Reviews & Analysis

Primary sclerosing cholangitis (PSC) is a progressive inflammatory and fibrosing condition, which can lead to chronic cholestasis and biliary cirrhosis. The pathogenesis of PSC is not clearly understood; therapies that impact disease progression are currently limited—liver transplantation is the only curative treatment modality. This Review provides an update on the current understanding and management of this condition and its associated complications.

Anemia is the most prevalent extraintestinal complication of IBD—it affects both quality of life and ability to work. Although the causes of anemia in IBD are multifactorial, iron deficiency anemia is the most common. In this Review, the authors provide an overview of iron homeostasis in health before discussing diagnostic and therapeutic strategies for iron deficiency anemia in patients with IBD.

The histopathological diagnosis of gastrointestinal cancers is usually unambiguous, but it does have its limitations. In the era of personalized medicine, molecular biomarkers are increasingly being explored, not only as viable diagnostic tools but also for predicting therapeutic response. In this Review, the authors discuss the most common clinically available biomarkers for cancers of the stomach, pancreas and colon, and the most promising molecular biomarkers for esophageal neoplasms.

In a prospective Chinese study in which bismuth was added to standard PPI-based triple therapy, the Helicobacter pylori eradication rate was above 90%. Increased treatment duration was also crucial—a therapeutic gain of 13% was achieved if the quadruple therapy was administered for 14 days instead of 7 days. Clarithromycin resistance was also overcome by the prolonged bismuth-containing quadruple therapy.

Despite steady improvement in survival after variceal bleeding in patients with cirrhosis, bleeding-related mortality remains high. Current treatment recommendations utilize a step-up strategy, in which only patients who rebleed despite drug and endoscopic therapy undergo TIPS (transjugular intrahepatic portosystemic shunt) implantation; however, in patients who are at high risk of rebleeding, early use of TIPS might greatly reduce mortality.

Endoscopic ultrasound (EUS) is the diagnostic modality of choice for various pancreatic pathologies. A recent study has suggested that EUS evaluation during diagnostic workup is a predictor of increased survival in patients with pancreatic cancer owing to improved pancreatic cancer staging and selection of suitable candidates for surgery.

Moderate sedation is typically used during lower gastrointestinal endoscopy procedures. Deep sedation with propofol is becoming widespread but carries the risk of cardiorespiratory depression. Nitrous oxide is an inhaled sedative administered routinely in dentistry that might prove to be a safe option for sedation during lower gastrointestinal endoscopy.

IBS is a common gastrointestinal condition characterized by abdominal pain associated with altered bowel habits. Limited and judicious use of diagnostic testing is recommended, particularly in patients with typical symptoms without alarm signs and symptoms. Management of IBS is multifaceted and is often driven by illness severity, predominant symptoms and patient and practitioner preferences. Sarah Khan and Lin Chang discuss the current evidence-based recommendations for the diagnosis and management of IBS.

Endoscopy is the mainstay for diagnosis and therapy of upper gastrointestinal bleeding. Early risk assessment is crucial for effective timing of endoscopy and determination of the need for other measures to be taken—scoring systems should be used for this purpose. A new prospective study suggests that the Blatchford score can identify patients who do not need endoscopic intervention.

Hemochromatosis associated with HFE C282Y homozygosity affects persons of western European descent, and is the most common and well-characterized primary iron overload disorder worldwide. New clinical practice guidelines summarize current knowledge of the prevalence and penetrance of C282Y homozygosity and provide evidence-based recommendations for diagnosis and management of patients with HFE hemochromatosis.

A confident and efficient diagnosis of IBS is an important aspect of clinical gastroenterology. How far to investigate a patient with typical IBS symptoms has been the subject of a number of clinical guidelines. A recent study has recommended, somewhat provocatively, that investigation for pancreatic exocrine insufficiency should be added to the tests undertaken in patients with suspected diarrhea-predominant IBS who are referred to a gastroenterologist.

A 38-year-old female was evaluated for a 3 year history of postprandial abdominal pain, refractory nausea, vomiting and hematemesis. Her medical history was significant for juvenile polyposis syndrome and Crohn's disease resulting in a total colectomy. Juvenile polyposis syndrome with outlet obstruction of the stomach and excessive hypergastrinemia was diagnosed and treatment started with acid suppressive therapy, prokinetic therapy and total parenteral nutrition. Repetitive endoscopic polypectomy (also known as debulking) was performed twice followed by gastrectomy with duodeoesophageal anastomosis.

Tuberculosis is one of the most important infectious diseases worldwide. Hepatotoxic effects are a serious problem in patients who are undergoing treatment for tuberculosis, as they can cause morbidity and mortality as well interrupt their therapy and limit the efficacy of the antitubercular regimen. In this Review, Senousy and colleagues discuss the hepatotoxic effects of antituberculosis drugs and the management of these effects.

Bowel cleansing is necessary before a colonoscopy or colonic radiological examination, but the procedure is not without risks. This Review describes the safety issues related to the three major osmotically acting cathartics currently in use for bowel cleansing: sodium-phosphate-based products, polyethylene glycol and electrolyte lavage solutions, and magnesium-citrate-based agents. This Review also includes recommendations for the safe use of these agents in bowel cleansing, and discusses which patients are at risk of serious adverse events.

This article considers the case of a 72-year-old woman who presented with a 2-month history of right upper quadrant abdominal pain and a 15-day history of jaundice. The patient was diagnosed with bile duct duplication and coexistent cholangiocarcinoma. This Case Study explores the diagnosis and management of this patient and is believed to be the first reported case in the literature of this unique variant of bile duct duplication.

The etiology of acute biliary pancreatitis is complex and, as outlined in this Review, involves multiple factors including anatomy, genetics, gallstones, bile and pancreatic juice exclusion and ampullary obstruction. In this article, the authors also discuss the importance of establishing a biliary origin in acute pancreatitis and how both serum biochemistry and imaging investigations are vital to confirm a diagnosis of acute biliary pancreatitis.

Hepatic encephalopathy is an important neuropsychiatric complication of liver disease that in severe cases can lead to coma and death. This Review describes the pathogenesis of hepatic encephalopathy including the role of ammonia, inflammation, neurosteroids and manganese in the development of this disorder. The authors also discuss how best to clinically manage patients with hepatic encephalopathy by highlighting the clinical scales and tests used to grade the disorder and the different treatment strategies available.

Surgical repair of complex anal fistulas has to achieve a balance between optimal primary healing and best preservation of continence. As traditional surgical techniques confer a risk of continence deterioration, innovative sphincter-preserving techniques have been introduced. A new study indicates that use of bioprosthetic plugs in the surgical treatment of complex anal fistulas is associated with a long-term success rate of 81%.

An improved understanding of thiopurine metabolism has enabled individualized dosing of these agents in patients with IBD. Ansari et al. describe the use of allopurinol to deliberately manipulate thiopurine metabolism in patients who previously could not tolerate therapeutic doses of azathioprine or 6-mercaptopurine. This therapeutic maneuver potentially enables this therapy to be given to a considerable subgroup of patients otherwise unable to tolerate thiopurine therapies.

In a large, randomized, controlled trial conducted in the UK, screening flexible sigmoidsocopy led to substantial reductions in the incidence of and mortality from distal colorectal cancer. Both fecal occult blood testing and flexible sigmoidoscopy screening are now proven to reduce colorectal cancer mortality.