Other highlights in the May 13 JNCI

The new guidelines specify that researchers should use time-to-event primary endpoints in phase II trials, but they should rely on overall survival as the main endpoint in phase III trials. Clinical endpoints that are most likely to be influenced by the underlying liver problems, such as progression- and disease-free survival, should be avoided. The panel also specifies what treatments should be used in the control arms for various stages of disease. Additionally, patient selection for the trials should be based on the Barcelona-Clinic Liver Cancer staging system, and new drugs should be tested initially on only patients who have good liver function.

“These rec¬ommendations are intended to provide a framework as of 2008 that will evolve as new evidence becomes available, including more pre¬cise information on the natural history of [hepatocellular carcinoma], novel therapies, and predictive biomarkers,” the authors write.

Contact: Josep Llovet, , +34 (93) 227-9156

Endoscopic Sphincterotomy Is Not Associated With Risk of Cholangiocarcinoma

Endoscopic sphincterotomy is not associated with an increased long-term risk of cholangiocarcinoma, or cancer of the bile ducts.

Endoscopic retrograde cholangiography (ERC) is used to diagnosis disorders of the bile ducts, pancreas, and gallbladder. If a problem is found during ERC, the surgeon may be able to treat it by performing a sphincterotomy of the ampulla of Vater during the procedure. Because sphincterotomy can lead to intestinal reflux and chronic inflammation, there has been concern that it may increase the incidence of subsequent cholangiocarcinoma.

Frank Viborg Mortensen, D.M.Sc., of the Aarhus University Hospital in Noerrebrogade, Denmark, and colleagues compared the rates of cholangiocarcinoma in 10,690 patients who had ERC with sphincterotomy with those of 10,690 patients who had undergone ERC alone, using data entered into the Danish National Patient Registry between 1977 and 2003.

Patients who had undergone ERC with sphincterotomy had a decreasing incidence of cholangiocarcinoma over time, with 404 cases per 100,000 person-years in the first year, 79 in the second year, 42 in years 3–5, and 27 after year 5. The numbers were similar for patients who had undergone ERC alone: 458 in the first year, 12 in the second, 10 in years 3–5, and 19 after year 5.

The researchers conclude that the high incidence in the patients with ERC plus sphincterotomy in years 1–5 were due to undiagnosed cancers at the time of the initial procedure. “The fact that cholangiocarcinoma incidence rates were similar for ERC patients with and without sphincterotomy from 5 years after ERC indicates that reflux after sphincterotomy does not have a causal role in the development of these cancers,” the authors write.

Contact: Frank Viborg Mortensen, , +45 86 11 02 10

Also in the May 13 JNCI:

• http://www.eurekalert.org/emb_releases/2008-05/jotn-pim050808.php