Pancreatic duct strictures: identifying risk of malignancy.

BACKGROUND: This study aimed to define PDS characteristics that predict malignancy and would thus invoke further diagnostic evaluation or aggressive treatment. METHODS: 355 cases of PDS were diagnosed by ERCP during a 7-year period at a single institution. A retrospective review identified clinical/demographic patient data and ERCP results. RESULTS: 218 (61%) patients with a PDS were found to have an isolated PDS. Twelve percent of isolated PDS and 79% of CBD stricture-associated PDS were malignant. The sensitivity and specificity for the double duct sign for malignancy were 77% and 80% respectively, and the positive predictive value was 65%. Predictors of malignancy were statistically similar for both isolated PDS and those associated with a CBD stricture. Univariate predictors of malignancy included stricture location in the pancreatic head/neck, jaundice, and patient age. Predictors of benign disease included a history of pancreatitis, the presence of multiple strictures, pancreatic duct stones, pseudocyst, pancreas divisum anatomy, irregular side branches, and irregular pancreatic duct morphology. Less than 1% of patients with either pancreas divisum anatomy, pancreatic duct stones, or pancreatic pseudocyst had malignancy. Using malignancy as the dependent variable, multivariate factors included in the final prognostic equation were history of pancreatitis (odds ratio 0.009 with history of pancreatitis), stricture location in the head or neck (odds ratio 42) and irregular pancreatic duct side branches (odds ratio 0.05 with irregular branches). CONCLUSIONS: This study demonstrates that certain characteristics of PDS can predict the subset of patients who have an increased risk of cancer.

Marked variability of melphalan plasma drug levels during regional hyperthermic isolated limb perfusion.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) with melphalan as treatment for locally recurrent or in-transit malignant melanoma is frequently performed but the principle for calculating drug dosage remains poorly understood. METHODS: This study examined the pharmacokinetic profile of 14 consecutive patients to determine what variables were associated with toxicity and tumor responses. RESULTS: Marked fourfold variability was noted in patient plasma melphalan concentrations. We defined a factor--the ratio of estimated limb volume (Vesti) to melphalan volume of distribution (Vss), Vesti/Vss--that was much more strongly correlated with acute regional toxicity than either area under concentration-time curve or peak plasma concentration. In addition, we found that AUX2 was the best correlate of tumor response. CONCLUSIONS: Pharmacokinetic evaluation of prospective HILP trials is critical to not only understand response and toxicity outcomes but also to potentially improve the therapeutic index of regional perfusion.