A phase I clinical and pharmacology study using amifostine as a radioprotector in dose-escalated whole liver radiation therapy.

Purpose: Diffuse intrahepatic tumors are difficult to control. Whole-liver radiotherapy has been limited by toxicity, most notably radiation-induced liver disease. Amifostine is a prodrug free-radical scavenger that selectively protects normal tissues and, in a preclinical model of intrahepatic cancer, systemic amifostine reduced normal liver radiation damage without compromising tumor effect.

Liver function after irradiation based on computed tomographic portal vein perfusion imaging.

Purpose: To determine whether individual and regional liver sensitivity to radiation could be assessed by measuring liver perfusion during a course of treatment using dynamic contrast-enhanced computed tomography scanning.

Methods And Materials: Patients with intrahepatic cancer undergoing conformal radiotherapy underwent dynamic contrast-enhanced computed tomography (to measure perfusion distribution) and an indocyanine extraction study (to measure liver function) before, during, and 1 month after treatment. We hoped to determine whether the residual functioning liver (i.

A phase II study of preoperative capecitabine and radiation therapy in patients with rectal cancer.

Objectives: The purpose of this study was to evaluate the safety and efficacy of preoperative capecitabine and radiation therapy (RT) in patients with locally advanced rectal cancer (LARC).

Methods: Patients with adenocarcinoma of the rectum stage >or=T3 or >or=N1 were treated with capecitabine 1330 mg/m per day in 2 divided doses days 1 to 42 and 50.4 Gy of RT in 28 1.

External-beam radiotherapy for localized extrahepatic cholangiocarcinoma.

Purpose: The role of radiation therapy (RT) in extrahepatic cholangiocarcinoma (EHCC) is not clear and only limited reports exist on the use of this modality. We have reviewed our institutional experience to determine the pattern of failure in patients after potentially curative resection and the expected outcomes after adjuvant RT and in unresectable patients.

Methods And Materials: After institutional review board approval, 81 patients diagnosed with EHCC (gallbladder 28, distal bile duct 24, hilar 29) between June 1986 and December 2004 were identified and their records reviewed.

Phase II trial of high-dose conformal radiation therapy with concurrent hepatic artery floxuridine for unresectable intrahepatic malignancies.

Purpose: A phase II trial was conducted to determine if high-dose radiation with concurrent hepatic arterial floxuridine would improve survival in patients with unresectable intrahepatic malignancies.

Patients And Methods: Three-dimensional conformal high-dose radiation therapy was delivered concurrently with hepatic arterial floxuridine in 128 patients. The radiation dose was based on a normal-tissue complication probability model and subjected the patient to an estimated maximum risk of radiation-induced liver disease of 10% to 15%.

National trends in the use and outcomes of hepatic resection.

Background: Hepatic resection is increasingly performed for primary and metastatic tumors. Reports from tertiary care centers show improved outcomes over time with lower operative mortality rates. The objective of this investigation was to characterize trends in the use and outcomes of hepatic resection in the US during a recent 13-year period.

Effects of dexamethasone or celecoxib on biliary toxicity after hepatic arterial infusion of 5-fluorodeoxyuridine in a canine model.

Previous work has shown that in humans the dose-limiting toxicity for fluorodeoxyuridine [2-fluoro-5'-deoxyuridine (FdUrd)] when administered by hepatic arterial infusion is biliary sclerosis. The current study was undertaken to attempt to modify this toxicity in a canine model that has been demonstrated to closely mimic the clinical situation. Unlike previous studies using this model, in which animals were sacrificed after extensive fibrosis had already occurred, the current experiments were designed so that observations of pathology were made at an earlier time, when the initial inflammatory injury underlying the fibrotic process was still taking place.

Hepatic resection in the United States: indications, outcomes, and hospital procedural volumes from a nationally representative database.

Background: Hepatic resection has become common in the United States for both primary and secondary hepatic tumors.

Hypothesis: Variation in outcomes after hepatic resection is related to patient characteristics, the indication for operation, and hospital procedural volume.

Design: Observational study using a nationally representative database.

Regional pharmacokinetics of amifostine in anesthetized dogs: role of the liver, gastrointestinal tract, lungs, and kidneys.

Amifostine is a prodrug in which selectivity is largely determined by the preferential formation and uptake of its cytoprotective metabolite, WR-1065, in normal tissues as a result of differences in membrane-bound alkaline phosphatase activity. In this study, we characterized the sites and extent of organ-specific activation by the liver, gastrointestinal tract, lungs, and kidneys after systemic administrations of amifostine. A total of 10 dogs were infused via the cephalic vein using sequential dose rates of drug at 0.