Digestive and Liver Disease - Articles in Press

Biliary cast syndrome in sclerosing cholangitis - Corrected Proof

V. Zimmer, J. Raedle, G. Treiber, F. Lammert — 2010-03-08

Due to end-stage dilatative cardiomyopathy, a 61-year-old woman underwent orthotopic heart transplantation with a complicated course including perioperative shock and artificial heart support as well as acute graft rejection. Four months after transplantation, extensive cholestasis was noted, and endoscopic retrograde cholangiography (ERC) with sphincterotomy and stent placement was performed. The patient was subsequently referred to our department due to progressive cholestasis and cholangitis. Abdominal ultrasound revealed discrete bile duct dilation with hyperechoic borders. Repeat ERC delineated a diffusely destroyed biliary system with multiple filling defects, rarification of intrahepatic ducts alternating with cystic dilations and minor common bile duct irregularities (). By retraction of a balloon catheter, a black mass could be retrieved through the papilla of Vater (). Despite aggressive endoscopic therapy, cholestasis relentlessly deteriorated, and microbial bile analysis revealed multiresistant E. faecium and C. albicans unresponsive to specific treatment regimens. The patient finally underwent successful liver transplantation for secondary sclerosing cholangitis (SSC).

From the metabolic syndrome to NAFLD or vice versa? - Corrected Proof

2010-03-08

Abstract: The metabolic syndrome encompasses metabolic and cardiovascular risk factors which predict diabetes and cardiovascular disease (CVD) better than any of its individual components. Nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum which includes variable degrees of simple steatosis (nonalcoholic fatty liver, NAFL), nonalcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is the hepatic manifestation of the metabolic syndrome, with insulin resistance as the main pathogenetic mechanism. Recent data indicate that hyperinsulinemia is probably the consequence rather than cause of NAFLD and NAFLD can be considered an independent predictor of cardiovascular disease. Serum free fatty acids derived from lipolysis of visceral adipose tissue are the main source of hepatic triglycerides in NAFLD, although hepatic de novo lipogenesis and dietary fat supply contribute to the pathogenesis of NAFLD. Approximately 10–25% NAFLD patients develop NASH, the evolutive form of hepatic steatosis. Presumably in a genetically predisposed environment, this increased lipid overload overwhelms the oxidative capacity and reactive oxygen species are generated, leading to lipid peroxidation, cytokine induction, chemoattraction of inflammatory cells, hepatic stellate cell activation and finally fibrogenesis with extracellular matrix deposition. No currently available therapies for NAFLD and NASH exist. Recently nuclear receptors have emerged as key regulators of lipid and carbohydrate metabolism for which specific pharmacological ligands are available, making them attractive therapeutic targets for NAFLD and NASH.

Diagnosis of jejunal diverticulosis by means of double balloon enteroscopy - Corrected Proof

G. Manes, G. Maconi, G. Bianchi Porro — 2010-03-08

Jejunal diverticula (JD) are rare entities, revealed in less than 5% of post-mortem examinations . JD are usually multiple and are determined by the herniation of the mucosa and submucosa through the muscular layer at the mesenteric border as a consequence of a disturbed motor function. JD are generally asymptomatic and thus diagnosed incidentally at laparotomy, but in some cases may determine symptoms, such as abdominal pain and bloating, and complications, mainly perforation, haemorrhage, obstruction, and diverticulitis . Diagnosis of JD is difficult due to difficulties in studying the small intestine, but the recent development of new endoscopic (capsule endoscopy and device-assisted enteroscopy-DAE) and radiologic (CT- and MR-enteroclysis) methods has increased the number of JD reports. We herein report a case of a 70-year-old woman presented with a clinical picture of partial intestinal obstruction. In the past she had suffered from bloating, fullness, and abdominal pain and had complained two episodes of partial intestinal obstruction. She had been investigated by means of abdominal ultrasound, upper endoscopy, colonoscopy and glucose breath test revealing only bacterial overgrowth. During the last hospitalization a bowel ultrasound showed a marked dilatation (up to 4cm) of jejunal loops, without mass or significant thickening of bowel walls. Small bowel follow through was not possible due to failed jejunal intubation and CT-enteroclysis demonstrated again dilation, but was unable to show stenosis at any level of the GI tract (C). Due to the inconclusive results of both US and CT, double balloon enteroscopy was performed. In the proximal jejunum, immediately after the Treitz's ligament, for an extension of about 150cm, a large number of diverticula of 1–4cm size were seen (A and B). The revision of CT picture according to the enteroscopy findings did not recognize any diverticula.

Prevention and treatment of nonalcoholic fatty liver disease - Corrected Proof

2010-03-08

Abstract: A better knowledge of the biochemical mechanisms implicated in the development and progression of nonalcoholic fatty liver disease, linking fatty liver to insulin resistance and the metabolic syndrome, has shifted the goal of treatment from a mere clearing of fat from the liver to a systematic treatment of metabolic risk factors for fatty liver. Any attempt to modify the “unhealthy” habits responsible for fatty liver requires an integrated approach, based on the cognitive theory of behaviour by a multidisciplinary team including physicians, psychologists, dieticians and physical exercise experts, and recent data demonstrate that this is feasible and effective. Whenever this goal is not attained, a treatment based on insulin-sensitizers remains the best option, to simultaneously tackle all metabolic alterations of the metabolic syndrome. However, in individual patients, both raised blood pressure and dyslipidemia need to be controlled, in order to reduce cardiovascular risk. In these areas, any attempt should be made to use of drugs less likely to induce a deterioration of glucose control. It remains to be determined whether these treatments are able to modify the natural history of nonalcoholic fatty liver disease in the long term.

Insulin resistance, adipose depots and gut: Interactions and pathological implications - Corrected Proof

A. Gastaldelli, A. Natali, R. Vettor, S. Ginanni Corradini — 2010-03-02

Abstract: This review article focuses on the many metabolic actions of insulin at the level of muscle, liver and adipose tissue. In terms of pathogenetic mechanisms, the condition of insulin resistance is complex, as multiple genetic and environmental factors, among which an increasingly sedentary lifestyle associated with high-fat diet, mutually interact according to variable patterns in time in any given individual. It is well recognized that obesity (in particular abdominal obesity) favours the development of insulin resistance. Here we evaluate the impact of obesity and ectopic fat accumulation (visceral and hepatic) on insulin resistance at the level of different target organs, i.e., muscle, liver and adipose tissue. The roles of the gut and the liver, in particular of bile acids and gut microflora, are also discussed as possible determinants of energy balance and glucose metabolism.

Gold standard in coeliac disease diagnosis - Corrected Proof

V. Villanacci — 2010-03-02

I read the paper of Salmi et al. on DLD 42 2010 about the “Diagnostic methods beyond conventional histology in coeliac disease diagnosis” with great interest and as a pathologist I only want to express my personal point of view on this matter, in particular on the authors’ conclusions in which we can read “Conventional histological examination as the golden standard in coeliac diagnosis is questionable”. I perfectly agree with this sentence, I think with others as recently published that today, the true gold standard is not histology but the real gold standard in the diagnosis of CD is the gastroenterologist, the only one who knows the patient, establishes the tests and their timing, and the only one who can reasonably interpret all the panels of available data (clinical, serological, histological and genetic). Today, the concept of a multidisciplinary team prevails in which a strict relationship is mandatory among different specialists, the clinician, the pathologist, the laboratory technician, but with the element of synthesis and an overall coordination covered by the clinician. The role of the pathologist is not diminished but rather is always an important element for CD diagnosis, especially today when there is a significant increase in borderline conditions similar to the initial lesions of CD but with different aetiologies, for example, infections (Giardia lamblia, Helicobacter pylori) immune deficiency (common variable immunodeficiency, X-linked agammaglobulinaemia) drugs (Nsaids and others) and some other conditions . In these situations an accurate assessment of the morphology of the duodenal mucosa, avoiding the drawing up of any clinical conclusion (which is very often misleading) is crucial for the final diagnosis of CD. I hope that similar experiences can be the start for a new approach based on an interactive collaboration and a proper methodology for CD diagnosis, without extremes, for example, the complete elimination of the biopsy in favour of new methods different from serology or genetics such as endoscopy which can generate false or doubtful diagnosis. In conclusion “in medio stat virtus” and the basic concept is the existence of a Multidisciplinary Team.

Secondary aortoenteric fistula treated by right subclavian-bifemoral bypass - Corrected Proof

Y. Yang, J. Zhao, L. Yan, B. Huang — 2010-03-02

For secondary aortoenteric fistula (SAEF), the best therapeutic option seems to be axillobifemoral revascularisation and subsequent graft removal . Detailed herein is a case of successful graft removal with right subclavian-bifemoral bypass in a patient who had paraprosthetic-jejunal erosion after an abdominal aortic aneurysm repair.

Autoimmune pancreatitis. A rare cause of cholestasis - Corrected Proof

M. Koulentaki, E. Chryssou, C. Coucoutsi, I. Koutroubakis — 2010-02-26

A 52-year old woman with a 3-month history of type II diabetes had recent onset of itching and jaundice. Laboratory tests revealed normal CBC and INR, Glucose 148mg/dl, AST 194U/L, ALT 373U/L, γ-GT 1425U/L, ALP 571U/L, total bilirubin 3.8mg/dl, normal serum and urine amylase, no recent infection with HAV, HBV, HCV, CMV, and EBV. ANA, anti-DNA, AMA, SMA were negative, IgG 1470 (normal 701–1545mg/dl), IgG4 1210 (normal 4–230mg/dl).

Bloody diarrhoea secondary to cytomegalovirus ileitis - Corrected Proof

A.A. Alkhatib, M.M. Ahdab, F.A. Elkhatib — 2010-02-22

A 61-year-old woman with rheumatoid arthritis on mycophenolate and prednisone underwent colectomy with ileostomy for presumptive diagnosis of refractory ulcerative colitis. The pathological findings of the subtotal colectomy were consistent with cytomegalovirus (CMV) colitis. The patient was treated with famciclovir for 3 weeks. Six weeks later, she presented with lower abdominal pain and bloody diarrhoea. Ileoscopic examination showed patchy inflammation with shallow ulcerations in the distal ileum (). The biopsies from the ileum showed focal ulcerations, chronic inflammation and granulation tissue. Several enlarged cells with viral inclusions were identified (A). CMV infection was confirmed using immunohistochemical studies (B). The patient was diagnosed with CMV ileitis and responded well to ganciclovir.

Contrast-enhanced ultrasonography in evaluating hepatic metastases from neuroendocrine tumours - Corrected Proof

2010-02-22

Abstract: Objectives: At presentation, gastroenteropancreatic neuroendocrine tumours (GEP NETs) frequently show prognostically negative hepatic involvement. The aim of this study was to characterise hepatic metastases of GEP NETs as revealed by contrast-enhanced ultrasonography (CEUS), which allows the fine definition of the microvascular system, and to correlate these findings to the biological behaviour of the tumour.Methods: Eighteen out of 62 GEP NET patients examined between January 2007 and September 2008 had histologically proven hepatic metastases from primary ileal (#6), gastric (#1) or rectal (#1) carcinoids, pancreatic tumours (#7), or primary duodenal (#2) or occult gastrinomas (#1), and all underwent low mechanical index real-time CEUS with SonoVue® injection.Results: Strong early enhancement in the arterial phase was observed in 15 cases (83%), and a rapid wash-out in the portal venous phase in 14 (78%). In the late venous phase, the lesions were hypoechoic in 12 cases (67%), isoechoic in five (28%), and hyperechoic in one (0.05%). The time of arterial enhancement correlated with the Ki-67 proliferative index (rs=0.516; p=0.028).Conclusions: Most of the neuroendocrine liver metastases showed increased arterial enhancement at CEUS, a behaviour that is similar to that of hepatocellular carcinomas and the opposite of that of other metastases. CEUS can be a useful diagnostic means of characterising such metastases.

Cooperative genotyping for Helicobacter pylori virulence determinants strengthens the predictive value of gastric cancer risk assessment - Corrected Proof

M. Douraghi, Y. Talebkhan, H. Zeraati, M. Mohammadi — 2010-02-22

Heterogeneous genetic profiles of Helicobacter pylori are considered as key components of host–pathogen-environment triad interaction and play crucial roles in the gastric carcinogenesis . Persistent colonisation and maintenance of H. pylori in the harsh environment of the stomach are attributed to a series of virulence determinants. Two potent polymorphic secretory toxins; vacA and cagA and the functionally active adhesin babA2 are identified as the more decisive virulence markers in the development of the more severe disease outcomes .

Update on primary sclerosing cholangitis - Corrected Proof

T.H. Karlsen, E. Schrumpf, K.M. Boberg — 2010-02-22

Abstract: Early studies in primary sclerosing cholangitis (PSC) were concerned with disease characterization, and were followed by epidemiological studies of PSC and clinical subsets of PSC as well as a large number of treatment trials. Recently, the molecular pathogenesis and the practical handling of the patients have received increasing attention. In the present review we aim to give an update on the pathogenesis of PSC and cholangiocarcinoma in PSC, as well as to discuss the current opinion on diagnosis and treatment of PSC in light of the recent European Association for the Study of the Liver and the American Association for the Study of Liver Diseases practice guidelines.

The original sin of oesophageal mucosa - Corrected Proof

M. Fassan, C. Lanza, V. Lazzarin, M. Rugge — 2010-02-22

During embryogenesis, the gastro-oesophageal junction (GEJ) evolves through different mucosal phenotypes . The histology of the GEJ (Plate-A) of a 20-week fetus (intrauterine death, without malformations) demonstrates a hybrid multilayered junctional epithelium. A double histochemical/immunohistochemical stain shows co-expression of markers of divergent cell-commitments (basal squamous cells: p63 immunostain [brown nuclei]; superficial mucosecreting cells: PAS after diastase digestion [purple cells]; Plate-B). This feature, which strictly recalls the Multilayered Epithelium (MLE) of adult oesophagus, raises the pathologists’ curiosity; MLE, in fact, is considered among precursors of the Barrett's metaplasia (BM) and, eventually, Barrett's adenocarcinoma.

Autoimmune hepatitis in children—Impact of cirrhosis at presentation on natural history and long-term outcome - Corrected Proof

2010-02-17

Abstract: Little is known regarding the natural history of autoimmune hepatitis in children. The aims of this longitudinal cohort study were to determine the long-term prognosis of children with autoimmune hepatitis and to determine the effect of cirrhosis at presentation on survival.Methods: Thirty-three children with autoimmune hepatitis who were seen at our institution over a 25-year period were studied retrospectively.Results: The median age of diagnosis was 12.9 years (2.7–18.1) with a female predominance of 3:1. Liver biopsies showed cirrhosis in 18 (55%) patients at time of diagnosis. Patients with cirrhosis at baseline had a similar 10-year survival 85% (70–100%) to those without cirrhosis 75% (49–100%) (p=0.97). The overall survival was significantly lower than the expected in the age- and gender-matched U.S. population (log-rank test; p<0.001). In Cox regression models, weight loss (p=0.037), baseline elevated bilirubin (p=0.028), prolonged International Normalized Ratio (INR) (p=0.013), and positive LKM-1 antibodies (p=0.007) were associated with shorter survival.Conclusion: AIH in children is associated with a significant shorter survival rate than the expected in the general population. Cirrhosis on initial liver biopsy does not seem to impact long-term survival in children with AIH.

A short version of a HRQoL questionnaire for Italian and Japanese patients with PBC - Corrected Proof

2010-02-17

Abstract: Background: The available self-report questionnaire for the quality of life in patients with primary biliary cirrhosis (PBC-40) is currently validated only in the British population but it lacks an evaluation of its dimensionality.Aims: To validate the Italian and Japanese versions of PBC-40 and to assess the dimensionality of the original structure of PBC-40 by a confirmatory factor analysis. PBC-40 was translated to Italian and Japanese using the forward–backward method and then reviewed in focus groups in the framework of a large multicentric study.Methods: A sample of 290 patients with PBC (125 Italian and 165 Japanese) was administered two questionnaires previously validated for PBC-specific (PBC-40) and general quality of life (SF-36).Results: The confirmatory model failed to fit adequately the original hypothesized structure. A principal component analysis led to a seven-factor structure, with exclusion of 13 items characterized by lower load; PBC-27 questionnaire was the final instrument. The validity of the PBC-27 was supported by its strong correlation with the SF-36 scores.Conclusion: We here propose an alternative structure of the quality of life questionnaire for PBC, namely PBC-27, which appears to be effective in detecting the impact of PBC on quality of life in Italian and Japanese patients.

13C-octanoic acid breath test (OBT) with a new test meal (EXPIROGer®): Toward standardization for testing gastric emptying of solids - Corrected Proof

2010-01-29

Abstract: Background: Standardization of the 13C-octanoic acid breath test is still lacking.Aim: To evaluate the accuracy of the 13C-octanoic acid breath test using a new standardized ready-to-eat, gluten-, glucose-, and lactose-free muffin.Methods: Healthy subjects were recruited and sorted by sex and age. Patients with diabetic gastroparesis and untreated celiac disease with known gastric motility disorders were also tested with the new labelled muffin. Expired breath 13CO2 was analysed and t1/2 was calculated.Results: Overall, 131 healthy subjects were enrolled. The reference range of t1/2 was 88±29min with the value of 146min as the upper limit of normal range. No significant difference in t1/2 was found among subjects sorted by sex or age. The within-subject variability of t1/2 was 17%. Mean (±standard deviation) t1/2 values were 179±50min in patients with diabetic gastroparesis (n=8) and 151±20min in those with untreated celiac disease (n=11) (p≤0.001 vs controls).Conclusions: A new standardized test meal simplifies the execution of the 13C-octanoic acid breath test, is not influenced by sex or age, has low intra-individual variability, is palatable, does not cause side effects, and is able to evaluate gastric emptying in both patients and healthy controls. Moreover, it can be used in subjects with lactose intolerance, diabetes, and celiac disease.

Total and covalently closed circular DNA detection in liver tissue of long-term survivors transplanted for HBV-related cirrhosis - Corrected Proof

2010-01-25

Abstract: Background: Life-long prophylaxis against HBV recurrence is recommended in patients transplanted for HBV-related disease. The risk of HBV reactivation is due to persistence of covalently closed circular (ccc) DNA in hepatocytes. Whether cccDNA persists in livers of long-term transplant survivors who received conventional prophylaxis is unknown.Aim: To investigate the presence of intrahepatic total and cccDNA in transplanted patients with no evidence of biochemical markers of HBV recurrence.Methods: Intrahepatic total and cccDNA were assessed using sensitive nested and real-time PCR from 44 HBsAg-positive patients (75% male; mean age 55.2±8.9 years) who had undetectable serum HBV-DNA at transplant. The mean follow-up after transplant was 88.3 months (range, 18–159).Results: One patient underwent HBV recurrence after transplant and was the only who tested positive for both intrahepatic total HBV-DNA and cccDNA. Of the 43 patients negative for all serological markers of HBV infection, only 2 tested positive for intrahepatic total HBV-DNA, but none for cccDNA.Conclusions: Most patients with undetectable HBV-DNA at transplant, who received conventional HBV prophylaxis, have no evidence of intrahepatic total HBV-DNA and cccDNA. cccDNA should be considered a new additional diagnostic tool, also to identify patients at low risk of HBV recurrence after liver transplantation.

Corrected Proof

M. Carbone — 2010-01-11

Format: Hardcover book. Purpose: The aim of this book is to provide basic knowledge of CT colonography from its indications to the technique, interpretation and role in the field of screening of colorectal cancer.

Altered mRNA expression of telomere binding proteins (TPP1, POT1, RAP1, TRF1 and TRF2) in ulcerative colitis and Crohn's disease - Corrected Proof

N. Da-Silva, R.P. Arasaradnam, K.M. Getliffe, E.Z.H. Sung, Y. Oo, C.U. Nwokolo — 2010-01-11

Abstract: Aims: To determine mRNA expression of telomeric binding proteins in inflammatory bowel disease (IBD), and to note any effects of pharmacotherapy on telomere binding protein expression.Methods: Peripheral blood mononuclear cells (PBMC) obtained from 31 IBD patients and 13 controls were activated with phytohaemagglutinin and purified to yield activated (CD25+) T lymphocytes. TPP1, POT1, RAP1, TRF1 and TRF2 mRNA expression in PBMC and activated T lymphocytes was measured with RT-PCR.Results: In activated (CD25+) T lymphocytes, mean TRF2 mRNA levels were lower in both UC (6.6 vs 10, p=0.004) and CD subjects (6.9 vs 10; p=0.004). Similarly. in activated (CD25+) T lymphocytes mean RAP1 mRNA expression was significantly lower in UC subjects (4.5 vs 9.8, p=0.029) but not in CD subjects. In resting PBMC, mean TRF1 mRNA levels were lower in both UC (2.6 vs 3.5; p=0.008) and CD subjects (1.0 vs 3.5; p=0.04). No difference in PBMC and activated (CD25+) T lymphocytes mRNA levels of TPP1 and POT1 were noted in either UC or CD subjects. An association with 5-aminosalicylate therapy (R2=0.4) was only detected with RAP1 mRNA expression. TRF2 mRNA expression was inversely associated with disease duration only in UC subjects (p=0.05; R2=−0.6).Conclusions: The downregulation of TRF2 and RAP1 mRNA expression in CD25+ T-lymphocytes in IBD suggests that these telomere binding proteins play a role in telomere regulation and may contribute to the telomeric fusions and chromosomal abnormalities observed in UC. These findings may also indicate a systemic process of telomere uncapping which could represent a biomarker for IBD associated cancer risk.

Efficacy of H. pylori eradication with a sequential regimen followed by rescue therapy in clinical practice - Corrected Proof

S. Pontone, M. Standoli, R. Angelini, P. Pontone — 2010-01-11

Abstract: Background: Current Italian guidelines suggest sequential therapy as first-line therapy and a levofloxacin-based rescue therapy for Helicobacter pylori eradication. We evaluated the efficacy of these therapies in clinical practice.Methods: 84 consecutive patients with dyspeptic symptoms and proven H. pylori infection by either UBT or upper endoscopy with biopsies were enrolled. Patients received a 10-day sequential therapy with lansoprazole 30mg plus amoxycillin 1g (all twice daily) for the first 5 days, followed by lansoprazole 30mg, clarithromycin 500mg, and metronidazole 500mg (all twice daily) for the remaining 5 days. Eradication failure patients received triple therapy with lansoprazole 30mg, levofloxacin 250mg, and amoxycillin 1g (all twice daily) for 10 days.Results: Following the sequential therapy H. pylori eradication was achieved in 70/84 (83.3%; 95% CI=75.4–91.3) patients, and in 70/77 (90.9%; 95% CI=84.5–97.3) patients at ITT and PP analyses, respectively. The infection was cured in all 7 eradication failure patients by using second-line therapy.Conclusions: A sequential regimen as first-line therapy and a 10-day levofloxacin-based triple regimen in those patients who failed to clear the infection, appear to be a valid therapeutic strategy for management of H. pylori infection in clinical practice.

Trends in acute non-variceal bleeding in Israel in 1996–2007: A significant decrease in the rates of bleeding peptic ulcers - Corrected Proof

T. Hershcovici, Z. Haklai, E.-S. Gordon, J. Zimmerman — 2010-01-08

Abstract: Background: A decrease in the incidence of hospital admissions for acute non-variceal upper GI bleeding (AUGIB) has been reported in regions with a low prevalence of Helicobacter pylori (HP) infection.Aim: To investigate trends in hospital admissions for AUGIB in Israel, where the prevalence of HP infection is intermediate.Methods: We have searched the National Hospital Discharge Database of the Israeli Ministry of Health, where all admissions to acute care hospitals for the period January 1, 1996 through December 31, 2007 are compiled. Using a validated strategy, we identified all admissions for AUGIB according to ICD-9-CM codes. Incidence rates were calculated and adjusted to reflect the age and gender distribution of the Israeli population.Results: The overall rates of hospital admissions for AUGIB decreased significantly from 29.3 to 16.8cases/105population/year (p<0.0001). The decreases were similar in both genders. This decrease was due to decreased rates of bleeding from duodenal ulcers (from 13.6 to 5cases/105population/year) and gastric ulcers (from 4.3 to 2.4cases/105population/year). The rates of bleeding from other causes remained unchanged. The rates of surgical interventions bleeding control decreased significantly (overall from 11 to 4%). The in-hospital mortality rate varied between 7.6 and 7%, did not change significantly in both genders but increased significantly with age during the study period.Conclusions: A decline in the overall incidence of AUGIB during the study period was due to a significant decrease in the rate of bleeding peptic ulcers.

Intrahepatic IgG/IgM plasma cells ratio helps in classifying autoimmune liver diseases - Corrected Proof

D. Cabibi, G. Tarantino, F. Barbaria, M. Campione, A. Craxì, V. Di Marco — 2010-01-08

Abstract: Background/Aim: Plasma cells infiltrate in the liver is a prototype lesion of autoimmune liver diseases. The possible role of plasma cells isotyping (IgM and IgG) in the liver in the diagnostic definition of autoimmune liver disease, and particularly in variant syndromes such as autoimmune cholangitis and the primary biliary cirrhosis/autoimmune hepatitis overlap syndrome, is less defined.Methods: We analysed the clinical, serological and histological features of 83 patients with autoimmune liver disease (40 primary biliary cirrhosis, 20 autoimmune hepatitis, 13 primary sclerosing cholangitis, 4 autoimmune cholangitis and 6 overlap syndrome) compared to 34 patients with chronic hepatitis C and evaluated the expression of IgM and IgG plasma cells in their liver by immunostaining.Results: By Spearman's correlation, the mean-counts of IgM plasma cells in portal tracts were significantly correlated with female gender, serum alkaline phosphatase, gamma-glutamyl transferase and IgM values, positivity for anti-mitochondrial antibody-M2 and, on liver biopsy, with bile duct changes, orcein-positive granules and granulomas. Whereas IgG plasma cells resulted more correlated with alanine aminotransferase levels. IgG/IgM ratio lower than 1 was found no only in primary biliary cirrhosis but also in all patients with autoimmune cholangitis. Conversely, all patients with overlap syndrome showed IgG/IgM ratio higher than 1.Conclusion: Immunostaining for IgM and IgG plasma cells on liver tissue can be a valuable parameter for better diagnosis of autoimmune liver disease and also for variant or mixed syndromes.

Emerging issues in the use of transjugular intrahepatic portosystemic shunt (TIPS) for management of portal hypertension: Time to update the guidelines? - Corrected Proof

O. Riggio, L. Ridola, C. Lucidi, S. Angeloni — 2009-12-28

Abstract: Since its first introduction in the 1980s, transjugular intrahepatic portosystemic shunt has played an increasingly important role in the management and treatment of the complications of portal hypertension. In 2005, the American Association for the Study of Liver Diseases published the Practice Guidelines for the use of transjugular intrahepatic portosystemic shunt in the management of portal hypertension. Since then, technical advances and new interesting data on transjugular intrahepatic portosystemic shunt have been presented in the literature. The present review focusses on the applications of transjugular intrahepatic portosystemic shunt and examines more recent studies on this topic; the current guidelines on the use of transjugular intrahepatic portosystemic shunt are also discussed. From the data presented in the most recent publications, it has become increasingly clear that the recommendations stemming from the current guidelines need to be reviewed and updated in several points. Changes in the American Association for the Study of Liver Diseases Practice Guidelines are needed for both common indications (variceal bleeding and refractory ascites) as well as uncommon ones (i.e., Budd-Chiari syndrome and portal cavernoma). In addition, a relevant technical advance has been the introduction of the polytetrafluoroethylene-covered stents, which greatly improved the patency and clinical efficacy of transjugular intrahepatic portosystemic shunt. Consequently, new studies are required to re-assess the role of transjugular intrahepatic portosystemic shunt performed with new covered stents as compared with other strategies in the management of portal hypertension.

Ursodeoxycholic acid treatment in patients with cystic fibrosis at risk for liver disease - Corrected Proof

2009-12-25

Abstract: Background: Meconium ileus has been detected as a risk factor for development of liver disease in cystic fibrosis, with influence on morbidity and mortality.Aims: To evaluate the effect of early treatment with ursodeoxycholic acid in patients with cystic fibrosis and meconium ileus to prevent chronic hepatic involvement and to explore the potential role of therapy on clinical outcomes.Methods: 26 cystic fibrosis patients with meconium ileus (16 M, mean age 8,4 years, range 3,5–9) were assigned to two groups: group 1 (14 patients) treated early with ursodeoxycholic acid (UDCAe); group 2 (12 patients) treated with ursodeoxycholic acid at the onset of cystic fibrosis liver disease (UDCAd). Anthropometric data, pulmonary function tests, pancreatic status, complications such as diabetes, hepatic involvement and Pseudomonas aeruginosa colonisation were compared among groups.Results: A higher prevalence of cystic fibrosis chronic liver disease was observed in the UDCAd group with a statistically significant difference at 9 years of age (p<0.05). Chronic infection by P. aeruginosa was found in 7% of UDCAe and 33% of UDCAd (p<0.05). No differences were observed in nutritional status and other complications.Conclusions: Early treatment with ursodeoxycholic acid may be beneficial in patients at risk of developing cystic fibrosis chronic liver disease such as those with meconium ileus. Multicentre studies should be encouraged to confirm these data.

Gender variation in oesophageal motor function: Analysis of 129 healthy individuals - Corrected Proof

K.J. Vega, C. Palacio, T. Langford-Legg, J. Watts, M.M. Jamal — 2009-12-25

Abstract: Background: Oesophageal manometry is the standard for diagnosis of oesophageal motor disorders. Minimal data exist assessing the effect of gender on normal oesophageal manometry values.Aim: Evaluate the impact of gender on normal oesophageal manometry values.Methods: Healthy volunteers were recruited from the Jacksonville metropolitan area. Exclusion criteria were symptoms suggestive of oesophageal disease, medication use or concurrent illness that could affect oesophageal manometry. All underwent oesophageal manometry using a solid-state system with wet swallows.Results: Sixty-three males and 66 females were enrolled. All completed oesophageal manometry without difficulty. Resting lower oesophageal sphincter pressure, distal oesophageal contraction duration and distal oesophageal body contraction amplitude values were significantly higher in females while distal oesophageal body contraction velocity was significantly lower in females (p<0.05). No differences were seen in other oesophageal manometry parameters.Conclusion: Significant gender differences exist in normal oesophageal manometry. Gender-specific reference values for oesophageal manometry are needed for accurate diagnosis of oesophageal motility disorders.

The diagnostic value of the duodenal biopsy: A clinico-pathologic analysis of 28,000 patients - Corrected Proof

S.W. Carmack, R.M. Genta — 2009-12-25

Abstract: Background: Duodenal biopsies are frequently obtained to investigate malabsorption, diarrhoea, and aneamia. The proportion of patients who have duodenal biopsies and their diagnostic yield are unclear.Aims: To determine what proportion of patients undergoing esophagogastroduodenoscopy in a private setting has duodenal biopsies and to evaluate the diagnostic yield relative to clinical indications and endoscopic findings.Methods: Records of patients who had duodenal biopsies diagnosed at a United States gastrointestinal pathology laboratory in a single year were analysed.Results: 28,210 patients with and 75,175 without duodenal biopsies were studied. Duodenal biopsy patients were younger (52 years versus 58 years, p<0.001) and more likely to be female (OR 1.46; p<0.0001); 87% of children and 27% of adults had duodenal biopsies. Suspicion of malabsorption or sprue, diarrhoea, aneamia, and weight loss were strong predictors of duodenal biopsy. More than 80% of patients had normal duodenum, except those biopsied for sprue, 64% of whom had normal findings. Marsh II–IIIc lesions were diagnosed in 23% of patients with suspected sprue, but in 3.0% of those with diarrhoea, weight loss, or aneamia, and in 1.5% of patients with dyspepsia or GERD.Conclusions: A clinical suspicion of sprue produces the highest yield of histopathologic abnormalities; women are biopsied more often than men despite having less duodenal pathology.

Obstructive jaundice due to primary neurofibroma of the common bile duct - Corrected Proof

Li Jiang, Lunan Yan, Nansheng Cheng, Lisheng Jiang — 2009-12-25

Biliary neurofibromas (BNs) are very rare, almost all of which occur subsequent to an injury to the nerves or iatrogenic biliary injury during cholecystectomy . Primary BNs are even more rarely seen. A 65-year-old woman presented to our department with a 1-month history of progressive jaundice. Physical examination was unremarkable except for severe jaundice. Liver function tests showed the following: total bilirubin, 92.6μmol/L (normal, 5–28μmol/L); direct bilirubin, 74.2μmol/L (<8.8μmol/L); ALT, 187IU/L (<38IU/L); AST, 104IU/L (<37IU/L). Other laboratory results such as routine analysis of blood, HBV marker, and tumor markers were all within normal limits except for elevated CA 19-9 of 35.2U/ml (<22U/ml). MRI revealed a 0.5cm diameter filling defect in the end of common bile duct (CBD) and a 1.5cm diameter stone in the gallbladder (Fig. 1a), and thickened biliary wall around the lesion (Fig. 1b). Cholangiocarcinoma was considered preoperatively. A gray, smooth mass, measuring 0.7cm×0.7cm×0.5cm, was observed arising from the end of CBD after pancreatoduodenectomy. The postoperative course was uneventful and she was discharged 8 days after surgery. Histological studies revealed a biliary neoplasm composed of long, spindle-shaped fibrous nerve cells but no malignant cells (Fig. 2), and the final diagnosis was of a primary BN.

Descriptive epidemiology of cholangiocarcinoma in Italy - Corrected Proof

2009-12-21

Abstract: Background: Very little data exist on the epidemiology of cholangiocarcinoma in Italy.Aim: We focus on the descriptive epidemiology of cholangiocarcinoma in Italy.Methods: Data on incidence were obtained from the Italian Association of Tumour Registries while mortality data were obtained from the Italian National Institute of Statistics.Results: A progressive increase of incidence with age was seen for extra-hepatic, intra-hepatic and not otherwise specified cholangiocarcinoma. Crude incidence rates were higher for extra-hepatic cholangiocarcinoma than those for intra-hepatic cholangiocarcinoma and in men compared to women. An increasing incidence trend was observed, from 1988 to 2005, for both extra-hepatic- and intra-hepatic cholangiocarcinoma with a 3–6% yearly increase and with a rate of increase higher for men than for women and for intra-hepatic- than for extra-hepatic cholangiocarcinoma. For intra-hepatic cholangiocarcinoma, the mortality rates progressively increased from 0.15 per million in 1980 to 5.9 per million in 2003, when mortality for this cancer surpassed extra-hepatic cholangiocarcinoma. Mortality rates for extra-hepatic cholangiocarcinoma showed an increasing trend from 1980 to 1994 but, in contrast to intra-hepatic cholangiocarcinoma, a stable or slightly decreasing trend from 1995 to 2003 was observed.Conclusions: In Italy, cholangiocarcinoma showed a progressive increase in incidence and mortality in the last two decades mainly in intra-hepatic cholangiocarcinoma.

The combined application of advanced endoscopic imaging techniques may increase the duodenal villous morphology definition in suspected celiac disease - Corrected Proof

P. Fedeli, G. Gasbarrini, G. Cammarota — 2009-12-21

We read with interest the commentary by Cucchiara and Di Nardo on the ability of advanced endoscopic imaging techniques to identify celiac disease (CD) . In this paper, the authors point out the role in the diagnosis of CD of optical coherence tomography, which has been reported by Masci et al. having a sensitivity and specificity of 82% and 100%, respectively . The authors also give a rapid overview of results obtained in identifying CD by other endoscopic tools such as high resolution endoscopy and water-immersion technique, as well as the promising results obtained in case series by confocal endomicroscopy.

No beneficial effects of amantadine in treatment of chronic hepatitis C patients - Corrected Proof

2009-12-17

Abstract: Background: Benefit of adding amantadine to antiviral therapy for hepatitis C is controversial.Aims: We aimed to examine whether such policy enhances sustained viral response in treatment-naïve patients.Methods: 297 naïve hepatitis C patients were randomized for treatment with amantadine 200mg or placebo, combined with weight-based ribavirin and 12-day high-dose interferon alpha-2b induction therapy, followed by PEG-interferon alpha-2b (1.5μg/kg/week up to 26 weeks and thereafter, 1.0μg/kg/week until week 52). Treatment was discontinued if hepatitis C virus (HCV) RNA was positive at week 24.Results: 49% of patients were (former) drug users. Genotype 1 occurred in 45%, high viral load in 70% and severe fibrosis/cirrhosis in 32%, without differences between amantadine or placebo groups. 90 patients prematurely discontinued treatment, mainly because of grade 3 or 4 toxicity. Intention-to-treat analysis revealed sustained viral response in 47% and 51% of amantadine and placebo groups (p=0.49). Amantadine did not enhance sustained viral response in patients with genotype 1 or high viral load nor did it improve primary non-response, breakthrough or relapse rates. Genotype non-1 and lower pre-treatment γGT levels were independent predictors for sustained viral response.Conclusion: Adding amantadine to antiviral therapy of previously untreated chronic hepatitis C patients has no beneficial effects.

Toll-like receptor 4 participates in gastric mucosal protection through Cox-2 and PGE2 - Corrected Proof

Yan Zhang, Huan Chen, Li Yang — 2009-12-17

Abstract: Aim: To elucidate the role of Toll-like receptors (TLRs) in gastric cytoprotection after ethanol injury.Methods: C57BL/6J, C3H/HeOuJ and C3H/HeJ mice were used. All mice were killed 4h after ethanol administration. TLR4, cyclooxygenase-2 (Cox-2) and prostaglandin E2 (PGE2) expression were measured by immunohistochemistry, western blotting and enzyme-linked immunosorbent assay (ELISA) separately.Results: The expression of TLR4 increased in C57BL/6J mice stomach 4h after ethanol injury. The cells expressing TLR4 included Cox-2 expressing cells and macrophages. The injury in C3H/HeJ mice was more severe than in C3H/HeOuJ mice 4h after ethanol injury. The expression of Cox-2 and PGE2 only increased in C3H/HeOuJ mice. The number of macrophages and the expression of macrophage-inflammatory protein-2 (MIP-2) also increased only in C3H/HeOuJ mice.Conclusion: TLR4 signal is activated in mice stomach 4h after ethanol injury. The protective effects of TLR4 signalling are mediated through the induction of Cox-2 expression and the production of PGE2.

ERCP-induced and non-ERCP-induced acute pancreatitis: Two distinct clinical entities with different outcomes in mild and severe form? - Corrected Proof

P.A. Testoni, C. Vailati, A. Giussani, C. Notaristefano, A. Mariani — 2009-12-17

Abstract: Background: Acute pancreatitis is a complication of endoscopic retrograde cholangio-pancreatography. Aim of the study was to compare endoscopic retrograde cholangio-pancreatography-related acute pancreatitis with attacks caused by other factors.Methods: A series of consecutive patients with non-endoscopic retrograde cholangio-pancreatography-related acute pancreatitis referred to our hospital in 2007–2008 were examined retrospectively, and compared with the same number of patients with post-endoscopic retrograde cholangio-pancreatography acute pancreatitis done in the same institution. Both groups comprised 116 patients and were comparable for mean age, sex, and body mass index. Duration of abdominal pain, pancreatic enzyme elevation, hospital stay, and type of analgesia administered were retrieved.Results: There were no differences between the groups as regards the severity of pancreatitis, mortality rate and hospitalisation, although mortality was double in severe post-endoscopic retrograde cholangio-pancreatography acute pancreatitis. In the mild acute pancreatitis cases, serum amylase fell 50% from the peak in a mean of 46.4h (range 24–72) in group 1 and 38.9h (range 24–72) in group 2 (p<0.001). The peak amylase serum level halved within 48h in 73.6% of cases with non-endoscopic retrograde cholangio-pancreatography-related acute pancreatitis, and in 92% of patients with endoscopic retrograde cholangio-pancreatography-related acute pancreatitis (p<0.001).Conclusions: Non-endoscopic retrograde cholangio-pancreatography- and endoscopic retrograde cholangio-pancreatography-induced pancreatitis did not differ as regards severity, hospital stay or mortality; in mild pancreatitis, serum amylase halved significantly sooner in post-endoscopic retrograde cholangio-pancreatography cases.

Comment to “The efficacy of Helicobacter pylori eradication regimen with and without vitamin C supplementation” - Corrected Proof

L. Filik — 2009-12-14

I read with a great interest the recently published article by Zojaji et al. . The article has important outcomes supporting the favourable effects of vitamin C on H. pylori eradication rates. However, there are some issues to be discussed. First one is the study population features. The authors did not define the previous H. pylori treatment history of patients. Are there any patients with a history of previous H. pylori treatment? If yes, the effect on the study results should be discussed. Secondly, vitamin C dietary consumption of patients should be reported and the impact on the study results should be considered. Thirdly, even though the eradication rates of new regimens in controlled studies are generally higher than 90%, the efficacy rates in clinical practice is somehow lower. In the literature, this is attributed to genetic composition and antibiotic resistance of H. pylori, and patients’ geographical localization . Lastly, untoward effects of vitamin C supplementation should also be considered . H. pylori is still a common health problem especially in the developing world and adverse effects (increased iron absorption, kidney stones, etc.) should also be considered before it is suggested to be included as a part of H. pylori treatment regimens.

Gastro-protective strategies in primary care in Italy: The “Gas.Pro.” survey - Corrected Proof

2009-12-11

Abstract: Introduction: Risk of gastrointestinal injury is relevant among users of anti-inflammatory or cardio-protective drugs. Adequate gastro-protection is warranted in high-risk patients.Aim: To assess the perceptions and practices of Italian primary care physicians regarding gastro-protective strategies.Methods: Nationwide cross-sectional observational study. A 14-question survey questionnaire was administered to 112 primary care physicians throughout Italy. Data collection covered consecutive outpatient candidates for the prescription of a potentially GI harmful medication, observed in the physicians’ office over a 3-week period.Results: Cohort included 3943 cases (2489 naïve and 1463 chronic NSAID/ASA users). Mean age and prevalence of cardiovascular comorbidity were significantly higher in the latter subgroup. Non-selective NSAIDs and low-dose aspirin were the most commonly prescribed drugs. Combined NSAIDS/ASA plus steroids/anticoagulant/antiplatelets were recorded in 161 cases. Helicobacter pylori status was known in only 38% of naïve and 33.2% of chronic users, being negative in 85.3% and 89.5%, respectively. When positive, H. pylori was eradicated by almost all physicians (97.9%), but in case of unknown H. pylori status, the presence of infection was investigated in only 8.6% and 14.9% of patients in the two subgroups. Gastro-protection was endorsed in 80.7% of patients, mostly PPIs (91%). In patients aged over 70, pantoprazole and lansoprazole were the preferred gastro-protective agents.Conclusions: There is a significant over-use of gastro-protection in the primary care setting in Italy and the role H. pylori is largely overlooked. Educational efforts should be directed to a more targeted gastro-protection only for at-risk patients as well as improved adherence to recommendations for testing and treating H. pylori infection.

A new practical alternative for tumoural gastrointestinal bleeding: Ankaferd blood stopper - Corrected Proof

E. Ozaslan, T. Purnak, A. Yildiz, I.C. Haznedaroglu — 2009-12-11

We read with great interest the paper written by Kurt et al. , describing the beneficial haemostatic effect of Ankaferd blood stopper (ABS) in 10 cases of neoplastic gastrointestinal (GI) bleeding. We would like to present our ABS experience in similar cases, and add a few comments about their results.

Garlic extract prevents CCl4-induced liver fibrosis in rats: The role of tissue transglutaminase - Corrected Proof

2009-12-09

Abstract: Background and aim: Tissue transglutaminase contributes to liver damage in the development of hepatic fibrosis. In a model of neurodegeneration, the therapeutic benefit of cystamine has been partly attributed to its inhibition of transglutaminase activity. Garlic extract contains many compounds structurally related to cystamine. We investigated the anti-fibrotic effect of garlic extract and cystamine as specific tissue transglutaminase inhibitors.Methods: Rat liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4) for 7 weeks. Cystamine or garlic extract was administrated by daily intraperitoneal injection, starting from the day after the first administration of CCl4. Hepatic function, histology, tissue transglutaminase immunostaining and image analysis to quantify Red Sirius stained collagen deposition were examined. Reverse transcription-polymerase chain reaction to detect alpha-SMA, IL-1β and tissue transglutaminase expression and Western blot for tissue transglutaminase protein amount were performed. Transglutaminase activity was assayed on liver homogenates by a radio-enzymatic method.Results: Transglutaminase activity was increased in CCl4 group and reduced by cystamine and garlic extract (p<0.05). Treatment with cystamine and garlic extract reduced the liver fibrosis and collagen deposition, particularly in the garlic extract group (p<0.01). Moreover, the liver damage improved and serum alanine aminotransferase was decreased (p<0.05). Tissue transglutaminase immunolocalised with collagen fibres and is mainly found in the ECM of damaged liver. Alpha-SMA, IL-1β, tissue transglutaminase mRNA and tissue transglutaminase protein were down-regulated in the cystamine and garlic extract groups compared to controls.Conclusion: These findings concurrently suggest that transglutaminase may play a pivotal role in the pathogenesis of liver fibrosis and may identify garlic cystamine-like molecules as a potential therapeutic strategy in the treatment of liver injury.

Lung cancer presenting with gastrointestinal symptoms: A tricky diagnosis - Corrected Proof

M.L. Morieri, Luca Santi, M. Renzulli, G. Poggioli — 2009-12-07

Gastrointestinal metastases of lung cancer are considered to be rare (<1%), but post-mortem studies suggest that they may be more frequent than previously thought because usually asymptomatic . Thus, almost all reported cases were diagnosed either at autopsy, or after emergency laparotomy to treat perforation, obstruction, or massive bleeding .

Pancreatic Endoscopic Ultrasound-guided Fine Needle Aspiration: Complication rate and clinical course in a single centre - Corrected Proof

S. Carrara, P.G. Arcidiacono, G. Mezzi, M.C. Petrone, C. Boemo, P.A. Testoni — 2009-12-02

Abstract: Background: Endoscopic Ultrasound-guided Fine Needle Aspiration (EUS-FNA) is effective for obtaining biopsy specimens from pancreatic lesions.Aim: To determine the frequency and severity of complications after EUS-FNA of solid and cystic pancreatic lesions in a single centre large series of patients.Patients and methods: From January 2005 to December 2008, information on all patients referred to our unit for pancreatic EUS was systematically entered in a computer database including clinical and morphologic data. Records were reviewed to evaluate whether complications such as haemorrhage, acute pancreatitis, intestinal perforation, or others occurred after EUS-FNA of the pancreas.Results: A total of 3296 pancreatic EUS were done in four years. In the 1034 pancreatic EUS-FNA, we observed 10 (0.96%) haemorrhages (7 intracystic, 2 in the pancreatic duct, and 1 in a small carcinoma), 2 (0.19%) acute severe pancreatitis and 1 (0.09%) duodenal perforation followed by complicated post-surgical hospitalization and death. The haemorrhages were all self-limiting. Overall, major complications (pancreatitis and perforation) arose in 0.29% of these examinations.Conclusions: EUS-FNA is safe, with a low risk of severe haemorrhage. Although rare, acute pancreatitis is generally mild or severe, requiring prolonged hospitalization. One fatal complication occurred after duodenal perforation in a patient with duodenal neuroendocrine tumour and pancreatic infiltration.

Cavoportal hemitransposition in an adult-to-adult, living-donor liver transplantation - Corrected Proof

Z. Shi, L. Yan, T. Wen, Z. Chen — 2009-11-30

We report a case involving adult-to-adult, right-lobe, living-donor liver transplantation with Jamieson IV type portal vein thrombosis necessitating cavoportal hemitransposition. An end-to-side anastomosis was performed between the graft portal vein (RPV) and the recipient's inferior vena cava (IVC) by interposition of the cold-preserved iliac vein (Interposition 1). Ligation of the IVC was performed to obtain portal flow. An interposition vein graft to the middle hepatic vein tributary of the liver graft (Interposition 2) was anastomosed to the recipient's IVC before reconstruction of the hepatic artery (RHA, ). The graft weighed 580g, and the graft-to-recipient-body-weight ratio was 1.14%. Doppler ultrasound tests following surgery showed the cavoportal interposition graft and hepatic artery (HA) to be patent (). The patient had an uneventful post-operative course, and the graft showed normal hepatic function.

Asymptomatic colon adenoma associated with Schistosoma mansoni - Corrected Proof

A. Kansagra, N. Nagaria, S. Ahlawat — 2009-11-30

Gastrointestinal involvement in schistosomiasis is well known; however, colon polyps associated with schistosoma are reported occasionally. To the best of our knowledge, colon adenoma associated with Schistosoma mansoni has not been reported. We describe a patient who had colon adenomatous polyp associated with S. mansoni on screening colonoscopy.

Synchronous Meckel's diverticulum and gastrointestinal stromal tumour presenting as acute bleeding - Corrected Proof

A.A. Lemos, F. Bredolo, F. Chiaraviglio, P.R. Biondetti — 2009-11-18

A 34-year-old Caucasian male presented at our Emergency Department with severe abdominal pain of increase intensity and melena. Oesophagogastroduodenoscopy (EGDS) showed haemorrhagic gastritis, whereas ultrasonography demonstrated a hyperechoic mass of 5cm×5cm in diameter located at the left iliac fossa, apparently separated from the urinary bladder. Multi-detector CT angiography (MDCTA) confirmed the presence of a round, well demarcated, non-homogeneous mass adjacent to the urinary bladder and to the small bowel (arrows, Fig. 1). There were no CT signs of invasion with regard to the surrounding adipose tissue and the urinary bladder.

Transcatheter arterial chemoembolisation for hepatocellular carcinoma in cirrhosis: Survival rate and prognostic factors - Corrected Proof

2009-11-16

Abstract: Background: The role of prognostic variables in the treatment of hepatocellular carcinoma (HCC) by transarterial chemoembolisation (TACE) is controversial.Aims: To evaluate the survival of patients with HCC on cirrhosis treated with TACE and to analyse the prognostic factors affecting survival.Methods: From 1996 to 2006, 580 consecutive patients with HCC in cirrhosis were observed. Of these 194 patients underwent TACE. The primary end-point was survival. Independent predictors of survival were identified using the Cox model.Results: The cumulative 1-year, 3-year, and 5-year survival rates were 96%, 60%, and 41%, respectively. The multivariate analysis showed significant reduction of survival among patients with serum bilirubin values >2mg/dl compared to patients with values <2mg/dl (Hazard ratio 3.84; CI 95% 1.70–8.66; p-value=0.001). Multivariate analysis performed in the group of patients treated with TACE alone showed that elevated serum bilirubin (Hazard ratio 2.96; CI 95% 1.20–7.3; p-value 0.02) and incomplete tumour response (Hazard ratio 2.88; CI 95% 1.18–7.05; p-value 0.02) are correlated with a worse outcome.Conclusions: TACE was well tolerated and overall survival rate was 41% after 5 years. Complete tumour response and serum bilirubin <2mg/dl were identified as predictors of survival.

Suspected autoimmune pancreatitis—An indication for steroid treatment? - Corrected Proof

H. Matsubayashi, K. Imai, K. Kusumoto, H. Ono — 2009-11-13

We report three cases of suspected autoimmune pancreatitis (AIP), which did not meet Japanese diagnostic criteria , but which responded to steroid therapy (). In summary, cases 1 and 2 did not demonstrate positive serum markers, involving large size vessels in spite of small mass size, with narrowing of localized main pancreatic duct, without multiple systemic lesions like typical AIP . Meanwhile, case 3 had a history of IgG4-related sclerosing cholangitis a year and four months before the onset of their pancreatic problems, but we could not evaluate the pancreatic duct system by endoscopic retrograde pancreatography (ERP) because of the previous surgery. Magnetic resonance pancreatography was therefore performed and it revealed characteristic changes of AIP. Although AIP was suspected also in the former two cases, it was difficult to rule out pancreatic cancer because of the lack of characteristic findings of AIP . AIP sometimes mimics and rarely accompanies pancreatobiliary cancer , so that it is often necessary to exclude malignancy by obtaining tissue. However, it is not easy to obtain tissue samples large enough to definitively diagnose AIP, especially when the lesion is small and localized to the pancreatic head, because strong angulations of the needle are necessary for FNA approach. We performed EUS-FNAB using 22-gauge needle (Echotip™, Wilson-Cook, NC) to exclude malignancy, however Trucut biopsy (EUS-TCB) using 19-gauge needle was refused by patients 1 and 2. A trial of steroid therapy was given and pancreatic lesions showed regression in all three cases.

Polycystins play a key role in the modulation of cholangiocyte proliferation - Corrected Proof

2009-11-09

Abstract: Background: Polycystin-1 and -2 (PC-1 and PC-2) are critical components of primary cilia, which act as mechanosensors and drive cell response to injury. PC-1 activation involves the cleavage/processing of PC-1 cytoplasmic tail, driven by regulated intramembrane proteolysis or ubiquitine/proteasome, translocation in the nucleus and activation of transcription factors. Mutations of PC-1 or PC-2 occur in polycystic liver where cholangiocyte proliferation is enhanced.Aim: We evaluated the involvement of PC-1 and PC-2 in modulating cholangiocyte proliferation.Methods: We investigated rat cholangiocytes induced to proliferate by 17β-oestradiol. Proliferation was evaluated by PCNA immunoblotting or [3H]-thymidine incorporation into DNA. PC-1 silencing was performed by siRNA, while inhibition of regulated intramembrane proteolysis or proteasome by γ-secretase inhibitor, leupeptin or MG115.Results: Cholangiocyte proliferation was associated with decreased PC-1 and PC-2 expression, which was inversely correlated with enhanced PCNA. The selective silencing of PC-1 induced activation of cholangiocyte proliferation in association with decreased PC-1 expression. Two different regulated intramembrane proteolysis inhibitors, γ-secretase-inhibitor and leupeptin, and the proteasome inhibitor, MG115, abolished the 17β-oestradiol proliferative effect.Conclusions: PC-1 and PC-2 play a major role as modulators of cholangiocyte proliferation suggesting that primary cilia may act as sensors of cell injury driving, when activated, a proliferative cholangiocyte response to trigger the reparative processes.

Endoscopic Ultrasound-guided cholangiopancreatography and rendezvous techniques - Corrected Proof

V.M. Shami, M. Kahaleh — 2009-11-09

Abstract: Endoscopic ultrasound-guided cholangiopancreatography (EUCP) has become an alternative to percutaneous drainage or surgery in patients with obstructive jaundice or pancreatic obstruction after failed conventional ERCP. The different techniques of biliary and pancreatic drainage are described and the literature is reviewed. Due to the technical complexity associated with this procedure, it should be reserved for endoscopists at tertiary care centers with advanced training in both EUS and ERCP.

In chronic viral hepatitis without malignancy, abnormal serum carbohydrate 19-9 antigen levels are associated with liver disease severity and are related to different viral aetiology - Corrected Proof

G. Bertino, A.M. Ardiri, G.S. Calvagno, P.M. Boemi — 2009-11-02

I read with interest the paper by Ventrucci et al. . Their study of 10 patients who had no evidence of malignant disease shows that persistent and significant elevation of serum carbohydrate antigen 19-9 (CA19-9) can be found in non-malignant and non-cholestatic disease. The authors have correctly evaluated all possible non-neoplastic causes of increased serum levels of CA19-9, and they have concluded that further studies on CA19-9 metabolism may help to understand the significance of CA19-9 elevation in the absence of malignancy.

Sustained remission after steroids and leukocytapheresis induced response in steroid-dependent ulcerative colitis: Results at 1 year - Corrected Proof

J.L. Cabriada, N. Ibargoyen, A. Hernández, A. Bernal, A. Castiella — 2009-10-15

Abstract: Background: Leukocytapheresis (LAP) could be an alternative treatment for steroid-dependent ulcerative colitis (UC).Aims: To assess the duration of response at 1 year after this treatment.Patients and methods: A prospective study in 18 patients with steroid-dependent UC treated with LAP plus steroids after failure or intolerance to immunomodulators. Clinical and endoscopic (Mayo Clinic index) examinations were performed at 1 month after the last apheresis and at 12 months. The clinical, endoscopic remission and the relapse during the 1-year follow-up were evaluated based on standard parameters.Results: Induction of remission: clinical remission: 10/18 (55%). Partial response: 4. Endoscopic remission: 9 (50%), always accompanied by clinical remission. A significant correlation was observed between clinical remission and endoscopic remission (rs=0.894; p≤0.001). At 1 year: sustained steroid-free clinical remission in 9 (50%), all of whom presented initial endoscopic remission. Remission and relapse before 1 year in 17%. A tendency for sustained remission at 1 year was observed when initial endoscopic remission was achieved.Conclusions: Initial remission can be maintained at 1 year in half of the patients without the need for additional steroids. Complete remission and endoscopic mucosal healing is proposed as an objective for achieving a lasting response.

Hepatocellular carcinoma in non-cirrhotic liver: A reappraisal - Corrected Proof

F. Trevisani, M. Frigerio, V. Santi, A. Grignaschi, M. Bernardi — 2009-10-15

Abstract: Although not frequently, hepatocellular carcinoma (HCC) can ensue in a non-cirrhotic liver. As compared to cirrhotic HCC, this kind of tumour has some peculiarities, such as: (a) a lower male preponderance and a bimodal age distribution; (b) a lower prevalence of the three main risk factors (hepatitis B and C virus infections and alcohol abuse), with an increased prevalence of other etiologic factors, such as exposure to genotoxic substances and sex hormones, inherited diseases, genetic mutations; (c) a more advanced tumour stage at the time of diagnosis, as it is usually detected due to the occurrence of cancer-related symptoms, outside any scheduled surveillance program; (d) a much higher amenability to hepatic resection, due to the low risk of liver failure even after extended parenchymal mutilation; (e) overall and disease-free survivals after resection of non-advanced tumours (meeting the Milano criteria) comparable to that obtained with liver transplantation in cirrhotic patients carrying an early tumour; (f) overall survival strictly dependent on tumour burden (and its recurrence) and barely influenced by liver function.

Colonic microflora imbalance and diverticular disease - Corrected Proof

A. Tursi — 2009-10-15

I have read with interest the recent review published by Ojetti et al. about the role of microflora imbalance in different gastrointestinal diseases. About the paragraph entitled “Diverticular Disease” (DD), they correctly identified abnormal colonic motility and an inadequate intake of dietary fibre as the two main factors playing a role in the pathogenesis of DD . However new physio-pathological data found that colonic microflora imbalance, and the consequent low-grade inflammation, probably play an important role, both in symptom development and in treatment.

Efficacy, safety, and pharmacokinetics of intramuscular hepatitis B immune globulin, Igantibe®, for the prophylaxis of viral B hepatitis after liver transplantation - Corrected Proof

2009-10-15

Abstract: Background: Long-term prophylaxis of hepatitis B virus (HBV) positive liver transplanted subjects with intravenous hepatitis B immunoglobulin (HBIG) is effective, however use of intramuscular HBIG could be as effective with fewer adverse events and lower cost.Aim: We conducted a prospective, non-randomized, clinical study to assess the efficacy and safety of HBIG from Grifols, Igantibe®, for the prophylaxis of HBV reactivation.Methods: Eighteen adult patients submitted to liver transplantation for HBV-related disease more than 18 months earlier were treated with doses of 2000I.U. intramuscular Igantibe® every 14 days for 6 months.Results: Mean trough serum HBsAb IgG titers from months 4 to 6 (primary efficacy variable) were protective (≥150I.U./L) at each time point. Individual measurements were also protective throughout the study. HBV replication remained negative for all available subjects until study completion. Pharmacokinetic analysis showed a half-life of 27 days and extensive exposure to the study drug. Safety and tolerability of intramuscular Igantibe® were good, with only one adverse event.Conclusion: Standard-dose intramuscular Igantibe® administration proved efficacious in post-liver transplantation prophylaxis by attaining protective levels for up to 6 months, was safe and well tolerated. Pharmacokinetic analysis revealed a long half-life and extensive exposure.