The following represent additions to UpToDate since the last version of What's New that were considered by the authors and editors to be of particular interest.
ANGIODYSPLASIA OF THE GASTROINTESTINAL TRACT
Treatment with thalidomide — Inhibitors of angiogenesis, such as thalidomide, may play a role in the treatment of angiodysplasia of the gastrointestinal tract. A randomized trial compared the use of thalidomide with control therapy (oral iron) in patients with recurrent or refractory bleeding from angiodysplasia [1]. The primary end point (decrease in bleeding episodes by at least 50 percent) was found more frequently in patients in the thalidomide group, who also experienced higher rates of cessation of bleeding and independence from transfusion. Thalidomide appears to be a reasonable treatment for patients with recurrent or refractory bleeding from gastrointestinal angiodysplasia who have failed to respond to other therapies. However, due to its teratogenic effects, thalidomide must not be used in women of child bearing potential who are unable to use two reliable forms of birth control from at least one month prior to starting thalidomide until one month after stopping it. (See "Angiodysplasia of the gastrointestinal tract".)
BARRETT'S ESOPHAGUS
Risk of esophageal cancer — A 2010 meta-analysis estimated the incidence of esophageal adenocarcinoma in patients with Barrett’s esophagus to be 6.3 cases per 1000 person-years [2]. However, a subsequent large study using the Danish Cancer Registry reported a rate of 1.2 cases per 1000 person-years [3]. This more recent study suggests that the risk of esophageal adenocarcinoma in patients with Barrett's esophagus may be lower than previously suggested. (See "Management of Barrett's esophagus", section on 'Influence of Barrett's esophagus on mortality'.)
CELIAC DISEASE
Small bowel biopsies — Patients with a positive IgA endomysial or transglutaminase antibody test should undergo a small bowel biopsy to diagnose celiac disease. However, the utility of duodenal bulb biopsies is not known. In a case-control study of 461 individuals (126 with newly diagnosed celiac disease, 85 with established celiac disease, and 250 controls), patients with a new diagnosis of celiac disease and established celiac disease were significantly more likely than controls to have villous atrophy in the duodenal bulb alone [4]. These results suggest that the optimal assessment of patients in whom celiac disease is suspected or established requires a duodenal bulb biopsy in addition to distal duodenal biopsies. (See "Diagnosis of celiac disease", section on 'Small bowel biopsy'.)
CONSTIPATION
Sodium phosphate enemas — Sodium phosphate enemas are used in the treatment of constipation and for preparation for flexible sigmoidoscopy. A retrospective series found that sodium phosphate enema use in older adults (mean age 80 years, range 61 to 89 years) was associated with complications including hypotension and volume depletion, hyperphosphatemia, hypo- or hyperkalemia, metabolic acidosis, severe hypocalcemia, renal failure, and EKG changes (prolonged QT interval) [5]. In patients over the age of 70 years, we suggest that warm water enemas rather than sodium phosphate enemas be used for the treatment of constipation. (See "Management of chronic constipation in adults", section on 'Disimpaction' and "Constipation in the older adult", section on 'Stool softeners, suppositories, and enemas'.)
CLOSTRIDIUM DIFFICILE
Recurrent C. difficile infection — Recurrent C. difficile infection often represents relapse rather than reinfection, regardless of the interval between episodes. Among 134 paired stool isolates from 102 patients with recurrent C. difficile infections, isolates obtained two to eight weeks apart were identical in 88 percent of cases; isolates obtained 8 weeks to 11 months apart were identical in 65 percent of cases [6]. (See "Clinical manifestations and diagnosis of Clostridium difficile infection in adults", section on 'Recurrent disease: relapse vs reinfection'.)
ENDOSCOPY
Sodium phosphate for flexible sigmoidoscopy — The preparation for flexible sigmoidoscopy typically involves two sodium phosphate enemas given the morning of the examination. However, sodium phosphate enemas have been associated with complications, particularly in older adults. A retrospective series found that sodium phosphate enema use in older adults (mean age 80 years, range 61 to 89 years) was associated with complications including hypotension and volume depletion, hyperphosphatemia, hypo- or hyperkalemia, metabolic acidosis, severe hypocalcemia, renal failure, and changes on the electrocardiogram (prolonged QT interval) [5]. As a result, in patients over the age of 70 years, the risks of oral preparations (eg, polyethylene glycol lavage or magnesium citrate) and sodium phosphate enemas need to be weighed for each individual patient before deciding upon an appropriate preparation. (See "Bowel preparation for flexible sigmoidoscopy and colonoscopy", section on 'Preparation for flexible sigmoidoscopy'.)
HEPATITIS B VIRUS INFECTION
Vaccination of patients with diabetes mellitus — The Advisory Committee on Immunization Practices recommends that hepatitis B virus (HBV) vaccination be given to unvaccinated adults with diabetes mellitus who are ages 19 to 59 [7]. For older patients with diabetes, vaccination can be administered at the discretion of the treating clinician based on the risk of acquiring HBV and the likelihood of an adequate immune response to vaccination. (See "Hepatitis B virus vaccination", section on 'Other high-risk groups'.)
HEPATITIS C VIRUS INFECTION
Treatment without peginterferon or ribavirin — Standard treatment regimens for hepatitis C virus (HCV) contain peginterferon and ribavirin, but a substantial number of patients cannot receive one or both drugs due to known intolerances or contraindications. Treatment regimens are being studied that do not use peginterferon or ribavirin. Two small studies (21 patients total) tested such regimens in patients with HCV genotype 1. Patients received 24 weeks of treatment with a combination of daclatasvir and asunaprevir, two experimental direct-acting antiviral agents [8,9]. Viral loads 24 weeks after stopping treatment were undetectable in 14 of the patients (67 percent), including one patient who was only treated for two weeks. These preliminary studies suggest that HCV treatment without peginterferon and ribavirin may be possible. (See "Investigational therapies for hepatitis C virus infection", section on 'Combinations that do not contain peginterferon or ribavirin'.)
Drug interactions with boceprevir in patients with HIV — Boceprevir is a protease inhibitor used in the treatment of patients with HCV genotype 1 infection. If boceprevir is used in combination with certain ritonavir-boosted HIV protease inhibitors (eg, atazanavir, lopinavir, darunavir), the effectiveness of boceprevir as well as the ritonavir-boosted medications may be decreased. The US Food and Drug Administration recommends that patients taking boceprevir along with one of the listed ritonavir-boosted protease inhibitors should be closely monitored for potential HCV and HIV virologic rebound [10]. (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Drug interactions with protease inhibitors'.)
HEREDITARY COLORECTAL CANCER
Aspirin for chemoprevention in patients with Lynch syndrome — Individuals with Lynch syndrome have an 80 percent risk of developing colorectal cancer in their lifetime. While an earlier placebo-controlled trial (CAPP2) did not find a benefit for aspirin for adenoma or colon cancer prevention in patients with Lynch syndrome after a mean of 29 months of follow-up, a subsequent analysis found a marginally significant reduction in colorectal cancer incidence in the subset of patients treated with 600 mg aspirin per day for more than two years [11]. A secondary analysis found a decreased rate of overall Lynch cancers in the aspirin-treated group. Further studies are needed to validate this potentially important result and determine if the benefits associated with aspirin outweigh the risks. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Screening and management of patients and families", section on 'Chemoprevention' and "NSAIDs (including aspirin): Role in prevention of colorectal cancer", section on 'Aspirin trials'.)
INFLAMMATORY BOWEL DISEASE
Antibiotic use and risk of IBD — Dysbiosis or an imbalance in the gut microbiome may contribute to the development of inflammatory bowel disease (IBD). In a case-control study, patients with IBD were significantly more likely to have been prescribed antibiotics two to five years before their diagnosis than controls [12]. In the same study, patients who received three or more antibiotic prescriptions two years before the study were 1.5 times more likely to have IBD. (See "Epidemiology and environmental factors in inflammatory bowel disease in adults", section on 'Altered gut flora'.)
Early mucosal healing and outcomes in ulcerative colitis — Mucosal healing has emerged as an important clinical outcome in the treatment of patients with Crohn's disease. However, the significance of mucosal healing in patients with ulcerative colitis (UC) is less clear. In an analysis of two multicenter, randomized controlled trials (Active Ulcerative Colitis [ACT]-1 and ACT-2) in which patients with moderate to severe UC were randomized to receive infliximab or placebo, early mucosal healing at week eight in patients treated with infliximab was associated with a lower risk of colectomy through 54 weeks and higher rates of symptomatic remission, steroid free remission, and subsequent mucosal healing at weeks 30 and 54 [13]. (See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults", section on 'Prognosis'.)
Risk of skin cancer — Data on the risk of nonmelanoma skin cancer (NMSC) in thiopurine exposed IBD patients have been conflicting. In a nested case-control analysis of a large historical cohort study, the use of thiopurines was associated with a significant increase in the risk of squamous cell skin cancer [14]. In another cohort study, both ongoing and past exposure to thiopurines was associated with a significant increase in the risk of NMSC in patients with IBD [15]. These results suggest that patients with IBD on thiopurines may benefit from protection against UV radiation and dermatologic screening. (See "Skin and eye manifestations of inflammatory bowel disease", section on 'Miscellaneous skin lesions'.)
LIVER TRANSPLANTATION
Malignancy following solid organ transplantation — An increased risk of a wide range of cancers is associated with solid organ transplantation, with specific cancer risk varying with the organ transplanted. A cohort study analyzed the frequency of malignancy in over 175,000 solid organ transplant recipients [16]. The standardized incidence ratio for developing cancer was 2.1 compared with the general population, with an excess absolute risk of 719 cases per 100,000 person-years. The biggest relative increases were seen for Kaposi sarcoma, nonmelanoma skin cancer, non-Hodgkin lymphoma, and cancers of the liver, anus, vulva, and lip. Lung cancer, kidney cancer, colorectal cancer, pancreatic cancer, Hodgkin lymphoma, and melanoma also contributed significantly to the excess risk. (See "Development of malignancy following solid organ transplantation", section on 'General epidemiology'.)
NUTRITION
Initiation of enteral nutrition in critically ill patients — Two strategies have been used to initiate enteral nutrition: incrementally increasing the infusion rate until the target maintenance rate is achieved or initiating the infusion at the target maintenance rate. The EDEN trial was a multicenter open-labelled trial that compared these approaches by randomly assigning 1000 mechanically ventilated patients with acute lung injury to receive either full enteral feeding or low-volume enteral feeding for six days, after which both groups received full enteral feeding [17]. The trial found no differences in the number of ventilator-free days, 60-day mortality, or the frequency of infectious complications. However, the low-volume feeding group had less vomiting, smaller gastric residual volumes, lower mean plasma glucose levels, and less constipation. These data suggest that initial low-volume enteral feeding has fewer undesirable effects than initial feeding at the target rate. (See "Nutrition support in critically ill patients: Enteral nutrition", section on 'Amount and rate'.)
Parenteral nutrition as an adjunct to enteral nutrition in critically ill patients — The use of parenteral nutrition as an adjunct to enteral nutrition to improve provision of calories and protein to critically ill patients may be harmful according to two studies. The first study was a multicenter trial that randomly assigned 4640 critically ill adults who were already receiving enteral nutrition to have supplemental parenteral nutrition initiated early (within 48 hours of ICU admission) or late (after the eighth day of ICU admission) [18]. Those who received early parenteral nutrition were more likely to develop a new infection and had a longer duration of mechanical ventilation, ICU stay, and hospitalization. The second study was an observational study that compared three groups: enteral nutrition alone, enteral nutrition plus early parenteral nutrition, and enteral nutrition plus late parenteral nutrition in mechanically ventilated critically ill adults [19]. Enteral nutrition plus either early or late parenteral nutrition was associated with increased mortality compared with enteral nutrition alone. (See "Nutrition support in critically ill patients: An overview", section on 'Parenteral nutrition'.)
PROTON PUMP INHIBITORS
C. difficile and proton pump inhibitors — Proton pump inhibitors (PPIs) may be associated with an increased risk of C. difficile-associated diarrhea (CDAD). The US Food and Drug Administration (FDA) issued a drug safety communication in February 2012 following a review of published literature [20]. Most studies reviewed found that the risk of C. difficile infection or disease, including CDAD, ranged from 1.4 to 2.75 times higher among patients with PPI exposure compared to those without PPI exposure. The relationship between the risk of C. difficile infection and PPI dose and duration of use is uncertain. Given the potential risk of CDAD, the FDA has also recommended that providers prescribe the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. (See "Epidemiology, microbiology, and pathophysiology of Clostridium difficile infection in adults", section on 'Gastric acid suppression' and "Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders", section on 'Clostridium difficile and other enteric infections'.)
Proton pump inhibitors in patients receiving high-dose methotrexate — The US Food and Drug Administration has issued a warning about use of proton pump inhibitors (PPIs) in patients receiving methotrexate, particularly high-dose methotrexate [21]. Case reports and published population pharmacokinetic studies suggest that concomitant use of PPIs, such as omeprazole, esomeprazole, and pantoprazole, with methotrexate (primarily at high dose), may elevate serum levels and prolong the half-life of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. (See "Therapeutic use of high-dose methotrexate", section on 'Use of proton pump inhibitors'.)
PORTAL VEIN THROMBOSIS
Prevention of portal vein thrombosis — Preliminary results are available from a prospective, randomized trial of enoxaparin for the prevention of portal vein thrombosis (PVT) in patients with cirrhosis [22]. During the one-year study period, PVT occurred significantly more often in those taking placebo (6 of 36, 17 percent) than in those taking enoxaparin (0 of 34). No hemorrhagic events were attributed to enoxaparin. Enoxaparin use was also associated with a significantly lower incidence of hepatic decompensation (53 versus 12 percent). (See "Coagulation abnormalities in patients with liver disease", section on 'Prevention'.)
UPPER GASTROINTESTINAL BLEEDING
Risk stratification — The use of risk stratification tools for patients with acute upper gastrointestinal bleeding is recommended by the International Consensus Upper Gastrointestinal Bleeding Conference Group. A new scoring system derived using a large database found that an easily calculated score based upon the patient's albumin, INR, mental status, systolic blood pressure, and age (AIMS65) had a high accuracy for predicting inpatient mortality [23]. The use of the AIMS65 score may be a useful addition to other scoring systems for predicting mortality in patients with acute upper gastrointestinal bleeding. (See "Approach to acute upper gastrointestinal bleeding in adults", section on 'Risk scores'.)
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.
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