers, but their association with gallbladder cancer (GBC) has not been well established. We evaluated the association of aspirin and statins with the risk of GBC. Patients with GBC managed at Mayo Clinic between 2000 and 2019 were matched 1:2 with a general patient pool by age and sex. Univariable and multivariable logistic regression models were used to assess associations between GBC and aspirin or statin use. The analysis included 795 cases and 1590 controls, with a median age of 67 years. Aspirin or statin use alone or in combination was higher in controls (p < 0.001). Univariate analysis showed that the use of aspirin [odds ratio (OR): 0.11; 95%CI: 0.08-0.15] or statins (OR: 0.29; 95%CI: 0.20-0.40) and their combined use (OR: 0.18; 95%CI: 0.13-0.24) was associated with lower risk of GBC. Multivariable analysis revealed that aspirin (OR: 0.12; 95%CI: 0.09-0.16) and combined statins and aspirin (OR: 0.46; 95%CI: 0.31-0.67) were associated with lower risk of GBC. Aspirin alone or in combination with statins is associated with a strongly reduced risk of GBC. Further prospective studies are needed to confirm these results and to elucidate their mechanisms.

BALAD and BALAD-2 predict survival of hepatocellular carcinoma patients: a North American cohort study.

BACKGROUND: The BALAD score and BALAD-2 class derived from bilirubin, albumin, AFP, AFP-L3, and des-gamma-carboxyprothrombin (DCP) are effective in predicting mortality in HCC, but have not been validated in North America. METHODS: 148 HCC patients from 2000 to 2015 who had all five biomarkers tested at diagnosis were included. Hazard ratios (HR) were calculated. RESULTS: 75 patients died during a median follow-up of 21.9 months. 1-and 3-year survival rates were 70.8% and 47.6%. 114 (77%) had cirrhosis. The HR (95%CI) for death were 1.24 (0.42-3.67), 1.79 (0.61-5.26), 2.83 (0.95-8.38), and 7.19 (2.26-22.91) for BALAD scores 1, 2, 3, and 4 vs. BALAD 0. The HR (95%CI) for death were 1.25 (0.65-2.40), 1.75 (0.94-3.23), and 6.20 (3.29-11.68) for BALAD-2 classes 2, 3, and 4 vs. BALAD-2 class 1. A multivariate model incorporating maximal tumor diameter, tumor number, neutrophil-lymphocyte ratio, and BALAD had HR of 1.43 (1.14-1.81) per increase of 1 BALAD score. A similar model with BALAD-2 had HR of 1.50 (1.18-1.90) per increase of 1 BALAD-2 class. CONCLUSION: BALAD models at diagnosis can predict the survival of HCC patients in North America. AFP, AFP-L3, and DCP reflect tumor progression and metastasis of HCC and distinguish the BALAD model from other predictive models.

Characteristics of Patients With Chronic Hepatitis B Virus Infection With Genotype E Predominance in Burkina Faso.

Hepatitis B virus (HBV) genotype E (HBV-E) accounts for the majority of chronic hepatitis B (CHB) infections in West Africa. We aimed to determine factors associated with HBV-E-induced hepatocellular carcinoma (HCC) in West Africa. Data on patients from Burkina Faso who were hepatitis B surface antigen positive (HBsAg+) and had CHB were analyzed. HBV viral load and hepatitis B e antigen (HBeAg) status were measured in 3,885 individuals with CHB without HCC (CHB HCC-) and 59 individuals with CHB with HCC (CHB HCC+). HBV genotyping was performed for 364 subjects with CHB HCC- and 41 subjects with CHB HCC+. Overall, 2.5% of the CHB HCC- group was HBeAg+ compared with 0% of the CHB HCC+ group. Of the 364 patients who were CHB HCC- with available genotyping, the frequencies of HBV genotypes E and C/E were 70.3% and 12.9%, respectively. Age (odds ratio [OR] for older age, 1.08; 95% confidence interval [CI], 1.06-1.10 per 1-year increase in age), male sex (OR, 2.03; 95% CI, 1.11-3.69), and HBV viremia (OR, 1.48; 95% CI, 1.31-1.67 per 1 log10 IU/mL) were each associated with HCC diagnosis. Patients with genotype E had a lower HBeAg prevalence (6.3% vs. 14.9%), lower HBV viral load, and higher prevalence of cirrhosis (14.5% vs. 4.8%) than patients with genotype C/E. Conclusion: HBV-E is the most common circulating strain (70.3%) in West African patients. HCC was associated with older age, male sex, and high HBV viral load. It is expected that these results will further inform guidance on clinical management of HBV infection in West Africa.

Esophageal Pathophysiologic Changes and Adenocarcinoma After Bariatric Surgery: A Systematic Review and Meta-Analysis.

INTRODUCTION: To assess the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on acid reflux and esophageal motor function and to evaluate the observation of esophageal adenocarcinoma (EAC) after bariatric surgery. METHODS: We searched 5 databases for adults who underwent SG or RYGB and had esophageal pH test and/or esophageal manometry before and after surgery. A separate systemic search of observational studies and a retrospective review at 3 institutions of adults who developed EAC after these surgeries were conducted. Outcomes were changes in manometric and pH parameters and EAC cases after SG and RYGB. RESULTS: A total of 27 nonrandomized studies (SG: 612 patients; RYGB: 470 patients) were included. After SG, lower esophageal sphincter pressure and esophageal body amplitude were decreased and the risk of ineffective esophageal motility was increased. Total and recumbent acid exposure times were increased. After RYGB, an increased risk of ineffective esophageal motility was observed. Total, upright, and recumbent acid exposure times were decreased. The total reflux episodes remained unchanged but with increased nonacid reflux and decreased acid reflux events. Including our largest series, 31 EAC cases have been reported to date after SG and RYGB. DISCUSSION: This systematic review demonstrates increased acid reflux after SG and decreased acid reflux after RYGB. An observed increased nonacid reflux after RYGB might contribute to failure of gastroesophageal reflux disease improvement. This refluxate might be noxious to the esophagus, warranting further studies. RYGB might not entirely preserve esophageal function as previously believed.

The efficacy, safety, and predictors of outcomes of transarterial radioembolization for hepatocellular carcinoma: a retrospective study.

OBJECTIVES: Yttrium-90 transarterial radioembolization (TARE) is a safe, effective modality of locoregional therapy for intermediate and advanced-stage hepatocellular carcinoma (HCC). We aim to identify novel predictors of important outcomes of TARE therapy. METHODS: A single-center retrospective study of 166 patients treated with TARE for HCC at Mayo Clinic Rochester between 2005-2015 and followed until December 2017. Multivariate logistic and stepwise regression analysis models were used to identify variables associated with overall survival (OS) and progression-free survival (PFS). RESULTS: The median OS and the median PFS were12.9  (95% CI: 11.0-17.3), and 8 months (95% CI: 6-11), respectively. Macrovascular invasion (HR: 1.9 [1.3-2.8]), Child-Pugh score (CPS) B or C vs. A (HR: 1.8 [1.2-2.7]), Eastern Cooperative Oncology Group Performance status (ECOG-PS) 2 or 1 vs. 0 (HR: 1.6 [1.1-2.4]) and activity (A) of administered radiation dose (HR: 1.005[1.00-1.010), independently correlated with poorer OS. Infiltrative HCC (HR: 2.4 [1.3-4.5), macrovascular invasion (HR: 1.6 [1.1-2.7]), and high activity of administered radiation dose (HR: 1.005 [1.00-1.010) were associated with worse PFS. CONCLUSION: In HCC patients treated with TARE; macrovascular invasion, the activity of radiation dose, CPS, ECOG-PS, and infiltrative HCC predict OS and PFS.

Effect of Statins on the Risk of Extrahepatic Cholangiocarcinoma.

BACKGROUND AND AIMS: Statins have been proven to be cytotoxic to human cholangiocarcinoma cells by inhibiting cell division and inducing apoptosis. We aimed to determine the effect of statin use on the risk of cancer development and survival in patients with extrahepatic cholangiocarcinoma (ECC), including perihilar cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA). APPROACH AND RESULTS: A total of 394 patients with ECC and hyperlipidemia who received care at Mayo Clinic Rochester between 2005 and 2015 were matched by age, sex, race, ethnicity, and residency to 788 controls with hyperlipidemia. Clinical and outcome data were abstracted. The odds ratios (ORs) for risk and hazard ratios for outcomes were calculated. The mean age and standard deviation (SD) for cases and controls was 65.6 years (13.8). The number of statin users in cases and controls was 73 (19%) and 403 (51%), respectively. Hepatitis C virus infection (OR, 15.84; 95% confidence interval [CI], 4.06-61.87; P < 0.001) was the most significant risk factor for pCCA followed by inflammatory bowel disease and cirrhosis, whereas other liver disease, including biliary stone disease (OR, 4.06; CI, 2.24-7.36; P < 0.001), was the only significant risk factor for dCCA. Statin use was associated with significantly reduced risk for all ECC (OR, 0.22; CI, 0.16-0.29) as well as for the subtypes pCCA (OR, 0.3; CI, 0.21-0.41) and dCCA (OR, 0.06; CI, 0.03-0.14), all P < 0.0001. Moderate-intensity dosage was found to decrease the risk of ECC (OR, 0.48; CI, 0.34-0.67; P < 0.001). Comparing statin ever users to nonusers, patients with dCCA who used statins had significantly overall better survival (hazard ratio = 0.53; CI, 0.29-0.97; P = 0.04). CONCLUSIONS: This case-control study suggests that statins decrease the risk of ECC and may improve survival in patients with dCCA. Additional validation studies are warranted.

Midterm Outcome of Laparoscopic Sleeve Gastrectomy in Asians: a Systematic Review and Meta-analysis.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a commonly performed bariatric surgery. Studies have suggested that LSG can provide effective and sustainable weight loss although most of them were conducted in Western populations. Our aim was to characterize the midterm outcome of LSG in Asians with obesity. METHODS: MEDLINE and EMBASE were searched through August 2019 for studies that reported % total body weight loss (TBWL) and/or % excess weight loss (EWL) at 3 and/or 5 years among adult Asians with obesity who underwent LSG. Data on complications and surgical revision rate were also extracted. The pooled effect size and 95% confidence interval (CI) were calculated using a random effects model. RESULTS: A total of 19 studies involving 6235 patients were included. The pooled mean %EWLs were 72.6% (95% CI 67.2-78.0, I2 = 97%); 67.1% (95% CI 61.7-72.6, I2 = 95%); and 59.1% (95% CI 48.8-69.4, I2 = 94%) at 1, 3, and 5 years, respectively. The pooled mean %TBWLs were 32.1%, 29.0%, and 25.5% at 1, 3, and 5 years, respectively. The pooled rates of revision due to gastroesophageal reflux disease and weight regain were 1.9% and 2.5%, respectively. CONCLUSIONS: Our meta-analysis suggests that LSG is an effective procedure for weight reduction that offers durable response for up to 5 years among Asians with obesity. The longer-term data is needed.

Isolated Asymptomatic Metastatic Melanoma to the Colon: A Case Report.

Metastatic melanoma is generally rare, and the colon is a very rare metastatic site. We report a case of asymptomatic, isolated metastatic melanoma to the colon. Asymptomatic patients are usually not expected to have metastatic lesions in the colon. Ninety-five percent of large bowel metastases are identified during a postmortem examination. Our patient was found to have metastatic melanoma to the colon during a follow-up colonoscopy done for the surveillance of colon polyps. An awareness that patients with melanoma may possibly develop colon metastases is needed.

GALAD Score for Hepatocellular Carcinoma Detection in Comparison with Liver Ultrasound and Proposal of GALADUS Score.

BACKGROUND: The GALAD score is a serum biomarker-based model that predicts the probability of having hepatocellular carcinoma (HCC) in patients with chronic liver disease. We aimed to assess the performance of the GALAD score in comparison with liver ultrasound for detection of HCC. METHODS: A single-center cohort of 111 HCC patients and 180 controls with cirrhosis or chronic hepatitis B and a multicenter cohort of 233 early HCC and 412 cirrhosis patients from the Early Detection Research Network (EDRN) phase II HCC Study were analyzed. RESULTS: The area under the ROC curve (AUC) of the GALAD score for HCC detection was 0.95 [95% confidence interval (CI), 0.93-97], which was higher than the AUC of ultrasound (0.82, P <0.01). At a cutoff of -0.76, the GALAD score had a sensitivity of 91% and a specificity of 85% for HCC detection. The AUC of the GALAD score for early-stage HCC detection remained high at 0.92 (95% CI, 0.88-0.96; cutoff -1.18, sensitivity 92%, specificity 79%). The AUC of the GALAD score for HCC detection was 0.88 (95% CI, 0.85-0.91) in the EDRN cohort. The combination of GALAD and ultrasound (GALADUS score) further improved the performance of the GALAD score in the single-center cohort, achieving an AUC of 0.98 (95% CI, 0.96-0.99; cutoff -0.18, sensitivity 95%, specificity 91%). CONCLUSIONS: The performance of the GALAD score was superior to ultrasound for HCC detection. The GALADUS score further enhanced the performance of the GALAD score. IMPACT: The GALAD score was validated in the United States.

Hypothyroidism is associated with worse outcomes of hepatocellular carcinoma patients after liver transplantation.

BACKGROUND/AIMS: Hypothyroidism has been associated with hepatocellular carcinoma (HCC) incidence; however, the relationship between hypothyroidism and HCC patient outcomes is unclear. We investigated the impact of hypothyroidism on outcomes after liver transplantation for HCC. MATERIALS AND METHODS: We retrospectively studied HCC patients transplanted between January 2000 and December 2015. Hypothyroidism was defined as a thyroid-stimulating hormone (TSH) level continuously greater than 5 mIU/L, a documented history of hypothyroidism, or treatment with thyroid hormone replacement therapy. Multivariate Cox regression was used to assess the impact of hypothyroidism on overall survival (OS) and recurrence-free survival (RFS) adjusting for potential confounders. Subgroup analyses and interaction tests were conducted to compare the impact of hypothyroidism in different subgroups and assess for possible synergistic effects. Sensitivity analyses were performed among different cohorts to verify the stability of the results. RESULTS: A total of 343 HCC patients who underwent liver transplantation were included in the analysis. The primary analysis was conducted among 288 patients diagnosed with HCC prior to transplantation. Hypothyroidism was independently associated with worse OS and RFS, as was elevated TSH. The adjusted hazard ratio (AHR) of hypothyroidism was 2.45 (95% confidence interval [CI], 1.44-4.18) for OS and 5.54 (2.36, 13.01) for RFS. The AHR of TSH for OS was 1.05 (1.02, 1.09) and 1.08 (1.03, 1.13) for RFS. No interaction was found among different subgroups categorized by etiology and comorbidity. The results were stable to sensitivity analyses. CONCLUSION: Hypothyroidism is associated with poorer overall and recurrence-free survival of HCC patients receiving liver transplantation. These results require validation.

Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models.

AIM: To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma (HCC) patients after liver transplant. METHODS: BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios (HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS: During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42 (1.18-5.00), 1.86 (0.98-3.52), and 2.83 (1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48 (1.15-1.91) and 1.59 (1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45 (1.06-1.98) and 1.38 (1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65, 0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant (S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION: BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter (S-LAD).

Non-alcoholic fatty liver disease as a risk factor for cholangiocarcinoma: a systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been recently identified as a risk factor of gastrointestinal tract cancers, especially hepatocellular carcinoma, and colorectal cancer. Whether NAFLD is a risk factor for cholangiocarcinoma (CCA) remains inconclusive. The aim of this study is to determine a potential association between NAFLD and CCA, stratifying by its subtypes; intrahepatic CCA (iCCA), and extrahepatic CCA (eCCA). METHODS: A search was conducted for relevant studies published up to April 2017 using MEDLINE, EMBASE, Scopus and Cochrane databases. Odds ratio (OR) and adjusted OR with 95% confidence interval (CI) were estimated using a random-effects model. Subgroup analyses were conducted with study characteristics. RESULTS: Seven case-control studies were included in the analysis, with a total of 9,102 CCA patients (5,067 iCCA and 4,035 eCCA) and 129,111 controls. Overall, NAFLD was associated with an increased risk for CCA, with pooled OR of 1.95 (95%CI: 1.36-2.79, I 2 =76%). When classified by subtypes, NAFLD was associated with both iCCA and eCCA, with ORs of 2.22 (95%CI: 1.52-3.24, I 2 =67%) and 1.55 (95%CI: 1.03-2.33, I 2 =69%), respectively. The overall pooled adjusted ORs were 1.97 (95%CI: 1.41-2.75, I 2 =71%), 2.09 (95%CI, 1.49-2.91, I 2 =42%) and 2.05 (95%CI, 1.59-2.64, I 2 =0%) for all CCAs, iCCA, and eCCA, respectively. CONCLUSIONS: This meta-analysis suggests that NAFLD may potentially increase the risk of CCA development. The magnitude of NAFLD on CCA risk is greater for iCCA than eCCA subtype, suggestive of a common pathogenesis of iCCA and hepatocellular carcinoma. Further studies to confirm this association are warranted. TRIAL REGISTRATION: The protocol for this study was registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016046573).