Digestive and Liver Disease - Articles in Press

Health-related quality of life is impaired in active collagenous colitis - Corrected Proof

2010-07-20

Abstract: Objectives: The characteristic clinical symptoms of collagenous colitis are non-bloody diarrhoea, urgency and abdominal pain. Treatment is aimed at reducing the symptom burden and the disease impact on patients’ health-related quality of life. The objective of this study was to analyse health-related quality of life in patients with collagenous colitis.Methods: In a cross-sectional, postal HRQL survey, 116 patients with collagenous colitis at four Swedish hospitals completed four health-related quality of life questionnaires, two disease-specific (Inflammatory Bowel Disease Questionnaire and Rating Form of IBD Patient Concerns), and two generic (Short Form 36, SF-36, and Psychological General Well-Being, PGWB), and a one-week symptom diary. Demographic and disease-related data were collected. Results for the collagenous colitis population were compared with a background population controlled for age and gender (n=8931).Results: Compared with a Swedish background population, patients with collagenous colitis scored significantly worse in all Short Form 36 dimensions (p<0.01), except physical function. Patients with active disease scored worse health-related quality of life than patients in remission. Co-existing disease had an impact on health-related quality of life measured with the generic measures. Lower education level and shorter disease duration were associated with decreased well-being.Conclusion: Health-related quality of life was impaired in patients with collagenous colitis compared with a background population. Disease activity is the most important factor associated with impairment of health-related quality of life. Patients in remission have a health-related quality of life similar to a background population.

Transjugular intrahepatic portosystemic shunt with expanded-polytetrafuoroethylene-covered stents in non-cirrhotic patients with portal cavernoma - Corrected Proof

2010-07-16

Abstract: Aims: To evaluate the feasibility and efficacy of Transjugular intrahepatic portosystemic shunt (TIPS) in non-cirrhotic patients with symptomatic portal hypertension secondary to portal cavernoma.Methods: Our cohort includes 13 consecutive patients. Eleven were considered for Transjugular intrahepatic portosystemic shunt placement for complications not manageable by medical/endoscopic treatment and two because of the need of oral anticoagulation in presence of high-risk varices. Expanded-polytetrafluoroethylene-covered stents were used in all.Results: One of the 13 patients was excluded because of a thrombosis of the superior cava and jugular veins. In 10 patients, Transjugular intrahepatic portosystemic shunt was successfully implanted [83.3%; 95% confidence interval: 52–98%]. One patient had an early shunt dysfunction with recurrence of variceal bleeding which required an emergency surgical shunt. Late shunt dysfunction occurred in two patients, successfully treated with angioplasty and re-stenting. Two patients experienced an episode of encephalopathy.Conclusions: Transjugular intrahepatic portosystemic shunt is feasible in most of the patients with portal cavernoma and should be considered in those with severe complications uncontrolled by conventional therapy. The use of Transjugular intrahepatic portosystemic shunt to achieve a lifelong anticoagulation therapy in selected patients with high-risk varices may be another possible indication. These patients should be referred to selected Units with large experience in Transjugular intrahepatic portosystemic shunt placement.

Primary leiomyosarcoma with multiple nodules arising from the greater omentum - Corrected Proof

Chun-Yan Xia, Wen-Ming Cong, Wen-Jun Han, Bin Wang — 2010-07-12

We report herein a rare case of primary leiomyosarcoma with multiple nodules arising from the greater omentum. To the best of our knowledge, only 23 cases of primary leiomyosarcomas of the greater omentum have ever been reported, and only 2 of these cases had multiple nodules .

The patient's expectation during H2 breath testing: Don’t underestimate the reader's expectation - Corrected Proof

Michele Di Stefano, Gino Roberto Corazza — 2010-07-12

We read with interest the paper by Vernia et al. , suggesting that a “nocebo” effect due to lactose administration may cause a false positivity for lactose intolerance. As the Authors correctly reported, it is known that the patient's expectations may be linked to a psycho-emotional mechanism inducing the onset of symptoms after placebo or food and side effects after drug administration. Anxiety, depression and somatisation were shown to have a role in the pathophysiology of the nocebo effect. The paper by Vernia et al. shows that, independently of H2 breath test results, a subgroup of patients, already tested for lactose malabsorption with lactose breath test, develop abdominal symptoms during a further breath test which foresees the administration of a solution containing 1g of glucose, a dose unable to increase breath H2 excretion. Three main criticisms must be raised. First, it is important to know whether the subgroup of patients showing such a symptomatic response after placebo was characterised by an increased prevalence or higher severity of anxiety, depression or somatisation compared to the large group of subjects who did not show any symptoms. In a recent survey, the prevalence of somatisation disorder was diagnosed in 30% of patients with IBS and was associated with significantly greater numbers of both gastrointestinal and non-gastrointestinal symptoms, but also with physician visits, telephone calls to physicians, urgent care visits and missed work days . Consequently, an increased prevalence of psychiatric illness in this subgroup might also explain the acceptance of a further diagnostic evaluation, making the selected group unreliable to draw the Authors’ conclusions. Second, the study did not follow a double-blind design, which is the only study design considered accurate for the aim of these studies.

Expression of Sonic hedgehog (SHH) and CDX2 in the columnar epithelium of the lower oesophagus - Corrected Proof

2010-07-09

Abstract: Background: Decreases in Sonic hedgehog (SHH) and CDX2 expression are associated with atrophy and intestinal metaplasia in the gastric mucosa. The pathogenesis of development of Barrett's oesophagus is still unclear.Objective: To examine the gene expression of CDX2 and SHH and their signalling pathways in the columnar epithelium and the association with endoscopic appearance, gastric pH or bile acids.Subjects/Methods: Sixty-three patients with metaplastic columnar epithelium of the lower oesophagus were studied. Whole biopsy specimens and microdissected tissues were examined for messenger RNA.Results: BMP4 expression was significantly higher in patients with tubular mucosal patterns of columnar epithelium visualised by Narrow Band Imaging with magnification. The expression of SHH was significantly lower and that of CDX2 was higher in the goblet columnar epithelium than in non-goblet columnar epithelium. CDX2 expression was significantly higher in the patients with hypoacidity than in the others. BMP4 and PTCH1 expression was significantly higher in the group with higher concentrations of deoxycholic acid than in the group with lower concentrations.Conclusions: SHH might be the initial factor inducing columnar metaplasia, and subsequent or simultaneous BMP4 stimuli might induce the CDX2 expression that causes goblet-cell metaplasia.

Referrals for bowel ultrasound in clinical practice: A survey in 12 nationwide centres in Italy - Corrected Proof

2010-07-09

Abstract: Background: The value of ultrasound (US) in assessing gastrointestinal diseases is well documented, but its demand in clinical practice is unknown. This survey evaluated the demand for bowel US in Italy.Methods: Twelve sonographers of the Gastroenterology Section of the Italian Society of Ultrasound participated in a 1-month survey; they compiled a questionnaire assessing total number of patients referred for abdominal US and for gastrointestinal tract US, type of referring physician, indications and results of examinations.Results: The survey included 2424 examinations, 586 of which (24%) investigated the gastrointestinal tract: 280 for signs or symptoms and 268 for follow-up of pre-existing gastrointestinal diseases. Referring physicians were mainly gastroenterologists (78%) and general practitioners (13%). Organic lesions were found or suspected in 292 examinations.Conclusions: Bowel US is used in Italy in routine practice, mainly by gastroenterologists and general practitioners, both for follow-up of pre-existing diseases and for gastrointestinal complaints.

Safe use of ursodeoxycholic acid in a breast-feeding patient with primary biliary cirrhosis - Corrected Proof

Libor Vítek, Miroslava Zelenková, Radan Brůha — 2010-07-09

Ursodeoxycholic acid (UDCA) is currently used as the treatment of choice in patients with primary biliary cirrhosis (PBC) . Although UDCA is not approved during pregnancy, it has been safely administered to pregnant patients with cholestatic diseases such as primary biliary cirrhosis or intrahepatic cholestasis of pregnancy mainly in the 2nd and 3rd trimester, with no harm to mothers or foetuses . During breast-feeding, UDCA is not approved; however, this treatment is believed to be safe for the baby . Despite its common use in pregnancy, the data on UDCA levels in the breast milk of treated patients are scarce. Thus, no specific recommendation on UDCA treatment has currently been stated in the recent guidelines on the treatment of patients with cholestatic liver diseases during lactation . In fact, there are only a few references in the literature concerning this topic. The first report on safe UDCA treatment of a PBC patient during breast-feeding was published by German authors in 1996 . In this patient, UDCA treatment at a dose of 750mg/day did not result in the appearance of UDCA in breast milk. In another study , seven patients with intrahepatic cholestasis of pregnancy were treated with UDCA at 14mg/kg/day for 14 days, until delivery; the UDCA levels in colostrum reached 5.7μmol/L (0.5–15.9).

The CCL21/CCR7 pathway plays a key role in human colon cancer metastasis through regulation of matrix metalloproteinase-9 - Corrected Proof

Jiang Li, Renhu Sun, Kaixiong Tao, Guobin Wang — 2010-07-08

Abstract: Purpose: CC chemokine receptor 7 (CCR7) and matrix metalloproteinase-9 (MMP-9) have been associated with lymph node metastasis in human colon cancer. Studies have suggested a potential link between CCR7 and MMP-9 in cancer; however, the molecular mechanism by which C–C ligand 21/CCR7 promotes tumour dissemination in human colon cancer is not well understood. Thus, we aimed to determine whether MMP-9 is regulated by the C–C ligand 21/CCR7 in human colon cancer.Method: RNA interference technology was employed to detect effect of CCR7 deficiency on the expression of MMP-9 in SW480 human colon cancer cells. We also evaluated the ability of CCR7 short hairpin RNA to inhibit MMP-9 production and tumour invasion in a xenografted mouse model by using whole-body fluorescence imaging and gelatin zymography.Result: We found that CCR7 short hairpin RNA significantly inhibited C–C ligand 21/CCR7-induced up-regulation of MMP-9 in SW480 cells. Furthermore, knockdown of CCR7 significantly limited the production of MMP-9 and colon cancer metastasis in a xenografted mouse model. Mice that received SW480/control cells had progressively enlarging tumours and more lymphatic metastases, and these animals did not survive as long as mice that received SW480/CCR7− cells.Conclusion: MMP-9 and CCR7 may be useful targets for the treatment of lymphatic metastasis in colon cancer.

Current topics in autoimmune hepatitis - Corrected Proof

2010-07-08

Abstract: Autoimmune hepatitis is a chronic liver disease of unknown aetiology characterized by interface hepatitis, hypergammaglobulinaemia and circulating autoantibodies. In the last decade a number of advancements have been made in the field of clinical and basic research: the simplified diagnostic criteria, the complete response defined as normalization of transaminase levels, the molecular identification of the antigenic targets of anti-liver cytosol antibody type 1 and anti-soluble liver antigen, the detection of anti-actin antibodies, the description of de novo autoimmune hepatitis after liver transplantation for non-autoimmune liver diseases, the characterization of autoimmune hepatitis with overlapping features of primary biliary cirrhosis or primary sclerosing cholangitis, the preliminary experience with novel treatment strategies based on cyclosporine, mycophenolate mofetil and budesonide, the role played by “impaired” regulatory T cells and the development of novel animal models of autoimmune hepatitis.

Diagnostic value and clinical utility of contrast enhanced ultrasound in intestinal diseases - Corrected Proof

2010-07-05

Abstract: Contrast enhanced ultrasound (CEUS) has recently gained increasing attention as it clearly improves the visualisation of perfusion in various tissues. The development of second generation contrast enhancing agents used in low-mechanical-index harmonic ultrasound has enabled real-time assessment of the microvascular circulation and quantification of bowel wall vascularity.For this review Medline was searched for clinical studies using CEUS to investigate the gastrointestinal tract.Many studies demonstrate that acute or chronic inflammation of the intestinal wall is accompanied by increased perfusion of the mesentery, which can be displayed semi-quantitatively using contrast enhanced ultrasound analyzing time intensity curves. In contrast, ischemia is characterized by hypoperfusion of the mesenteric arteries and the bowel wall. The most promising sonographic approach in assessing splanchnic arteries and the bowel wall is combining the analysis of superior and inferior mesenteric inflow by pulsed Doppler scanning (systolic and diastolic velocities, resistance index) with the end-organ vascularity by CEUS.CEUS at a preliminary stage has been described as clinically important in a variety of gastrointestinal disorders, particularly in patients with Crohn's disease. CEUS facilitates the detection of disease extent and activity, and its luminal and extraluminal complications.

Five year time course of celiac disease serology during gluten free diet: results of a community based “CD-Watch” program - Corrected Proof

2010-07-02

Abstract: Background: Little information is available on the effect of a follow-up strategy in celiac disease patients during gluten-free diet.Aims: To assess 5 year time course of t-transglutaminase antibodies (t-TG) in celiac disease patients enrolled in a community based follow-up program.Methods: Annual t-TG testing and periodical clinic visit in 2245 patients.Results: Proportion of patients with negative t-TG progressively increased from 83% to 93% during the 5-year follow-up: poor adherence to gluten-free diet (HR 4.764), long duration of gluten-free diet (HR 0.929) and female gender (HR 1.472) were independently associated with serological outcome. In individual patients, 69% tested t-TG “persistently negative”, 1% “persistently positive” and 30% “intermittently negative or positive”. By applying mathematical modelling to t-TG conversion rates observed in this latter group at beginning and end of the follow-up program, the predicted proportion of t-TG negative population increased from 90% to 95% over 5 years.Conclusions: Time-course of t-TG serology in the community fluctuates in 1/3 of celiac disease patients suggesting inconstant adherence to gluten-free diet and need of follow-up strategy. Periodical serological and clinical follow-up is a viable and efficacious strategy to promote adherence to gluten-free diet as inferred from time-course of t-TG serology.

Mucinous cystadenoma of the peritoneum: A rare cause of ascites - Corrected Proof

Adnan Taş, Erdem Akbal, Şükran Akgedik, Seyfettin Köklü — 2010-07-02

Mucinous cystadenoma is a rare benign tumour. Because it has no specific clinical manifestations or imaging features, preoperative clinical and radiological diagnoses are difficult to make . We report here a case of primary mucinous cystadenoma of peritoneum. To our knowledge, this is the first such case reported in the literature.

Cholangiocarcinoma in Italy: A national survey on clinical characteristics, diagnostic modalities and treatment. Results from the “Cholangiocarcinoma” committee of the Italian Association for the Study of Liver disease - Corrected Proof

2010-06-28

Abstract: Background: Very few studies assessed cholangiocarcinoma clinical characteristics.Aim: To evaluate the clinical characteristics of intra-hepatic (IH) and extra-hepatic (EH)-CCA.Methods: We performed a national survey based on a questionnaire.Results: 218 cholangiocarcinomas were observed (47% EH-CCA, 53% IH-CCA) with an age at the diagnosis higher for EH-CCA. Coexistence of cirrhosis or viral cirrhosis was more frequent in IH-CCA than EH-CCA. An incidental asymptomatic presentation occurred in 28% of IH-CCA vs 4% EH-CCA whilst, 74% EH-CCA vs 28% IH-CCA presented with jaundice. 91% of IH-CCA presented as a single intra-hepatic mass, whilst 50% of EH-CCA was peri-hilar. In the diagnostic work-up, 70% of all cholangiocarcinoma cases received at least 3 different imaging procedures. Tissue-proven diagnosis was obtained in 80% cholangiocarcinoma. Open surgery with curative intent was performed in 45% of IH-CCA and 29% EH-CCA. 18% IH-CCA vs 4% EH-CCA did not received treatment.Conclusions: In Italy IH-CCA is managed as frequently as EH-CCA. In comparison to EH-CCA, IH-CCA occurs at younger age and is more frequently associated with cirrhosis and with an incidental asymptomatic presentation. In contrast, most EH-CCAs are jaundiced at the diagnosis. Cholangiocarcinoma diagnostic management is cost- and time-consuming with curative surgical treatment applicable more frequently in IH-CCA.

Relationship between portal chronic inflammation and disease severity in paediatric non-alcoholic fatty liver disease - Corrected Proof

2010-06-28

Abstract: Background: The non-alcoholic steato-hepatitis Clinical Research Network has recently shown that portal chronic inflammation is associated with liver fibrosis in American children with non-alcoholic fatty liver disease.Aim: We tested whether the portal chronic inflammation-fibrosis association was present in a series of Italian children with non-alcoholic fatty liver disease.Methods: We re-assessed the liver biopsies of 144 consecutive Italian children with non-alcoholic fatty liver disease aged 3–18 years and followed at the “Bambino Gesù” Paediatric Hospital. Non-alcoholic fatty liver disease and portal chronic inflammation were diagnosed using the non-alcoholic steato-hepatitis Clinical Research Network criteria. Anthropometry, body composition, liver enzymes, metabolic parameters and blood pressure were measured in all children.Results: Two children had no portal chronic inflammation, 84 had mild and 58 more than mild portal chronic inflammation according to the non-alcoholic steato-hepatitis Clinical Research Network criteria. Children with no or mild portal chronic inflammation had the same clinical features of those with more than mild portal chronic inflammation except for insulin resistance, which was greater. There was no association between steatosis, lobular inflammation, ballooning, fibrosis and portal chronic inflammation.Conclusion: We were not able to confirm the existence of a clinico-pathological association between portal chronic inflammation and disease severity in a series of Italian children with non-alcoholic fatty liver disease. Some clinico-pathological correlates of paediatric non-alcoholic fatty liver disease may be population-specific.

Cigarette smoking and appendectomy: Effect on clinical course of diverticulosis - Corrected Proof

2010-06-25

Abstract: Aim: To investigate the effect of appendectomy and cigarette smoking on the clinical course of diverticulosis.Materials and methods: A retrospective case–control study of 207 consecutive patients (45.8% male mean age 64.0 years), 150 with asymptomatic diverticulosis, and 57 with acute diverticulitis. Diagnosis of diverticulosis was defined on the basis of clinical and colonoscopic criteria, diverticulitis was defined by means of clinical, colonoscopic and computerised tomography criteria. Logistic regression function was used to define the relationship between the dependent variable (diverticulitis) and several covariates: sex, age, body mass index, smoking habit, and history of appendectomy.Results: According to the final model, the risk of diverticulitis was 4.94-fold higher (95% confidence interval: 1.98–12.37) in patients with a history of appendectomy with emergency resection, compared to patients not submitted to appendectomy or with a history of elective resection (P<0.001); and 2.79-fold higher (95% confidence interval: 1.30–5.96) in smokers than in non-smokers (P=0.008). The effects of the two determinants were found to be independent, thus the cumulative risk of diverticulitis was 13.78-fold higher for smokers with a history of emergency surgical treatment.Conclusion: Smoking and emergency appendectomy are important predictive factors for the clinical course of diverticulosis.

The impact of endoscopy and specialist care on 30-day mortality among patients with acute non-variceal upper gastrointestinal hemorrhage: An Italian population-based study - Corrected Proof

2010-06-21

Abstract: Objective: To analyze the effects of endoscopy and care in a gastroenterology ward on 30-day mortality among Italian patients hospitalized for acute non-variceal upper gastrointestinal hemorrhage (UGIH).Methods: We conducted a population-based study based on administrative data contained in the Regional Hospital Information System (RHIS) for the Lazio Region (Italy). We identify all hospitalizations with a main diagnosis of UGIH during period 2000–2005. Discharge data were analyzed for procedures performed, ward where the patient was cared for, comorbidities, vital status at discharge. Vital status 30 days after admission was cross-checked with the Regional Registry of Causes of Death. Logistic regression models were performed taking into account patients’ risk factors (OR and C.I. 95%).Results: A total of 13,427 hospitalizations for UGIH (mean patient age, 68 years; 60% males) were identified. The 30-day mortality was 6.9%. Significantly lower rates were observed among hospitalizations that included endoscopy (OR 0.30, 95% C.I. 0.26–0.34), specialist care (OR 0.55, 95% C.I. 0.37–0.82), or both (OR 0.12, 95% C.I. 0.07–0.22). The protective effects of endoscopy and specialist care remained strong after adjustment for potential risk factors.Conclusions: Endoscopy, per se, reduces mortality among patients hospitalized for UGIH, and care in a gastroenterology ward may offer additional protective effects.

Lamivudine-resistance mutations can be selected even at very low levels of hepatitis B viraemia - Corrected Proof

2010-06-21

Abstract: Objective: To investigate lamivudine (LAM)-resistance profiles of hepatitis B virus (HBV) at the early stages of virological breakthrough (serum HBV-DNA 12–345IU/ml) or when HBV-DNA is undetectable.Methods: Sixty-four HBV-mono-infected patients were enrolled: 25 had virological breakthrough with serum HBV-DNA ranging from 12 to 345IU/ml during first-line LAM-monotherapy; 24 were on LAM-monotherapy, and 15 were on LAM+adefovir dipivoxil (ADV) with undetectable serum HBV-DNA (<12IU/ml).Results: HBV-reverse transcriptase was successfully sequenced in 22 (88.0%) LAM-treated patients with HBV-DNA between 12 and 345IU/ml, and in 12 (30.8%) patients receiving LAM (±ADV) with HBV-DNA<12IU/ml.Drug-resistance mutations were observed in 17 (77.2%) LAM-treated patients with virological breakthrough: 8 M204V, 7 M204I, 1 M204I/V, and 1 A181T. One or ≥2 compensatory mutations were found in 10 (58.8%) and in 4 (23.5%) patients.Drug-resistance mutations were present also in patients with undetectable serum HBV-DNA: M204I was detected in 2 patients receiving LAM-monotherapy, and V84M in 1 patient receiving LAM+ADV.Conclusion: Overall findings support the existence of drug-resistance mutations even at very low levels of viral replication. The persistence of low-level HBV replication and consequent drug-resistance emergence should be considered when choosing therapeutic strategies.

Efficacy and safety of endoscopic balloon dilation of symptomatic intestinal Crohn's disease strictures - Corrected Proof

2010-06-21

Abstract: Aim: To evaluate prospectively the clinical efficacy and safety of endoscopic hydrostatic balloon dilation in a consecutive cohort of symptomatic intestinal Crohn's disease strictures.Methods: Between September 2003 and December 2008 we performed endoscopic balloon dilations in 37 Crohn's disease patients with 39 intestinal symptomatic strictures (4 naïve and 35 postoperative). Dilations were performed using a Rigiflex through-the-scope balloon. Clinical success rate was claimed if a patient remained asymptomatic and did not require surgery or further endoscopic dilation, following technical success. Actuarial curves of clinical, endoscopic (redilation) and surgical recurrence were obtained by Kaplan–Meier method. Demographic and disease variables were related to the main outcomes.Results: After a mean follow-up of 26.3 months (range, 2–61 months), the long-term global benefit rate was 89% (33/37). The 1–2–3 years cumulative symptom-free rates were respectively: 76%, 55% and 46%. Four patients were operated upon. Technical success predicts a lower rate of surgery. There were no complications related to the endoscopic procedures.Conclusions: Endoscopic balloon dilation of symptomatic Crohn's disease strictures may achieve clinical benefit in many patients and is a valid alternative to surgery in the management of the disease. Dilation may be repeated in recurrent intestinal obstructions and appears safe without morbidity.

Forecasting the morbidity and mortality associated with prevalent cases of pre-cirrhotic chronic hepatitis C in the United States - Corrected Proof

2010-06-18

Abstract: Background: Without diagnosis and antiviral therapy, many patients with chronic hepatitis C infections will develop end-stage liver disease and die from complications.Aims: To evaluate the future impacts of preventive interventions and treatment advances, this paper forecasts a baseline estimate of the future morbidity and mortality of prevalent hepatitis C when left untreated.Methods: We simulated the future disease progression and death for all Americans with prevalent hepatitis C in 2005. To validate the model, we used past seroprevalence to forecast contemporary outcomes. We used the validated model to forecast future cases of end-stage liver disease, transplants, and deaths from 2010 to 2060, and we estimated credible intervals using Monte Carlo simulation.Results: When programmed with past data, our model predicted current levels of hepatitis C outcomes with accuracy between ±1% and 13%. Morbidity and mortality from hepatitis C will rise from 2010 to a peak between the years 2030 and 2035. We forecasted a peak of 38,600 incident cases of end-stage liver disease; 3200 referrals for transplant; and 36,100 deaths.Conclusions: Because current rates of screening and treatment are low, future morbidity and mortality from hepatitis C are likely to increase substantially without public health interventions to increase treatment.

The management of patients with new onset of upper gastro-intestinal symptoms in primary care - Corrected Proof

2010-06-17

Abstract: Background: Data dealing with dyspepsia management in general practice are lacking, and most of the studies investigated a subset of patients with suspected peptic ulcer disease either with or without previous complaints.Aims: To evaluate the one-year management of patients presenting new onset upper abdominal symptoms without alarming features.Methods: 275 patients were enrolled by 63 Italian general practitioners.Results: Referral to upper gastro-intestinal tract endoscopy resulted significantly higher in patients with predominant epigastric pain compared to subjects with non-painful symptoms or non-dominant symptoms. Amongst drug therapies, only prokinetics and antacids and anti-secretory therapies were prescribed differently amongst clinical subgroups. The rate and type of management and referrals resulted were not influenced by the age of patients or the use of anti-inflammatory drugs. The most frequent diagnosis at one-year follow-up was reflux oesophagitis. The absence of organic disease was less frequent in patients with dominant epigastric pain than non-painful or non-dominant symptoms.Conclusion: The management of these patients in primary care in Italy is mainly determined by clinical presentation, independent of age. Any judgement about appropriateness of the treatment should consider not only conventional features such as age, but the more complex individual frameworks as well.

Therapeutic pancreatic endoscopy - Corrected Proof

Andrew S. Ross, Richard A. Kozarek — 2010-06-16

Abstract: Although the common indications for therapeutic pancreatic endoscopy – management of ductal strictures and calculi – have remained constants, the last decade has witnessed the emergence of several new endoscopic techniques for managing pancreatic disorders. While many of the advances in therapeutic pancreatic endoscopy have paralleled the shift of endoscopic ultrasound from a purely diagnostic to therapeutic modality, other new techniques are simply modifications on existing procedures. Despite these exciting times in therapeutic endoscopy, it is important to recognize that the endoscopist is one part of an interdisciplinary team of experts – a model which is essential in the successful management of patients with pancreatic disorders.

Searching for wheat plants with low toxicity in celiac disease: Between direct toxicity and immunologic activation - Corrected Proof

2010-06-16

Abstract: Background: Natural or induced variations in the noxiousness of gluten proteins for celiac disease (CD) patients are currently being investigated for their potential in breeding wheat crops with reduced toxicity.Aims: We evaluated the bread wheat line C173 for its effects on the in vitro-grown duodenal mucosa of CD patients.Methods: In vitro-grown duodenal mucosa biopsies of 19 CD patients on a gluten-free diet were exposed to peptic/tryptic-digested prolamins from bread wheat line C173 lacking gliadin–glutenin subunits, analyzed for morphology, cytokine and anti-tTG antibody production, and compared with mucosa biopsies exposed to prolamins from wild-type cv. San Pastore.Results: Duodenal mucosa biopsies exposed to prolamins from C173 and San Pastore released higher amounts of IFN-γ, IL-2, IL-10 and anti-tTG antibodies in the culture medium than untreated controls. The line C173 differed from cv. San Pastore as it did not produce negative effects on enterocyte height, suggesting that manipulating prolamin composition can affect innate immune responses of CD mucosa to wheat gluten.Conclusions: Our data demonstrated that this gliadin-deficient wheat has a lower direct toxicity but activates an immunologic reaction of the duodenal mucosa like that of the common wheat species.

HCV-positive status and hepatitis flares in patients with B-cell non-Hodgkin's lymphoma treated with rituximab-containing regimens - Corrected Proof

2010-06-16

Abstract: Background: Rituximab has provided a revolutionary contribution to the treatment of B-cell non-Hodgkin's lymphomas (NHL). A high prevalence of hepatitis C virus (HCV) infection has been described in B-cell NHL patients. Cases of liver dysfunction in HCV-positive patients have been reported with rituximab-containing regimens.Aim: to evaluate the liver-related effects of rituximab-containing regimens on HCV-positive CD20-positive B-cell NHL patients.Patients and methods: Retrospective analysis of 104 consecutive patients. HCV status was determined, and development of hepatitis flares analysed.Results: Nine patients (8.6%) were HCV-positive. No correlation was shown between viral load and alanine transaminase levels. Three of the 9 HCV-positive, and none of the 95 HCV-negative developed hepatitis flares (p<0.001). At the 12-month follow-up hepatitis flare patients were alive and in remission for their haematological disease and no hepatitis flares, liver-related death had developed.Conclusions: HCV-positive status may represent a risk factor for the development of hepatic flares in B-cell NHL patients receiving rituximab-containing regimens. Despite the increase in liver function tests, there were no major clinical events.

Adiponectin isoforms, insulin resistance and liver histology in nonalcoholic fatty liver disease - Corrected Proof

2010-06-16

Abstract: Background: Nonalcoholic fatty liver disease is associated with insulin resistance and low adiponectin levels. Adiponectin circulates as high-, medium- and low-molecular weight complexes, possibly exerting different insulin-sensitising effects.Aim: We investigated adiponectin isoforms in nonalcoholic fatty liver disease in relation to liver disease severity and insulin resistance.Patients and methods: Total adiponectin and isoform distribution were measured in 54 biopsy-proven, non-diabetic nonalcoholic fatty liver disease subjects, divided according to their fasting and 120-min glucose levels during an oral glucose tolerance test, as well as in 44 matched healthy controls. Insulin resistance/sensitivity was estimated in nonalcoholic fatty liver disease by the homeostasis model assessment and the oral glucose insulin sensitivity during oral glucose tolerance test. Total adiponectin and adiponectin isoforms were determined by in-house assays.Results: Total adiponectin was reduced in nonalcoholic fatty liver disease (5.32±1.85mg/L vs. 9.11±3.46mg/L), with a relative abundance of high-molecular weight (34% vs. 47%) and low-molecular weight adiponectin (16% vs. 19%), coupled with dearth of medium-molecular weight adiponectin (50% vs. 34%) (P<0.001 for all comparisons). In nonalcoholic fatty liver disease, adiponectin did not differ in relation to homeostasis model assessment, but levels were remarkably higher in relation to oral glucose insulin sensitivity-determined insulin sensitivity. However, the distribution of isoforms did not vary with disease severity, BMI class, glucose regulation or insulin resistance.Conclusion: Adiponectin levels are reduced in nonalcoholic fatty liver disease, without any significant contribution of isoform distribution to progressive liver disease.

Feline oesophagus: An unusual cause of dysphagia - Corrected Proof

Vidya Shankaran, Piero M. Fisichella — 2010-06-07

“Feline oesophagus” is a term used to describe the finding of transverse folds within the mid- and proximal-oesophagus. We describe an incidental finding of feline oesophagus in a patient with symptoms of oesophageal dysmotility. An 82-year-old male patient with a longstanding history of dysphagia and regurgitation presented for further evaluation. He denied odynophagia and described more difficulty with solids than liquids. He had previously undergone oesophagoscopy and conventional oesophageal manometry at another institution which showed “intact peristalsis with low amplitude contractions”. The patient was referred for a barium oesophagram for further evaluation of functional or anatomic abnormalities contributing to his dysphagia. In this study, a small hiatal hernia was demonstrated and oesophageal reflux was suggested by barium backing into the oesophagus. In addition, transient, transverse striations in the mid- and proximal-oesophagus were noted (see ). The figure demonstrates fine, transverse folds in the mid- and proximal-oesophagus, a phenomenon known as “feline oesophagus”, as it mimics the appearance of the distal oesophagus in cats. This phenomenon has been attributed to transient contractions of the oesophageal muscularis mucosa .

HLA-DRB103 and DRB104 are associated with atrophic gastritis in an Italian population - Corrected Proof

2010-06-04

Abstract: Background: Atrophic gastritis (AG) is often considered an autoimmune disorder and is associated with other autoimmune diseases. HLA-DRB1 alleles are often associated with autoimmune diseases, however HLA-DRB1 genotyping data in AG patients are lacking. The objective of the study was to evaluate the prevalence of HLA-DRB1 in AG patients.Methods: The occurrence of HLA-DRB1 alleles was assessed in 89 Italian AG patients (69.1% female) and 313 controls (47.3% females). Genomic DNA was extracted from peripheral venous blood, PCR-coamplified for HLA-DRB1 and typed using a reverse line-blot assay.Results: Compared to controls, prevalence of HLA-DRB1*03 (28.1% vs. 15.9%, p=0.01) and HLA-DRB1*04 (25.8% vs. 14.4%, p=0.01) was greater in AG patients, conferring an OR of 2.05 and 2.07, respectively. HLA-DRB1*01 occurred more frequently in controls than in AG patients (11.5% vs. 3.4%, p=0.01) conferring an OR of 0.27. AG patients carrying the HLA-DRB1*03 or *04 alleles were characterised by having more frequently autoimmune thyroid disease (70.4% vs. 42.2%, p=0.01) and intestinal metaplasia (86.4% vs. 62.2%, p=0.01).Conclusions: In our population, over 50% of AG patients carry the HLA-DRB1*03 or *04 alleles associated with autoimmune diseases, suggesting that this subset of AG patients has a genetic predisposition to autoimmunity.

Molecular mechanisms underlying human adipose tissue-derived stromal cells differentiation into a hepatocyte-like phenotype - Corrected Proof

2010-06-04

Abstract: Background: Adipose tissue-derived stromal cells (ATSCs) hold great promises in regenerative medicine. In the last decade, several studies have reported the plasticity of ATSCs toward a hepatocyte-like phenotype. Nonetheless, the molecular mechanisms underlying the conversion from a mesenchymal to an epithelial phenotype remain poorly understood.Aim: In this study, we compared the full genome expression profiles of ATSCs cultured for 4 weeks under pro-hepatogenic conditions to undifferentiated ATSCs, in order to depict the molecular events involved in ATSC hepatic transdifferentiation.Methods: Analysis was performed using the Affymetrix human focus arrays. Sets of differentially expressed genes were functionally categorized in order to understand which pathways drive the hepatic conversion and interesting targets were validated by Q-PCR.Results: ATSC-derived hepatocyte-like cells activate several genes associated with specific liver functions, including protein metabolism, innate immune response regulation, and biodegradation of toxic compounds. Furthermore, microarray analysis highlighted downregulation of transcripts associated with the mesenchymal lineage, while epithelial-related genes were overexpressed.Conclusion: Our data suggest that the in vitro system used in this study drove ATSCs toward a hepatic conversion through a subtle regulation of molecular pathways controlling lineage commitment that promote mesenchymal-epithelial transition.

Familial pancreatic cancer in Italy. Risk assessment, screening programs and clinical approach: A position paper from the Italian Registry - Corrected Proof

2010-06-03

Abstract: In Italy, pancreatic cancer is the fifth leading cause of tumor related death with about 7000 new cases per year and a mortality rate of 95%. In a recent prospective epidemiological study on the Italian population, a family history was found in about 10% of patients suffering from a ductal adenocarcinoma of the pancreas (PDAC). A position paper from the Italian Registry for Familial Pancreatic Cancer was made to manage these high-risk individuals. Even though in the majority of high-risk individuals a genetic test to identify familial predisposition is not available, a screening protocol seems to be reasonable for subjects who have a >10-fold greater risk for the development of PDAC. However this kind of screening should be included in clinical trials, performed in centers with high expertise in pancreatic disease, using the least aggressive diagnostic modalities.

The specialty of gastroenterology: Between a past of excellence and a somewhat uncertain future - Corrected Proof

Angelo Andriulli — 2010-06-01

Looking back over the odd 35 years from 1960 through the mid-1990s, one can discern an upward expansion in several fields of gastroenterology, a specialty that has witnessed an exciting time marking major milestones such as the discovery of viral hepatitis, the identification of Helicobacter pylori as the causative agent of peptic ulcer, and the marketing of new classes of drugs that ultimately have succeeded in fighting the most relevant gastrointestinal diseases. Thanks to these discoveries, in the most developed countries of the world future generations will benefit from a healthier liver, a healthier stomach, and a healthier colon.

Ectopic pancreas at the jejunum - Corrected Proof

Yasuhiro Takeda, Hiroshi Nakase, Tsutomu Chiba — 2010-05-31

A 77-year-old man with tricuspid incompetence and chronic atrial fibrillation was admitted to our hospital for investigation of melena. Esophagogastroduodenoscopy and colonoscopy revealed no any abnormalities. Video capsule endoscopy (VCE), which was performed to investigate the source of gastrointestinal bleeding, revealed overt bleeding from an angioectasia at the jejunum. Double-balloon enteroscopy (DBE) was performed for endoscopic hemostasis of the angioectasia. A submucosal tumor (SMT), with a caterpillar-like appearance on endoscopy, was incidentally observed at the jejunum during DBE (Fig. 1A).

Biliary Variant in a Potential Liver Donor - Corrected Proof

Matteo Renzulli, Vincenzo Lucidi, Emanuela Giampalma, Rita Golfieri — 2010-05-31

A 55 year-old man with no known medical conditions or surgical history presented to our hospital to be evaluated as potential living liver donor. In our centre donor candidates are evaluated using a specific living donor protocol; this includes imaging studies for liver volumetrics (to quantify the amount of parenchyma that could be donated versus the remnant) and liver vascular anatomy, and magnetic resonance cholangiopancreatography (MRCP) to evaluate anatomy of the biliary tree. Computed tomography scanning was performed to estimate volume of the right and left lobes of the liver: the right lobe would be harvested for transplantation into the recipient, while the left would be the donor's remnant liver; the test confirmed adequate volume of both liver lobes.

Long-term home parenteral nutrition in children with chronic intestinal failure: A 15-year experience at a single Italian centre - Corrected Proof

2010-05-31

Abstract: Background and aims: Chronic intestinal failure is a condition causing severe impairment of intestinal functions; long-term total parenteral nutrition is required to provide adequate nutritional support.Methods: This is a 15-year follow-up study of paediatric patients with intestinal failure receiving long-term home parenteral nutrition.Results: Thirty-six patients were included in the study, all aged <16 years. Total parenteral nutrition and home parenteral nutrition were administered respectively to 100.97 and 85.20 patients-year. Today, 12 out of 36 patients are still on parenteral nutrition. A total of 99 central venous catheters were inserted, for mean 2.75 catheters/patient. The overall incidence rates of catheter-related complications was 1.79 per 1000 days-catheter for sepsis and 3.37 per 1000 days-catheter for mechanical complications. Two multivariate Cox-models have been used to examine the role of some predictors for septic or mechanical complications. The only risk factor for septic complications was the indication for parenteral nutrition, and the only predictor of mechanical complications was the insertion period.Conclusions: Our experience in the treatment of paediatric patients with gastrointestinal diseases confirms that long-term parenteral nutrition has become a safe and appropriate method in the treatment of severe chronic intestinal failure.

The origin of non-H. pylori-related positive Giemsa staining in human gastric biopsy specimens: A prospective study - Corrected Proof

2010-05-20

Abstract: Background: Upper gastrointestinal endoscopically biopsied specimens are usually sent for the diagnosis of Helicobacter pylori infection. The study aimed to determine the relationship between the origin of positive Giemsa staining and the grade of gastritis based on the updated Sydney system.Methods: Gastric biopsy specimens taken at the lesser curvature and greater curvature sides of the corpus and greater curvature side of the antrum were stained with H&E, Giemsa, anti-East Asian-specific antibody and anti-H. pylori antibody stains. Pyrosequencing analysis was performed in cases that showed discrepancy between the Giemsa and anti-H. pylori antibody staining.Results: Seventy-two out of 150 cases (48%) stained positive for anti-H. pylori antibody, of which 68 (94.4%) stained positive for anti-East Asian-specific antibody stain. Twelve of the 20 cases with discrepant results for Giemsa and anti-H. pylori antibody stains exhibited Campylobacter hyointestinalis infection. The grades of neutrophil activity (p<0.001) and chronic inflammation (p<0.001) were lower for Campylobacter infection than for East Asian CagA H. pylori-related infection.Conclusion: C. hyointestinalis is the most common cause of non-H. pylori-related Giemsa positive infection, and is associated with lower grades of neutrophil activity and chronic inflammation than East Asian CagA H. pylori-related infection.

Inflammatory bowel disease-patients are insufficiently educated about the basic characteristics of their disease and the associated risk of colorectal cancer - Corrected Proof

2010-05-17

Abstract: Background/aim: Limited data are available about inflammatory bowel disease-patients’ knowledge of disease and associated risks. We assessed patients’ knowledge of disease and its associated risks/complications, and their perspectives on current recommendations for colectomy when low-grade dysplasia is found.Methods: Inflammatory bowel disease-patients at a regional patient-information-day were asked to anonymously complete a survey (group-A). A 2nd group was recruited online through the Dutch inflammatory bowel disease-patients’ association (group-B).Results: In group-A, 109 inflammatory bowel disease-patients completed the survey (76% Crohn's disease, 24% ulcerative colitis, 78% female). Thirty-three patients (30%) were unaware of their disease-localization; 30% thought inflammatory bowel disease shortened their life-expectancy; 26% thought it was likely for a severe complication to occur during colonoscopy. Patients estimated their 10-year colorectal carcinoma-risk at 25%. Mean perceived colorectal carcinoma-associated mortality-risk was 13%. Patients would agree to colectomy if their current colorectal carcinoma-risk was at least 53% and 70% would refuse physicians’ recommendation for colectomy if dysplasia were detected with a 20% risk of concomitant colorectal carcinoma. Group-B (n=393 inflammatory bowel disease-patients) verified the results above. However, fewer patients (52%) would refuse physicians’ recommendation for colectomy, p=0.01.Conclusion: Inflammatory bowel disease-patients are ill-informed about their disease and its associated risks. Improvement of patient-education is necessary to appropriately involve patients in the decision-making process.

Relationship between white blood cell count and nonalcoholic fatty liver disease - Corrected Proof

2010-05-17

Abstract: Background: Higher levels of white blood cell (WBC) count are known to be associated with metabolic syndrome and insulin resistance. Nonalcoholic fatty liver disease (NAFLD) is also considered a hepatic manifestation of insulin resistance.Aims: The present study aimed to determine the relation between WBC count and the presence of NAFLD based on abdominal sonographic findings.Methods: A cross-sectional study with 3681 healthy subjects (2066 men, 1615 women) undergoing medical check-up was conducted. The odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were calculated using multivariate logistic regression analyses across WBC quartiles.Results: A graded independent relationship between higher levels of WBC count and the prevalence risk of NAFLD was observed. After adjusting for age, smoking status, regular exercise, body mass index (BMI), blood pressure, fasting plasma glucose, triglyceride, and HDL-cholesterol, the ORs (95% CIs) for NAFLD according to WBC quartiles were 1.00, 1.48 (1.10–1.98), 1.59 (1.18–2.14), and 1.84 (1.35–2.51) for men and 1.00, 1.15 (0.67–1.96), 1.88 (1.13–3.11), and 2.74 (1.68–4.46) for women.Conclusions: WBC count was found to be independently associated with the presence of NAFLD regardless of classical cardiovascular risk factors and other components of metabolic syndrome.

Oesophagogastroduodenoscopy in patients with cirrhosis: Extending the range of detection beyond portal hypertension - Corrected Proof

Stefania De Lisi, Sergio Peralta, Andrea Arini, Fabio Simone, Antonio Craxì — 2010-05-14

Abstract: Background: Oesophagogastroduodenoscopy is currently recommended for the screening of varices in cirrhosis. In addition to the assessment of varices, oesophagogastroduodenoscopy can detect conditions that, while unrelated to portal hypertension, may require treatment.Aims: We evaluated in a large cohort of cirrhotic patients the prevalence of upper digestive findings other than oesophagogastric varices, the associations between upper gastrointestinal findings, portal hypertension and features of cirrhosis, and the incidence of new lesions in the course of a surveillance program.Methods: Analysis of the records of 611 consecutive cirrhotic patients undergoing oesophagogastroduodenoscopy for screening and surveillance.Results: 232 patients (38%) presented endoscopic lesions not related to portal hypertension: peptic diseases (n=193), proliferative diseases (n=27) and vascular diseases (n=12). In the screening group, 127 patients (39.4%) had pathologic lesions. At multivariate analysis, an association was found between peptic diseases and the absence of portal hypertensive gastropathy (RR 3.3; 95% CI 2.2–4.8); vascular diseases were associated with endoscopic signs of portal hypertension (p=0.01). During surveillance, 9/55 patients (16.3%) in the group without previous pathologic findings developed new lesions.Conclusions: Oesophagogastroduodenoscopy in patients with cirrhosis undergoing endoscopy for screening diagnosed pathologic lesions unrelated to portal hypertension requiring a change in management in 39.4% of asymptomatic subjects.

Novel narrow-band imaging magnifying endoscopic classification for early gastric cancer - Corrected Proof

2010-05-12

Abstract: Background: Narrow-band imaging magnifying endoscopy is widely used in Japan, but still there is no set of consistent guidelines for gastric lesions.Aims: To introduce a new narrow-band imaging magnifying endoscopic classification and report the accuracy of diagnosis in comparison to underlying histopathology of gastric lesions.Methods: Two hundred and fifty-seven consecutive patients with early gastric cancer lesions were enrolled into this study. Narrow-band imaging magnifying images were classified into four categories based on abnormal microvascular patterns and irregularities in the superficial glandular structure: fine-network pattern, corkscrew pattern, intra-lobular loop pattern-1 and intra-lobular loop pattern-2. The narrow-band imaging magnifying endoscopic classification was compared with the histopathological findings.Results: Amongst the differentiated-type adenocarcinoma lesions, fine-network pattern, intra-lobular loop pattern-1, intra-lobular loop pattern-2 and corkscrew pattern were observed in 15.7%, 59.6%, 24.2% and 0.5%, respectively. Differentiated-type adenocarcinomas mainly exhibited fine-network pattern or intra-lobular loop pattern. In undifferentiated-type adenocarcinoma lesions, intra-lobular loop pattern-2 and corkscrew pattern were observed in 41.2% and 58.8%, respectively. Therefore, undifferentiated-type adenocarcinomas were all classified as intra-lobular loop pattern-2 and corkscrew pattern. The histopathological types were not equivalent with the narrow-band imaging magnifying classification categories (P<0.001).Conclusions: The new narrow-band imaging magnifying classification that incorporates the intra-lobular loop pattern may be able to predict the histological subtype of most gastric carcinomas.

Risk factors for serum alanine aminotransferase elevation: A cross-sectional study of healthy adult males in Tokyo, Japan - Corrected Proof

2010-05-11

Abstract: Background: Liver-protective effects of light-to-moderate alcohol consumption have been suggested.Aims: To determine predictors of ALT elevation in asymptomatic subjects with and without ultrasonographical evidence of fatty liver.Methods: Cross-sectional survey of 9703 healthy males. Exclusion criteria were HBV or HCV infection, any use of hepatotoxic medication, history of alcohol abuse, chronic renal or hepatic failure, or treatment for metabolic disorders. Presence of fatty liver was evaluated by ultrasonography; visceral adipose tissue (VAT) was measured by computed tomography (CT).Results: 7148 males (mean age, 50.3±7.8 years) were included; 2406 (33.7%) had fatty liver at ultrasonography. ALT was elevated in 163 (3.4%) and 554 subjects (23.0%) of fatty liver-negative and fatty liver-positive subgroups, respectively. Light (40–140g/week) alcohol consumption was significantly and independently associated with reduced prevalence of ALT elevation in the fatty liver-negative subgroup (OR=0.568, 95% CI=0.342–0.943, P=0.029). ALT elevation was significantly related to age, VAT, high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) in the fatty liver-negative subgroup.Conclusion: Light alcohol consumption is not associated with serum ALT elevation in the Japanese male population. Metabolic syndrome factors are significantly associated with prevalence of ALT elevation, irrespective of the presence of fatty liver.

Music for colonoscopy: A single-blind randomized controlled trial - Corrected Proof

2010-05-10

Abstract: Background: Several methods have been reported to minimize patient discomfort during colonoscopy, none are currently recommended by clinical practice guidelines. We performed a single-blind randomized controlled trial to assess the efficacy of music for colonoscopy.Methods: 109 patients were randomized to music-delivering or mute headphones before and during colonoscopy. Physicians were blinded to the trial. Sedation was given on demand. Primary outcome was pain measured on linear analogue scale from 0 to 10. Secondary endpoints were the difficulty of the procedure, need of sedation, overall patient satisfaction and willingness to repeat the procedure.Results: Mean pain score was 5.9±2.2 in the control group vs. 3.8±1.9 in the music group (p<0.00001); correspondingly overall satisfaction and willingness to repeat the procedure were significantly improved by music and the difficulty perceived by physicians was significantly reduced. Total administered midazolam was 36mg in the control group vs. 13 in the music group (p<0.007), pethidine was 860mg vs. 465mg (p=0.07) and patients requiring sedation were 22 vs. 9, respectively (p=0.003). A multivariable analysis to adjust treatment effect for potential confounding factors confirmed the significant beneficial effect of music.Conclusions: Music significantly reduces discomfort and should be routinely offered to patients undergoing colonoscopy.

The proton pump inhibitor test for gastroesophageal reflux disease: Optimal cut-off value and duration - Corrected Proof

2010-05-10

Abstract: Background: There is no accepted gold standard for the diagnosis of gastroesophageal reflux disease (GERD).Aim: To assess the optimal cut-off value and duration of the proton pump inhibitor (PPI) test in GERD patients with and without oesophagitis.Methods: Prospective study of 544 patients undergoing upper GI endoscopy and treated for 2 weeks with PPIs at double dose, and for 3 additional months at standard dose. The status of the patient at end of treatment was used as an independent diagnostic standard, i.e. patients completely asymptomatic were considered as “true” GERD patients.Results: PPI test was positive in 89.7–97.8% of the patients according to the cut-off or duration of test used. Test sensitivity ranged from 95.5% to 98.8%, whereas specificity did not exceed 36.3%. Positive predictive values ranged from 87% to 80%, negative predictive values ranged from 58% to 70%, respectively.Conclusions: The PPI test is a sensitive but poorly specific test in GERD patients. Its optimal duration is 1 week, and the optimal cut-off value is a decrease of heartburn score ≥75%. The diagnostic yield is higher in erosive oesophagitis compared with non-erosive reflux disease patients, similarly to the symptomatic response to 3-month PPI therapy.

Altered expression of innate immunity genes in different intestinal sites of children with ulcerative colitis - Corrected Proof

2010-05-10

Abstract: Background: Innate immunity has been very rarely investigated in ulcerative colitis and never in paediatrics. The present study was aimed at describing expression of innate immunity genes (NOD2, RIP2, α-defensins HD5 and HD6) in inflamed colon and in ileum of children with ulcerative colitis. Expression of TNFα and IL-1β was also analyzed.Methods: 15 children with ulcerative colitis (9 pancolitis, 6 left-sided colitis) and 10 control children were enrolled. mRNA and protein expressions were detected by real time PCR and western blot assays.Results: NOD2, RIP2, IL-1β, TNFα expression levels were significantly increased in colonic mucosa of patients compared to controls (p<0.01). These genes were also upregulated (p<0.01) in the ileum of both pancolitis and left-sided colitis children. HD5 and HD6 were significantly upregulated (p<0.01) in the inflamed colon of patients as well as in the ileum of those with pancolitis.Conclusions: An increased mucosal expression of innate immunity genes was found in the inflamed colon of children with ulcerative colitis, outlining the role of the innate immune response in disease pathogenesis. Involvement of the ileum in ulcerative colitis suggests that an immune activation can also be established in intestinal sites classically uninvolved by the inflammation, carrying implications for the treatment and course of the disease.

Low prevalence of idiopathic peptic ulcer disease: An Italian endoscopic survey - Corrected Proof

2010-05-05

Abstract: Background: Peptic ulcer disease (PUD) represents a common condition, although its incidence is decreasing. Previous studies reported a high rate of idiopathic PUD prevalence.Aim: To investigate prevalence, relative distribution of etiologic factors and prevalence of complication of PUD in an Italian endoscopic series.Materials and methods: All gastroscopies performed in adult patients during 3 years were considered. Patients with PUD, with antral and corporal histology, were included in the study. Helicobacter pylori infection was assessed by histology. Idiopathic PUD was defined as an ulcer without evidence H. pylori infection or prior exposure to NSAIDs.Results: 300 patients with PUD out of 11,148 gastroscopies were included in our study accounting for a prevalence of 2.7%. H. pylori-associated PUD was diagnosed in 62.3%, NSAID/aspirin-associated PUD in 22%, H. pylori/NSAID/aspirin-associated PUD in 11.6%, and idiopathic PUD in the remaining 4% of cases. Regarding ulcer complications the logistic regression analysis identified the following significant risk factors for GI bleeding: NSAIDs and/or aspirin use, age >65 years and coexistent gastric and duodenal ulcers.Conclusion: Our data found a low endoscopic prevalence of peptic ulcer. Both H. pylori infection and NSAIDs and/or aspirin use remain the main determinants and idiopathic ulcer prevalence is very low.

Current practice of hepatitis C treatment in Southern Italy - Corrected Proof

2010-05-03

Abstract: Background: Only a small proportion of subjects referring to hospitals for hepatitis C virus (HCV) positivity receives antiviral therapy.Aim: To evaluate the rate of antiviral treatment and the causes for no treatment in HCV-RNA positive subjects seen in hospital settings.Patients and methods: A prospective study enrolling over a 6-month period (February–July 2009) all consecutive anti-HCV positive subjects initially referred (naïve patients) to 12 liver units in Southern Italy for HCV treatment.Results: Out of 608 subjects evaluated, 74 (12.2%) had no detectable HCV-RNA in the serum and thus were excluded. Of the remaining 534 HCV-RNA positive subjects, 357 (66.9%) were not treated for the following reasons: 49.9% were older than 65 years of age (75% of them >70 years), 14.3% had normal liver enzymes, 13.2% had compensated/decompensated cirrhosis, 10.4% refused treatment, 9.8% had ongoing substance or alcohol abuse. Multivariate analysis showed that females (O.R. 2.27; C.I. 95% 1.05–4.90) and subjects with low educational level (O.R. 4.38; C.I. 95% 1.27–15.11) were more likely to decline therapy.Conclusions: The majority of patients with HCV infection does not receive antiviral treatment. The effectiveness of the current standard therapy for HCV infection is low despite its good efficacy.

Critical flicker frequency fails to disclose brain dysfunction in patients with primary biliary cirrhosis - Corrected Proof

2010-04-30

Abstract: Background: Recent studies suggest that stage-independent symptoms of primary biliary cirrhosis (PBC) such as chronic fatigue are a consequence of structural and functional abnormalities of the brain. Critical flicker frequency (CFF) is a psychophysiological modality analysing function of cerebral cortex.Aim: To analyse the usefulness of CFF in detection of brain dysfunction in patients with PBC.Methods: Fifty-one (37 non-cirrhotic/14 cirrhotic) patients with PBC were included. Control group consisted of 31 matched healthy individuals. Fatigue and health-related quality of life (HRQoL) were assessed using Fatigue Impact Scale (FIS) and questionnaire PBC-40. CFF was analysed with HEPAtonorm Analyzer®.Results: When compared to healthy controls all patients with PBC showed significantly impaired HRQoL in majority of PBC-40 domains and increased fatigue level in physical domain of FIS. No differences in HRQoL and PBC-40 domains were seen, when patients with and without cirrhosis where compared. CFF analysis showed no difference between healthy controls and patients with PBC. CFF did not correlate with PBC-40 and FIS domains.Conclusion: CFF fails to determine brain dysfunction in non-encephalopatic patients with PBC, suggesting that functional efficiency of their cerebral cortex remains unaffected and other central mechanisms are responsible for chronic fatigue in these patients.

Esophageal motility and symptoms in restricting and binge-eating/purging anorexia - Corrected Proof

2010-04-30

Abstract: Background: Esophageal symptoms are common in anorexia nervosa, but it is not known whether they are associated with motility disorders, with different forms of the disease, and whether they respond to nutritional rehabilitation.Methods: To clarify these points, 23 patients with anorexia nervosa (12 binge-eating/purging, “purgers”; 11 restricting type, “restricters”) were studied by esophageal manometry before and after 22 weeks rehabilitation. Manometric parameters of 35 age and sex-matched patients were used as controls. Patients with anorexia also filled questionnaires on eating disorder psychopathology, psychopathological distress and esophageal, gastric and colonic symptoms before and after 4 and 22 weeks of a rehabilitation program.Results: Symptoms were more severe in patients than in controls. Gastric and colonic, but not esophageal symptoms improved with treatment. LES basal pressure was higher in restricters (restricters 32.1±4.6; purgers 14.9±2.2; controls 17.1±1.1mmHg, p<0.005), but still within normal range; this difference disappeared after treatment. Postdeglutitive body waves were normally propagated. Their amplitude was significantly higher in anorexia than in controls. No correlation was found between results of psychopathological tests (improved after treatment), esophageal symptoms and manometry.Conclusions: In anorexia, esophageal symptoms are frequent and severe. They are not adequately explained by psychological or manometric derangements.

Identification of substance use and dependence among patients with viral hepatitis - Corrected Proof

2010-04-26

Abstract: Background: As drug abuse and addiction have been shown to decrease adherence to treatment of hepatitis C virus (HCV) or HIV, screening for substance use should be standard clinical practice in those undergoing an evaluation for these diseases.Aims: To assess the effectiveness of the Kreek–McHugh–Schluger–Kellogg (KMSK) scale to quantify substance use and dependence among patients with viral hepatitis.Methods: The KMSK scale, a validated instrument that quantifies lifetime use of alcohol, cocaine, heroin, and tobacco, was distributed to 161 consecutive patients referred to a hepatology clinic at an academic, tertiary-care center over a 1-year period.Results: Of the 159 patients who returned the KMSK scale, 62% reported illicit drug use and 30% met defined criteria for lifetime dependence on cocaine or heroin. We found that 15% of our population at some time had been co-dependent on cocaine and heroin. The KMSK scale identified significantly more cocaine, heroin, and alcohol use than that detected through the medical record (χ2=7.61, p<0.01, χ2=9.66, p<0.002, respectively). Cocaine dependence was significantly higher among HCV/HIV co-infected than among mono-infected patients (χ2=5.46, p<0.02).Conclusions: The KMSK scale may be useful to diagnose drug and alcohol use and dependence among patients undergoing evaluation for treatment of viral hepatitis.

Cost analysis of recall strategies for non-invasive diagnosis of small hepatocellular carcinoma - Corrected Proof

2010-04-26

Abstract: Background: Which is the least expensive recall policy for nodules in the cirrhotic liver remains unclear.Aim: Aim of the study was to analyze the costs of different recall diagnostic strategies of hepatocellular carcinoma (HCC) on cirrhosis on a real series of patients.Methods: 75 consecutive small liver nodules (10–30mm) detected at conventional ultrasonography in 60 patients with cirrhosis were submitted to contrast-enhanced ultrasound, computed tomography and gadolinium-magnetic resonance imaging with a final diagnosis established according to the latest guidelines which include different strategies for nodules 10–19mm or ≥20mm. The actual costs required to fully characterise any nodule and staging HCC in every patient, if one or the other imaging modality had been used as the first diagnostic step, were calculated. The theoretical hypothesis that each nodule was present in eaach patient was also investigated from an economical point of view.Results: The recall strategy starting with contrast-enhanced ultrasound plus computed tomography is the least expensive strategy for patients with at least one nodule 10–19mm in size, in nearly all combinations (single or double nodules). In patients with single 20–30mm nodules the least expensive strategy is to start with computed tomography and to use contrast-enhanced ultrasound as a second step technique.Conclusions: wider use of contrast-enhanced ultrasound has the potential to save healthcare costs after first ultrasound detection of a single small nodule in cirrhosis.

Influence of amantadine on CD81 expression on lymphocytes in chronic hepatitis C - Corrected Proof

2010-04-26

Abstract: Introduction: Interferon alpha (IFN) down regulates CD81 expression on peripheral blood mononuclear cells (PBMC) in patients with chronic hepatitis C virus (HCV) infection. Aim of our study was to investigate whether amantadine alters IFN associated down regulation of CD81 expression on PBMC in patients with chronic hepatitis C.Methods: Nineteen patients with chronic HCV infection received peginterferon alpha-2a/ribavirin (SOC) for 48 weeks. Patients were randomised to 12 weeks amantadine therapy (n=12) or no additional treatment (n=7). FACS analysis of CD81 expression on CD4(+), CD8(+), CD19(+), and CD56(+) cells was performed at baseline, week (TW) 4, TW12, and TW24 of antiviral therapy.Results: A significant decline of CD81 expression was observed on CD4(+), CD8(+), and CD56(+) cells (p=0.011, p<0.001, p=0.015, respectively) but not on CD19(+) cells (p>0.2). CD81 expression on CD4(+), CD8(+), CD19(+), and CD56(+) cells was not different between patients treated with SOC plus amantadine and patients treated with SOC alone.Conclusion: The current study confirms that CD81 expression is down regulated by SOC on CD4(+), CD8(+) and CD56(+) cells. Amantadine treatment was not associated with CD81 expression. Interaction between amantadine and CD81 is unlikely to be involved in potential antiviral activity of amantadine in chronic HCV infection.

Reactivation of Crohn's disease after pandemic aH1N1 and seasonal flu vaccinations - Corrected Proof

Andrea Lisotti, Giulia Roda, Stefano Brillanti, Enrico Roda — 2010-04-26

We report a case of a prompt reactivation of a quiescent Crohn's disease with pain, fever and abdominal abscess occurred after seasonal and pandemic flu vaccinations. Based on the clinical history and the timing of the events, we could relate the relapse of CD to the double vaccinations.

In vivo characterisation of superficial colorectal neoplastic lesions with high-resolution probe-based confocal laser endomicroscopy in combination with video-mosaicing: A feasibility study to enhance routine endoscopy - Corrected Proof

2010-04-22

Abstract: Background: Recent technological advances in miniaturisation have allowed for a confocal scanning microscope to be integrated into trans-endoscopic probes enabling endoscopists to collect in vivo virtual biopsies of the gastrointestinal mucosa during endoscopy.Aims: The aim of the present study was to assess prospectively the clinical applicability and predictive power of a probe-based confocal laser endomicroscopy for the in vivo diagnosis of colorectal neoplasia.Methods: Patients with evidence of colorectal superficial neoplasia at routine endoscopy, were included prospectively in this study. Lesions were identified using white-light endoscopy followed by pCLE imaging recorded by a Coloflex UHD-type probe. The images were interpreted as either neoplastic or not according to vascular and cellular changes. pCLE readings were then compared with histopathological results from endoscopically resected lesions and/or targeted biopsy specimens.Results: A total of 32 lesions were identified in 20 consecutive patients. Histopathology diagnosis was of adenomas in 19 cases, hyperplastic polyps in 11 cases and adenocarcinoma in 2 cases. For the detection of neoplastic tissue pCLE had a sensitivity of 100%, a specificity of 84.6%, an accuracy of 92.3, a PPV of 90.5% and a NPV of 100%.Conclusions: pCLE permits high-quality imaging, enabling prediction of intraepithelial neoplasia with a high level of accuracy.

Digestive and Liver Disease - Articles in Press

Health-related quality of life is impaired in active collagenous colitis - Corrected Proof

Transjugular intrahepatic portosystemic shunt with expanded-polytetrafuoroethylene-covered stents in non-cirrhotic patients with portal cavernoma - Corrected Proof

Primary leiomyosarcoma with multiple nodules arising from the greater omentum - Corrected Proof

The patient's expectation during H2 breath testing: Don’t underestimate the reader's expectation - Corrected Proof

Expression of Sonic hedgehog (SHH) and CDX2 in the columnar epithelium of the lower oesophagus - Corrected Proof

Referrals for bowel ultrasound in clinical practice: A survey in 12 nationwide centres in Italy - Corrected Proof

Safe use of ursodeoxycholic acid in a breast-feeding patient with primary biliary cirrhosis - Corrected Proof

The CCL21/CCR7 pathway plays a key role in human colon cancer metastasis through regulation of matrix metalloproteinase-9 - Corrected Proof

Current topics in autoimmune hepatitis - Corrected Proof

Diagnostic value and clinical utility of contrast enhanced ultrasound in intestinal diseases - Corrected Proof

Five year time course of celiac disease serology during gluten free diet: results of a community based “CD-Watch” program - Corrected Proof

Mucinous cystadenoma of the peritoneum: A rare cause of ascites - Corrected Proof

Cholangiocarcinoma in Italy: A national survey on clinical characteristics, diagnostic modalities and treatment. Results from the “Cholangiocarcinoma” committee of the Italian Association for the Study of Liver disease - Corrected Proof

Relationship between portal chronic inflammation and disease severity in paediatric non-alcoholic fatty liver disease - Corrected Proof

Cigarette smoking and appendectomy: Effect on clinical course of diverticulosis - Corrected Proof

The impact of endoscopy and specialist care on 30-day mortality among patients with acute non-variceal upper gastrointestinal hemorrhage: An Italian population-based study - Corrected Proof

Lamivudine-resistance mutations can be selected even at very low levels of hepatitis B viraemia - Corrected Proof

Efficacy and safety of endoscopic balloon dilation of symptomatic intestinal Crohn's disease strictures - Corrected Proof

Forecasting the morbidity and mortality associated with prevalent cases of pre-cirrhotic chronic hepatitis C in the United States - Corrected Proof

The management of patients with new onset of upper gastro-intestinal symptoms in primary care - Corrected Proof

Therapeutic pancreatic endoscopy - Corrected Proof

Searching for wheat plants with low toxicity in celiac disease: Between direct toxicity and immunologic activation - Corrected Proof

HCV-positive status and hepatitis flares in patients with B-cell non-Hodgkin's lymphoma treated with rituximab-containing regimens - Corrected Proof

Adiponectin isoforms, insulin resistance and liver histology in nonalcoholic fatty liver disease - Corrected Proof

Feline oesophagus: An unusual cause of dysphagia - Corrected Proof

HLA-DRB1*03 and DRB1*04 are associated with atrophic gastritis in an Italian population - Corrected Proof

Molecular mechanisms underlying human adipose tissue-derived stromal cells differentiation into a hepatocyte-like phenotype - Corrected Proof

Familial pancreatic cancer in Italy. Risk assessment, screening programs and clinical approach: A position paper from the Italian Registry - Corrected Proof

The specialty of gastroenterology: Between a past of excellence and a somewhat uncertain future - Corrected Proof

Ectopic pancreas at the jejunum - Corrected Proof

Biliary Variant in a Potential Liver Donor - Corrected Proof

Long-term home parenteral nutrition in children with chronic intestinal failure: A 15-year experience at a single Italian centre - Corrected Proof

The origin of non-H. pylori-related positive Giemsa staining in human gastric biopsy specimens: A prospective study - Corrected Proof

Inflammatory bowel disease-patients are insufficiently educated about the basic characteristics of their disease and the associated risk of colorectal cancer - Corrected Proof

Relationship between white blood cell count and nonalcoholic fatty liver disease - Corrected Proof

Oesophagogastroduodenoscopy in patients with cirrhosis: Extending the range of detection beyond portal hypertension - Corrected Proof

Novel narrow-band imaging magnifying endoscopic classification for early gastric cancer - Corrected Proof

Risk factors for serum alanine aminotransferase elevation: A cross-sectional study of healthy adult males in Tokyo, Japan - Corrected Proof

Music for colonoscopy: A single-blind randomized controlled trial - Corrected Proof

The proton pump inhibitor test for gastroesophageal reflux disease: Optimal cut-off value and duration - Corrected Proof

Altered expression of innate immunity genes in different intestinal sites of children with ulcerative colitis - Corrected Proof

Low prevalence of idiopathic peptic ulcer disease: An Italian endoscopic survey - Corrected Proof

Current practice of hepatitis C treatment in Southern Italy - Corrected Proof

Critical flicker frequency fails to disclose brain dysfunction in patients with primary biliary cirrhosis - Corrected Proof

Esophageal motility and symptoms in restricting and binge-eating/purging anorexia - Corrected Proof

Identification of substance use and dependence among patients with viral hepatitis - Corrected Proof

Cost analysis of recall strategies for non-invasive diagnosis of small hepatocellular carcinoma - Corrected Proof

Influence of amantadine on CD81 expression on lymphocytes in chronic hepatitis C - Corrected Proof

Reactivation of Crohn's disease after pandemic aH1N1 and seasonal flu vaccinations - Corrected Proof

In vivo characterisation of superficial colorectal neoplastic lesions with high-resolution probe-based confocal laser endomicroscopy in combination with video-mosaicing: A feasibility study to enhance routine endoscopy - Corrected Proof

HLA-DRB103 and DRB104 are associated with atrophic gastritis in an Italian population - Corrected Proof