Hepcidin levels correlate to liver iron content, but not steatohepatitis, in non-alcoholic fatty liver disease.

BACKGROUND: One-third of patients with non-alcoholic fatty liver disease (NAFLD) develop dysmetabolic iron overload syndrome (DIOS), the pathogenesis of which is unknown. Altered production of the iron-regulatory peptide hepcidin has been reported in NAFLD, but it is unclear if this is related to iron accumulation, lipid status or steatohepatitis. METHODS: Eighty-four patients with liver disease, 54 of which had iron overload, underwent liver biopsy (n = 66) and/or magnetic resonance imaging (n = 35) for liver iron content determination. Thirty-eight of the patients had NAFLD, 29 had chronic liver disease other than NAFLD, and 17 had untreated genetic hemochromatosis. Serum hepcidin was measured with ELISA in all patients and in 34 controls. Hepcidin antimicrobial peptide (HAMP) mRNA in liver tissue was determined with real-time-quantitative PCR in 36 patients. RESULTS: Serum hepcidin was increased similarly in NAFLD with DIOS as in the other chronic liver diseases with iron overload, except for genetic hemochromatosis. HAMP mRNA in liver tissue, and serum hepcidin, both correlated to liver iron content in NAFLD patients (r2 = 0.45, p < 0.05 and r2 = 0.27, p < 0.05 respectively) but not to body mass index, NAFLD activity score or serum lipids. There was a good correlation between HAMP mRNA in liver tissue and serum hepcidin (r2 = 0.39, p < 0.01). CONCLUSIONS: In NAFLD with or without dysmetabolic iron overload, serum hepcidin and HAMP mRNA in liver correlate to body iron content but not to the degree of steatohepatitis or lipid status. Thus, the dysmetabolic iron overload syndrome seen in NAFLD is not caused by an altered hepcidin synthesis.

A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients With Pancreatic Cancer.

We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT. Both TAAs were highly expressed in the original tumor tissue suggesting that HSCT promoted a clinically relevant, long-lasting cellular immune response. In contrast to untreated controls, who succumbed to progressive disease, both patients are tumor-free 9 years after diagnosis. Radical surgery combined with HSCT may cure pancreatic adenocarcinoma and change the cellular immune repertoire capable of responding to clinically and biologically relevant TAAs.

Diffusion-weighted MR imaging of pancreatic cancer: A comparison of mono-exponential, bi-exponential and non-Gaussian kurtosis models.

OBJECTIVES: To compare two Gaussian diffusion-weighted MRI (DWI) models including mono-exponential and bi-exponential, with the non-Gaussian kurtosis model in patients with pancreatic ductal adenocarcinoma. MATERIALS AND METHODS: After written informed consent, 15 consecutive patients with pancreatic ductal adenocarcinoma underwent free-breathing DWI (1.5T, b-values: 0, 50, 150, 200, 300, 600 and 1000 s/mm2). Mean values of DWI-derived metrics ADC, D, D*, f, K and DK were calculated from multiple regions of interest in all tumours and non-tumorous parenchyma and compared. Area under the curve was determined for all metrics. RESULTS: Mean ADC and DK showed significant differences between tumours and non-tumorous parenchyma (both P < 0.001). Area under the curve for ADC, D, D*, f, K, and DK were 0.77, 0.52, 0.53, 0.62, 0.42, and 0.84, respectively. CONCLUSION: ADC and DK could differentiate tumours from non-tumorous parenchyma with the latter showing a higher diagnostic accuracy. Correction for kurtosis effects has the potential to increase the diagnostic accuracy of DWI in patients with pancreatic ductal adenocarcinoma.

Correlation between preoperative imaging and intraoperative risk assessment in the prediction of postoperative pancreatic fistula following pancreatoduodenectomy.

BACKGROUND: Prediction of postoperative pancreatic fistula (POPF) can be carried out with the intraoperative assessment of pancreatic consistency (PC) and via pancreatic duct width (iPDW). Preoperative computed tomography (CT) calculated pancreatic remnant volume (PRV) and duct width (rPDW) have also been shown to offer useful information about the risk of POPF. OBJECTIVE: The objective of this study was to determine the predictive value of the preoperative radiological features as compared with the intraoperative risk estimation for the subsequent development of POPF. METHOD: All patients undergoing pancreatoduodenectomy between September 2007 and March 2012 at the Karolinska University Hospital Stockholm were included. PRV and rPDW were determined on preoperative CT and in parallel, intraoperative PC and iPDW of the remnant pancreas were independently assessed. RESULTS: A total of 296 consecutive pancreatoduodenectomies were included. POPF occurred in 45 patients (15.2 %). Of those with a preoperatively calculated PRV < 23.0 cm(3), 2.8 % developed POPF compared with 25.7 % of those with a corresponding volume > 46.0 cm(3). In patients with an rPDW > 7.0 mm, 4.1 % had a POPF as compared with 38.7 % for those with rPDW < 2.0 mm. The POPF risk estimates based on PRV and rPDW and the intraoperative risk assessments were found to be identical (p < 0.001). In the receiver operating characteristic analysis, area under the curve was 0.80 (95 % confidence interval [CI] 0.72-0.87) and 0.80 (95 % CI 0.72-0.88) for the CT-based and intraoperative risk prediction models, respectively. CONCLUSIONS: Preoperative CT-based and intraoperative gland risk assessments offer comparable predictive information on the risk of POPF after pancreatoduodenectomy. These results imply that accurate POPF risk estimation can be carried out in the preoperative setting to opt for improved patient selection into relevant research protocols and the availability of surgical expertise and techniques.

Time-resolved computed tomography of the liver: retrospective, multi-phase image reconstruction derived from volumetric perfusion imaging.

OBJECTIVE: To assess feasibility and image quality (IQ) of a new post-processing algorithm for retrospective extraction of an optimised multi-phase CT (time-resolved CT) of the liver from volumetric perfusion imaging. METHODS: Sixteen patients underwent clinically indicated perfusion CT using 4D spiral mode of dual-source 128-slice CT. Three image sets were reconstructed: motion-corrected and noise-reduced (MCNR) images derived from 4D raw data; maximum and average intensity projections (time MIP/AVG) of the arterial/portal/portal-venous phases and all phases (total MIP/ AVG) derived from retrospective fusion of dedicated MCNR split series. Two readers assessed the IQ, detection rate and evaluation time; one reader assessed image noise and lesion-to-liver contrast. RESULTS: Time-resolved CT was feasible in all patients. Each post-processing step yielded a significant reduction of image noise and evaluation time, maintaining lesion-to-liver contrast. Time MIPs/AVGs showed the highest overall IQ without relevant motion artefacts and best depiction of arterial and portal/portal-venous phases respectively. Time MIPs demonstrated a significantly higher detection rate for arterialised liver lesions than total MIPs/AVGs and the raw data series. CONCLUSION: Time-resolved CT allows data from volumetric perfusion imaging to be condensed into an optimised multi-phase liver CT, yielding a superior IQ and higher detection rate for arterialised liver lesions than the raw data series. KEY POINTS: • Four-dimensional computed tomography is limited by motion artefacts and poor image quality. • Time-resolved-CT facilitates 4D-CT data visualisation, segmentation and analysis by condensing raw data. • Time-resolved CT demonstrates better image quality than raw data images. • Time-resolved CT improves detection of arterialised liver lesions in cirrhotic patients.

MRI of Focal Liver Lesions.

Magnetic resonance imaging, MRI has more advantages than ultrasound, computed tomography, CT, positron emission tomography, PET, or any other imaging modality in diagnosing focal hepatic masses. With a combination of basic T1 and T2 weighted sequences, diffusion weighted imaging, DWI, and hepatobiliary gadolinium contrast agents, that is gadobenate dimeglumine (Gd-BOPTA) and gadoxetic acid (Gd-EOB), most liver lesions can be adequately diagnosed. Benign lesions, as cyst, hemangioma, focal nodular hyperplasia, FNH or adenoma, can be distinguished from malignant lesions. In a non-cirrhotic liver, the most common malignant lesions are metastases which may be hypovascular or hypervascular. In the cirrhotic liver hepatocellular carcinoma, HCC, is of considerable importance. Besides, intrahepatic cholangiocarcinoma and other less common malignancies has to be assessed. In this review, the techniques and typical MRI features are presented as well as the new algorithm issued by American Association for the Study of the Liver Diseases (AASLD).

Low tube voltage CT for improved detection of pancreatic cancer: detection threshold for small, simulated lesions.

BACKGROUND: Pancreatic ductal adenocarcinoma is associated with dismal prognosis. The detection of small pancreatic tumors which are still resectable is still a challenging problem.The aim of this study was to investigate the effect of decreasing the tube voltage from 120 to 80 kV on the detection of pancreatic tumors. METHODS: Three scanning protocols was used; one using the standard tube voltage (120 kV) and current (160 mA) and two using 80 kV but with different tube currents (500 and 675 mA) to achieve equivalent dose (15 mGy) and noise (15 HU) as that of the standard protocol.Tumors were simulated into collected CT phantom images. The attenuation in normal parenchyma at 120 kV was set at 130 HU, as measured previously in clinical examinations, and the tumor attenuation was assumed to differ 20 HU and was set at 110HU. By scanning and measuring of iodine solution with different concentrations the corresponding tumor and parenchyma attenuation at 80 kV was found to be 185 and 219 HU, respectively.To objectively evaluate the differences between the three protocols, a multi-reader multi-case receiver operating characteristic study was conducted, using three readers and 100 cases, each containing 0-3 lesions. RESULTS: The highest reader averaged figure-of-merit (FOM) was achieved for 80 kV and 675 mA (FOM=0,850), and the lowest for 120 kV (FOM=0,709). There was a significant difference between the three protocols (p<0,0001), when making an analysis of variance (ANOVA). Post-hoc analysis (students t-test) shows that there was a significant difference between 120 and 80 kV, but not between the two levels of tube currents at 80 kV. CONCLUSION: We conclude that when decreasing the tube voltage there is a significant improvement in tumor conspicuity.

A new manganese-based oral contrast agent (CMC-001) for liver MRI: pharmacological and pharmaceutical aspects.

Manganese is one of the most abundant metals on earth and is found as a component of more than 100 different minerals. Besides being an essential trace element in relation to the metabolic processes in the body, manganese is also a paramagnetic metal that possesses similar characteristics to gadolinium with regards to T1-weighted (T1-w) magnetic resonance imaging (MRI). Manganese, in the form of manganese (II) chloride tetrahydrate, is the active substance in a new targeted oral contrast agent, currently known as CMC-001, indicated for hepatobiliary MRI. Under physiological circumstances manganese is poorly absorbed from the intestine after oral intake, but by the use of specific absorption promoters, L-alanine and vitamin D(3), it is possible to obtain a sufficiently high concentration in the liver in order to achieve a significant signal enhancing effect. In the liver manganese is exposed to a very high first-pass effect, up to 98%, which prevents the metal from reaching the systemic circulation, thereby reducing the number of systemic side-effects. Manganese is one of the least toxic trace elements, and due to its favorable safety profile it may be an attractive alternative to gadolinium-based contrast agents for patients undergoing an MRI evaluation for liver metastases in the future. In this review the basic pharmacological and pharmaceutical aspects of this new targeted oral hepatobiliary specific contrast agent will be discussed.

Optimising diffusion-weighted MR imaging for demonstrating pancreatic cancer: a comparison of respiratory-triggered, free-breathing and breath-hold techniques.

OBJECTIVES: To compare respiratory-triggered, free-breathing, and breath-hold DWI techniques regarding (1) image quality, and (2) signal intensity (SI) and ADC measurements in pancreatic ductal adenocarcinoma (PDAC). METHODS: Fifteen patients with histopathologically proven PDAC underwent DWI prospectively at 1.5 T (b = 0, 50, 300, 600 and 1,000 s/mm(2)) with the three techniques. Two radiologists, independently and blindly, assigned total image quality scores [sum of rating diffusion images (lesion detection, anatomy, presence of artefacts) and ADC maps (lesion characterisation, overall image quality)] per technique and ranked them. The lesion SI, signal-to-noise ratio, mean ADC and coefficient of variation (CV) were compared. RESULTS: Total image quality scores for respiratory-triggered, free-breathing and breath-hold techniques were 17.9, 16.5 and 17.1 respectively (respiratory-triggered was significantly higher than free-breathing but not breath-hold). The respiratory-triggered technique had a significantly higher ranking. Lesion SI on all b-values and signal-to-noise ratio on b300 and b600 were significantly higher for the respiratory-triggered technique. For respiratory-triggered, free-breathing and breath-hold techniques the mean ADCs were 1.201, 1.132 and 1.253 × 10(-3) mm(2)/s, and mean CVs were 8.9, 10.8 and 14.1 % respectively (respiratory-triggered and free-breathing techniques had a significantly lower mean CV than the breath-hold technique). CONCLUSION: In both analyses, respiratory-triggered DWI showed superiority and seems the optimal DWI technique for demonstrating PDAC. KEY POINTS : • Diffusion-weighted magnetic resonance imaging is increasingly used to detect pancreatic cancer • Images are acquired using various breathing techniques and multiple b-values • Breathing techniques used: respiratory-triggering, free-breathing and breath-hold • Respiratory-triggering seems the optimal breathing technique for demonstrating pancreatic cancer.

Manganese chloride tetrahydrate (CMC-001) enhanced liver MRI: evaluation of efficacy and safety in healthy volunteers.

OBJECT: To evaluate the efficacy of three dose levels of the oral hepatobiliary manganese-based magnetic resonance imaging (MRI) contrast agent CMC-001, and assess its safety profile and patient acceptability. MATERIALS AND METHODS: After ethics committee approval, 32 healthy volunteers (males/females: 18/14) were included. Liver MRI was performed before and 3 h after ingestion of 0.8, 0.4, and 0.2 g of CMC-001 on separate occasions. Liver-to-muscle signal intensity (SI) ratio from baseline to post-contrast and image quality was assessed. Adverse drug reactions/adverse events (ADRs/AEs) and clinico-laboratory tests were monitored. RESULTS: The increase in liver-to-muscle SI ratio was significantly higher after 0.8 g (0.696) compared to 0.4 g (0.458) and 0.2 g (0.223) (in all pair-wise comparisons, P < 0.0001). The overall image quality was superior after 0.8 g. ADRs/AEs were dose-related and predominantly of mild intensity. CONCLUSION: Liver MRI using 0.8 g CMC-001 has the highest efficacy and still acceptable ADRs and should therefore be preferred.

MRI of colorectal cancer liver metastases: comparison of orally administered manganese with intravenously administered gadobenate dimeglumine.

OBJECTIVES: To compare the sensitivity of MRI to detect colorectal cancer liver metastases (CRLM) after ingestion of manganese-based contrast agent (CMC-001) with that of a comprehensive intravenous gadobenate dimeglumine protocol, and to assess the safety and acceptability of oral manganese. METHODS: 20 patients suspected of having 1-6 CRLM were included prospectively in this randomised cross-over study. Liver MRI was performed with a one-week interval at 1.5 T and included T1-w VIBE and T2-HASTE, before and after administration of 1.6 g CMC-001 or 0.1 mmol/kg gadobenate dimeglumine. The metastasis-to-liver signal intensity (SI) ratio was calculated. Standard of reference was histopathology after surgery, or combination of other imaging studies and/or follow up. Adverse events (AE) and clinicolaboratory tests were monitored. RESULTS: Of 44 metastases, 41 were detected after CMC-001 (93%) and 42 after gadobenate dimeglumine (95%). Fifteen false-positive lesions were found after CMC-001 and 2 after gadobenate dimeglumine. The metastasis-to-liver SI ratio was significantly higher after CMC-001 than after gadobenate dimeglumine (0.51 and 0.21 respectively, P < 0.0001). More AE occurred after manganese compared to gadobenate dimeglumine. CONCLUSIONS: CMC-001 is as sensitive as an extensive intravenous gadobenate dimeglumine protocol in detecting CRLM. It was relatively well tolerated but had higher rates of gastrointestinal AE. KEY POINTS: • Liver MRI after ingestion of manganese is highly sensitive for detecting metastases • High false-positive rate necessitates further evaluation, in some cases • The MR examination time is short • Oral ingestion of manganese seems safe and relatively well tolerated by patients • Manganese compounds may be useful for liver metastasis surveillance after colorectal cancer.

The added value of contrast-enhanced ultrasound in patients with colorectal cancer undergoing preoperative evaluation with extensive gadobenate dimeglumine liver MRI.

OBJECTIVES: To evaluate the added value of pre- and intraoperative contrast-enhanced ultrasound (transabdominal, or TCEUS and intraoperative, or ICEUS, respectively) in patients with known or highly suspected colorectal cancer liver metastases (CRLM) who have previously undergone extensive gadobenate dimeglumine (Gd-BOPTA) liver MRI. METHODS: Fifteen patients with a total of 31 lesions were included in the comparison of TCEUS vs. MRI and nine patients with a total of 19 lesions were included in the comparison of ICEUS vs. MRI. MRI examinations were performed before TCEUS and ICEUS. The analysis was performed lesion by lesion. Sensitivity, positive predictive value (PPV) and accuracy were calculated and compared. RESULTS: On comparing TCEUS with MRI, sensitivity differed significantly, with values of 87% and 100%, respectively (p value < 0.05), but there was no significant difference in PPV and accuracy. The comparison of ICEUS with MRI, however, showed no significant difference in sensitivity, PPV or accuracy. CONCLUSIONS: Transabdominal and intraoperative contrast-enhanced ultrasound have no added value in the preoperative evaluation of patients with CRLM undergoing extensive gadobenate dimeglumine liver MRI.

Impact of pancreatic gland volume on fistula formation after pancreatic tail resection.

CONTEXT: Resection of the body and tail of the pancreas (distal pancreatectomy) is associated with high postoperative morbidity, most of which is due to leakage from the pancreatic transection surface. OBJECTIVE: The aim of the current study was to analyze factors which may affect the risk of pancreatic fistula formation. PATIENTS: All consecutive distal pancreatectomies prospectively registered in our hospital database from 1999 to 2007 were included. Clinically relevant pancreatic fistula grades B and C, defined according to the International Study Group on Pancreatic Fistula (ISGPF) definition were assessed. MAIN OUTCOME MEASURES: The impact of patient, tumor, surgery, and radiology-related factors on the risk of pancreatic fistula formation were assessed by univariate and multivariate analyses. RESULTS: A distal pancreatectomy was performed in 51 patients (median age: 59 years; range: 26-76 years), 22 of whom had malignant and 29 benign or premalignant disease. Pancreatic fistulas were diagnosed in 17 (33.3%) of the patients. An additional three patients had a local abscess without apparent but assumed pancreatic leakage. Multivariate analysis showed that pancreatic fistulas occurred more frequently after hand suturing of the transection area versus the use of a stapler (69.2% vs. 21.1%; OR: 40.4, 95% CI: 3.36-486; P=0.004) and a large volume of the pancreatic remnant (greater, or equal to, 34 cm3) increased the subsequent risk of pancreatic fistula (57.1% vs. 20.8%; OR: 6.14, 95% CI: 1.14-39.0; P=0.035). CONCLUSIONS: Development of pancreatic fistula after distal pancreatectomy remains a challenge. The volume of the remaining pancreas and the technique of closure of the transected pancreas were found to affect this risk, thus allowing future preventive measures to be explored and evaluated in clinical trials.

Simultaneous quantification of glycine- and taurine-conjugated bile acids, total bile acids, and choline-containing phospholipids in human bile using 1H NMR spectroscopy.

Bile acids, phospholipids, and cholesterol are the major lipid components in human bile. The composition of bile is altered in various cholestatic diseases, and determining such alterations will be of great clinical importance in understanding the pathophysiology of these diseases. A robust method for the simultaneous quantification of major biliary lipids--glycine-conjugated bile acids (GCBAs), taurine-conjugated bile acids (TCBAs), total bile acids (TBAs) and choline-containing phospholipids (choline-PLs) has been devised using (1)H NMR spectroscopy. Bile samples were obtained from patients with various hepatopancreatobiliary diseases (n=10) during an endoscopic retrograde cholangiopancreatography (ERCP) examination. Peak areas of metabolite-signals of interest were obtained simultaneously by deconvoluting the experimental spectrum, making the present method robust. GCBAs and TCBAs have been quantified using the peak areas of their characteristic methylene (CH(2)) signals resonating at 3.73 and 3.07 ppm, whereas TBA and choline-PLs were quantified using their methyl (CH(3)) and trimethylammonium (-N(+)(CH(3))(3)) signals resonating at 0.65 and 3.22 ppm respectively. The present method was compared with an NMR-based literature method (which involves dissolving bile in DMSO), and a good correlation was observed between the two methods with regression coefficients - 0.97, 0.99, 0.98 and 0.93 for GCBAs, TCBAs, TBAs, and choline-PLs respectively. This method has the potential to be extended to in vivo applications for the simultaneous quantification of various biliary lipids non-invasively.

Pancreatic duct changes are not associated with early signs of chronic pancreatitis at magnetic resonance imaging (MRI) in patients with primary sclerosing cholangitis.

OBJECTIVE: The association between chronic pancreatitis (CP) and primary sclerosing cholangitis (PSC) has been reported previously. The aims of the present study were to evaluate the presence of early pancreatic abnormalities and duct changes, using MRCP/MRI in PSC and to evaluate possible risk factors for these changes and their clinical importance. MATERIALS AND METHODS: One hundred and three patients with PSC were identified among all MRI liver/pancreas referrals in 2001-2005. MRCP was used to grade pancreatic duct changes in three groups: grade 0 (normal), grade 1 (mild) and grade 2 (severe). For detection of early MRI signs of CP, the pancreas-spleen signal intensity ratio (SIR), the arterial and early venous phase ratio (A/PV ratio) and the age-related size of the pancreas were evaluated. RESULTS: Pancreatic duct changes were found in 24% of the PSC patients. The pancreatic duct changes were associated with extrahepatic biliary involvement and long duration of PSC but not associated with pancreas-spleen SIR, A/PV ratio, pancreas size, previous post-ERCP or acute pancreatitis. Severe pancreatic duct changes were significantly associated to abdominal pain. Clinically significant CP was seen in one PSC patient (1%). CONCLUSIONS: Pancreatic duct changes are associated with extrahepatic bile duct strictures and not with the early MRI signs of CP. Therefore, pancreatic duct changes seem to be part of the spectrum of PSC and should not be defined as CP. Pancreatic duct changes are of limited clinical importance but may contribute to abdominal pain in PSC.

Gallbladder emptying in patients with primary sclerosing cholangitis.

AIM: To assess gallbladder emptying and its association with cholecystitis and abdominal pain in patients with primary sclerosing cholangitis (PSC). METHODS: Twenty patients with PSC and ten healthy subjects were investigated. Gallbladder fasting volume, ejection fraction and residual volume after ingestion of a test meal were compared in patients with PSC and healthy controls using magnetic resonance imaging. Symptoms, thickness and contrast enhancement of the gallbladder wall and the presence of cystic duct strictures were also assessed. RESULTS: Median fasting gallbladder volume in patients with PSC [67 (19-348) mL] was twice that in healthy controls [32 (16-55) mL] (P < 0.05). The median postprandial gallbladder volume in patients with PSC was significantly larger than that in healthy controls (P < 0.05). There was no difference in ejection fraction, gallbladder emptying volume or mean thickness of the gallbladder wall between PSC patients and controls. Contrast enhancement of the gallbladder wall in PSC patients was higher than that in controls; (69% +/- 32%) and (42% +/- 21%) (P < 0.05). No significant association was found between the gallbladder volumes and occurrence of abdominal pain in patients and controls. CONCLUSION: Patients with PSC have increased fasting gallbladder volume. Gallbladder Mucosal dysfunction secondary to chronic cholecystitis, may be a possible mechanism for increased gallbladder.

Detection and quantification of D-glucuronic acid in human bile using 1H NMR spectroscopy: relevance to the diagnosis of pancreatic cancer.

OBJECTIVE: There are no specific biomarkers available for the definitive diagnosis of pancreatic cancer. Analysis of D-glucuronic acid (GlcUA) in bile could be valuable in this regard. MATERIALS AND METHODS: Bile samples obtained from patients with pancreatic cancer (n = 4), chronic pancreatitis (n = 3) and control patients with biliary obstruction (n = 10) were analyzed by (1)H NMR spectroscopy. GlcUA was quantified from the peak area of the alpha-(1)CH signal (at 5.24 ppm) obtained by deconvolution. RESULTS: GlcUA was detected in human bile by one-dimensional (1)H NMR and two-dimensional (1)H-(1)H COSY and TOCSY experiments. Quantification of GlcUA was achieved by measuring the peak area of the alpha-(1)CH signal using CPMG experiment, and the quantities of GlcUA were calibrated to account for the attenuation due to T (2) relaxation. GlcUA was observed at elevated levels in bile samples obtained from pancreatic cancer patients, whereas it was either absent or found in negligible amounts in control and chronic pancreatitis patients. The reason for the presence of elevated levels of GlcUA could be the hydrolysis of biliary bilirubin diglucuronide by beta-glucuronidase, released excessively from pancreatic tissue during the course of malignancy. CONCLUSION: Analysis of D-glucuronic acid in bile could be valuable in the detection of pancreatic cancer, and detecting GlcUA by in vivo (1)H MRS has the potential to help in the non-invasive diagnosis of pancreatic cancer. Given that only four cancer patients have been studied so far, the new biomarker is regarded as a preliminary finding, but one that warrants further investigation.