Cancer Risk in Collagenous Colitis.

Data on malignancy in patients with collagenous colitis (CC) is scarce. We aimed to determine the incidence of cancers in patients with CC. In a two-stages, observational study, data on cancers in patients diagnosed with CC during 2000-2015, were collected from two cohorts. The risk was calculated according to the age-standardized rate for the first cohort and according to the standardized incidence ratio for the second cohort. The first cohort comprised 738 patients (394 from Scotland and 344 from Sweden; mean age 71 ± 11 and 66 ± 13 years, respectively). The incidence rates for lung cancer (RR 3.9, p = 0.001), bladder cancer (RR 9.2, p = 0.019), and non-melanoma skin cancer (NMSC) (RR 15, p = 0.001) were increased. As the majority of NMSC cases (15/16) came from Sweden, a second Swedish cohort, comprising 1141 patients (863 women, mean age 65 years, range 20-95 years) was collected. There were 93 cancer cases (besides NMSC). The risk for colon cancer was decreased (SIR 0.23, p= 0.0087). The risk for cutaneous squamous cell carcinoma was instead markedly increased (SIR 3.27, p = 0.001).

Small bowel capsule endoscopy and portal hypertensive enteropathy in cirrhotic patients: results from a tertiary referral centre.

BACKGROUND AND RATIONALE: Portal hypertensive enteropathy (PHE) remains difficult to diagnose in patients with cirrhosis and portal hypertension. Limited test choices exist for the inspection of the small bowel in these patients. Small bowel capsule endoscopy (SBCE) is ideal in this situation but rarely performed. We aimed to determine the prevalence of PHE using SBCE in a cirrhotic patient population and correlate its presence with clinical and CT imaging findings. MATERIAL AND METHODS: We retrospectively analysed data from cirrhotic patients who underwent SBCE at our unit. Studies were evaluated for the presence of cirrhosis-related findings in the oesophagus, stomach and small-bowel. The relationships between PHE and patients' clinical characteristics were evaluated. RESULTS: 53 patients with cirrhosis underwent SCBE. We used PillCam®SB on 36 patients and MiroCam® capsule on 17. Thirty patients were referred for iron deficiency anaemia, 15 for obscure gastrointestinal bleeding, and 4 for other indications. Four data sets were not available for review, leaving 49 patients. Mean age was 61.19 ± 14.54 years (M/F = 27/22). Six SBCE examinations were incomplete. Thirty three patients had evidence of portal hypertensive gastropathy (PHG) and 17 had evidence of oesophageal varices. In total, 29 patients had SCBE evidence of PHE (57%). 28/29 (96.5%) patients with PHE had also evidence of PHG. 13/17 (76.4%) patients with oesophageal varices had also evidence of PHE. CONCLUSIONS: The prevalence of PHE in our study was 57%. SBCE is a useful tool in evaluating PHE in cirrhotic patients irrespective of aetiology.

Do prokinetics influence the completion rate in small-bowel capsule endoscopy? A systematic review and meta-analysis.

BACKGROUND: The use of purging for bowel cleansing prior to small-bowel capsule endoscopy (SBCE) has now been established in clinical practice. Despite that, the number of incomplete SBCEs is still around 15-20%. To date, the use of prokinetics in SBCE - aiming to improve completion rate (CR) - remains a contentious issue resulting in lack of consensus among capsule experts. METHODS: Extensive medical literature searches were conducted (to November 2012), using suitable MeSH terms and keywords, in search of studies that compared capsule ingestion with prokinetic agents vs. controls or placebo. We examined the effects of prokinetic administration on SBCE CR (primary end point), as well as on the following secondary end points: diagnostic yield (DY), gastric transit time (GTT) and small-bowel transit time (SBTT) by meta-analysis of all relevant studies. RESULTS: A total of 17 eligible studies (14 prospective, 3 retrospective) were identified, including 1028 individuals who ingested the capsule with no prokinetic vs. 876 who received a prokinetic. Overall, there was a higher CR in patients who ingested the capsule with prokinetics vs. controls (OR [95% CI]: 1.96 [1.38-2.78]). Of the two most readily available prokinetics, metoclopramide was associated with superior SBCE CR vs. control (OR [95% CI]: 2.8 [1.35-3.21]), while erythromycin showed no benefit (OR [95% CI]: 1.36 [0.61-3.03]). Where prokinetics were used alone, neither metoclopramide nor erythromycin showed any benefit on CR. There was no benefit of prokinetics (over controls) on DY. However, metoclopramide had a significant effect on GTT and SBTT. LIMITATIONS: The majority of the included studies were heterogeneous, and the effect of prokinetics on image quality and mucosal visualization was not examined. CONCLUSION: Our pooled data shows that the use of prokinetics for capsule ingestion improves CR in SBCE. This effect appears to be particularly evident with metoclopramide, when used concurrently with purging and/or use of real-time monitoring. In a small number of studies, erythromycin showed - through its gastrokinetic effect - marginal benefit. No prokinetic has a beneficial effect on SBCE DY.

Impaired gluconeogenesis in a porcine model of paracetamol induced acute liver failure.

AIM: To investigate glucose homeostasis and in particular gluconeogenesis in a large animal model of acute liver failure (ALF). METHODS: Six pigs with paracetamol induced ALF under general anaesthesia were studied over 25 h. Plasma samples were withdrawn every five hours from a central vein. Three animals were used as controls and were maintained under anaesthesia only. Using (1)H NMR spectroscopy we identified most gluconeogenic amino acids along with lactate and pyruvate in the animal plasma samples. RESULTS: No significant changes were observed in the concentrations of the amino acids studied in the animals maintained under anaesthesia only. If we look at the ALF animals, we observed a statistically significant rise of lactate (P < 0.003) and pyruvate (P < 0.018) at the end of the experiments. We also observed statistically significant rises in the concentrations of alanine (P < 0.002), glycine (P < 0.005), threonine (P < 0.048), tyrosine (P < 0.000), phenylalanine (P < 0.000) and isoleucine (P < 0.01). Valine levels decreased significantly (P < 0.05). CONCLUSION: Our pig model of ALF is characterized by an altered gluconeogenetic capacity, an impaired tricarboxylic acid (TCA) cycle and a glycolytic state.

Regional variations in the concentrations of ketone bodies in cirrhosis and hepatic encephalopathy: a study in patients with TIPSS.

BACKGROUND: Little is known about the metabolism of acetoacetate and ß-hydroxybutyrate in patients with cirrhosis and encephalopathy. AIMS: We investigated the fate of ketone bodies in these conditions. MATERIALS AND METHODS: We studied 18 cirrhotic patients with encephalopathy and 17 cirrhotics without. At the time of insertion of a transjugular intrahepatic portosystemic stent shunt (TIPSS) or at the time of portographical assessment of the shunt's patency, we collected blood from the internal jugular, the right atrium, the inferior vena cava, the hepatic, the portal, the splenic veins and the radial artery. We used nuclear magnetic resonance spectroscopy to measure the concentrations of acetoacetate and ß-hydroxybutyrate. RESULTS: There was no difference in the total ketone body concentrations between the two groups. The mitochondrial redox potential was significantly higher in the encephalopathics (142/54=2.63 vs 52/83=0.62) (P<0.01). ß-hydroxybutyrate was significantly lower in the portal vein of encephalopathics (52 ± 4 vs 28 ± 3) (P<0.02) and in the splenic vein (48 ± 6 vs 32 ± 5) (P<0.04). Acetoacetate was significantly higher in encephalopathics in the internal jugular vein (134 ± 12 vs 92 ± 16) (P<0.03), the right atrium (112 ± 18 vs 68 ± 11) (P<0.03), the hepatic vein (162 ± 25 vs 115 ± 19) (P<0.05), the portal vein (133 ± 20 vs 81 ± 14) (P<0.02) and the splenic vein (167 ± 24 vs 122 ± 21) (P<0.04). All measurements are expressed in µmols/L. CONCLUSIONS: There are significant variations in the regional concentrations of the ketone bodies in encephalopathy.

Is Chios mastic gum effective in the treatment of functional dyspepsia? A prospective randomised double-blind placebo controlled trial.

BACKGROUND: Herbal remedies are increasingly popular for the treatment of functional dyspepsia. Chios mastic gum is a resinous exudate from the stem of Pistacia lentiscus var. chia. It is a traditional natural remedy used throughout the eastern Mediterranean. The aim of this study was to assess the efficacy of Chios mastic gum in patients with functional dyspepsia. METHODS: One hundred and forty eight patients fulfilling Rome II criteria for functional dyspepsia were randomly assigned to receive either Chios mastic gum 350 mg three times daily or placebo. After 3 weeks of treatment the change from baseline in the severity of symptoms of functional dyspepsia was assessed using the Hong Kong index of dyspepsia. Patients' global assessment of efficacy was also evaluated. RESULTS: The symptom score after treatment was significantly lower in the Chios mastic gum than in the placebo group ((14.78+/-1.78) vs (19.96+/-1.83)) (p<0.05). There was a marked improvement of symptoms in 40% of patients receiving placebo and in 77% of patients receiving Chios mastic gum (p<0.02). Individual symptoms that showed significant improvement with Chios mastic gum were: stomach pain in general, stomach pain when anxious, dull ache in the upper abdomen and heartburn (<0.05 for all four symptoms). CONCLUSION: Chios mastic gum significantly improves symptoms in patients with functional dyspepsia compared to placebo.

Comparison of bioenergetic activity of primary porcine hepatocytes cultured in four different media.

Primary hepatocytes have extensively been used in biochemical, pharmacological, and physiological research. Recently, primary porcine hepatocytes have been regarded as the cells of choice for bioartificial liver support systems. The optimum culture medium for hepatocytes to be used in such devices has yet to be defined. In this study we investigated the effectiveness of four culture media in driving energy metabolism of primary porcine hepatocytes. The media selected were William's E medium, medium 1640, medium 199, and hepatocyte medium. Cells (3 x 10(10); viability 87 +/- 6%) were isolated from weanling piglets and seeded on 90-mm plates in the above media supplemented with antibiotics and hormones at a density of 8 x 10(6) viable cells per plate. Using 1H NMR spectroscopy we looked at indices of glycolysis, gluconeogenesis. ketogenesis, and ureagenesis on days 2, 4, and 6 of the experiments (n = 9). We also studied urea and albumin synthesis and total P450 content. The examined metabolic pathways of the hepatocytes were maintained by all media, although there were statistically significant differences between them. All media performed well in glycolysis, ureagenesis, and albumin synthesis. William's E medium and medium 199 outperformed the rest in gluconeogenesis. Medium 199 was best in ketogenesis. Overall, medium 199 was the best at driving energy metabolism from its constituent substrates and we think that it preferentially should be used in the culture of primary porcine hepatocytes.

Biochemical prognostic markers of outcome in non-paracetamol-induced fulminant hepatic failure.

BACKGROUND: Fulminant hepatic failure (FHF) is associated with major metabolic disturbances, the onset and severity of which can predict clinical outcome. This study uses admission blood samples to identify early biochemical markers of clinical outcome in patients with non-paracetamol-induced FHF. PATIENTS AND METHODS: Fifty-nine patients admitted to the Scottish Liver Transplant Unit with non-paracetamol-induced FHF were studied. Plasma samples were collected at a median of 5.4 hr after admission to our unit and analyzed using conventional laboratory tests and nuclear magnetic resonance spectroscopy. RESULTS: A total of 19 patients underwent transplantation, 15 patients died without undergoing transplantation, and 25 patients survived with medical management alone. There were significantly lower levels of lactate, alanine, valine, and bilirubin and significantly higher levels of pyruvate and albumin in patients who survived spontaneously compared with the other two groups. By use of multiple logistic regression analysis, an equation was devised that best predicted clinical outcome: 0.5x(albumin [g/L])-2x(lactate [mmol/L])-36x(valine [mmol/L])-38x(pyruvate [mmol/L]). Values of less than 2 were associated with poor clinical outcome and had a positive predictive value of 91%, a negative predictive value of 86%, a sensitivity of 94%, and a specificity of 86% for death or transplantation. This algorithm can be applied on admission, thus expediting decision-making. CONCLUSION: We identified biochemical markers that may be useful in predicting outcome in patients with non-paracetamol-induced FHF and should be evaluated further in a different patient population.

The effect of hypothermia on primary porcine hepatocyte metabolism monitored by (1H) nuclear magnetic resonance spectroscopy.

OBJECTIVE: The aim of our study was to use (1H) nuclear magnetic resonance (NMR) spectroscopy as a tool to assess metabolic functions of hepatocytes and to monitor major metabolic pathways of these cells during culture following hypothermic preservation. METHODS: After isolation, 2 x 10(7) primary porcine hepatocytes were preserved at 4 degrees C in supplemented Leibovitz L-15 medium for 48 h. Viability was assessed at isolation, 24 and 48 h. At isolation and at 48 h cells were plated and cultured with serum free supplemented Williams E medium. 1H NMR spectroscopy was used to assess indices of glucose metabolism, ammonia clearance indices and ketone bodies precursors at 48 h post-plating. Peak integration was applied with sodium 3-(trimethylsilyl-2,2,3,3-2H4)-1-propionate as an internal standard to obtain quantitative results. RESULTS: Results were obtained from six isolations. Viability was 78.1 +/- 1.2% at isolation, 69 +/- 3.4% at 24 h and 58.9 +/- 3.8% at 48 h of hypothermia. Plating efficiency was 87 +/- 4% for freshly isolated cells and 33.6 +/- 7.6% for hypothermically preserved cells. Glucose consumption was comparable in both groups. Hypothermically preserved cells consumed more threonine, produced more pyruvate and alanine but less lactate. They also produced less acetate and consumed less tyrosine. Glutamate and glutamine concentrations were similar under both conditions. CONCLUSION: 1H NMR spectroscopy is a valid method for assessing metabolic pathways of cultured primary porcine hepatocytes. Although hypothermically preserved cells had a reduced plating efficiency, they were still metabolically active. Thus, hypothermia can be used as a temporary preservation technique for primary porcine hepatocytes.

1H NMR spectroscopy as a tool to evaluate key metabolic functions of primary porcine hepatocytes after cryopreservation.

Proton NMR spectroscopy of biological fluids has produced interesting results lately. We used the technique to investigate the effects of cryopreservation on primary porcine hepatocytes as successful cryopreservation of primary porcine hepatocytes is of importance to the development of bioartificial liver support systems. After isolation 10(8) hepatocytes were cryopreserved for 1 week in Williams E/10% DMSO, either by quick freezing (-5 to -30 degrees C/min), slow freezing (-0.3 to -3 degrees C/min) or stepwise freezing protocols on cell suspensions and confluent cell plates. Plating efficiency was assessed by percentage LDH release. Metabolic functions of cryopreserved hepatocytes at 24 h post-thawing were compared with those of fresh hepatocyte cultures at 48 h. 1H nuclear magnetic resonance spectroscopy of the culture medium post-incubation, using the presaturation technique, assessed the following: glucose metabolism, transamination and glutamine synthesis and succinate synthesis. Freshly isolated cells had a viability of 82 +/- 4.3% and a plating efficiency of 87 +/- 3.8%. All cryopreservation protocols resulted in significantly reduced viability and plating efficiency. No significant differences were observed between different cryopreservation media or protocols. When comparing cryopreserved with freshly isolated cells, we observed that metabolism of acetyl-CoA precursors was significantly impaired in cryopreserved cells. Lactate and pyruvate production was also significantly less, although glucose consumption was similar. No differences were observed in gluconeogenic amino acid metabolism, transamination and urea synthesis. 1H NMR spectroscopy can be used to provide information about metabolic activity and functions of cultured primary cells.