Idiopathic benign biliary strictures in surgically resected patients with presumed cholangiocarcinoma.

OBJECTIVE: Distinguishing between malignant and benign biliary strictures remains problematic. The aim of this study was to compare and contrast the clinical features of patients with benign and malignant biliary strictures. METHODS: Medical records of patients who underwent surgical resection for presumed cholangiocarcinoma were reviewed. Immunohistochemistry for hypoxia inducible factor-1-alpha (HIF-1-alpha) was performed on all bile ductule samples. RESULTS: Twelve patients with benign strictures (group I) were compared to 26 patients with cholangiocarcinoma (group II). Group I was predominantly female (ratio 2: 1), (p<0.01), whereas the gender ratio was 1: 1 in patients in group II. Bismuth-Corlette type strictures in group I were more likely to be type I/II, whereas type III strictures predominated in group II. The CA 19-9 was <100 U/ml in 6 and >100 U/ml in 1 patient of group I and <100 in 13 and >100 in 11 patients in group II. Half of the patients in group I had positive immunoreactivity for HIF-1-alpha in bile ductules. CONCLUSION: Benign biliary strictures masquerading as cholangiocarcinomas occur more often in women, are less often Bismuth-Corlette type III, have serum CA 19-9 values <100 U/ml, and hypoxia may play a role in a subset of these strictures.

Hepatocyte apoptosis is a pathologic feature of human alcoholic hepatitis.

BACKGROUND/AIMS: The pathogenesis of alcoholic hepatitis (AH) remains poorly understood. Although apoptosis is now recognized as a mechanism of liver injury, the extent and mechanisms of apoptosis in human AH remain unknown. Thus, our aims were to quantify hepatocyte apoptosis in patients with AH, correlate it with disease severity, and identify the mechanisms of apoptosis induction. METHODS: Hepatocyte apoptosis was assessed in 26 patients with AH and 27 controls without liver disease using the TUNEL assay and immunohistochemistry for activated caspase 3. Liver specimens were also graded for disease severity. The expression of the death receptors, Fas and tumor necrosis factor-alpha receptor 1 (TNF-R1), was assessed by immunohistochemistry. RESULTS: In contrast to normal livers, TUNEL- and caspase 3-positive hepatocytes were readily observed in the livers of patients with AH. In the AH group, hepatocyte apoptosis was significantly higher in patients with a serum bilirubin of > 3 mg/dl. Apoptosis was also greater in grade 4 steatohepatitis. The Fas receptor was strongly expressed in hepatocytes in AH, but not in normal livers; the TNF-R1 expression was comparable in both groups. CONCLUSIONS: The present results demonstrate that hepatocyte apoptosis is significantly increased in human AH and justify therapeutic strategies aimed at inhibiting apoptosis in this disease.

Endoscopic application of photodynamic therapy for cholangiocarcinoma.

BACKGROUND: Previous studies indicate that photodynamic therapy provides effective relief from biliary obstruction in advanced cholangiocarcinoma. This report describes a method of applying photodynamic therapy in the biliary tract by using accessories available in the United States. METHODS: Endoscopic retrograde cholangiography was performed to define the proximal and distal extent of intraductal tumor. Patients were injected with 2 mg/kg of sodium porfimer. Forty-eight hours later a commercially available cylindrical diffusing laser fiber was inserted into an 8F biliary catheter equipped with a 0.038 inch side-hole at its distal tip. After positioning of a 0.035 inch guidewire proximal to the biliary stricture, the preloaded catheter was advanced over the guidewire by using the monorail technique. Laser light was applied at a power of 400 mW/cm fiber for a total energy of 180 J/cm.(2) RESULTS: Fourteen treatments were performed on 6 patients with tumors of Bismuth types IV (n = 2), III (n = 3), or II (n = 1). By using the preloaded biliary catheter, adequate positioning of the laser fiber was achieved in all patients. A fracture of the diffuser tip occurred during 1 of the treatments. Two patients developed acute cholangitis and 2 patients experienced skin phototoxicity. CONCLUSIONS: Photodynamic therapy for cholangiocarcinoma is safe and technically feasible with a preloaded biliary catheter and a monorail technique for catheter positioning.