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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.
Duration of benefit of one-time screening sigmoidoscopy (June 2017)
Sigmoidoscopy is one of several methods to screen for colorectal cancer in average-risk persons. In extended follow-up of a randomized trial, a one-time screening flexible sigmoidoscopy for people aged 55 to 64 years was associated with reduced colorectal cancer incidence and mortality even 17 years after the initial screening exam . Similar benefits had been seen at 11-year follow-up. Although these findings support one-time flexible sigmoidoscopy as a potential screening method, most groups that include sigmoidoscopy as a screening option currently recommend repeated testing, although the optimal repeat interval is not known. In agreement with recommendations of the US Preventive Services Task Force, when flexible sigmoidoscopy is chosen as a screening modality, we offer flexible sigmoidoscopy alone every five years or flexible sigmoidoscopy every 10 years plus fecal immunochemical testing (FIT) every year. (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".)
Interval to colonoscopy following a positive fecal immunochemical test (May 2017)
How soon follow-up colonoscopy should be done to evaluate a positive fecal immunochemical test (FIT) is uncertain. In a retrospective cohort study of over 70,000 patients aged 50 to 70 years who had a positive FIT, rates of detection of any colorectal cancer (CRC) or advanced-stage CRC increased with increased time intervals between positive FIT and colonoscopy . Based on these findings, we encourage follow-up colonoscopy as soon as possible (and definitely within a few months) for patients who have a positive FIT. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'A suggested approach'.)
ESOPHAGEAL AND GASTRIC DISEASE
PPI use and mortality (July 2017)
It is unclear if proton pump inhibitor (PPI) use is associated with an increase in risk of death. In an observational cohort study, the incident death rate among 275,977 new PPI users was higher than among 73,335 new histamine-2 receptor antagonist (H2RA) users over a median follow-up of 5.7 years (4.5 versus 3.3 per 100 person-years) . After adjusting for potential confounders, PPI use was associated with increased all-cause mortality compared with H2RA use (HR 1.25); the risk of death increased with the duration of PPI use. Limitations of the study include its generalizability as the study cohort primarily consisted of older white males and lack of data on the cause of mortality. The underlying basis for this apparent increased risk of death with PPI use is not known, and further studies are needed to evaluate whether the association is due to unmeasured confounding. However, we continue to recommend that PPIs be prescribed at the lowest dose for the shortest duration appropriate for the condition being treated. (See "Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders", section on 'Mortality'.)
ACG guidelines on the treatment of H. pylori (May 2017)
The American College of Gastroenterology has published updated guidelines on the treatment of Helicobacter pylori . According to these guidelines, the choice of initial antibiotic regimen to treat H. pylori should be guided by risk factors for macrolide resistance and penicillin allergy. Risk factors for macrolide resistance include prior exposure to macrolides and local clarithromycin rates ≥15 percent (assumed in the United States). In patients with risk factors for macrolide resistance, bismuth quadruple therapy is a first-line treatment option. (See "Treatment regimens for Helicobacter pylori", section on 'Approach to selecting an antibiotic regimen'.)
Future options for HCV-infected patients who have failed DAA regimens (June 2017)
Patients with chronic hepatitis C virus (HCV) infection who have failed treatment with all-oral direct-acting antiviral (DAA) regimens have limited options for retreatment, but regimens in the late stages of development are expected to be effective. In two trials involving over 600 patients with genotypes 1 through 6 infection who had failed either an NS5A inhibitor-containing regimen or a non-NS5A-inhibitor DAA regimen, 12 weeks of sofosbuvir-velpatasvir-voxilaprevir (the last of which is a novel protease inhibitor) resulted in sustained virologic response (SVR) rates of 96 and 98 percent, respectively . Glecaprevir-pibrentasvir, a novel pangenotypic combination of a protease inhibitor and an NS5A inhibitor, also resulted in high SVR rates for genotype 1 infection with prior NS5A exposure . (See "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults", section on 'Prior failure of sofosbuvir-based regimens' and "Treatment regimens for chronic hepatitis C virus genotypes 4, 5, and 6 infection in adults", section on 'Prior failure of direct-acting antiviral regimens' and "Treatment regimens for chronic hepatitis C virus genotype 1 infection in adults", section on 'Prior failure with an NS5A-inhibitor regimen'.)
HBV reactivation during HCV antiviral therapy (May 2017)
Reactivation of hepatitis B virus (HBV) can occur during direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection. Among 29 cases reported to the US Food and Drug Administration (FDA) or described in the literature between 2013 and 2016, reactivation occurred at an average of 53 days into DAA treatment and was not associated with a particular HCV genotype or DAA regimen . Two cases were fatal, and one patient required liver transplant. 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 coinfected patients who do not initially meet HBV treatment criteria should be monitored for reactivation during HCV treatment. (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 'Monitoring during antiviral therapy'.)
Immunoassay for acetaminophen-induced liver injury (May 2017)
Establishing the diagnosis of acetaminophen (APAP) poisoning in patients who present greater than 24 hours to several days after ingestion, when a serum APAP level may no longer be detectable, can be difficult. However, a recent observational cohort study found excellent performance for a rapid immunoassay that measures serum APAP-protein adducts in identifying patients with APAP-induced acute liver injury (ALI) . In this study, a point of care immunoassay (AcetaSTAT) had 100 percent sensitivity and 100 percent negative predictive value, compared with results of high performance liquid chromatography as a reference standard, for identifying patients with such injury. If these results are validated in future clinical trials, this assay may provide a rapid means to distinguish APAP-induced ALI from other causes, and to begin appropriate management quickly. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis", section on 'Evaluation following delayed presentation'.)
Ileal bile acid transport inhibitors for pruritus in cholestasis (April 2017)
Available pharmacologic treatments for pruritus associated with cholestasis have limited efficacy. Preliminary data suggest that ileal bile acid transport (IBAT) inhibitors, which interrupt enterohepatic circulation of bile acids, might be an effective future option. In a randomized, placebo-controlled crossover trial of 22 patients with pruritus associated with primary biliary cirrhosis, treatment with an investigational selective inhibitor of human IBAT for two weeks reduced total and conjugated bile acid levels and pruritus . Diarrhea was the most frequent treatment-related adverse event but did not require dose reduction or discontinuation. Larger studies of longer duration are warranted to assess the efficacy of IBAT inhibitors in the treatment of pruritus in cholestasis. (See "Pruritus associated with cholestasis", section on 'Pruritus refractory to standard treatment'.)
PANCREATIC AND BILIARY DISEASE
Early refeeding in acute pancreatitis (August 2017)
The optimal timing of refeeding in acute pancreatitis is uncertain. In a systematic review of 11 randomized trials that included 948 patients with acute pancreatitis, early refeeding (≤48 hours after hospitalization) did not increase adverse effects or exacerbate symptoms compared with delayed refeeding . In four of seven trials that included patients with mild to moderate pancreatitis, it reduced length of hospital stay. However, there was significant heterogeneity in feeding protocols and reported outcomes, and several studies had a high risk of bias. Additional randomized trials are needed to define the benefits of early enteral nutrition in acute pancreatitis. (See "Management of acute pancreatitis", section on 'Oral'.)
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
Eculizumab in early-onset protein-losing enteropathy associated with inherited CD55 deficiency (July 2017)
Protein-losing enteropathy is characterized by an excessive loss of serum proteins into the gastrointestinal tract and can be caused by a diverse group of disorders. Whole genome sequencing of 11 patients with early-onset protein-losing enteropathy and primary intestinal lymphangiectasia has identified novel homozygous loss of function mutations in the gene encoding CD55 (decay activating factor). This autosomal recessively inherited syndrome is characterized by CD55 deficiency, hyperactivation of complement, angiopathic thrombosis, and early-onset protein-losing enteropathy (CHAPLE syndrome) . In a separate case report, three patients in a family with CHAPLE syndrome were treated with eculizumab, a humanized monoclonal antibody to C5 . Within 100 days of initiation of therapy there was reduction in complement activation, increase in serum albumin and total protein concentration, and improvement in diarrhea. While these data suggest the importance of complement activation in a subset of patients with protein-losing enteropathy, the role of complement blockade in the treatment of protein-losing gastroenteropathy is unclear. (See "Protein-losing gastroenteropathy", section on 'Treatment of the underlying disease'.)
Tofacitinib for ulcerative colitis (May 2017)
Tofacitinib, an oral inhibitor of Janus kinase 1-3 used for rheumatoid arthritis, also appears promising for refractory ulcerative colitis (UC). In two randomized trials that each included over 500 patients with moderate to severe UC, induction therapy with tofacitinib resulted in a higher rate of remission compared with placebo (17 to 19 percent versus 4 to 8 percent) . In another trial of nearly 600 patients who had clinical response to induction therapy, maintenance therapy with two different doses of tofacitinib resulted in higher sustained remission rates at 52 weeks compared with placebo (35 to 41 versus 11 percent). Tofacitinib was associated with more infections overall, including more cases of herpes zoster. Future trials can help determine the exact role of tofacitinib in the treatment of UC. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Tofacitinib'.)
USPSTF statement on screening for celiac disease (April 2017)
Testing for celiac disease in the absence of suggestive signs or symptoms is controversial. A US Preventive Services Task Force report has concluded that there are insufficient data to support screening for celiac disease . However, we continue to test for celiac disease in asymptomatic first-degree relatives of patients with a confirmed diagnosis of celiac disease because of their increased risk for disease. We also recommend screening asymptomatic children with several conditions associated with celiac disease, including type 1 diabetes and Down syndrome. Our recommendations are consistent with guidelines from the American College of Gastroenterology and from Pediatric Gastroenterology societies . (See "Diagnosis of celiac disease in adults", section on 'Who should be tested'.)
Risk of colon cancer in patients with diverticulitis (April 2017)
The utility of routine colonoscopy after acute diverticulitis is debated. An analysis of data from a Danish registry showed that patients hospitalized for diverticulitis were twice as likely to develop colon cancer over the 18-year study period as those without diverticulitis, and over 50 percent of colon cancers were diagnosed within one year of diagnosis of diverticulitis . This study underscores the importance of endoscopic surveillance in patients with diverticular disease and supports our recommendation for performing a colonoscopy after the complete resolution of an episode of acute diverticulitis in patients who have not had a colonoscopy within a year. (See "Acute colonic diverticulitis: Medical management", section on 'Colonoscopy for all patients'.)
Investigational transabdominal tomography technique for Crohn disease (April 2017)
Multispectral optoacoustic tomography (MSOT), a transabdominal imaging technique that detects bowel wall inflammation by quantifying surrogate markers such as hemoglobin-dependent tissue perfusion, can accurately assess Crohn disease (CD) activity. In a preliminary study of 44 patients with CD, MSOT parameters successfully distinguished active versus nonactive disease, as determined by endoscopic findings . Although not yet available for use in practice, MSOT holds promise as a noninvasive clinical tool to evaluate inflammatory bowel disease activity. (See "Clinical manifestations, diagnosis and prognosis of Crohn disease in adults", section on 'Multispectral optoacoustic tomography'.)
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".)
OTHER GASTROENTEROLOGY AND NUTRITION
Self-administered hypnotherapy for functional abdominal pain in children and adolescents (June 2017)
Increasing evidence suggests that gut-directed hypnotherapy reduces pain frequency and intensity in children and adolescents with functional abdominal pain disorders (FAPDs). In a trial of this therapy that randomly assigned children (age 8 to 18 years) with FAPDs to a self-administered home-based approach using a compact disc or to individual therapy with a qualified therapist for three months, over 60 percent of each group had ≥50 percent reduction in pain frequency and intensity at one-year follow-up . These findings suggest that self-directed hypnotherapy is a reasonable option for children and adolescents with FAPDs, particularly if trained therapists are not available. (See "Functional abdominal pain in children and adolescents: Management in primary care", section on 'Improved coping'.)
Decreased susceptibility to fluoroquinolones in Shigella infection (April 2017)
When treatment for Shigella infection is indicated, susceptibility testing should be performed to guide antimicrobial selection. In the United States, an increasing proportion of Shigella isolates have minimum inhibitory concentrations (MIC) to ciprofloxacin of 0.12 to 1 mcg/mL . Although these MIC values are considered susceptible and their impact on treatment outcomes in Shigella is unknown, they are associated with resistance genes that result in worse outcomes with fluoroquinolone treatment in other Enterobacteriaceae. Clinicians should request the MIC to ciprofloxacin if it is not provided with susceptibility results and avoid fluoroquinolones if the MIC is ≥0.12 mcg/mL. (See "Shigella infection: Clinical manifestations and diagnosis", section on 'Susceptibility testing' and "Shigella infection: Treatment and prevention in adults", section on 'Antibiotic selection'.)
- Atkin W, Wooldrage K, Parkin DM, et al. Long term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up: the UK Flexible Sigmoidoscopy Screening randomised controlled trial. Lancet 2017; 389:1299.
- Corley DA, Jensen CD, Quinn VP, et al. Association Between Time to Colonoscopy After a Positive Fecal Test Result and Risk of Colorectal Cancer and Cancer Stage at Diagnosis. JAMA 2017; 317:1631.
- Xie Y, Bowe B, Li T, et al. Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open 2017; 7:e015735.
- Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2017; 112:212.
- Bourlière M, Gordon SC, Flamm SL, et al. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection. N Engl J Med 2017; 376:2134.
- Poordad F, Felizarta F, Asatryan A, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology 2017; 66:389.
- Bersoff-Matcha SJ, Cao K, Jason M, et al. Hepatitis B Virus Reactivation Associated With Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus: A Review of Cases Reported to the U.S. Food and Drug Administration Adverse Event Reporting System. Ann Intern Med 2017.
- Roberts DW, Lee WM, Hinson JA, et al. An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure. Clin Gastroenterol Hepatol 2017; 15:555.
- Hegade VS, Kendrick SF, Dobbins RL, et al. Effect of ileal bile acid transporter inhibitor GSK2330672 on pruritus in primary biliary cholangitis: a double-blind, randomised, placebo-controlled, crossover, phase 2a study. Lancet 2017; 389:1114.
- Vaughn VM, Shuster D, Rogers MAM, et al. Early Versus Delayed Feeding in Patients With Acute Pancreatitis: A Systematic Review. Ann Intern Med 2017; 166:883.
- 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.
- Ozen A, Comrie WA, Ardy RC, et al. CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis. N Engl J Med 2017; 377:52.
- Kurolap A, Eshach-Adiv O, Hershkovitz T, et al. Loss of CD55 in Eculizumab-Responsive Protein-Losing Enteropathy. N Engl J Med 2017; 377:87.
- Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med 2017; 376:1723.
- US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening for Celiac Disease: US Preventive Services Task Force Recommendation Statement. JAMA 2017; 317:1252.
- Rubio-Tapia A, Hill ID, Kelly CP, et al. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 2013; 108:656.
- Mortensen LQ, Burcharth J, Andresen K, et al. An 18-Year Nationwide Cohort Study on The Association Between Diverticulitis and Colon Cancer. Ann Surg 2017; 265:954.
- Knieling F, Neufert C, Hartmann A, et al. Multispectral Optoacoustic Tomography for Assessment of Crohn's Disease Activity. N Engl J Med 2017; 376:1292.
- 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.
- Rutten JMTM, Vlieger AM, Frankenhuis C, et al. Home-Based Hypnotherapy Self-exercises vs Individual Hypnotherapy With a Therapist for Treatment of Pediatric Irritable Bowel Syndrome, Functional Abdominal Pain, or Functional Abdominal Pain Syndrome: A Randomized Clinical Trial. JAMA Pediatr 2017; 171:470.
- CDC Health Alert Network. CDC Recommendations for Diagnosing and Managing Shigella Strains with Possible Reduced Susceptibility to Ciprofloxacin. April 18, 2017. https://emergency.cdc.gov/han/han00401.asp (Accessed on April 24, 2017).