Cetuximab in Pancreatic Cancer Therapy: A Systematic Review and Meta-Analysis.

INTRODUCTION: The present study evaluated the potential benefit of adding cetuximab to neoadjuvant, adjuvant, or palliative standard therapy for pancreatic cancer. METHODS: A systematic literature search was performed in MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). Only randomised controlled trials (RCTs) investigating the effect of adding cetuximab to standard chemotherapy in pancreatic cancer were included. Evaluated outcomes were overall survival, progression-free survival, objective response, and toxicity. For overall survival and progression-free survival, hazard ratios (HR) with 95% confidence intervals (CI) were chosen as effect measure. For objective response, odds ratios (OR) with 95% CI were used. Analysis was based on a random effects model. RESULTS: After screening 568 publications, a total of 4 RCTs with 924 patients were included. In all trials, patients were adequately randomised with balanced intervention and control groups. There was no significant difference in overall survival (HR 1.04; 95% CI: 0.90-1.19; p = 0.60), progression-free survival (HR 1.06; 95% CI: 0.93-1.22; p = 0.36), or objective response (OR 0.99; 95% CI: 0.66 -1.49; p = 0.96) when adding cetuximab to a standard therapy. Toxicity was the same or higher in each of the included trials. According to GRADE, the certainty of the evidence is high. Therefore, adding cetuximab to pancreatic cancer therapy has no clinically relevant benefit. CONCLUSION: In the presence of no survival benefit, increased toxicity, and higher costs, a decreased cost-benefit ratio compared to the standard care must be suggested. Conducting further RCTs in unselected pancreatic cancer populations is unlikely to change this conclusion.

Application of DC beads in hepatocellular carcinoma: clinical and radiological results of a drug delivery device for transcatheter superselective arterial embolization.

AIM: Application of a drug delivery device for transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Clinical and radiological treatment assessment. PATIENTS AND METHODS: 24 patients with liver cirrhosis and uni- or multifocal HCC underwent TACE with doxorubicin beads (DC Bead). The underly-ing cause of liver cirrhosis was hepatitis (A: n = 7; B: n = 10) or alcohol consumption (n = 7). Patients presented with Child Pugh stage A (n = 15) and B (n = 9). The mean intrahepatic tumor size, considering the sum of diameters of all lesions treated, was 3.83 cm (+/-2.4). Liver function and hematological parameters were documented before and after each TACE. Magnetic resonance imaging (MRI) was performed before and 4 weeks after TACE. The T1-w 3D volume-interpolated breathhold exam (VIBE) sequence was applied for evaluation of the therapy response. RESULTS: 24 patients received a total number of 69 TACE treatments with DC beads (mean dose 160 mg). The elevation of liver function parameters after treatment did not affect the patients' clinical condition. The T1-w VIBE sequence proved very valuable for assessment of the intrahepatic tumor spread. Post-contrast images enabled delineation of the viable HCC lesions, hence facilitating the selective transcatheter approach. The tumor marker a-fetoprotein (AFP), available in 19/24 patients, dropped from 347.5 to 299.5 ng/ml, without being a reliable predictor of treatment response. A decrease of tumor size after TACE from 3.83 (+/-2.40) to 3.01 cm (+/-2.67; p < 0.0001) was evident on the T1w-VIBE sequences. The mean follow-up period was 30 months. At the time of data analysis, 10 (42%) out of 14 patients were alive. CONCLUSION: TACE with DC beads in HCC offers a safe and efficient treatment resulting in tumor response within a very short time.

Enhanced iNOS gene expression in the steatotic rat liver after normothermic ischemia.

BACKGROUND: Impaired hepatic microcirculation in the steatotic liver has been identified as a considerable factor for increased vulnerability after ischemia/reperfusion (I/R). Changes in regulation and synthesis of vasoactive mediators, such as nitric oxide (NO) and endothelin (ET-1), may result in functional impairment of postischemic sinusoidal perfusion. The aim of the current study was to assess the impact of I/R injury on postischemic gene expression of NO and ET-1 in steatotic livers. MATERIALS AND METHODS: Male Sprague-Dawley rats with or without hepatic steatosis (induced by carbon tetrachloride treatment) were subjected to normothermic I/R injury. Steady-state mRNA levels were assessed using RT-PCR to study the expression of genes encoding ET-1, NO synthase (endothelial cell NO synthase and inducible NO synthase, iNOS). Immunohistochemistry was performed for detection of iNOS. RESULTS: I/R injury was followed by increased iNOS gene expression (RT-PCR/immunohistochemistry) in animals with hepatic steatosis, predominately in hepatocytes with fatty degeneration. A mild increase in mRNA levels for ET-1 was found in steatotic rat livers. I/R induced a further increase in ET-1 gene expression in some but not all reperfused steatotic livers. CONCLUSIONS: We show an enhanced gene expression of iNOS in postischemic steatotic rat livers. Hepatocytes with fatty degeneration appear to be the major source for NO generation. Furthermore, I/R may also induce ET-1 gene expression. Dysregulation of sinusoidal perfusion by NO and ET-1 is therefore likely to contribute to I/R injury of the steatotic liver.

Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study.

Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal albumin dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP) analysis. Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior standard medical therapy (SMT). Patients were randomized to receive SMT with ECAD or without (control). ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer (MW cutoff < 60 kd) against 15% albumin. Albumin-bound molecules transfer to dialysate albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer. ECAD was associated with improved 30-day survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P <.05). Plasma bile acids and bilirubin decreased on average by 43% and 29%, respectively, in the ECAD group after 1 week of treatment, but not in the control group. Renal dysfunction and hepatic encephalopathy improved in the ECAD group, but worsened significantly in the control group. ECAD was safe, with adverse events being rare and identical in both groups. In conclusion, ECAD appears to be effective and safe for the short-term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation.

Modalities of testing Helicobacter pylori in patients with nonmalignant bile duct diseases.

AIM: This paper describes the procedure of detection of Helicobacter pylori (H. pylori) in bile specimens in patients suffering from benign diseases of biliary ducts (lithiasis with/without nonspecific cholangitis). METHODS: The group of 72 patients entering the study consisted of 32 male and 40 female (45% and 55%, respectively). Bile was obtained during ERCP in 68 patients, and during cholecystectomy in 4 patients. A fast urease test (FUT) to determine the existence of H. pylori in gastric mucosa was carried out for all the patients during the endoscopic examination. The existence of genetic material of H. pylori was determined by detection of ureA gene by the method of nested PCR. The results of this reaction were shown by electrophoresis on 10g.L(-1) agarose gel in a band of 256bp. RESULTS: The majority of the patients included in our study had biliary lithiasis without signs of cholangitis (48 patients, 67%), whereas other patients were complicated by cholangitis (17 patients, 24%). Seven patients (9%) had normal ERCP, forming thus the control group. In the group of patients with lithiasis 26 patients (54.2%) had positive PCR of H. pylori in bile and among the patients with associated cholangitis positive PCR was detected in 9 patients (52.9%). Among the seven patients with normal ERCP only one (14%) had positive PCR of H. pylori. A high percentage of H. pylori infection of gastric mucosa was observed (57 patients, 79%). It was also observed that its slightly higher positivity was in the patients with distinct bile pathology: 81% FUT positive patients in the group with choledocholithiasis alone and 76% in the group with choledocholithiasis associated with cholangitis. Seventy-one percent of the patients with regular findings had positive FUT. CONCLUSION: The prevalence of H. pylori infection both in bile and in gastric mucosa in patients with benign diseases of biliary ducts does not show a statistically significant difference in relation to the prevalence of the same with the patients with normal ERCP. The existence of H. pylori infection possibly does not play a role in pathogenesis of benign biliary diseases.