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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
Flexible sigmoidoscopy and colorectal cancer screening in older women (January 2017)
Flexible sigmoidoscopy is one of several screening modalities recommended by the US Preventive Services Task Force for colorectal cancer (CRC) screening. However, sigmoidoscopy is less effective at detecting lesions in the right side of the colon (beyond the 60 cm reach of the sigmoidoscope) than the left side, and right-sided lesions are more common in older women. A study that pooled results from three randomized trials (nearly 300,000 individuals) comparing screening by sigmoidoscopy with no screening found that the incidence of CRC at 10 to 12 years was decreased in men but, in women, only in those younger than 60 years . Current screening recommendations do not indicate gender-based preferences for screening options, but these findings call into question the effectiveness of flexible sigmoidoscopy as a screening modality for women over age 60 years. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Evidence of effectiveness' and "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Comparison of tests'.)
Fecal immunochemical testing for colorectal cancer screening (January 2017)
Multiple test strategies are available for screening in people with average risk for colorectal cancer (CRC). Annual stool testing for occult blood using a guaiac reagent (gFOBT) has been widely implemented and is one of the screening strategies endorsed by the US Preventive Services Task Force. Fecal immunochemical testing (FIT) is another option and has the potential advantages of better test performance (improved sensitivity for CRC and advanced adenomas) and better patient adherence (one stool sample, no diet restrictions) compared with gFOBT. The US Multi-Society Task Force has published consensus guidelines recommending FIT over gFOBT when occult blood stool testing is elected for CRC screening . (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Immunochemical tests for fecal blood' and "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Comparison of tests'.)
Colonoscopy preparation and sessile-serrated polyp detection rates (September 2016)
Previous studies have not demonstrated an association between split-dose colonoscopy preparation (ie, one half the evening prior to the colonoscopy and the second half the morning of) and improvement in sessile-serrated polyp detection rates. In a randomized trial, 341 patients were assigned to 2 liters of polyethylene glycol electrolyte lavage solution with ascorbic acid either as single-dose or split-dose regimen . Split-dose lavage resulted in significantly lower duration and intensity of bowel movements, less disruption of sleep, and better quality of bowel preparation. There were no differences in adenoma detection rates between the two groups; however, split-dose lavage resulted in significantly higher sessile-serrated polyp detection rates (10 versus 2 percent). These data support current recommendations that colonoscopy preparations be administered as split-dose rather than being given entirely the evening prior to the colonoscopy. (See "Bowel preparation for colonoscopy and flexible sigmoidoscopy in adults", section on 'Split-dose lavage'.)
ESOPHAGEAL AND GASTRIC DISEASE
Unclear role of montelukast in eosinophilic esophagitis (October 2016)
Initial experience suggested that montelukast may be helpful for symptom reduction in patients with eosinophilic esophagitis, but subsequent experience has been mixed. In a small randomized trial, patients with eosinophilic esophagitis were assigned to maintenance treatment with montelukast or placebo for 26 weeks following steroid-induced symptomatic remission . There were no significant differences in the proportion of patients that remained in remission between the two groups. Thus, the role of montelukast in eosinophilic esophagitis, if any, remains unclear. (See "Treatment of eosinophilic esophagitis", section on 'Montelukast'.)
ACG guidelines on the evaluation of abnormal liver chemistries (January 2017)
The American College of Gastroenterology has published new guidelines on the evaluation of abnormal liver chemistries . These guidelines define normal alanine aminotransferase (ALT) ranges as 29 to 33 international units/L for males and 19 to 25 international units/L for females, which are lower than the reference ranges of many clinical laboratories. They recommend that ALT levels repeatedly above these upper limits of normal be evaluated. In addition, they provide a framework for the evaluation of elevated ALT, aspartate aminotransferase (AST), and alkaline phosphatase levels (which should be characterized as liver chemistries or tests rather than markers of liver function) based on the degree and pattern of elevations. (See "Approach to the patient with abnormal liver biochemical and function tests", section on 'Aminotransferases'.)
Tenofovir alafenamide for the treatment of chronic hepatitis B virus infection (December 2016)
Tenofovir disoproxil fumarate is a first-line therapy for chronic hepatitis B virus (HBV) infection. A newer formulation of tenofovir, tenofovir alafenamide, was approved by the US Food and Drug Administration in November 2016 for the treatment of chronic HBV in patients with compensated liver disease . In two large randomized noninferiority trials among patients with chronic HBV infection (both treatment-naive and experienced, and including patients positive or negative for HBV e antigen), tenofovir alafenamide resulted in similar rates of HBV suppression and fewer adverse effects on renal function and bone density at 48 weeks compared with tenofovir disoproxil fumarate [7,8]. Given these findings, tenofovir alafenamide is our preferred formulation for patients with chronic HBV who initiate therapy with tenofovir. We also favor switching those initially started on tenofovir disoproxil fumarate to tenofovir alafenamide. Given limited available safety data, we do not currently use tenofovir alafenamide in pregnant women. (See "Hepatitis B virus: Overview of management", section on 'Nucleos(t)ide analogues'.)
Prevention of graft reinfection in HCV-infected patients undergoing liver transplantation (December 2016)
In the absence of viral suppression or clearance of chronic hepatitis C virus (HCV) in patients who undergo liver transplantation, the new liver is almost always reinfected. In an open-label study, 16 HCV genotype 1-infected patients undergoing their first liver transplantation from an uninfected donor received a single dose of ledipasvir-sofosbuvir the day they arrived at the hospital for transplantation and once daily for four weeks postoperatively . The sustained virologic response rate 12 weeks after completion of treatment was 88 percent, suggesting that an abbreviated perioperative course of direct-acting antiviral (DAA) treatment can prevent reinfection of the graft. Additional studies are warranted to confirm the efficacy and safety of this approach in other HCV-infected populations and with other DAA regimens. (See "Recurrence of hepatitis C virus infection following liver transplantation", section on 'Perioperative therapy'.)
HBV reactivation during HCV antiviral therapy (October 2016)
Reactivation of hepatitis B virus (HBV) infection, including cases with fatal fulminant hepatitis, has been reported in several patients receiving direct-acting antiviral therapy for hepatitis C virus (HCV) infection . Patients should be tested for HBV coinfection prior to initiation of HCV therapy, with HBV treatment initiated for those who meet criteria (table 1). HBV surface antigen (HBsAg) positive patients who do not initially meet HBV treatment criteria should be monitored with HBV DNA testing during HCV treatment. In patients with a positive HBV core antibody (HBcAb) but negative HBsAg, we check liver enzymes during HCV treatment and perform reflex HBsAg and HBV DNA testing for unexplained elevations. (See "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection", section on 'HBV coinfection' and "Overview of the management of chronic hepatitis C virus infection", section on 'Other monitoring'.)
PANCREATIC AND BILIARY DISEASE
Optimal timing of surgery for acute cholecystitis (March 2017)
Although early surgery is advocated for acute cholecystitis, the recommendation for cholecystectomy within seven days of admission is imprecise. An administrative database study of over 15,000 cholecystectomies for acute cholecystitis reported that the lowest overall morbidity and mortality rates were achieved with surgery on the first or second day after admission . Surgery on the day of admission was associated with a lower rate of biliary injury but a higher rate of nonbiliary complications compared with surgery on subsequent days. Thus, patients with acute cholecystitis should undergo surgery within two days of admission, but only after they have been fully resuscitated and when the most qualified surgeon is available. (See "Treatment of acute calculous cholecystitis", section on 'Timing of cholecystectomy'.)
SMALL BOWEL AND COLONIC DISEASE
Treatment of acute diverticulitis without antibiotics (February 2017)
Acute diverticulitis is typically treated with antibiotics. However, in a Dutch trial (DIABOLO) that randomly assigned over 500 low-risk patients with first-episode, acute, uncomplicated diverticulitis confirmed with computed tomography to either observation or antibiotic therapy, outcomes were similar for both groups . Because almost all of the patients were admitted to the hospital for one or more days, this trial did not establish the safety of avoiding antibiotic therapy in low-risk outpatients. Thus, until further data become available, UpToDate continues to recommend antibiotic treatment of acute diverticulitis in patients meeting criteria for outpatient management. (See "Acute colonic diverticulitis: Medical management", section on 'Outpatient treatment' and "Acute colonic diverticulitis: Medical management".)
Bezlotoxumab for secondary prevention of C. difficile infection (February 2017)
Bezlotoxumab is a monoclonal antibody against Clostridium difficile toxin B (which is essential for the virulence of the organism) that received US Food and Drug Administration approval in 2016 for secondary prevention of C. difficile infection in patients at high risk for recurrence. In two randomized trials including more than 2500 patients with C. difficile infection, the addition of bezlotoxumab to standard oral antibiotic therapy lowered the rate of recurrence (16 to 17 versus 26 to 28 percent with antibiotics alone) . However, further evaluation to identify those who would be most likely to benefit is needed to define the optimal role of bezlotoxumab relative to other approaches to C. difficile infection treatment, including fecal microbiota transplant. (See "Clostridium difficile in adults: Treatment", section on 'Alternative therapies'.)
Donor fecal microbiota transplant for recurrent Clostridium difficile infection (December 2016)
Strong evidence to support fecal microbiota transplant (FMT) in patients with recurrent Clostridium difficile infection (CDI) has been lacking. In a randomized trial, patients with three or more recurrences of CDI who had received vancomycin for their most recent acute episode were assigned to FMT administered by colonoscopy with donor stool or their own stool (as a control) . Patients who received donor FMT achieved higher clinical cure rates (92 versus 63 percent). These data support our recommendations to treat patients with recurrent CDI despite multiple courses of antibiotic therapy with donor FMT. (See "Fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection", section on 'Colonoscope'.)
Ustekinumab for anti-TNF refractory Crohn disease (November 2016)
Ustekinumab is approved for use in adult patients with moderate to severely active Crohn disease who have failed conventional therapy, but efficacy in inducing clinical remission in patients with disease refractory to anti-tumor necrosis factor (anti-TNF) therapy had not been previously established. In two randomized induction trials, approximately 1300 patients with Crohn disease and nonresponse or intolerable side effects to anti-TNF therapy were assigned to eight weeks of intravenous ustekinumab or placebo . Those who responded to ustekinumab were assigned to 44 weeks of subcutaneous maintenance with ustekinumab or placebo. Patients assigned to ustekinumab had significantly higher clinical response rates at week six and rates of remission at week 44 as compared with placebo, demonstrating a role for ustekinumab in patients who have failed anti-TNF therapy. (See "Overview of the medical management of severe or refractory Crohn disease in adults", section on 'Ustekinumab'.)
- Holme Ø, Schoen RE, Senore C, et al. Effectiveness of flexible sigmoidoscopy screening in men and women and different age groups: pooled analysis of randomised trials. BMJ 2017; 356:i6673.
- Robertson DJ, Lee JK, Boland CR, et al. Recommendations on fecal immunochemical testing to screen for colorectal neoplasia: a consensus statement by the US Multi-Society Task Force on colorectal cancer. Gastrointest Endosc 2017; 85:2.
- Horton N, Garber A, Hasson H, et al. Impact of Single- vs. Split-Dose Low-Volume Bowel Preparations on Bowel Movement Kinetics, Patient Inconvenience, and Polyp Detection: A Prospective Trial. Am J Gastroenterol 2016; 111:1330.
- Alexander JA, Ravi K, Enders FT, et al. Montelukast Does not Maintain Symptom Remission After Topical Steroid Therapy for Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2017; 15:214.
- Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol 2017; 112:18.
- U.S. Food and Drug Administration Approves Gilead’s Vemlidy (Tenofovir Alafenamide) for the Treatment of Chronic Hepatitis B Virus Infection. http://www.gilead.com/news/press-releases/2016/11/us-food-and-drug-administration-approves-gileads-vemlidy-tenofovir-alafenamide-for-the-treatment-of-chronic-hepatitis-b-virus-infection (Accessed on November 28, 2016).
- Chan HL, Fung S, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: A randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol 2016; 1:185.
- Buti M, Gane E, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-negative chronic hepatitis B virus infection: A randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol 2016; 1:196.
- Levitsky J, Verna EC, O'Leary JG, et al. Perioperative Ledipasvir-Sofosbuvir for HCV in Liver-Transplant Recipients. N Engl J Med 2016; 375:2106.
- FDA Drug Safety Communication: FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C http://www.fda.gov/Drugs/DrugSafety/ucm522932.htm (Accessed on October 05, 2016).
- Blohm M, Österberg J, Sandblom G, et al. The Sooner, the Better? The Importance of Optimal Timing of Cholecystectomy in Acute Cholecystitis: Data from the National Swedish Registry for Gallstone Surgery, GallRiks. J Gastrointest Surg 2017; 21:33.
- Daniels L, Ünlü Ç, de Korte N, et al. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg 2017; 104:52.
- Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N Engl J Med 2017; 376:305.
- Kelly CR, Khoruts A, Staley C, et al. Effect of Fecal Microbiota Transplantation on Recurrence in Multiply Recurrent Clostridium difficile Infection: A Randomized Trial. Ann Intern Med 2016; 165:609.
- Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. N Engl J Med 2016; 375:1946.