An incidence model of the cost of advanced prostate cancer in Spain.

BACKGROUND: Prostate cancer (PCa) is the second leading cancer diagnosed among men. In Spain the incidence of PCa was 70.75 cases per 100,000 males. Advanced PCa has spread outside of the prostate capsule and may involve other parts of the body. The aim of this study was to estimate the lifetime costs of a cohort of advanced PCa patients diagnosed in Spain in 2012. METHODS: A partitioned economic model was developed in EXCEL incorporating Spanish incidence, mortality, and cost data supplemented with data from the international literature. Progression from Stage III to Stage IV was permitted. Costs were discounted at the standard rate of 3%. Lifetime costs were presented on an individual basis and for the entire cohort of newly diagnosed Stage III and Stage IV PCa patients. RESULTS: Lifetime costs for advanced PCa were ∼€19,961 per patient (mean survival of 8.4 years). Using the projected incident cases for 2012 (3047), the total cost for the incident cohort of patients in 2012 would amount to €61 million. These results were more sensitive to changes in the ongoing costs (post-initial 12 months) of Stage III PCa, the rate of progression from Stage III to Stage IV, and the discount rate applied to costs. CONCLUSIONS: This study provides an estimate of the lifetime costs of advanced PCa in Spain and a framework for further research. The study is limited by the availability of long-term Spanish data and the need to make inferences from international studies. However, until long-term prospective or observational data do become available in Spain, based on the assumptions, the current results indicate that the burden of advanced PCa in Spain is substantial. Any treatments that could potentially reduce the economic burden of the disease should be of interest to healthcare decision makers.

Access to information and expectations of treatment decisions for prostate cancer patients--results of a European survey.

We surveyed patients in France, Germany, Italy, Spain and Poland to examine information requirements and expectations of patients with prostate cancer. Patients were identified via their healthcare teams or via existing databases and interviewed by telephone, or in face-to-face interviews (Italy). Survey questions were either multiple choice or rank-based, and additional information was available to assist patient comprehension. Overall, 80% of patients received information about prostate cancer at diagnosis and 76% rated their physician as the most useful information source. However, around a third of French and German patients did not receive any information about their condition at diagnosis, compared with 8%, 12% and 10% of Spanish, Italian and Polish patients, respectively. Most patients rated the information they received as 'very informative', but there were regional variations, with German patients being the least satisfied with the quality of information received. Despite receiving the least amount of information at diagnosis, more patients from France and Germany preferred to be involved in treatment decisions than patients from Spain, Italy and Poland. Results from this survey highlight important gaps in information provision for patients with prostate cancer in terms of information supplied and patient expectations regarding treatment decisions.

Clinical Trial of the Pan-Caspase Inhibitor, IDN-6556, in Human Liver Preservation Injury.

Cold ischemia/warm reperfusion (CI/WR) injury remains a problem in liver transplantation. The aim of the current study was to assess the utility of the pan-caspase inhibitor IDN-6556 on CI/WR injury during human liver transplantation. This report is a post hoc analysis of a Phase II, multi-center, randomized, placebo-controlled, double-blinded, parallel group study. Subjects were assigned to four treatment groups: Group 1 (Organ storage/flush: Placebo-Recipient: Placebo); Group 2 (Organ storage/flush: 15 microg/mL-Recipient: Placebo); Group 3 (Organ storage/flush: 5 microg/mL-Recipient: 0.5 mg/kg); and Group 4 (Organ storage/flush: 15 microg/mL-Recipient: 0.5 mg/kg). Liver cell apoptosis was assessed by serum concentrations of the apoptosis-associated CK18Asp396 ('M30') neo-epitope, TUNEL assay and caspase 3/7 immunohistochemistry. Liver injury was assessed by serum AST/ALT determinations. Serum markers of liver cell apoptosis were reduced in all groups receiving drug as compared to placebo. However, TUNEL, caspase 3/7 positive cells and serum AST/ALT levels were only consistently reduced in Group 2 (drug exposed to organ only). This reduction in serum transaminases was significant and observed across the study. In conclusion, IDN-6556 when administered in cold storage and flush solutions during liver transplantation offers local therapeutic protection against CI/WR-mediated apoptosis and injury. However, larger studies are required to confirm these observations.

Death by association: BH3 domain-only proteins and liver injury.

Apoptosis, a prominent form of cell death, is a prime feature of many acute and chronic liver diseases. Apoptosis requires mitochondrial dysfunction, which is regulated by proteins of the Bcl-2 family. Whether or not a cell should live or die is controlled by the interaction of multidomain Bcl-2 proteins with proapoptotic BH3 domain-only proteins of this family. Current models suggest multidomain, antiapoptotic Bcl-2 proteins prevent mitochondrial dysfunction by sequestering and/or preventing activation of its proapoptotic relatives. BH3-only proteins initiate cell death by neutralizing and or ligating multidomain prosurvival Bcl-2 proteins. Thus BH3 domain-only proteins are paramount in the apoptotic process as exemplified by the role of the BH3 domain-only protein Bid in liver injury. In this concise review, we will focus on how these BH3 domain-only proteins are regulated in the cell, their association with the Bcl-2 family of proteins, and finally, current information regarding their involvement in liver cell apoptosis and injury.

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.

Cathepsin B inactivation attenuates hepatocyte apoptosis and liver damage in steatotic livers after cold ischemia-warm reperfusion injury.

Hepatic steatosis predisposes the liver to cold ischemia-warm reperfusion (CI/WR) injury by unclear mechanisms. Because hepatic steatosis has recently been associated with a lysosomal pathway of apoptosis, our aim was to determine whether this cell-death pathway contributes to CI/WR injury of steatotic livers. Wild-type and cathepsin B-knockout (Ctsb(-/-)) mice were fed the methionine/choline-deficient (MCD) diet for 2 wk to induce hepatic steatosis. Mouse livers were stored in the University of Wisconsin solution for 24 h at 4 degrees C and reperfused for 1 h at 37 degrees C in vitro. Immunofluorescence analysis of the lysosomal enzymes cathepsin B and D showed a punctated intracellular pattern consistent with lysosomal localization in wild-type mice fed a standard diet after CI/WR injury. In contrast, cathepsin B and D fluorescence became diffuse in livers from wild-type mice fed MCD diet after CI/WR, indicating that lysosomal permeabilization had occurred. Hepatocyte apoptosis was rare in both normal and steatotic livers in the absence of CI/WR injury but increased in wild-type mice fed an MCD diet and subjected to CI/WR injury. In contrast, hepatocyte apoptosis and liver damage were reduced in Ctsb(-/-) and cathepsin B inhibitor-treated mice fed the MCD diet following CI/WR injury. In conclusion, these findings support a prominent role for the lysosomal pathway of apoptosis in steatotic livers following CI/WR injury.

Intraoperative cholangiography is still indicated after preoperative endoscopic cholangiography for gallstone disease.

BACKGROUND: Intraoperative cholangiography (IOC) is frequently omitted in patients undergoing laparoscopic cholecystectomy (LC) if they have had successful preoperative endoscopic retrograde cholangiography (ERC). METHODS: A prospectively maintained divisional laparoscopic cholecystectomy database was searched from 1991 to 1997 for patients who had IOC after preoperative ERC. The presence of recurrent or residual common duct stones seen on IOC and their impact on subsequent management were evaluated. RESULTS: We identified a group of 127 patients who underwent preoperative ERC. Thirty-one patients (31/127, or 24%) went on to receive an IOC during cholecystectomy. In 15 patients whose preoperative ERC was reported normal, five (33%) had an abnormal IOC. In 16 patients whose ERC was reported as having cleared the duct, eight (50%) had an IOC abnormality. Eight of these 31 patients required a further procedure to clear the duct. CONCLUSION: Retained or recurrent common duct stones at cholecystectomy following diagnostic or therapeutic ERC were more common than expected. Therefore, IOC is recommended during LC regardless of the findings yielded by the preoperative ERC.