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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.
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'.)
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'.)
ESOPHAGEAL AND GASTRIC DISEASE
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'.)
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'.)
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'.)
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
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".)
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'.)
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'.)
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