Jennifer A. Flemming

Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria.

We report on the long‐term intention‐to‐treat (ITT) outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing downstaging to within Milan/United Network for Organ Sharing T2 criteria before liver transplantation (LT) since 2002 and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The downstaging subgroups include 1 lesion >5 and ≤8 cm (n = 43), 2 or 3 lesions at least one >3 and ≤5 cm with total tumor diameter ≤8 cm (n = 61), or 4‐5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n = 14). In the downstaging group, 64 patients (54.2%) had received LT and 5 (7.5%) developed HCC recurrence. Two of the five patients with HCC recurrence had 4‐5 tumors at presentation. The 1‐ and 2‐year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the downstaging group versus 20.3% and 25.6% in the T2 group (P = 0.04). Kaplan‐Meiers 5‐year post‐transplant survival and recurrence‐free probabilities were 77.8% and 90.8%, respectively, in the downstaging group versus 81% and 88%, respectively, in the T2 group (P = 0.69 and P = 0.66, respectively). The 5‐year ITT survival was 56.1% in the downstaging group versus 63.3% in the T2 group (P = 0.29). Factors predicting dropout in the downstaging group included pretreatment alpha‐fetoprotein ≥1,000 ng/mL (multivariate hazard ratio [HR]: 2.42; P = 0.02) and Childs B versus Childs A cirrhosis (multivariate HR: 2.19; P = 0.04). Conclusion: Successful downstaging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post‐transplant survival, comparable to those meeting T2 criteria without downstaging. Owing to the small number of patients with 4‐5 tumors, further investigations are needed to confirm the efficacy of downstaging in this subgroup. (Hepatology 2015;61:1968–1977)

Reduction in liver transplant wait‐listing in the era of direct‐acting antiviral therapy

Direct‐acting antiviral (DAA) therapy, recently approved for patients with decompensated cirrhosis (DC) secondary to hepatitis C virus (HCV), is associated with improved hepatic function. We analyzed trends in liver transplant (LT) wait‐listing (WL) to explore potential impact of effective medical therapy on WL registration. This is a cohort study using the Scientific Registry of Transplant Recipients database from 2003 to 2015. A total of 47,591 adults wait‐listed for LT from HCV, hepatitis B virus (HBV), and nonalcoholic steatohepatitis (NASH) were identified. LT indication was defined as DC if the Model for End‐Stage Liver Disease (MELD) at WL was ≥15 or hepatocellular carcinoma (HCC). Era of listing was divided into interferon (IFN; 2003‐2010), protease inhibitor (PI; 2011‐2013), and direct‐acting antiviral (DAA; 2014‐2015). Annual standardized incidence rates of WL were analyzed using Poisson regression. Adjusted incidences of LT WL for DC in HCV patients decreased by 5% in the PI era (P = 0.004) and 32% in the DAA era (P < 0.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (–17%; P = 0.002) and DAA eras (–24%; P < 0.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P < 0.001) and 81% in the DAA era (P < 0.001). WL for HCC in both the HCV and NASH populations increased in both the PI and DAA eras (P < 0.001 for all) whereas HCC WL in HBV remained stable (P > 0.05 for all). Conclusion: The rate of LT WL for HCV complicated by DC has decreased by over 30% in the era of DAA therapy. Further reductions in WL are anticipated with increased testing, linkage to care, and access to DAA therapy. (Hepatology 2017;65:804‐812).

Split-dose picosulfate, magnesium oxide, and citric acid solution markedly enhances colon cleansing before colonoscopy: a randomized, controlled trial.

BACKGROUND Picosulfate, magnesium oxide, and citric acid solution is a small-volume agent for colon cleansing before colonoscopy that is extremely well tolerated by patients, safe, and efficacious. Studies of other cleansing agents have suggested that split-dose regimens may further enhance efficacy. OBJECTIVE To examine whether split-dosing of picosulfate, magnesium oxide, and citric acid solution increases bowel cleansing efficacy while maintaining tolerability and safety. DESIGN Prospective, randomized, single-blinded, controlled trial. SETTING Outpatient tertiary care center. PATIENTS A total of 236 patients underwent colonoscopy (mean age 56 years, 53.8% female). INTERVENTIONS Patients in the traditional arm (n = 123) consumed 1 sachet of solution at 5:00 pm and 10:00 pm the night before the colonoscopy. Patients in the split-dose arm (n = 127) consumed 1 sachet at 7:00 pm the night before and another sachet 4 hours before their colonoscopy appointment. MAIN OUTCOME MEASUREMENTS Ottawa Bowel Preparation Scale (OBPS) score, Aronchick score, safety, tolerability. RESULTS The 113 and 109 patients in the split-dose and traditional arms, respectively, had OBPS scores for analysis. Overall, the OBPS scores in the split-dose group were significantly improved compared with the traditional dose group (4.05 vs 5.51, P < .001). This was mostly attributed to improvements in right-sided colon cleansing (1.22 in split-dose vs 2.14 in traditional arm, P < .001). Both regimens were well tolerated by patients, and no safety issues were identified. LIMITATIONS This was a single-center study. Disturbances in sleep related to the preparation were not assessed. CONCLUSIONS The split-dose regimen of picosulfate, magnesium oxide, and citric acid solution is superior to the traditional dosing regimen for colon cleansing before colonoscopy. ( CLINICAL TRIAL REGISTRATION NUMBER NCT00885274.).

Risk prediction of hepatocellular carcinoma in patients with cirrhosis: The ADRESS-HCC risk model

All patients with cirrhosis are at risk of developing hepatocellular carcinoma (HCC). This risk is not uniform because other patient‐related factors influence the risk of HCC. The objective of the current study was to develop an HCC risk prediction model to estimate the 1‐year probability of HCC to assist with patient counseling.

A low-residue breakfast improves patient tolerance without impacting quality of low-volume colon cleansing prior to colonoscopy: a randomized trial.

OBJECTIVES:We compared the efficacy and patient tolerance of two dietary regimens used as an adjunct to standard bowel cleansing in preparation for elective colonoscopy.METHODS:Our prospective, randomized, single-blind, controlled, noninferiority trial compared two dietary regimens administered the day before colonoscopy. Subjects received low-volume bowel preparation. The primary outcome was efficacy of colon cleansing, rated by the Ottawa bowel preparation scale (OBPS). Patient acceptance of the assigned dietary regimen was assessed as a secondary outcome.RESULTS:The mean OBPS score for the standard clear-fluid diet group was 4.47, compared with 4.62 for the low-residue breakfast group, meeting criteria for noninferiority. The groups reported similar mean intensity of hunger on a visual analog hunger scale. However, overall satisfaction was higher with the low-residue diet than with the clear-fluid diet.CONCLUSIONS:A low-residue breakfast on the day before elective colonoscopy does not compromise the overall quality of bowel preparation as compared with a standard clear-fluid diet and is likely to be preferred by patients.

Fulvestrant for systemic therapy of locally advanced or metastatic breast cancer in postmenopausal women: a systematic review

A systematic review was undertaken to examine all available evidence to develop and support clinical recommendations regarding the use of fulvestrant (Faslodex®) as systemic therapy of locally advanced or metastatic breast cancer in postmenopausal women. MEDLINE, EMBASE, American Society of Clinical Oncology Annual Meeting proceedings, San Antonio Breast Cancer Symposia proceedings, and the Cochrane Library were searched through to April of 2008 for reports of randomized controlled trials that met established inclusion criteria. Four relevant Phase III trials were available for inclusion based on established criteria. Three of four Phase III superiority trials found no significant difference between fulvestrant and control, either anastrozole or exemestane, across efficacy and safety endpoints following prior endocrine therapy failure, with two trials further confirming non-inferiority of fulvestrant to anastrozole retrospectively. Fulvestrant can therefore be considered as alternative therapy to anastrozole or exemestane in postmenopausal women with locally advanced or metastatic breast cancer that has recurred on prior adjuvant endocrine therapy or progressed on prior endocrine therapy for advanced disease. There are, however, important methodological concerns across reviewed trials that should be taken under consideration as they may limit the strength of such a conclusion.

Liver biopsies for chronic hepatitis C: Should nonultrasound-guided biopsies be abandoned?

BACKGROUND/OBJECTIVE Liver biopsy has been the gold standard for grading and staging chronic hepatitis C virus (HCV)- mediated liver injury. Traditionally, this has been performed by trained practitioners using a nonimage-guided percutaneous technique at the bedside. Recent literature suggests an expanding role for radiologists in obtaining biopsies using an ultrasound (US)-guided technique. The present study was undertaken study to determine if the two techniques produced liver biopsy specimens of similar quality and hypothesized that at our institution, non-US-guided percutaneous liver biopsies for HCV would be of higher quality than US-guided specimens. METHODS Liver biopsies from 100 patients with chronic HCV infection (50 consecutive US-guided and 50 consecutive non-US-guided), were retrospectively identified using a hospital histopathology database. All original biopsy slides were coded and prospectively reanalyzed by a single hepatopathologist who was blinded to the technique used in obtaining the biopsy. Additionally, all liver biopsies for chronic HCV infection completed at the centre from 1998 to 2007 were identified and the technique used was recorded. Biopsy quality was determined primarily by the number of complete portal tracts (CPTs) identifiable in the slides. The total length of specimen and the degree of fragmentation were secondary outcome measures. RESULTS There was a slight difference observed between the US-guided and non-US-guided groups in mean age (46.3 years versus 42.5 years, respectively; P=0.018) but no differences in sex, presence of cirrhosis, bilirubin, creatinine, international normalized ratio, and grade or stage of disease. Biopsies obtained using the US-guided technique produced higher quality specimens than the non-US-guided technique based on our primary outcome of number of CPTs in the biopsy (11.8 versus 7.4; P<0.001). US-guided specimens also were longer (24.4 mm versus 19.7 mm; P=0.001), had less fragmentation (P=0.016), and a higher overall histopathological quality assessment (P=0.026) than the non-US-guided biopsies. However, there was no significant difference between the two groups in the ability to grade and stage the disease (96% US-guided versus 90% in non-US-guided (P=0.20). Over a 10-year period, 763 biopsies for chronic HCV infection were identified with an obvious trend toward the increased use of US-guided technique observed at 2% in 1998 to 85% in 2007. CONCLUSIONS US-guided liver biopsies for chronic HCV are the most common method of obtaining specimens at the Kingston General Hospital, Kingston, Ontario, and are of higher quality than non-US-guided specimens. However, there is no significant difference in the two techniques in the ability to grade and stage chronic HCV.

β-Trace Protein Assays: A Comparison Between Nephelometric and ELISA Methodologies

To the Editor: b-Trace protein (BTP) is a low-molecular-weight glycoprotein with multiple isoforms of varying molecular weight (23-29 kDa) and an emerging marker of glomerular filtration rate (GFR). Equations for estimated GFR (eGFR) that incorporate BTP have been proposed. As of 2013, assays for BTP in biological fluids were commercially available from Cayman Chemicals (an immunometric ELISA using monoclonal murine antibodies) and Siemens (a particle-enhanced nephelometric immunoassay using polyclonal rabbit antibodies against human urinary BTP). The assays use different analytical techniques and different antibodies, which may recognize different glycoprotein epitopes and therefore may not bind to all BTP isoforms.Unlike creatinine and cystatinC, there are no higher order referencematerials available for BTP. The aim of this studywas to examine differences in these BTP assays and their impact on eGFR. We also sought to examine differences in the Siemens BTP assay in different laboratories and over time. Detailed methods are in Item S1. Frozen serum was measured in 2015 and came from the following adult sources: kidney transplant recipients (sampled 2007-2012; n 5 77), patients with cirrhosis (sampled 2014; n 5 103), and patients with chronic kidney disease (CKD; sampled 2014; n 5 101). Serum was split 3 ways, frozen, and shipped to the participating laboratories. BTP was measured using the Siemens N Latex BTP assay at the Children’s Hospital of Eastern Ontario (CHEO), Canada, and at the University of Minnesota, United States. The University of Sherbrooke, Canada, measured BTP using the Cayman assay. Absolute differences between paired BTP values were calculated. Paired t tests were used to compare mean differences. This analysis was repeated after stratifying patients by BTP less than and greater than the median of the average of the 2 assays being compared and by population. Percentages of samples with paired values within 10% (P10) and 30% (P30) of each other were calculated. A similar analysis was performed using eGFR calculated using the CKD-EPI BTP equation, assuming a 65-year-old woman. Relationships between paired BTP and paired eGFR results were also examined using Deming regression and Bland-Altman analysis, respectively. Siemens CHEO concentrations were 0.77 6 1.01 mg/L lower than Cayman concentrations (P , 0.001), with greater absolute difference in the higher BTP subgroup (Table 1). Similar

Increased incidence but improved median overall survival for biliary tract cancers diagnosed in Ontario from 1994 through 2012: A population-based study

To the authors’ knowledge, the incidence of biliary tract cancer (BTC) in Canada is unknown. In the current study, the authors sought to describe the epidemiology of BTC using a large population‐based cancer database from Ontario, Canada.

Is there a sex effect in colon cancer? Disease characteristics, management, and outcomes in routine clinical practice

INTRODUCTION The incidence of colon cancer varies by sex. Whether women and men show differences in extent of disease, treatment, and outcomes is not well described. We used a large population-based cohort to evaluate sex differences in colon cancer. METHODS Using the Ontario Cancer Registry, all cases of colon cancer treated with surgery in Ontario during 2002-2008 were identified. Electronic records of treatment identified use of surgery and adjuvant chemotherapy. Pathology reports for a random 25% sample of all cases were obtained, and disease characteristics, treatment, and outcomes in women and men were compared. A Cox proportional hazards model was used to identify factors associated with overall (os) and cancer-specific survival (css). RESULTS The study population included 7249 patients who underwent resection of colon cancer; 49% (n = 3556) were women. Stage of disease and histologic grade did not vary by sex. Compared with men, women were more likely to have right-sided disease (55% vs. 44%, p ≤ 0.001). Surgical procedure and lymph node yield did not differ by sex. Adjuvant chemotherapy was delivered to 18% of patients with stage ii and 64% of patients with stage iii disease; when adjusted for patient- and disease-related factors, use of adjuvant chemotherapy was similar for women and men [relative risk: 0.99; 95% confidence interval (ci): 0.94 to 1.03]. Adjusted analyses demonstrated that os [hazard ratio (hr): 0.80; 95% ci: 0.75 to 0.86] and css (hr: 0.82; 95% ci: 0.76 to 0.90) were superior for women compared with men. CONCLUSIONS Long-term survival after colon cancer is significantly better for women than for men, which is not explained by any substantial differences in extent of disease or treatment delivered.