Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
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.
USPSTF recommendations for colorectal cancer screening (July 2016)
The United States Preventive Services Task Force (USPSTF) issued new guidelines for colorectal cancer screening in average risk adults . The guidelines make a strong recommendation for screening, starting at age 50 years and continuing to age 75 for most patients, but in a departure from prior recommendations do not give preference for any one of seven screening test strategies over another. Options for screening are shown in a table. We agree with this screening test strategy based on shared decision making. Incorporating patient personal preferences may increase the likelihood that ongoing screening will occur. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'USPSTF guidelines'.)
Blood test for colorectal cancer screening (April 2016)
In 2016, the US Food and Drug Administration (FDA) approved a second-generation plasma assay for the detection of circulating methylated Septin 9 (Epi proColon 2.0) for colorectal cancer screening . This test detects Septin 9 DNA, which is hypermethylated in colorectal cancer but not in normal colon tissue. The test is intended for average-risk patients who refuse screening by guideline-recommended methods (eg, colonoscopy, sigmoidoscopy, fecal occult blood, or fecal DNA testing). A positive blood test should be followed up with a colonoscopy. However, there is no strong evidence of the effectiveness of screening for colorectal cancer with available plasma or serum markers. Until further evidence is available, we do not recommend blood tests for colorectal cancer screening. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Blood-based markers'.)
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'.)
Toronto consensus for treatment of Helicobacter pylori (June 2016)
The Toronto consensus has published new guidelines for the treatment of Helicobacter pylori in adults . These guidelines recommend a longer duration of treatment for all eradication regimens (14 versus 10 days), limiting the use of triple therapy to areas with low clarithromycin resistance or high eradication rates, and using quadruple (bismuth-containing or non-bismuth) therapy as a first line in all other areas. This is consistent with our approach. (See "Treatment regimens for Helicobacter pylori", section on 'Sequential therapy'.)
H. pylori eradication and risk of gastric cancer (May 2016)
It has been unclear if eradication of Helicobacter pylori infection reduces the risk of gastric cancer among asymptomatic individuals in populations that are not at high risk for gastric cancer. A meta-analysis of 27 studies included approximately 48,000 individuals, among whom 4800 were infected with H. pylori and approximately 700 had incident gastric cancers . Individuals with eradication of H. pylori had a lower incidence of gastric cancer compared with those who did not receive eradication therapy. H. pylori eradication was associated with a greater reduction in the incidence of gastric cancer in patients from populations with higher baseline rates of gastric cancer than in those from populations with lower baseline rates of gastric cancer. (See "Association between Helicobacter pylori infection and gastrointestinal malignancy", section on 'Does treatment reduce risk of gastric cancer?'.)
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. 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 laboratory testing'.)
Sofosbuvir-velpatasvir for all genotypes of chronic HCV infection (July 2016)
All-oral, direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have proliferated over the past two years. Sofosbuvir-velpatasvir, a coformulated combination of an NS5B and an NS5A inhibitor, is the first such regimen that has high, well-established efficacy for all genotypes, even in patients with cirrhosis or prior treatment failure with interferon-based regimens [8-10]. This agent was approved by the US Food and Drug Administration in June 2016 and is now our preferred or one of our preferred regimens for adults with chronic HCV infection of any genotype because of its efficacy, simplicity of administration, and limited drug interactions. Sofosbuvir-velpatasvir is given for 12 weeks for all genotypes. For genotype 3 infection, the addition of ribavirin may be warranted, depending on the presence of cirrhosis, the prior treatment history, and the presence of mutations associated with NS5A resistance. (See "Treatment regimens for chronic hepatitis C virus genotype 1 infection in adults", section on 'Selection of treatment regimens' and "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults", section on 'Selection of treatment regimen' and "Treatment regimens for chronic hepatitis C virus genotypes 4, 5, and 6 infection in adults", section on 'Selection of treatment regimens'.)
Declining use of feeding tubes in advanced dementia (August 2016)
Patients with advanced dementia commonly have eating problems in the final stages of illness, and caregivers are faced with decisions about whether to continue oral feeding by hand or place a long-term feeding tube. The available evidence fails to demonstrate any health benefits of tube feeding over ongoing hand feeding, and an increasing number of consensus-based guidelines advocate against feeding tube placement in this setting. In keeping with these recommendations, a recent study in the United States found that the proportion of nursing home residents with advanced dementia who received a feeding tube within one year of the onset of feeding problems decreased by approximately 50 percent between the years 2000 and 2014 . Advance care planning is critical in the management of patients with dementia and should include preparatory discussions about eating problems and other common complications encountered in the advanced stages of the disease. (See "Palliative care of patients with advanced dementia", section on 'Oral versus tube feeding'.)
PANCREATIC AND BILIARY DISEASE
68-Ga DOTATATE approved for imaging of neuroendocrine tumors (June 2016)
Most well-differentiated neuroendocrine tumors arising in the gastrointestinal tract, pancreas, bronchus, and other sites express somatostatin receptors, and they can be imaged using radiolabeled somatostatin analogs. Uptake of radiolabeled somatostatin analogs is predictive of a clinical response to somatostatin analogs such as octreotide, and a positive scan can also identify an otherwise occult primary site in patients presenting with metastatic disease. Newer positron-emitting somatostatin analogs such as Gallium 68-Ga DOTATATE (68-Ga DOTATATE) have emerged which, when combined with high-resolution positron emission tomography (PET) scanning, are more sensitive than conventional 111-In pentetreotide imaging (OctreoScan) for detection of small lesions . A kit for preparation of 68-Ga DOTATATE injection as a radioactive diagnostic agent for PET imaging (Netspot) was approved by the US Food and Drug Administration in June 2016 . Due to its greater sensitivity, 68-Ga DOTATATE PET may be preferred over conventional 111-In pentetreotide scanning in certain clinical settings (eg, small volume disease), where available. (See "Neuroendocrine neoplasms of unknown primary site", section on 'Initial workup' and "Metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors: Presentation, prognosis, imaging, and biochemical monitoring", section on 'Somatostatin receptor-based imaging techniques'.)
Adverse outcomes with lack of follow-up following emergency department visit for biliary colic (April 2016)
Proper follow-up of patients being discharged from the emergency department following an episode of symptomatic gallstones is important to avoid adverse outcomes. This was examined in a study of more than 11,000 Texas Medicare patients age 66 and older with symptomatic gallstones who were discharged from the emergency department without undergoing cholecystectomy . A quarter of the patients did not see a physician in follow-up. Subsequent emergency hospitalization was required in 78 percent of those patients (compared with 8 percent of those who saw a surgeon and 15 percent of those who saw a physician other than a surgeon). Of the patients with biliary colic, 17 percent required emergency cholecystectomy, with a complication rate of 41 percent (compared with a 19 percent complication rate for elective cholecystectomy). This study reinforces the importance of appropriate follow-up and management for patients with symptomatic gallstones. (See "Uncomplicated gallstone disease in adults", section on 'Cholecystectomy'.)
Underutilization of pancreatic enzyme replacement therapy in advanced pancreatic cancer (April 2016)
Patients with advanced pancreatic cancer often have extreme weight loss, and one contributory factor is pancreatic exocrine insufficiency, which leads to maldigestion, fat malabsorption, steatorrhea, and weight loss. Despite recommendations from expert groups that patients who are suspected of having fat malabsorption should be treated empirically with oral pancreatic enzyme replacement therapy (PERT), the available evidence suggests that PERT is underutilized. In a review of 129 patients with metastatic pancreatic cancer who were referred to a specialist palliative care service in Australia, over 70 percent had symptoms that could be attributed to malabsorption (abdominal pain, bloating, gaseousness and steatorrhea), yet only 21 percent were prescribed PERT . (See "Supportive care of the patient with locally advanced or metastatic exocrine pancreatic cancer", section on 'Pancreatic exocrine insufficiency'.)
SMALL BOWEL AND COLONIC DISEASE
Biosimilars for tumor necrosis factor inhibitors (August 2016)
Copies of biologic agents, termed biosimilars, including several of the tumor necrosis factor (TNF) inhibitors and other medications, have been marketed or are under development for use in the rheumatic diseases. A recent systematic review of 19 observational studies and clinical trials compared biosimilar TNF-alpha inhibitors with their reference biologic products, including infliximab, etanercept, and adalimumab, with testing done in healthy volunteers and in patients with rheumatoid arthritis, inflammatory bowel disease, and ankylosing spondylitis . Pharmacokinetic measurements were within defined equivalence margins, and similar clinical responses and adverse events were found for the tested products and their reference drugs. Additionally, similar efficacy and safety were observed in four cohort studies in which patients were switched from the reference product to a biosimilar medication. Limitations for many of the studies included small sample size and short trial duration, but collectively these data illustrate the potential utility of these agents. (See "Overview of biologic agents and kinase inhibitors in the rheumatic diseases", section on 'Biosimilars for biologic agents'.)
Investigational stem cell therapy for complex perianal fistulas in Crohn disease (August 2016)
Complex fistulas in Crohn disease are often refractory to medical therapy. In a randomized trial, 212 patients with treatment-refractory, draining complex perianal fistulas were assigned to a single intralesional injection of allogeneic, expanded, adipose-derived mesenchymal stem cells (Cx601) or saline solution in addition to their concomitant baseline treatment . Rates of combined remission at 24 weeks were significantly higher in patients treated with Cx601 compared with placebo. The incidence of anal abscess and proctalgia, the most frequent serious treatment-related adverse events, were slightly higher in the placebo group. Additional studies with long-term follow-up are needed to assess the safety and efficacy of this therapy and its mechanism of action. (See "Investigational therapies in the medical management of Crohn disease", section on 'Stem cell therapy'.)
AAP guidance on use of biologic response modifiers (July 2016)
Biologic response modifiers (BRMs) are immunosuppressive agents that are used to treat autoimmune disorders such as juvenile idiopathic arthritis and inflammatory bowel disease. Patients receiving BRMs have an increased risk of infection, particularly mycobacterial, viral, and fungal infections. Thus, the American Academy of Pediatrics has published guidance for clinicians using these agents . A thorough history is recommended to help determine infectious risk, with performance of screening tests as indicated depending upon the history and biologic agent chosen. Administration of routine immunizations at least two weeks prior to starting a BRM is advised for inactivated or subunit vaccines and at least four weeks prior for live vaccines, if treatment can be safely delayed. Administration of live vaccines is not recommended during treatment with BRMs. An infectious disease specialist should be consulted if a live vaccine is deemed necessary while a patient is on biologic therapy. Inactivated and subunit vaccines can be given while on therapy, and an annual inactivated influenza vaccine is recommended. (See "Systemic juvenile idiopathic arthritis: Treatment", section on 'Biologic therapy'.)
Oral vaccine to prevent cholera in high-risk travelers (June 2016)
Cholera, caused by infection with the bacterium Vibrio cholerae, is characterized by severe watery diarrhea, which can rapidly lead to dehydration. In June 2016, a live attenuated oral cholera vaccine (Vaxchora) was approved by the US Food and Drug Administration for prevention of cholera caused by serogroup O1 in adults 18 through 64 years of age traveling to affected areas . Most travelers are at low risk for cholera infection; those who warrant vaccination include aid, refugee, and health care workers planning to work among or near displaced populations (eg, in crowded camps and urban slums) in endemic or epidemic settings. Long-stay travelers in very high-risk countries are also appropriate vaccine recipients. In a trial of healthy volunteers, a single dose of vaccine given prior to an oral challenge with a V. cholerae O1 strain was 80 to 90 percent effective in preventing moderate to severe cholera . The effectiveness of Vaxchora for populations living in cholera-affected areas has not been established. (See "Immunizations for travel", section on 'Cholera vaccine'.)
Rome IV criteria for functional gastrointestinal disorders (June 2016)
The Rome Foundation has released revised criteria (Rome IV) for the diagnosis of functional gastrointestinal disorders . Examples of notable revisions include the changes to the criteria for irritable bowel syndrome and its subtypes, new criteria for reflux hypersensitivity, and inclusion of diagnoses with known etiologies that alter gut-brain interaction (eg, opioid-induced constipation). (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults", section on 'Diagnostic criteria'.)
Diagnostic criteria for opioid-induced constipation (May 2016)
Constipation is the most common and persistent side effect of opioid analgesics. Diagnostic criteria for opioid-induced constipation are now available (the Rome-IV criteria), which are based upon reduced bowel frequency, development or worsening of straining, a sense of incomplete evacuation, or a patient's perception of distress related to bowel habits . (See "Cancer pain management with opioids: Prevention and management of side effects", section on 'Diagnosis'.)
Ozanimod for ulcerative colitis (May 2016)
Ozanimod, an experimental agent, is an oral agonist of the sphingosine-1-phosphate receptor subtypes 1 and 5 that decreases circulating activated lymphocytes. In a randomized trial, 197 patients with moderate to severe ulcerative colitis were assigned to ozanimod (1 mg or 0.5 mg daily) or placebo for 32 weeks . At eight weeks, patients treated with the higher dose of ozanimod had a slightly higher rate of clinical remission compared with placebo (16 versus 6 percent). There were no significant differences in adverse effects between the groups. Larger trials with extended treatment are needed to establish the clinical efficacy and safety of ozanimod. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Sphingosine-1-phosphate receptor agonist'.)
OTHER GASTROENTEROLOGY AND NUTRITION
Outbreak of Burkholderia cepacia infection associated with contaminated oral liquid docusate (June 2016)
In June 2016, a multistate outbreak of Burkholderia cepacia infection was reported in the United States . B. cepacia typically causes lung colonization and infection in patients with cystic fibrosis (CF), but most cases in this outbreak have involved mechanically ventilated intensive care unit patients without CF. The types of infections involved have not yet been reported. Because cases in one state have been associated with contaminated oral liquid docusate, the United States Centers for Disease Control and Prevention (CDC) recommends that facilities not use liquid docusate products for any patient. PharmaTech LLC, the manufacturer of the contaminated product, Diocto Liquid, has voluntarily recalled all non-expired lots . Updated information about the outbreak and public health reporting can be found on the CDC’s website. (See "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Outbreak of Burkholderia cepacia infection'.)
Proton pump inhibitors and chronic kidney disease (May 2016)
Two observational studies suggest that protein pump inhibitors (PPIs) may increase the risk of chronic kidney disease (CKD). In one study, data were analyzed from over 10,000 participants in the Atherosclerosis Risk in Communities (ARIC) study, and from a large integrated health care system in the United States . In an analysis adjusted for multiple variables, PPI use was associated with increased risk of CKD compared with no PPI use (hazard ratio [HR] 1.5), and compared with use of H2 receptor antagonists (HR 1.4). In a study of over 170,000 new PPI users and 20,000 new H2 receptor antagonist users followed for over five years, the PPI group had an increased risk of CKD (HR 1.3) and end-stage renal disease (HR 2.0), and increasing duration of use was associated with a progressively higher CKD risk . The mechanism underlying the association between PPIs and risk of CKD is not known, nor is it clear whether decreasing PPI use decreases the risk of CKD. Moreover, PPIs are used to prevent gastroduodenal mucosal injury from nonsteroidal anti-inflammatory agents (NSAIDs), and only one of the two studies evaluated NSAID use and found that it was higher among PPI users compared with PPI nonusers . Additional studies are needed to define a causal relationship between PPI use and the development and worsening of CKD. (See "Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders", section on 'Kidney disease'.)
- US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2016; 315:2564.
- http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/MolecularandClinicalGeneticsPanel/UCM390238.pdf (Accessed on April 25, 2016).
- 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 Reductions Following Topical Steroid Therapy for Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2016.
- Fallone CA, Chiba N, van Zanten SV, et al. The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults. Gastroenterology 2016; 151:51.
- Lee YC, Chiang TH, Chou CK, et al. Association Between Helicobacter pylori Eradication and Gastric Cancer Incidence: A Systematic Review and Meta-analysis. Gastroenterology 2016; 150:1113.
- 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).
- Feld JJ, Jacobson IM, Hézode C, et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med 2015; 373:2599.
- Everson GT, Towner WJ, Davis MN, et al. Sofosbuvir With Velpatasvir in Treatment-Naive Noncirrhotic Patients With Genotype 1 to 6 Hepatitis C Virus Infection: A Randomized Trial. Ann Intern Med 2015; 163:818.
- Pianko S, Flamm SL, Shiffman ML, et al. Sofosbuvir Plus Velpatasvir Combination Therapy for Treatment-Experienced Patients With Genotype 1 or 3 Hepatitis C Virus Infection: A Randomized Trial. Ann Intern Med 2015; 163:809.
- Mitchell SL, Mor V, Gozalo PL, et al. Tube Feeding in US Nursing Home Residents With Advanced Dementia, 2000-2014. JAMA 2016; 316:769.
- Sadowski SM, Neychev V, Millo C, et al. Prospective Study of 68Ga-DOTATATE Positron Emission Tomography/Computed Tomography for Detecting Gastro-Entero-Pancreatic Neuroendocrine Tumors and Unknown Primary Sites. J Clin Oncol 2016; 34:588.
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm504524.htm (Accessed on June 07, 2016).
- Dimou FM, Adhikari D, Mehta HB, Riall TS. Trends in Follow-Up of Patients Presenting to the Emergency Department with Symptomatic Cholelithiasis. J Am Coll Surg 2016; 222:377.
- Landers A, Muircroft W, Brown H. Pancreatic enzyme replacement therapy (PERT) for malabsorption in patients with metastatic pancreatic cancer. BMJ Support Palliat Care 2016; 6:75.
- Chingcuanco F, Segal JB, Kim SC, Alexander GC. Bioequivalence of Biosimilar Tumor Necrosis Factor-α Inhibitors Compared With Their Reference Biologics: A Systematic Review. Ann Intern Med 2016.
- Panés J, García-Olmo D, Van Assche G, et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial. Lancet 2016; 388:1281.
- American Acedemy of Pediatrics Clinical Report: Infectious complications with the use of biologic response modifiers in infants and children. http://pediatrics.aappublications.org/content/pediatrics/early/2016/07/14/peds.2016-1209.full.pdf (Accessed on July 19, 2016).
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm506305.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Accessed on June 13, 2016).
- Chen WH, Cohen MB, Kirkpatrick BD, et al. Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor. Clin Infect Dis 2016; 62:1329.
- Mearin F, Lacy BE, Chang L, et al. Bowel Disorders. Gastroenterology 2016.
- Sandborn WJ, Feagan BG, Wolf DC, et al. Ozanimod Induction and Maintenance Treatment for Ulcerative Colitis. N Engl J Med 2016; 374:1754.
- Centers for Disease Control and Prevention. Healthcare-assocated infection. Multistate outbreak of Burkholderia cepacia infections. https://www.cdc.gov/hai/outbreaks/b-cepacia/index.html (Accessed on July 14, 2016).
- US Food and Drug Administration. Oral liquid docusate sodium by PharmaTech: Recall - contaminated with B. cepacia. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm511528.htm (Accessed on July 19, 2016).
- Lazarus B, Chen Y, Wilson FP, et al. Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Intern Med 2016; 176:238.
- Xie Y, Bowe B, Li T, et al. Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD. J Am Soc Nephrol 2016; 27:3153.