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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.
Blood test for colorectal cancer screening (April 2016)
In 2016, the US Food and Drug Administration (FDA) approved a second-generation serum 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 serum test should be followed up with a colonoscopy. However, there is no strong evidence of the effectiveness of screening for colorectal cancer with available serum markers. Until further evidence is available, we do not recommend serum tests for colorectal cancer screening. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Serum markers'.)
Updated guidelines for endoscopic surveillance after treatment of colorectal cancer (March 2016)
Updated guidelines for posttreatment endoscopic surveillance from a United States Multi-Society Task Force on Colorectal Cancer are available . The most notable change is a recommendation for flexible sigmoidoscopy or endoscopic ultrasound every three to six months for the first two to three years after surgery for rectal cancer in patients who are at increased risk for a local recurrence, including those with localized rectal cancer who have undergone surgery without total mesorectal excision (TME), those who have undergone transanal local excision or endoscopic submucosal dissection alone, and those with locally advanced rectal cancer who did not receive neoadjuvant chemoradiotherapy followed by TME. (See "Surveillance after colorectal cancer resection", section on 'Proctosigmoidoscopy'.)
ESOPHAGEAL AND GASTRIC DISEASE
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?'.)
Vonoprazan-based triple therapy for H. pylori eradication (March 2016)
Vonoprazan is a novel oral potassium-competitive acid blocker (PCAB). In a randomized noninferiority trial, 650 H. pylori-positive patients with a history of a gastric or duodenal ulcer were assigned to first-line triple therapy with amoxicillin, clarithromycin, and either lansoprazole or vonoprazan . Patients failing first-line therapy received open-label second-line therapy with vonoprazan, amoxicillin, and metronidazole. Vonoprazan-based first-line therapy was noninferior to lansoprazole-based therapy with H. pylori eradication rates of 93 and 76 percent, respectively. There were no significant differences in adverse effects. The eradication rate with vonoprazan-based second-line triple therapy was 98 percent. Vonoprazan may be an effective option for H. pylori eradication in combination with antibiotics; however, further studies are needed. (See "Treatment regimens for Helicobacter pylori", section on 'Other regimens'.)
Proton pump inhibitors and risk of dementia in older adults (February 2016)
A new study has identified a possible link between proton pump inhibitors (PPIs) and risk of dementia in older adults. In a prospective cohort study of >73,000 adults aged 75 years and older who were free of dementia at baseline, regular use of a PPI was associated with a 1.4-fold increase in the risk of incident dementia, independent of age, gender, depression, stroke, heart disease, and polypharmacy . Possible factors that could contribute to this finding include PPI-induced vitamin B12 deficiency or an interaction between PPIs and amyloid beta deposition, although these factors were not examined in this study. On the other hand, the association may reflect residual confounding by factors related to both use of PPIs and the development of dementia, and more studies are needed to confirm or refute this association. (See "Epidemiology, pathology, and pathogenesis of Alzheimer disease", section on 'Medications'.)
Defibrotide for hepatic sinusoidal obstruction syndrome (April 2016)
Hepatic sinusoidal obstruction syndrome (SOS) is an uncommon but serious complication of allogeneic hematopoietic cell transplantation (HCT). It accounts for a significant fraction of transplant-related mortality and, in its severe form, is almost always fatal when treated with supportive care alone. Small single-arm prospective trials have demonstrated modest improvement in patients with severe SOS treated with defibrotide. In the largest international study, 102 adults and children with SOS and multiorgan failure were treated with defibrotide . When compared with historical controls, defibrotide was associated with higher response rates and improved survival (38 versus 25 percent at day +100). Based on this and other studies, defibrotide has been approved by the US Food and Drug Administration for the treatment of severe SOS . It is our preferred therapy for such patients. (See "Treatment and prevention of hepatic sinusoidal obstruction syndrome following hematopoietic cell transplantation", section on 'Defibrotide'.)
Liver cancer death rates increasing in the United States (March 2016)
Over the past 30 years, death rates in the United States have declined for all common cancers (eg, breast, prostate, and lung), with the exception of liver cancer. In the Annual Report to the Nation on the Status of Cancer, 1975-2012, the overall cancer death rates for men and women of all major racial and ethnic populations decreased by 1.5 percent per year between 2003 and 2012 . However, during this same period, liver cancer death rates increased by 2.8 percent per year in men and 3.4 percent per year in women, while liver cancer incidence rates increased by 3.5 percent per year in men and 3 percent per year in women. (See "Epidemiology and etiologic associations of hepatocellular carcinoma", section on 'Epidemiology'.)
Zika virus and tissue/gamete donation (March 2016)
Zika virus has been detected in a number of tissues and body fluids. To avoid possible transmission of Zika virus infection, the US Food and Drug Administration (FDA) has issued donor deferral recommendations for hematopoietic stem cells, tissues, and donor sperm or eggs; the recommendations do not apply to solid organs . Living donors with Zika virus infection or relevant epidemiologic exposure (residence in or travel to an area where mosquito-borne transmission of Zika virus infection has been reported, or unprotected sexual contact with a person who meets these criteria) should be considered ineligible for donation for six months. Deceased donors with Zika virus infection in the preceding six months should also be considered ineligible. The deferral period recommended by the FDA for blood donors with risk factors for Zika virus infection remains at four weeks. (See "Zika virus infection: An overview", section on 'Blood/tissue donation'.)
Elbasvir-grazoprevir for chronic HCV infection (February 2016)
Despite the proliferation of interferon-free regimens for the treatment of chronic hepatitis C (HCV) infection, safety concerns have limited options for patients with severe renal impairment, who have been excluded from trials of most available regimens. In January 2016, the US Food and Drug Administration approved the new combination regimen elbasvir-grazoprevir for the treatment of patients with genotypes 1 and 4 HCV infection, including those with any degree of renal impairment (including dialysis dependence) . In a randomized, placebo-controlled trial of genotype 1-infected patients with estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m2, the sustained virologic response (SVR) rate was 94 percent among the 122 patients who received elbasvir-grazoprevir for 12 weeks, and adverse event rates were similar between treatment and placebo groups . These results were comparable to those among patients with normal renal function. Elbasvir-grazoprevir is given for 12 to 16 weeks with or without ribavirin, depending on the presence of pre-existing resistance-associated variants in the NS5A protein and prior exposure to HCV protease inhibitors. (See "Treatment of chronic hepatitis C infection in adults with renal impairment", section on 'Regimens with direct-acting antivirals'.)
Hepatitis B virus reactivation in patients undergoing chemotherapy for solid tumors (January 2016)
Patients with serologic evidence of hepatitis B virus (HBV) infection (hepatitis B surface antigen [HBsAg]-positive or hepatitis B core antibody [anti-HBc]-positive) are at risk for HBV reactivation if they receive immunosuppressive therapy. However, the magnitude of risk for patients receiving chemotherapy for solid tumors has not been well established. In a systematic review of such patients, the risk of reactivation among those who were HBsAg-positive ranged from 4 to 68 percent, with most studies reporting a reactivation risk greater than 10 percent . Antiviral therapy administered during chemotherapy was associated with an approximately 90 percent reduction in HBV reactivation risk as well as reductions in HBV-related hepatitis and the need for chemotherapy interruption. Although some expert groups disagree, we check HBV serologies before initiating therapy with any potentially immunosuppressive chemotherapy. Our recommendations for prophylactic antiviral therapy depend upon the HBsAg status of the patient and the type of chemotherapy used. (See "Hepatitis B virus reactivation associated with immunosuppressive therapy", section on 'Who is at risk for HBV reactivation'.)
Investigational combination of sofosbuvir plus velpatasvir for chronic HCV infection (November 2015)
The selection of all-oral antiviral regimens for patients with chronic hepatitis C virus (HCV) infection currently depends on the infecting genotype, treatment history, and the presence of cirrhosis. The investigational agent sofosbuvir-velpatasvir, a coformulated combination of an NS5B and an NS5A inhibitor, appears extremely effective across viral genotypes and patient characteristics, and thus offers the possibility of a streamlined approach to regimen selection. In a randomized, placebo-controlled trial of patients with genotypes 1, 2, 4, 5, and 6 infection, including those with cirrhosis and prior treatment failure with interferon-containing regimens, the sustained virologic response (SVR) rate among the 624 patients who were assigned to receive sofosbuvir-velpatasvir for 12 weeks was 99 percent . In another study, the regimen resulted in an SVR rate of 98 percent among 163 treatment-naïve genotype 3-infected patients without cirrhosis . SVR rates were somewhat lower, but still high (89 to 93 percent), in the setting of genotype 3 infection with cirrhosis and/or prior treatment failure. (See "Investigational therapies for hepatitis C virus infection", section on 'Sofosbuvir and velpatasvir'.)
PANCREATIC AND BILIARY DISEASE
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 advanced exocrine pancreatic cancer", section on 'Pancreatic exocrine insufficiency'.)
Progression from acute to chronic pancreatitis (December 2015)
There are limited data on the natural history of acute pancreatitis. In a meta-analysis that included over 8000 patients with acute pancreatitis, the pooled prevalence of recurrent acute pancreatitis and chronic pancreatitis were 22 and 10 percent, respectively . The prevalence of chronic pancreatitis following the first episode and following recurrent acute pancreatitis were 10 and 36 percent, respectively. Among individuals with a history of smoking or alcohol use, the prevalence of chronic pancreatitis was 65 and 61 percent, respectively. The risk of progression to chronic pancreatitis was higher in men than in women after controlling for age and severity of acute pancreatitis. (See "Clinical manifestations and diagnosis of acute pancreatitis", section on 'Disease course'.)
SMALL BOWEL AND COLONIC DISEASE
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'.)
Skin disorders associated with TNF inhibitor use (February 2016)
A variety of skin disorders have been reported in association with the use of tumor necrosis factor (TNF) inhibitors for inflammatory and autoimmune conditions. The largest of several recent studies of patients with inflammatory bowel disease (IBD) receiving these agents involved a cohort of 917 consecutive patients with IBD on TNF inhibitors for a median of 3.5 years, in whom 29 percent developed skin lesions (12.4 per 100 patient-years) . Specific cutaneous lesions included (from most to least common) psoriasiform eczema, eczema, xerosis cutis, palmoplantar pustulosis, and psoriasis; other abnormalities were mostly infectious and inflammatory skin lesions and alopecia. The majority of patients were managed without discontinuation of TNF inhibitor therapy. Limitations of the analysis included uncertainty regarding the relative roles of the treatment and the underlying disease due to the lack of a matched control group not receiving TNF inhibitors. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Cutaneous reactions'.)
Eluxadoline for irritable bowel syndrome with diarrhea (January 2016)
Eluxadoline, a mu-opioid receptor agonist and a delta-opioid receptor antagonist, has been evaluated for treatment of irritable bowel syndrome with diarrhea (IBS-D). In two phase 3 studies, over 2000 adults with IBS-D were randomly assigned to two different doses of eluxadoline or placebo twice daily for 26 and 52 weeks, respectively . The primary endpoint was the proportion of patients who had a composite response of less abdominal pain and improvement in stool consistency for at least 50 percent of the days. For weeks 1 through 26, significantly more patients receiving higher-dose eluxadoline achieved the primary endpoint (29 to 33 percent) compared with placebo (19 to 20 percent) in both trials. The most common adverse events associated with eluxadoline were nausea, constipation, and abdominal pain, and pancreatitis developed in 0.3 percent. Eluxadoline has been approved for treatment of IBS-D, but is not commercially available. Further studies are needed to identify sub-populations of patients with IBS-D who may benefit most from eluxadoline. (See "Treatment of irritable bowel syndrome in adults", section on 'Antidiarrheal agents'.)
Frozen fecal microbiota transplantation for Clostridium difficile infection (January 2016)
Treatment with fecal microbiota transplantation (FMT) has been hampered by logistic difficulties in preparation and administration of the fecal suspension. In a randomized non-inferiority trial, 219 patients with recurrent Clostridium difficile infection (CDI) or refractory CDI were assigned to receive frozen-and-thawed or fresh FMT via rectal enema . In the modified intention-to-treat population, rates of clinical resolution in the frozen FMT group were non-inferior to fresh FMT, and there were no differences in adverse events between the two groups. The use of frozen FMT also has the potential advantage of immediate availability. Frozen FMT is currently an investigational technique for the treatment of C. difficile. (See "Fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection", section on 'Suggested protocol'.)
Sigmoid resection versus laparoscopic lavage for perforated diverticulitis (January 2016)
The laparoscopic lavage and drainage procedure was introduced as a potentially less morbid alternative to sigmoid resection for patients with perforated diverticulitis. In the SCANDIV trial, 199 patients with perforated diverticulitis were randomized to undergo either laparoscopic lavage or sigmoid resection . At 90 days, laparoscopic lavage did not improve mortality rates (14 versus 12 percent) or major morbidity rates (31 versus 26 percent) compared with sigmoid resection. Furthermore, patients who underwent laparoscopic lavage were more likely to require reoperation (20 versus 6 percent) for complications such as secondary peritonitis or missed sigmoid cancer. Based upon these results and other available data, sigmoid resection with or without fecal diversion remains the preferred intervention for patients with perforated diverticulitis. (See "Management of acute complicated diverticulitis".)
Acute diverticulitis: Risk of recurrence (December 2015)
There are limited data on the natural history of acute diverticulitis. In a population-based study that included over 3000 patients with acute diverticulitis, recurrent diverticulitis in a 10-year period after the index and second diverticulitis episode occurred in 22 and 55 percent of patients, respectively . The risk of recurrence was higher in younger individuals and in women. Increasing age was associated with a higher risk of both local and systemic complications. (See "Clinical manifestations and diagnosis of acute diverticulitis in adults", section on 'Disease course'.)
OTHER GASTROENTEROLOGY AND NUTRITION
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. (See "Screening for chronic kidney disease", section on 'Risk factors for chronic kidney disease'.)
Reversal agent for factor Xa inhibitors (November 2015)
Lack of reversal agents for the direct oral anticoagulants has been a concern. Andexanet alfa is a recombinant protein designed to reverse factor Xa inhibitors by binding to the drugs and sequestering them away from endogenous factor Xa. In a randomized trial in healthy volunteers, an andexanet bolus reduced anti-factor Xa activity by 94 percent and 92 percent for volunteers taking apixaban or rivaroxaban, respectively, compared with reductions of 21 and 18 percent for a placebo bolus . A study evaluating andexanet efficacy in patients with factor Xa inhibitor-associated bleeding is ongoing. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Antidotes under development'.)
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