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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.
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'.)
Laparoscopic versus open surgery for rectal cancer (October 2015)
Curative resection of a rectal carcinoma was traditionally carried out with open techniques. Although earlier randomized trials had shown that laparoscopic rectal cancer surgery was equivalent to open surgery, two subsequent trials failed to prove that laparoscopic surgery is non-inferior to open surgery [2,3]. In the two more recent trials, successful resections, defined as simultaneously achieving negative distal and circumferential margins as well as a complete total mesorectal excision, were achieved in approximately 82 percent with laparoscopic surgery versus 87 to 89 percent with open surgery. Given the conflicting results, the best surgical approach to treating rectal cancer needs to be determined individually by tumor and patient characteristics, as well as surgeon experience. When performing laparoscopic rectal surgery for cancer, surgeons should have a low threshold for converting to open surgery when difficulties arise with dissection. (See "Surgical resection of primary rectal adenocarcinoma", section on 'Laparoscopic versus open approach'.)
ESOPHAGEAL AND GASTRIC DISEASE
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'.)
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'.)
Hepatic decompensation associated with ombitasvir-paritaprevir-ritonavir for chronic HCV infection (November 2015)
With more widespread use of ombitasvir-paritaprevir-ritonavir with or without dasabuvir for patients with chronic hepatitis C virus (HCV) genotypes 1 and 4 infection, reports of associated hepatic injury and decompensation have emerged . Most cases occurred in patients with existing cirrhosis and within one to four weeks of drug initiation; some cases resulted in death or need for liver transplantation. Patients with compensated cirrhosis who use this regimen should be monitored closely for signs of decompensation and undergo interval transaminase and bilirubin testing after initiation. The regimen is contraindicated in individuals with Child B and C class cirrhosis. (See "Direct-acting antivirals for the treatment of hepatitis C virus infection", section on 'Ombitasvir-paritaprevir-ritonavir with or without dasabuvir'.)
Primary biliary cirrhosis is now known as primary biliary cholangitis (October 2015)
The term "primary biliary cirrhosis" has been used to describe the T-lymphocyte-mediated attack on small intralobular bile ducts. However, the terminology is changing to "primary biliary cholangitis" to describe the disorder and its natural history more accurately . With the advent of treatment with ursodeoxycholic acid, the majority of patients now have normal life expectancies and only a minority of patients develops cirrhosis. (See "Clinical manifestations, diagnosis, and prognosis of primary biliary cholangitis (primary biliary cirrhosis)", section on 'Introduction'.)
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'.)
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
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", section on 'Laparoscopic lavage'.)
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'.)
Suspected small bowel bleeding should no longer be referred to as "obscure" (October 2015)
Bleeding from the small bowel is uncommon, but it is responsible for the majority of patients with gastrointestinal bleeding that persists or recurs without an obvious etiology after upper endoscopy, colonoscopy, and possibly radiologic evaluation of the small bowel . In the past, if no source of bleeding was found after an endoscopic evaluation, the bleeding was referred to as being "obscure." However, a 2015 guideline from the American College of Gastroenterology has been proposed that the term obscure only be used if patients have not had a source of bleeding identified after a thorough examination of the entire gastrointestinal tract, including the small bowel . Most cases of what was previously referred to as obscure bleeding are more correctly categorized as suspected small bowel bleeding. (See "Evaluation of suspected small bowel bleeding (formerly obscure gastrointestinal bleeding)", section on 'Introduction'.)
OTHER GASTROENTEROLOGY AND NUTRITION
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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- Stevenson AR, Solomon MJ, Lumley JW, et al. Effect of Laparoscopic-Assisted Resection vs Open Resection on Pathological Outcomes in Rectal Cancer: The ALaCaRT Randomized Clinical Trial. JAMA 2015; 314:1356.
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- US Food and Drug Administration. Donor Screening Recommendations to Reduce the Risk of Transmission of Zika Virus by Human Cells, Tissues, and Cellular and Tissue-Based Products: Guidance for Industry, March 2016. http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Tissue/UCM488582.pdf (Accessed on March 07, 2016).
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- Cleynen I, Van Moerkercke W, Billiet T, et al. Characteristics of Skin Lesions Associated With Anti-Tumor Necrosis Factor Therapy in Patients With Inflammatory Bowel Disease: A Cohort Study. Ann Intern Med 2016; 164:10.
- Lembo AJ, Lacy BE, Zuckerman MJ, et al. Eluxadoline for Irritable Bowel Syndrome with Diarrhea. N Engl J Med 2016; 374:242.
- Lee CH, Steiner T, Petrof EO, et al. Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA 2016; 315:142.
- Schultz JK, Yaqub S, Wallon C, et al. Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis: The SCANDIV Randomized Clinical Trial. JAMA 2015; 314:1364.
- Bharucha AE, Parthasarathy G, Ditah I, et al. Temporal Trends in the Incidence and Natural History of Diverticulitis: A Population-Based Study. Am J Gastroenterol 2015; 110:1589.
- Pasha SF, Leighton JA, Das A, et al. Double-balloon enteroscopy and capsule endoscopy have comparable diagnostic yield in small-bowel disease: a meta-analysis. Clin Gastroenterol Hepatol 2008; 6:671.
- Gerson LB, Fidler JL, Cave DR, Leighton JA. ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding. Am J Gastroenterol 2015; 110:1265.
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