Fluorescence lifetime spectroscopy of tissue autofluorescence in normal and diseased colon measured ex vivo using a fiber-optic probe.

We present an ex vivo study of temporally and spectrally resolved autofluorescence in a total of 47 endoscopic excision biopsy/resection specimens from colon, using pulsed excitation laser sources operating at wavelengths of 375 nm and 435 nm. A paired analysis of normal and neoplastic (adenomatous polyp) tissue specimens obtained from the same patient yielded a significant difference in the mean spectrally averaged autofluorescence lifetime -570 ± 740 ps (p = 0.021, n = 12). We also investigated the fluorescence signature of non-neoplastic polyps (n = 6) and inflammatory bowel disease (n = 4) compared to normal tissue in a small number of specimens.

Differences in phosphatidylcholine and bile acids in bile from Egyptian and UK patients with and without cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CC) is a fatal malignancy, the incidence of which is increasing worldwide, with substantial regional variation. Current diagnostic techniques to distinguish benign from malignant biliary disease are unsatisfactory. Metabolic profiling of bile may help to differentiate benign from malignant disease. No previous studies have compared the metabolic profiles of bile from two geographically and racially distinct groups of CC patients. OBJECTIVES: This study aimed to compare metabolic profiles of bile, using in vitro proton magnetic resonance spectroscopy, from CC patients from Egypt and the UK, and from patients with CC and patients with non-malignant biliary disease. METHODS: A total of 29 bile samples, collected at cholangiography, were analysed using an 11.7-T system. Samples were from eight CC patients in either Egypt (n = 4) or the UK (n = 4) and 21 patients with benign biliary disease (choledocholithiasis [n = 8], sphincter of Oddi dysfunction [n = 8], primary sclerosing cholangitis [n = 5]). RESULTS: Bile phosphatidylcholine (PtC) was significantly reduced in CC patients. Egyptian CC patients had significantly lower biliary PtC levels compared with UK patients. Taurine- and glycine-conjugated bile acids (H-26 and H-25 protons, respectively) were significantly elevated in bile from patients with CC compared with bile from patients with benign diseases (P = 0.013 and P < 0.01, respectively). CONCLUSIONS: Biliary PtC levels potentially differentiate CC from benign biliary disease. Reduced biliary PtC in Egyptian compared with UK patients may reflect underlying carcinogenic mechanisms.

Two-stage resection for bilobar colorectal liver metastases: R0 resection is the key.

BACKGROUND: Two-stage liver resection (2-SLR) is used clinically in conjunction with portal vein embolization for bilobar disease to increase the number of patients suitable for liver resection. The long-term outcomes after 2-SLR for multiple bilobar colorectal liver metastases (CLM) was examined. METHODS: Patients who sought care between November 2003 and April 2006 with multiple CLM considered suitable for 2-SLR were prospectively followed. Clinicopathological data were collected. Surgical outcomes were defined as complete clearance of tumor (R0/R1/R2), postoperative morbidity (within 3 months), 30 day mortality, disease-free survival (DFS), and overall survival (OS). RESULTS: A total of 131 patients with CLM underwent liver resection during the study period, 38 of whom were planned for a 2-SLR for multiple bilobar disease. Only 33 (87%) completed the 2-SLR with a curative intent. Five patients did not undergo stage II resection because of disease progression. The postoperative morbidity was 11 and 33% after stage I and stage II liver resections, respectively. Five patients (13%) encountered postoperative complications specific to liver surgery. The median interval from stage II resection to disease recurrence in the R0 group was 18 months versus 3 months in the R1/R2 group (P < 0.001). R0 resection with curative intent versus R1/R2 noncurative resection has a significantly longer period of DFS (P < 0.001) and OS (P = 0.04). CONCLUSIONS: The 2-SLR combined with portal vein embolization is an effective and safe method for resecting previously unresectable multiple bilobar CLM. However, a positive resection margin leads to poor DFS and OS.

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.

Imaging of liver cancer.

Improvements in imaging technology allow exploitation of the dual blood supply of the liver to aid in the identification and characterisation of both malignant and benign liver lesions. Imaging techniques available include contrast enhanced ultrasound, computed tomography and magnetic resonance imaging. This review discusses the application of several imaging techniques in the diagnosis and staging of both hepatocellular carcinoma and cholangiocarcinoma and outlines certain characteristics of benign liver lesions. The advantages of each imaging technique are highlighted, while underscoring the potential pitfalls and limitations of each imaging modality.

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 (H) and phosphorus-31 (P) NMR spectra were obtained from all samples using an 11.7 Tesla NMR spectroscopy system. RESULTS: Complementary information was obtained from the H and P NMR spectra. Signals were assigned to phosphatidylcholine in both H and P 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 H and P 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.