Devinder S. Bansi

Autologous Infusion of Expanded Mobilized Adult Bone Marrow-Derived CD34+ Cells Into Patients With Alcoholic Liver Cirrhosis

OBJECTIVES: Recent advances in regenerative medicine, including hematopoietic stem cell (HSC) transplantation, have brought hope for patients with severe alcoholic liver cirrhosis (ALC). The aim of this study was to assess the safety and efficacy of administering autologous expanded mobilized adult progenitor CD34+ cells into the hepatic artery of ALC patients and the potential improvement in the liver function.METHODS: Nine patients with biopsy-proven ALC, who had abstained from alcohol for at least 6 months, were recruited into the study. Following granulocyte colony-stimulating factor (G-CSF) mobilization and leukapheresis, the autologous CD34+ cells were expanded in vitro and injected into the hepatic artery. All patients were monitored for side effects, toxicities, and changes in the clinical, hematological, and biochemical parameters.RESULTS: On average, a five-fold expansion in cell number was achieved in vitro, with a mean total nucleated cell count (TNCC) of 2.3 × 108 pre infusion. All patients tolerated the procedure well, and there were no treatment-related side effects or toxicities observed. There were significant decreases in serum bilirubin (P < 0.05) 4, 8, and 12 wk post infusion. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) showed improvement through the study period and were significant (P < 0.05) 1 wk post infusion. The Child-Pugh score improved in 7 out of 9 patients, while 5 patients had improvement in ascites on imaging.CONCLUSION: It is safe to mobilize, expand, and reinfuse autologous CD34+ cells in patients with ALC. The clinical and biochemical improvement in the study group is encouraging and warrants further clinical trials.

Proton and phosphorus-31 nuclear magnetic resonance spectroscopy of human bile in hepatopancreaticobiliary cancer.

Objective Hepatopancreaticobiliary cancers can be difficult to diagnose. Nuclear magnetic resonance (NMR) spectroscopy provides non-invasive information on phospholipid metabolism, and previous studies of liver tissue have highlighted changes in phospholipids in malignancy. We hypothesised that in-vitro NMR spectroscopy of human bile may provide independent diagnostic indices in cancer management through an assessment of the phospholipid content. Design and methods Bile samples from 24 patients were collected at endoscopic retrograde cholangiopancreatography and from one subject at cholecystectomy. Thirteen patients had cancer: pancreatic carcinoma (eight), cholangiocarcinoma (three) and metastatic liver disease (two). The remaining 12 patients had non-malignant pathology. In-vitro proton (1H) and phosphorus-31 (31P) NMR spectra were obtained from all samples using an 11.7 Tesla NMR spectroscopy system. Results Complementary information was obtained from the 1H and 31P NMR spectra. Signals were assigned to phosphatidylcholine in both 1H and 31P NMR spectra. Phosphatidylcholine levels were significantly reduced in the bile from cancer patients when compared with bile from non-cancer patients (P=0.007). Conclusion These preliminary studies suggest that 1H and 31P NMR spectroscopy of bile may be used to detect differences in phospholipid content between cancer and non-cancer patients. This may have implications for the development of novel diagnostic strategies in hepatopancreaticobiliary cancers. Further larger-scale studies are warranted.

Metabolic profiling of bile in cholangiocarcinoma using in vitro magnetic resonance spectroscopy

OBJECTIVES Cholangiocarcinoma (CCA) has a poor prognosis and its aetiology is inadequately understood. Magnetic resonance spectroscopy (MRS) of bile may provide insights into the pathogenesis of CCA and help identify novel diagnostic biomarkers. The aim of this study was to compare the chemical composition of bile from patients with CCA with that of bile from patients with benign biliary disease. METHODS Magnetic resonance spectra were acquired from the bile of five CCA patients and compared with MRS of control bile from patients with benign biliary disease (seven with gallstones, eight with sphincter of Oddi dysfunction [SOD], five with primary sclerosing cholangitis [PSC]). Metabolic profiles were compared using both univariate and multivariate pattern-recognition analysis. RESULTS Univariate analysis showed that levels of glycine-conjugated bile acids were significantly increased in patients with CCA, compared with the benign disease groups (P= 0.002). 7 beta primary bile acids were significantly increased (P= 0.030) and biliary phosphatidylcholine (PtC) levels were reduced (P= 0.010) in bile from patients with CCA compared with bile from gallstone patients. These compounds were also of primary importance in the multivariate analysis: the cohorts were differentiated by partial least squares discriminant analysis (PLS-DA). CONCLUSIONS These preliminary data suggest that altered bile acid and PtC metabolism play an important role in CCA aetiopathogenesis and that specific metabolites may have potential as future biomarkers.

Polychlorinated biphenyls in bile of patients with biliary tract cancer.

BACKGROUND Polychlorinated biphenyls (PCBs) are anthropogenic, organic compounds. Although banned in the 1970s, PCBs are poorly biodegradable and hence ubiquitous in the environment. They accumulate in adipose tissue and are implicated various malignancies, including breast and pancreatic cancer. The hepatobiliary system is the main excretory route for such xenobiotic toxins. Incidence rates of intrahepatic biliary tract cancer are increasing worldwide. Measurement and comparison of PCB levels in bile from human patients with benign and malignant bile duct disease has not previously been done. OBJECTIVES To compare PCB concentrations in bile from patients with malignant (n=8) and non-malignant (n=7) biliary disease. METHODS AND RESULTS Fifteen human bile samples, collected endoscopically, were analysed using gas chromatography mass spectrometry for seven target PCB congeners (28, 52, 101, 118, 153, 138, and 180), known to occur in the environment and food. Amongst males, total PCB concentrations in bile ranged from 6 ng mL(-1) (aged 73 years) to 49 ng mL(-1) (aged 90 years); and in females between 8 ng mL(-1) (aged 33 years) to 43 ng mL(-1) (aged 67 years) bile. Although there was no overall difference in mean PCB levels between non-cancer and cancer patients, levels of congener 28 were significantly higher in patients with biliary tract cancer (p<0.05). CONCLUSIONS Despite the banning of PCBs over 30 years ago, these xenobiotics are present in the bile of patients with biliary disease. PCB levels tend to increase with age, suggesting chronic bioaccumulation. Further research is necessary to investigate the relevance of increased levels of congener 28 in bile in biliary tract cancer.