Prokop, Larry J.

Multiphasic computed tomography (CT) and magnetic resonance imaging (MRI) are both used for noninvasive diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. To determine if there is a relative diagnostic benefit of one over the other, we synthesized evidence regarding the relative performance of CT, extracellular contrast–enhanced MRI, and gadoxetate‐enhanced MRI for diagnosis of HCC in patients with cirrhosis. We also assessed whether liver biopsy versus follow‐up with the same versus alternative imaging is best for CT‐indeterminate or MRI‐indeterminate liver nodules in patients with cirrhosis. We searched multiple databases from inception to April 27, 2016, for studies comparing CT with extracellular contrast–enhanced MRI or gadoxetate‐enhanced MRI in adults with cirrhosis and suspected HCC. Two reviewers independently selected studies and extracted data. Of 33 included studies, 19 were comprehensive, while 14 reported sensitivity only. For all tumor sizes, the 19 comprehensive comparisons showed significantly higher sensitivity (0.82 versus 0.66) and lower negative likelihood ratio (0.20 versus 0.37) for MRI over CT. The specificities of MRI versus CT (0.91 versus 0.92) and the positive likelihood ratios (8.8 versus 8.1) were not different. All three modalities performed better for HCCs ≥2 cm. Performance was poor for HCCs <1 cm. No studies examined whether adults with cirrhosis and an indeterminate nodule are best evaluated using biopsy, repeated imaging, or alternative imaging. Concerns about publication bias, inconsistent study results, increased risk of bias, and clinical factors precluded support for exclusive use of either gadoxetate‐enhanced or extracellular contrast–enhanced MRI over CT.Conclusion:CT, extracellular contrast–enhanced MRI, or gadoxetate‐enhanced MRI could not be definitively preferred for HCC diagnosis in patients with cirrhosis; in patients with cirrhosis and an indeterminate mass, there were insufficient data comparing biopsy to repeat cross‐sectional imaging or alternative imaging. (Hepatology2018;67:401‐421).

Patients with hepatocellular carcinoma (HCC) who are listed for liver transplantation (LT) are often treated while on the waiting list with locoregional therapy (LRT), which is aimed at either preventing progression of HCC or reducing the measurable disease burden of HCC in order to receive increased allocation priority. We aimed to synthesize evidence regarding the effectiveness of LRT in the management of patients with HCC who were on the LT waitlist. We conducted a comprehensive search of multiple databases from 1996 to April 25, 2016, for studies that enrolled adults with cirrhosis awaiting LT and treated with bridging or down‐staging therapies before LT. Therapies included transcatheter arterial chemoembolization, transarterial radioembolization, ablation, and radiotherapy. We included both comparative and noncomparative studies. There were no randomized controlled trials identified. For adults with T1 HCC and waiting for LT, there were only two nonrandomized comparative studies, both with a high risk of bias, which reported the outcome of interest. In one series, the rate of dropout from all causes at 6 months in T1 HCC patients who underwent LRT was 5.3%, while in the other series of T1 HCC patients who did not receive LRT, the dropout rate at median follow‐up of 2.4 years and the progression rate to T2 HCC were 30% and 88%, respectively. For adults with T2 HCC awaiting LT, transplant with any bridging therapy showed a nonsignificant reduction in the risk of waitlist dropout due to progression (relative risk [RR], 0.32; 95% confidence interval [CI], 0.06‐1.85; I 2 = 0%) and of waitlist dropout from all causes (RR, 0.38; 95% CI, 0.060‐2.370; I 2 = 85.7%) compared to no therapy based on three comparative studies. The quality of evidence is very low due to high risk of bias, imprecision, and inconsistency. There were five comparative studies which reported on posttransplant survival rates and 10 comparative studies which reported on posttransplant recurrence, and there was no significant difference seen in either of these endpoints. For adults initially with stage T3 HCC who received LRT, there were three studies reporting on transplant with any down‐staging therapy versus no downstaging, and this showed a significant increase in 1‐year (two studies, RR, 1.11; 95% CI, 1.01‐1.23) and 5‐year (1 study, RR, 1.17; 95% CI, 1.03‐1.32) post‐LT survival rates for patients who received LRT. The quality of evidence is very low due to serious risk of bias and imprecision. Conclusion: In patients with HCC listed for LT, the use of LRT is associated with a nonsignificant trend toward improved waitlist and posttransplant outcomes, though there is a high risk of selection bias in the available evidence. (H epatology 2018;67:381‐400).

Summary Objective The outcomes of patients with metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL) are unclear. We performed a systematic review and meta‐analysis of baseline characteristics and mortality rates of patients with metastatic PHEO and PGL (PPGL). Design Ovid MEDLINE In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, Web of Science, and references of key articles were searched from inception to 2016. Patients Studies comprised ≥20 patients with metastatic PPGL and reported baseline characteristics and follow‐up data. Measurements Reviewers extracted standardized data and assessed risk of bias using a modified Newcastle‐Ottawa tool. Random‐effects meta‐analysis was used to pool event rates across studies. Results Twenty retrospective noncomparative studies reported on 1338 patients with metastatic PHEO (685/1296, 52.9%) and PGL (611/1296, 47.1%), diagnosed at a mean age of 43.9 ± 5.2 years. Mean follow‐up was 6.3 ± 3.2 years. Of 532 patients with reported data, 40.4% had synchronous metastases. Five‐year (7 studies, n = 738) and 10‐year (2 studies, n = 55) mortality rates for patients with metastatic PPGL were 37% (95% CI, 24%‐51%) and 29% (95% CI, 17%‐42%), respectively. Higher mortality was associated with male sex (RR 1.50; 95% CI, 1.11‐2.02) and synchronous metastases (RR 2.43; 95% CI, 1.01‐5.85). Conclusions Available low‐quality evidence from heterogeneous studies suggests low mortality rates of patients with metastatic PPGL. Male sex and synchronous metastases correlated with increased mortality. The outcomes of patients with metastatic PPGL have been inadequately assessed, indicating the need for carefully planned prospective studies.

AbstractBackgroundColonic pseudo‐obstruction (CPO) is characterized by colonic distention in the absence of mechanical obstruction or toxic megacolon. Concomitant secretory diarrhea (SD) with hypokalemia (SD‐CPO) due to gastrointestinal (GI) loss requires further characterization.AimTo perform a systematic review of SD‐CPO, report a case study, and compare SD‐CPO with classical CPO (C‐CPO).MethodsWe performed a search of MEDLINE, EMBASE, Cochrane, and Scopus for reports based on a priori criteria for CPO, SD and GI loss of potassium. An additional case at Mayo Clinic was included.ResultsNine publications met inclusion criteria, with a total of 14 cases. Six studies had high, three moderate, and our case high methodological quality. Median age was 74 years (66‐97), with 2:1 male/female ratio. Kidney disease was present in 6/14 patients. Diarrhea was described as profuse, watery, or viscous in 10 patients. Median serum, stool, and urine potassium concentrations (mmol/L) were 2.4 (range: 1.9‐3.1), 137 (100‐180), and 17 (8‐40), respectively. Maximal diameter of colon and cecum (median) were 10.2 cm and 10.5 cm, respectively. Conservative therapy alone was effective in five out of 14 patients. Median potassium supplementation was 124 mEq/d (40‐300). Colonic decompression was effective in three out of six patients; one had a total colectomy; three out of 14 had died. The main differences between SD‐CPO and C‐CPO were lower responses to treatments: conservative measures (35.7% vs 73.6%, P=.01), neostigmine (17% vs 89.2%, P<.001), and colonic decompression (50% vs 82.4%, P=.02).ConclusionSD‐CPO is a rare phenotype associated with increased fecal potassium and is more difficult to treat than C‐CPO.

Abstract Objective: Multiple interventions are available to reduce excess body weight in children. We appraised the quality of evidence supporting each intervention and assessed the effectiveness on different obesity-related outcomes. Methods: We conducted a systematic search for systematic reviews of randomized controlled trials evaluating pediatric obesity interventions applied for ≥6 months. We assessed the quality of evidence for each intervention using GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach. Results: From 16 systematic reviews, we identified 133 eligible randomized controlled trials. Physical activity interventions reduced systolic blood pressure and fasting glucose (low to moderate quality of evidence). Dietary interventions with low-carbohydrate diets had a similar effect to low-fat diets in terms of body mass index (BMI) reduction (moderate quality of evidence). Educational interventions reduced waist circumference, BMI, and diastolic blood pressure (low quality of evidence). Pharmacological interventions reduced BMI (metformin, sibutramine, orlistat) and waist circumference (sibutramine, orlistat) and increased high-density lipoprotein cholesterol (sibutramine) but also raised systolic and diastolic blood pressure (sibutramine). Surgical interventions (laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, sleeve gastrectomy) resulted in the largest BMI reduction (moderate quality of evidence). Combined interventions consisting of dietary modification, physical activity, behavioral therapy, and education significantly reduced systolic and diastolic blood pressure, BMI, and triglycerides. Combined parent–child interventions and parent-only interventions had similar effects on BMI (low quality of evidence). Conclusions: Several childhood obesity interventions are effective in improving metabolic and anthropometric measures. A comprehensive multicomponent intervention, however, appears to have the best overall outcomes.

Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage–specific risk of all‐cause and liver‐related mortality in NAFLD. Through a systematic review and meta‐analysis, we identified five adult NAFLD cohort studies reporting fibrosis stage–specific mortality (0‐4). Using fibrosis stage 0 as a reference population, fibrosis stage–specific mortality rate ratios (MRRs) with 95% confidence intervals (CIs) for all‐cause and liver‐related mortality were estimated. The study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. Included were 1,495 NAFLD patients with 17,452 patient years of follow‐up. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all‐cause mortality, and this risk increased with increases in the stage of fibrosis: stage 1, MRR = 1.58 (95% CI 1.19‐2.11); stage 2, MRR = 2.52 (95% CI 1.85‐3.42); stage 3, MRR = 3.48 (95% CI 2.51‐4.83); and stage 4, MRR = 6.40 (95% CI 4.11‐9.95). The results were more pronounced as the risk of liver‐related mortality increased exponentially with each increase in the stage of fibrosis: stage 1, MRR = 1.41 (95% CI 0.17‐11.95); stage 2, MRR = 9.57 (95% CI 1.67‐54.93); stage 3, MRR = 16.69 (95% CI 2.92‐95.36); and stage 4, MRR = 42.30 (95% CI 3.51‐510.34). Limitations of the study include an inability to adjust for comorbid conditions or demographics known to impact fibrosis progression in NAFLD and the inclusion of patients with simple steatosis and nonalcoholic steatohepatitis without fibrosis in the reference comparison group. Conclusion: The risk of liver‐related mortality increases exponentially with increase in fibrosis stage; these data have important implications in assessing the utility of each stage and benefits of regression of fibrosis from one stage to another. (H epatology 2017;65:1557‐1565).