Peter A L Bonis, MD
Anne C Travis, MD, MSc, FACG, AGAF
Shilpa Grover, MD, MPH, AGAF
Kristen M Robson, MD, MBA, FACG
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.
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".)
Pembrolizumab for advanced colorectal cancer and other refractory solid tumors with deficient DNA mismatch repair (May 2017)
In a small study comparing pembrolizumab administration in patients with mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) or with MMR proficient (pMMR) mCRC, the objective response rate and disease control rate were 50 and 89 percent, respectively, for patients with dMMR mCRC and 0 and 16 percent for the pMMR group [2-4]. Largely based upon these data, the US Food and Drug Administration granted accelerated approval to pembrolizumab for the treatment of patients with advanced microsatellite instability-high (MSI-H) or dMMR mCRC that has progressed following conventional chemotherapy . The approval of pembrolizumab also extended to a variety of other advanced solid tumors (including endometrial, other gastrointestinal, breast, prostate, bladder, and thyroid) that were MSI-H or dMMR, had progressed following prior treatment, and for which there were no satisfactory alternative treatment options. (See "Systemic chemotherapy for metastatic colorectal cancer: Completed clinical trials", section on 'Immune checkpoint inhibitors and mismatch repair deficient tumors' and see "Treatment of recurrent or metastatic endometrial cancer", section on 'Immune checkpoint inhibitors'.
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'.)
Oral fluid intake before anesthesia (August 2017)
Oral intake is generally restricted for two hours before anesthesia, but the volume of clear liquids that should be allowed before this deadline is unclear. In a study of patients who drank ≥2 liters of bowel preparation solution before colonoscopy, no difference in gastric residual volume or gastric pH was observed between those who finished the solution as late as three hours prior to the procedure versus those who finished it the night before . These data provide support for allowing patients free access to clear liquids until two hours prior to anesthesia and are particularly relevant to enhanced recovery after surgery protocols, which may include ingestion of 300 to 400 mL of carbohydrate drinks up to two hours prior to surgery. (See "Preoperative fasting guidelines", section on 'Clear liquids'.)
ESOPHAGEAL AND GASTRIC DISEASE
Recurrence of acid reflux after laparoscopic anti-reflux surgery (October 2017)
Although over 90 percent of patients are satisfied with the results of their anti-reflux surgery, criteria defining treatment success or failure vary among studies. In a population-based study from Sweden including over 2600 patients who underwent laparoscopic anti-reflux surgery, 18 percent developed recurrent reflux necessitating either long-term use of anti-reflux medications (393 patients) or repeat anti-reflux surgery (77 patients) at median follow-up of 5.6 years . Risk factors for recurrence included female sex, older age, and comorbidity. (See "Surgical management of gastroesophageal reflux in adults", section on 'Long-term efficacy'.)
Four-food elimination diet for eosinophilic esophagitis (July 2017)
The traditional six-food (cow's milk, hen's egg, soy, wheat, peanut/tree nuts, and fish/shellfish) elimination diet for eosinophilic esophagitis (EoE) results in resolution of EoE in approximately three-quarters of children but is challenging and can have negative nutritional consequences. In a prospective study of four-food elimination (milk, soy, egg, wheat) in 78 children with EoE, histologic remission was achieved in 64 percent, with decreased symptoms in 91 percent . Thus, we now suggest either the four-food or six-food empiric elimination diet for most patients who opt for dietary management of EoE. (See "Dietary management of eosinophilic esophagitis", section on 'Elimination diets'.)
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'.)
Increase in immune globulin dose for prevention of hepatitis A (September 2017)
Intramuscular immune globulin (IG) is protective against hepatitis A virus (HAV) infection and is used for pre- and postexposure prophylaxis instead of vaccination in certain situations. The level of neutralizing anti-HAV antibodies in GamaSTAN, the intramuscular IG product available in the United States, appears suboptimal, reflecting low prevalence of prior HAV infection among plasma donors . Therefore, increased dosing for GamaSTAN is now recommended when used for HAV prevention [13,14]. The new dose for preexposure prophylaxis is 0.1 mL/kg (for anticipated risk of exposure up to one month) or 0.2 mL/kg (for anticipated risk of exposure up to two months, with repeat dosing every two months for longer anticipated risk). The new dose for postexposure prophylaxis is 0.1 mL/kg. (See "Hepatitis A virus infection: Prevention", section on 'Passive immunization'.)
HEV infection in Europe and outbreaks in Africa (August 2017)
Hepatitis E virus (HEV) infection has a global distribution and is most commonly transmitted through contaminated food or water. In July 2017, World Health Organization reported an outbreak of HEV in Nigeria, where a humanitarian crisis has resulted in poor access to safe water and health services . An earlier outbreak in nearby Niger had been reported in May 2017. In a separate 2017 surveillance analysis, the European Centre for Disease Prevention reported an increase in the number of confirmed HEV cases in Europe from 514 cases in 2005 to 5617 cases in 2015 . It is unclear if this represents a true rise in HEV incidence in Europe or an increase in case detection due to growing awareness and testing for HEV. (See "Hepatitis E virus infection", section on 'Epidemiology'.)
Anticoagulant therapy in patients with cirrhosis and portal vein thrombosis (August 2017)
Anticoagulant therapy may be beneficial for patients with cirrhosis and portal vein thrombosis. In a meta-analysis of eight studies including over 350 such patients, patients treated with anticoagulants (ie, low molecular-weight heparin or warfarin) had higher rates of either partial or complete recanalization compared with untreated patients (71 versus 42 percent) . In six studies, the overall rate of bleeding was similar with or without anticoagulation (11 percent in both groups). We individualize the decision to anticoagulate in this setting, taking into account several factors including the risk of bleeding, the risk of further thrombosis, and whether the patient is awaiting liver transplantation. (See "Chronic portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management", section on 'Cirrhotic patients'.)
Novel HBV mutation associated with tenofovir and entecavir failure (August 2017)
For patients with chronic hepatitis B virus (HBV) infection, tenofovir is one of the preferred antiviral agents. To date, no signature tenofovir-resistance mutations have been identified in HBV. However, in a report of two HBV-infected patients with persistent viremia despite therapy with tenofovir and entecavir, molecular analyses identified a shared distinct mutation, rtS78T/sC69, which was associated with decreased susceptibility to both tenofovir and entecavir in vitro . The prevalence and significance of this mutation remains to be determined. (See "Tenofovir for the treatment of adults with chronic HBV infection", section on 'Risk of resistance'.)
Glecaprevir-pibrentasvir and sofosbuvir-velpatasvir-voxilaprevir for chronic HCV infection (August 2017)
Treatment options for patients with chronic hepatitis C virus (HCV) continue to grow. Two new combination therapies, glecaprevir-pibrentasvir and sofosbuvir-velpatasvir-voxilaprevir, were recently approved by the Food and Drug Administration in the United States and are expected to be approved in Europe this year. Glecaprevir-pibrentasvir is highly effective for patients with genotypes 1 through 6 infection, offers the possibility of an eight-week regimen for most patients without cirrhosis, and can be used in patients with renal impairment (including those on dialysis) [19-22]. It is now one of our preferred regimens for all genotypes; regimen duration depends on the genotype, the presence of cirrhosis, and the treatment history (algorithm 1 and algorithm 2 and algorithm 3 and algorithm 4). Sofosbuvir-velpatasvir-voxilaprevir is highly effective in patients with genotypes 1 through 6 infection who have failed a prior direct acting antiviral (DAA) regimen and is now the main treatment option for those who have failed an NS5A inhibitor-containing regimen . Like other contemporary DAA regimens, these new combinations are well tolerated, with common but mild side effects. (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'.)
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
Partial pancreaticoduodenectomy versus duodenum-preserving pancreatic head resection for chronic pancreatitis (September 2017)
Head-dominant chronic pancreatitis can be treated surgically with either partial pancreaticoduodenectomy or duodenum-preserving pancreatic head resection (DPPHR). In a multicenter randomized trial (ChroPac), the two procedures resulted in similar quality of life at 24 months with no significant differences in major morbidity and mortality rates . DPPHR resulted in shorter operative time (4.7 versus 5.3 hours), but more readmissions due to chronic pancreatitis (27 versus 11 percent). Given that both procedures are equally effective and morbid, surgeons should choose based on their experience and the patient's anatomical and clinical conditions. (See "Surgery for chronic pancreatitis", section on 'Head-dominant 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'.)
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'.)
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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