Digestive and Liver Disease - Articles in Press

Porcelain gallbladder and thalassaemia intermedia: Association or coincidence? - Corrected Proof

Vipin Gupta, Chalapathi Rao, Surinder S. Rana, Deepak K. Bhasin — 2012-05-18

A 55-year-old woman was referred to our centre for the management of non-healing ulcer of the left leg. She also reported recent onset of exertional breathlessness. Clinical examination revealed chronic venous ulcer over the left leg, pallor, features of congestive cardiac failure and hepatosplenomegaly. Haematological examination revealed microcytic anaemia with a haemoglobin level of 5.3g/dL. Bone marrow examination revealed erythroid hyperplasia and serum ferritin was markedly elevated (4739μg/L; normal: 4–200μg/L). Haemoglobin electrophoresis revealed elevated foetal haemoglobin (HbF: 27.90%; normal: <1%) with a normal level of HbA2 suggesting thalassaemia intermedia. Abdominal radiography showed calcification in the right upper quadrant (). Abdominal ultrasound and contrast enhanced computed tomography showed cholelithiasias with porcelain gallbladder (). The patient was treated with transfusions of packed red blood cells, intravenous antibiotics, and daily dressing of the ulcer. Following this treatment she improved and thereafter has been referred to haematology and general surgery; elective cholecystectomy is scheduled.

Genetic predisposition and increasing dietary fructose exposure: The perfect storm for fatty liver disease in Hispanics in the U.S. - Corrected Proof

Michael I. Goran, Emily E. Ventura — 2012-05-17

As the prevalence of overall obesity has increased in much of the developed and developing world, non-alcoholic fatty liver disease (NAFLD) is of increasing concern. A study of autopsy samples found that 38% of obese children had NAFLD , showing that NAFLD is a critical issue for obese children as well as for adults. NAFLD may lead to non-alcoholic steatohepatitis, cirrhosis, and eventually hepatocarcinoma, and is also associated with the development of type 2 diabetes.

No higher risk for colorectal cancer in atrophic gastritis-related hypergastrinemia - Corrected Proof

2012-05-17

Abstract: Background: Atrophic gastritis of the corporal mucosa is a frequent cause of hypergastrinemia. Hypergastrinemia is implicated in colorectal cancer development.Aim: To assess whether hypergastrinemic atrophic gastritis is associated with a higher risk of neoplastic colorectal lesions.Methods: Among 441 hypergastrinemic atrophic gastritis patients, 160 who were aged >40 and underwent colonoscopy for anaemia, diarrhoea or colorectal cancer-screening were retrospectively selected. Each patient was age- and gender-matched with a normogastrinemic control with healthy stomach. Controls had colonoscopy, gastroscopy with biopsies and gastrin assessment.Results: 160 hypergastrinemic atrophic gastritis patients and 160 controls were included. 28 atrophic gastritis patients and 36 controls had neoplastic colorectal lesions (p=0.33). Patients and controls did not differ for frequency of colorectal adenomas (10.6% vs. 13.1%, p=0.60) or cancer (6.9% vs. 9.4%, p=0.54). Hypergastrinemic atrophic gastritis was not associated with a higher probability of developing colorectal cancer (OR 1.03, 95% CI 0.34–3.16). Age >50 years (OR 3.86) but not hypergastrinemia (OR 0.61) was associated with colorectal cancer.Conclusions: Hypergastrinemic atrophic gastritis is not associated with higher risk for colorectal cancer. Atrophic gastritis-related hypergastrinemia is not associated with an increased risk of neoplastic colorectal lesions. Closer surveillance of colonic neoplasia in atrophic gastritis patients seems not appropriate.

Hepatitis E infection is an under recognized cause of acute decompensation in patients with chronic liver disease - Corrected Proof

2012-05-16

Abstract: Background/aims: We aimed to assess characteristics of patients with a positive hepatitis E virus serology with emphasis on acute on chronic liver disease.Methods: This was a retrospective audit performed at a large teaching hospital.Results: Of the 164 patients tested, 15(9.1%) had a positive serology (hepatitis E virus IgG and or IgM) of whom two also had a positive hepatitis E virus RNA. Six (42.8%) had underlying chronic liver disease and presented with deteriorating liver tests±decompensation. In one patient (16%) acute hepatitis E virus infection was the aetiology for the decompensation and in three the positive hepatitis E virus IgG was a reflection of prior subclinical infection. However, in two of the six patients with unexplained decompensation there was delay (150–270 days) in obtaining a hepatitis E virus serology, which may have resulted in a negative hepatitis E virus IgM at time of testing.Conclusions: 9.1% of patients presenting with abnormal liver tests at a large teaching hospital in south east England have a positive hepatitis E virus serology of whom 42.8% have acute on chronic liver disease. In 16% hepatitis E virus infection is the aetiology for the acute decompensation. This may be an under representation as in >30% of patients with unexplained decompensation there is considerable delay in requesting a hepatitis E virus serology.

Quality in colonoscopy reporting: An assessment of compliance and performance improvement - Corrected Proof

2012-05-14

Abstract: Background: An ASGE-ACG task force developed quality indicators (QI) for documenting quality endoscopic procedures. Acceptable compliance rates have not been determined.Aims: To determine our degree of compliance to the intra-procedure colonoscopy QI prior to intervention, design an educational intervention to improve those with low compliance, and to compare the degree of compliance after intervention.Methods: 300 patients undergoing colonoscopy in the pre-intervention time period followed by 300 patients after the educational intervention were reviewed. Endoscopists were instructed on the required QI and provided with their individual baseline compliance results. Dictated endoscopy reports were reviewed for compliance.Results: Four QIs; documentation of bowel preparation adequacy, appendiceal orifice, photographs of cecum, and polyp shape, had low pre-intervention achievement (64%, 53%, 20%, and 15% respectively) and significant change was observed (83%, 68%, 63%, and 54% respectively, all p<0.001). Four QIs; documentation of ileocecal valve, polyp size description, polyp location description, and follow up recommendations, had high levels of achievement prior to intervention (92%, 98%, 97% and 81% respectively) and no significant change was observed (all p≥0.16).Conclusion: This study provides benchmarks for ASGE/QIs in colonoscopy cases in a large group practice model. It demonstrates that a quality improvement intervention can result in improved compliance.

Safety and effectiveness of sorafenib in patients with hepatocellular carcinoma in clinical practice - Corrected Proof

2012-05-14

Abstract: Background: Sorafenib is currently the only approved systemic treatment for hepatocellular carcinoma.Aim: to evaluate safety and effectiveness of sorafenib in the field of practice.Methods: We report a single-centre experience on 116 advanced hepatocellular carcinoma patients treated with sorafenib between February 2008 and March 2011. Every 4 weeks, adverse events were graded using Common Toxicity Criteria version 3.0, and every 3 months tumour response was assessed according to modified Response Evaluation Criteria in Solid Tumours for hepatocellular carcinoma.Results: Cirrhosis was present in 95.7% of patients (83.6% Child-Pugh A class), hepatitis C was the main etiological factor. Median therapy duration was 3 months and median daily dose was 642mg. Median time-to-radiological progression in the per-protocol population was 12 months and median overall survival in the intention-to-treat population was 13 months. 91.4% of patients experienced mild adverse events (grade 1 or 2), the most frequent were gastrointestinal and dermatological. Jaundice and bleeding were the main causes of definitive drug discontinuation. 3-month overall disease control rate was 70.6%: stable disease in 37.2%, partial response in 30.8%, and complete response in 2.6% patients. The 3-month radiological response correlated with overall survival.Conclusions: In daily clinical practice, sorafenib confirmed its safety and efficacy in hepatocellular carcinoma patients.

Comment to “Prevalence and incidence of microscopic colitis in patients with diarrhoea of unknown aetiology in a region in central Spain” - Corrected Proof

Angelo Zullo, Cesare Hassan, Vincenzo Bruzzese — 2012-05-14

We read the interesting study by Guagnozzi et al. on the prevalence of microscopic colitis in patients with diarrhoea of unknown aetiology in Spain, which found that microscopic colitis was finally diagnosed in 32 out of 234 patients with normal appearing mucosa at colonoscopy . A high (21.9%) prevalence of autoimmune diseases was observed in these patients, with coeliac disease, thyroiditis, and psoriasis being the most common. However, the comparison of autoimmune disease prevalence between the 32 patients with and the 202 patients without microscopic colitis was not performed, leaving the information incomplete. In addition, the potential role of either proton pump inhibitor (PPI) therapy or nonsteroidal anti-inflammatory drugs (NSAIDs) was not evaluated in these patients. Indeed, this aspect was evaluated only in patient subgroups with either irritable bowel syndrome (IBS) (71 patients) or in IBS-like microscopic colitis (9 patients), showing a significant association with NSAIDs, but not with PPI therapy. However, the role of PPIs – particularly lansoprazole – and of NSAIDs – particularly ticlopidine – as well as other drugs has been widely described in the pathogenesis of microscopic colitis . By considering that health-related quality of life is significantly impaired in patients with microscopic colitis , to further demonstrate an association with these drugs which are widely used in clinical practice would be clinically relevant.

Comment to “Socioeconomic position and education in patients with coeliac disease” - Corrected Proof

Carl Johan Wingren, Juan Merlo — 2012-05-11

We have, with great interest, read the article by Olen et al. recently published ahead of print in the Journal. The authors analyze the association between socioeconomic position (SEP) and coeliac disease (CD). However, we are concerned because the authors seem not to be aware of a publication from our research group on exactly the same topic and using similar methods but published five months earlier. We also presented the results of our study as a poster presentation at the 3rd Congress of the European Academy of Paediatric Societies held in Copenhagen, Denmark during October 2010 .

CARD15 and Toll-like receptor 4 mutations in Italian patients with inflammatory bowel disease - Corrected Proof

2012-05-09

Inflammatory bowel diseases (IBD) are thought to be strictly related to a deregulated immune response to intestinal microflora, involving CARD15 and Toll-like receptor (TLR) molecules . Accordingly, mutation of the CARD15 gene (SNP13, SNP8 and SNP12) and, recently, polymorphism of the TLR4, have been associated with increased incidence and/or specific features of Crohn's disease . Nonetheless, unsolved biases in collecting clinical data still need to be taken into account, and combined genetic alterations have been poorly investigated.

Selecting families eligible for pancreatic cancer screening: Another brick in the wall for the early detection of pancreatic ductal adenocarcinoma and its precursors - Corrected Proof

Raffaele Pezzilli, Antonio Maria Morselli-Labate — 2012-05-07

There are few candidates for curative surgery in patients with pancreatic ductal adenocarcinoma (PDA) since, during the early phases of the disease, the symptoms are scarce or non-specific, and when the symptoms become manifest, prognosis is poor. The serum marker CA 19-9 has been investigated for screening and early diagnosis of PDA but has also failed: the main reason for which biochemical screening fails in PDA is that production of CA 19-9 becomes readily detectable only in advanced stages, after the onset of clinical symptoms; therefore, it does not provide the opportunity of early diagnosis and cure . Thus, new screening strategies are clearly needed. A screening test must identify the disease at an early stage in order to be effective; therefore, it is necessary to define the concept of “early” PDA. A quantitative analysis of the timing of the genetic evolution of PDA indicates that there is at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell . Thus, at least five additional years are required for the acquisition of metastatic ability, and patients die on an average of two years thereafter . This conclusion indicates that the concept of early diagnosis of PDA should be moved back several years compared to current practice, and these findings further indicate the need for an effective screening programme.

Sustained liver regeneration after portal vein embolization – A human molecular pilot study - Corrected Proof

2012-05-07

Abstract: Background: Portal vein embolization is a treatment option to achieve a sufficient future remnant liver volume for patients with central liver tumours requiring an extended resection with an extensive parenchymal loss. However, molecular mechanisms of this intervention are up to now poorly understood. The objective of this prospective pilot study was the characterization of molecular events leading to late hypertrophy of the non-embolized liver tissue in the human liver.Methods: Liver tissue of ten patients was collected before and intraoperatively more than one month after embolization. Investigation of molecular features was performed by pangenomic chips, polymerase chain reaction, immunostaining of proliferation marker Ki-67 and immunofluorescence measurements.Results: Significantly elevated genes hint towards angiogenesis and signalling by insulin-like growth factor and associated binding proteins. Increased transcript levels of activator protein 1 complex members like c-jun were reflecting potential molecular events of liver growth after embolization. Immunofluorescence data confirmed a predominant upregulation of β-catenin and c-jun (p<0.1) supported by Ki-67 (p<0.05) in the non-embolized liver. In silico analysis of transcriptomic dysplasia and hepatocellular carcinoma data showed divergent signatures compared to embolization.Conclusions: Our findings indicate a sustained regeneration after portal vein embolization reflected in hyperplasia and angiogenesis in the human liver and provide novel molecular mechanisms of interlobe crosstalk.

A new case of immunoproliferative small intestinal disease associated with Campylobacter jejuni - Corrected Proof

Bruno Mesnard, Bénédicte De Vroey, Vincent Maunoury, Marc Lecuit — 2012-05-01

A 41-year-old man from Algeria presented with a 6-month history of diarrhoea, cachexia, metabolic acidosis, hypokaliemia and hypoalbuminemia, consistent with secretory diarrhoea and exudative enteropathy. C-reactive protein level was normal and stool cultures unremarkable. Protein electrophoresis showed increased IgA, decreased IgG and IgM levels. Immunoelectrophoresis showed α-heavy chain precipitation without associated light chain. Upper endoscopy revealed mucosal oedema of the duodenum with whitish granulations mimicking rice grains spread out between thickened folds suggestive of lymphangectasias, shortened and widened villi and crypt hypertrophy, with an extension to the whole jejunum, confirmed, to our knowledge for the first time, at wireless capsule endoscopy (WCE) (). Pathologic examination of duodenal biopsies showed villous atrophy and lamina propria infiltration with plasmacytic cells; immunohistochemical staining for immunoglobulin light chain was negative but immunofluorescence directed to α-heavy chain was strongly positive. The diagnosis of immunoproliferative small intestinal disease (IPSID) was made . Doxycycline 200mg daily was initiated for 6 months, following past therapeutic experience, with resolution of symptoms within a week, normalization of immunoelectrophoresis and regression of endoscopic lesions at 6 months. A Campylobacter jejuni-specific PCR assay was performed , positive in initial duodenal biopsies, and negative in biopsies obtained after antimicrobial therapy. In contrast, Helicobacter pylori-specific PCR, performed both on gastric and duodenal biopsies at diagnosis and after antimicrobial therapy, was negative.

Nutritional therapy versus 6-mercaptopurine as maintenance therapy in patients with Crohn's disease - Corrected Proof

2012-04-30

Abstract: Background: 6-Mercaptopurine is often used as maintenance therapy in patients with Crohn's disease. However, toxicities like myelosuppression limit its clinical benefit.Aims: To evaluate the efficacy of elemental diet versus 6-mercaptopurine as maintenance therapy in Crohn's disease.Methods: Ninety-five eligible patients with Crohn's disease activity index ≤150 were randomly assigned to: 6-mercaptopurine (0.5–1.5mg/kg/day, n=30); Elental as an elemental diet (≥900kcal/day, n=32); none (control, n=33). In the three groups, patients were and remained on 5-aminosalicylic acid (2250–3000mg/day). Patients were observed for 2 years and the rate of relapse (Crohn's disease activity index ≥200) was monitored.Results: At 24 months, the fractions of patients who had maintained remission were 60%, 46.9% and 27.2% for 6-mercaptopurine, Elental and the control groups, respectively. Log-rank test showed better efficacy for 6-mercaptopurine (P=0.0041) and Elental (P=0.0348) versus control. No significant difference was found between 6-mercaptopurine and Elental. Further, in the 6-mercaptopurine group, 2 patients experienced liver injury and one developed alopecia.Conclusions: This 24 months comparison study showed that Elental as maintenance therapy in Crohn's disease patients was as effective as 6-mercaptopurine. Elental should be useful for long-term maintenance therapy in Crohn's disease. This is the first comparison study evaluating nutritional therapy versus 6-mercaptopurine.

Autoimmune pancreatitis and non-necrotizing acute pancreatitis: Computed tomography pattern - Corrected Proof

2012-04-30

Abstract: Objectives: To retrospectively differentiate diffuse autoimmune pancreatitis from non-necrotizing acute pancreatitis at clinical onset with multi detector row computed tomography.Methods: 36 Patients suffering from diffuse autoimmune pancreatitis (14) or non-necrotizing acute pancreatitis (22) were enrolled. Qualitative analysis included stranding, retroperitoneal fluid film, capsule-like rim enhancement and pleural effusion. In quantitative analysis pancreatic density was measured in all phases. The vascularization behaviour was assessed using the relative enhancement rate across all phases.Results: Pancreatic density resulted lower in non-necrotizing acute pancreatitis compared to diffuse autoimmune pancreatitis patients in pre-contrast phase and higher in pancreatic phase. Relative enhancement rate evaluation confirmed different vascularization behaviours of the two diseases. Only non-necrotizing acute pancreatitis Patients presented peripancreatic stranding and fluid in the retromesenteric interfascial plane.Conclusions: Multi detector row computed tomography is a useful technique for differentiating diffuse autoimmune pancreatitis from non-necrotizing acute pancreatitis at clinical onset. Peripancreatic stranding and retroperitoneal fluid film, characteristic of non-necrotizing acute pancreatitis, and late-phase peripheral rim enhancement, characteristic of diffuse autoimmune pancreatitis, provide qualitative clues to the differentiation. A quantitative study of contrast enhancement patterns, considering the relative enhancement rate, can assist in the differential diagnoses of two diseases.

Positivity rates and performances of immunochemical faecal occult blood tests at different cut-off levels within a colorectal cancer screening programme - Corrected Proof

2012-04-30

Abstract: Background: Immunochemical faecal occult blood tests have greater sensitivity for colorectal cancer screening than guaiac-based tests; however the number of positive tests required is still under discussion.Methods: A direct comparison of Hemoccult II with two immunochemical quantitative tests (OC-Sensor and FOB-Gold) using a 2-sample strategy was performed in over 30,000 patients undergoing colorectal cancer screening in France.Results: Positivity ratio between immunochemical tests and Hemoccult II varied between 2.2 (OC-Sensor) and 2.4 (FOB-Gold) for the lowest cut-off value and 1.5–1.4 for the highest cut-off value. The positive predictive value for colorectal cancer was similar for immunochemical tests and Hemoccult II, and significantly higher for immunochemical tests for advanced adenomas. The detection rate of both colorectal cancer and advanced adenomas was higher with immunochemical tests than with Hemoccult II. With the 2-sample strategy and the lowest cut-off value the detection rate of colorectal cancer almost doubled and for advanced adenomas quadrupled.Conclusion: For colorectal cancer screening with immunochemical faecal occult blood tests, an acceptable strategy would be 2-day sampling with at least one positive test at a cut-off between 150 and 200ng/mL (OC-Sensor) and 176 and 234ng/mL (FOB-Gold). Data on the ease of test interpretation and cost-effectiveness now necessary to make definitive choices.

Complications of percutaneous endoscopic gastrostomy in children: Results of an Italian multicenter observational study - Corrected Proof

2012-04-27

Abstract: Background: Percutaneous endoscopic gastrostomy is the preferred way to achieve an artificial feeding route for patients requiring long-term enteral nutrition. Although the procedure is well-standardized, it carries early and late complications.Aim: To establish the mortality and morbidity of this technique in a large cohort of children.Methods: A multi-centre prospective clinical data collection from children undergoing percutaneous endoscopic gastrostomy tube implantation has been conducted from January 2004 to December 2007. Previous abdominal surgery was the only exclusion criterion. Follow-up visits were carried out at 1, 3, 6, 12, and 24months after the procedure.Results: 239 children (males, 55.2%; mean age 6.05±6.1years) were enrolled from nine tertiary Italian centres. Major complications occurred in 8 patients (3.3%). The cumulative incidence of complications was 47.7% at 24months. The presence of thoraco-abdominal deformity was an independent predictor of complications at 12months. No risk factors were identified in association to complications during the 1st tube replacement.Conclusion: In children undergoing percutaneous endoscopic gastrostomy placement minor complications are common, while severe morbidities are rare. Accurate follow up is essential to recognize every complication, in particular when risk factors such as thoraco-abdominal deformity exist.

Hepatitis C in the elderly: A multicentre cross-sectional study by the Italian Association for the Study of the Liver - Corrected Proof

2012-04-26

Abstract: Background: The prevalence of hepatitis C virus infection increases with advancing age, but elderly hepatitis C virus patients remain an understudied population.Aim: To define the virological, epidemiological and clinical profiles of Italian outpatients aged 65 years and over infected by hepatitis C virus.Methods: We evaluated 1544 anti-hepatitis C virus positive patients aged ≥65 years referred to 34 Italian outpatient specialty clinics over a two-year period.Results: The study population included 1134 (73%) early elderly (65–74 years) and 410 (27%) late elderly patients (≥75 years). Late elderly subjects were less likely to have their virus genotyped, their viral load assessed or a histological evaluation of liver disease. Overall, 30% of patients had advanced liver disease whose prevalence increased with increasing age. In both age groups, about 40% of patients had normal transaminase levels. Excluding patients with past infection, 51% had not received any antiviral treatment and only 25% were treated after the age of 65. Late elderly patients, women and patients with advanced liver diseases had been less frequently treated. The main reason for exclusion from treatment was age followed by the presence of comorbid conditions.Conclusions: Elderly hepatitis C virus patients referred to Italian specialty clinics have advanced and underestimated liver disease. Nevertheless, they are progressively understudied in parallel with increasing age.

Safety of methotrexate for inflammatory bowel disease - Corrected Proof

Ricardo Moreno-Otero, Luisa García-Buey, María Trapero-Marugán — 2012-04-26

Saibeni et al. demonstrate the effectiveness of methotrexate (MTX) in IBD patients; nevertheless, its tolerability raises critical concerns, as side effects developed in 49 patients (43.7%), and MTX was discontinued in 38 (33.9%). MTX-induced hepatotoxicity can occur with long-term use, occasionally presenting as acute transaminase flares; we observed a patient with this symptom in whom serological and histological characteristics of autoimmune hepatitis (AIH) appeared, which resolved with corticosteroids .

Management of cytomegalovirus infection in inflammatory bowel diseases - Corrected Proof

Sylvie Pillet, Bruno Pozzetto, Camille Jarlot, Stéphane Paul, Xavier Roblin — 2012-04-26

Abstract: Cytomegalovirus is a deoxyribonucleic acid virus that infects a large part of the human population; after primary infection, it develops a latent state and can be reactivated, notably after a decrease in host immune defences. In patients with inflammatory bowel diseases, cytomegalovirus is frequently involved, either as an agent of colitis or through local asymptomatic reactivation. Due to the immune context of inflammatory bowel diseases and to the immunosuppressive therapies that are used to treat them, cytomegalovirus entertains complex relationships with these diseases. Whereas Crohn's disease seems little impacted by cytomegalovirus, this agent interferes strongly with the natural progression of ulcerative colitis. While immune treatments have a clear influence on the occurrence of cytomegalovirus colitis in ulcerative colitis (favourable for steroids and cyclosporine and rather inhibitory for infliximab), the role of cytomegalovirus infection on ulcerative colitis is more debated with roles ranging from innocent bystander to key pathogen suggested. There is however growing evidence for a participation of intestinal cytomegalovirus infection in the resistance of ulcerative colitis to steroids and the investigation of cytomegalovirus infection in intestinal biopsies by immunohistochemistry or quantitative polymerase chain reaction assay is strongly recommended. In several studies, treatment of cytomegalovirus infection by ganciclovir was shown to restore the response to immunomodulatory therapies and even to prevent the need for colectomy. All of these recently acquired data need to be validated by randomised clinical trials conducted on a large panel of ulcerative colitis patients.

Advanced gallbladder cancer misdiagnosis - Corrected Proof

Salvatore Guarino, Deborah Maria Giusti, Salvatore Sorrenti, Enrico De Antoni — 2012-04-25

An 80 year-old male patient, with no major co-morbidities, was admitted to our department via the emergency room with a few hours’ history of right upper quadrant pain and moderate grade fever. On physical examination Murphy's sign was positive and a mild jaundice was present. Blood tests were normal apart from mild hyperbilirubinemia. Upon admission ultrasonography scan (USS) revealed two large stones within a thick-walled and enlarged gallbladder. A heterogeneous hypoechoic lesion was also seen within the fundus of the gallbladder, invading the surrounding hepatic lobes. Intravenous antibiotics were started.

A pill for cholesterol and a capsule for bleeding - Corrected Proof

Brendan P. Halloran, Fred J. Stam, Stijn.J.B. Van Weyenberg — 2012-04-23

A 77-year old male patient was admitted with melena and fatigue. Past medical history included hypertension-related chronic renal failure and sick sinus syndrome with pacemaker insertion. Medication use included simvastatin and acenocoumarol. At admittance, haemoglobin was 3.1mmol/L and INR was >7.5. Conventional upper and lower endoscopy did not reveal the bleeding source. Therefore video capsule endoscopy was performed to evaluate the small intestine.

Colorectal cancer screening: Why immunochemical faecal occult blood test performs as well with either one or two samples - Corrected Proof

2012-04-23

Abstract: Background: Immunochemical faecal occult blood tests perform as well with either one or two samples, and better than guaiac tests with 6 samples.Aims: Clarifying relationship between tests’ performance, bleeding pattern and observation level.Methods: The data of 32,225 average-risk subjects who performed both Hemoccult II (guaiac) and Magstream (immunochemical) tests were re-analysed by varying the cutoff and number of samples of Magstream.Results: The identical performances obtained using one or two samples of Magstream (lower cutoff for one sample) at the population level were explained by opposite patterns of bleeding according to the presence of advanced neoplasias. They translated into discrepancy at the individual level: for example a 60% increase in sensitivity and 20% in specificity observed with one (39ng Hb/ml cutoff) or two samples (63ng Hb/ml cutoff) Magstream compared with Hemoccult II meant that 28.5% of the subjects testing positive with one sample (18.0% in subjects with advanced neoplasias) would have been considered negative by using two samples of Magstream at a higher cutoff (and reciprocal).Conclusion: The identical performance of immunochemical tests using one or two samples (different cutoff), explained by opposite pattern of bleeding according to advanced neoplasias is true only at the population level, the appropriate level for mass screening.

Competency assessment: It's time to expect more from our simulator - Corrected Proof

Robert E. Sedlack — 2012-04-23

Computer colonoscopy simulators were introduced a little more than a decade ago with a great amount of hype and hope as to what they could accomplish. As a result of research efforts, it is now generally accepted that these simulators do indeed have an impact as a training tool, although limited to the initial stages of colonoscopy training. Educators however, have had far less luck in demonstrating any usefulness of these commercially available simulators as assessment tools.

Evaluation of hands-on training in colonoscopy: Is a computer-based simulator useful? - Corrected Proof

Alessandra Elvevi, Paolo Cantù, Giovanni Maconi, Dario Conte, Roberto Penagini — 2012-04-20

Abstract: Background and aims: The advantages of using a computer-based simulator during colonoscopy training are debated. We aimed to explore its usefulness in objectively measuring trainees’ competence in colonoscopy.Methods: Twelve colonoscopy trainees (fully trained in upper GI endoscopy) were evaluated using a computer-based simulator (GI-Mentor, Symbionix) before and during hands-on training (i.e. after 60 colonoscopies); the controls were 15 experts (>90% of caecal intubation). Both trainees and experts performed two “screening” simulations (easy and difficult) in a randomised order, and the time to reach the caecum and withdrawal time was assessed.Results: The percentage of caecal intubation progressively increased during hands-on training. All of the trainees intubated the caecum during the easy and difficult simulations, both before and during hands-on training. The median time (interquartile range) to reach the caecum upon easy simulation was the only variable influenced by hands-on training: 2.7min (2.1–3.2) before and 1.9min (1.6–2) during training (p<0.01). Withdrawal time was ≥6min in the case of five trainees before training, and three during hands-on training. Computer-based simulator performance did not correlate with hands-on training performance.Conclusions: The computer-based simulator was not found to be useful in evaluating competence during hands-on training in colonoscopy.

Cholangioscopy in a patient with Roux-en-Y limb via a gastric access loop - Corrected Proof

Georgios Mavrogenis, Yves Hoebeke, Philippe Warzée — 2012-04-16

A 60-year-old patient with history of minor thalassemia was addressed for recurrent episodes of cholangitis. He had undergone a pancreaticojejunostomy with Roux-en-Y hepaticojejunostomy (Puestow procedure) because of chronic pancreatitis 10 years earlier. Previous episodes of cholangitis had been managed endoscopically, once, through a transient jejunostomy and twice by single balloon enteroscopy (Fig. 1a). Given the frequent episodes of cholangitis and the continuous need of enteroscopy, we decided to create a gastro-jejunal anastomosis by surgical means , in order to gain a permanent access point to the biliary tree. In this way the length of the gastrointestinal tube that has to be traversed to access the common bile duct is short enough for a standard endoscope (Fig. 1b). Cholangioscopy was performed (Fig. 2a) and biliary stones were extracted (Fig. 2b). Other options of biliary access include percutaneous transhepatic cholangiography, which endeavours a low risk of biliary leakage, liver abscess and bleeding and single/double balloon enteroscopy (BE). This later has been proven safe and efficient, however its use depends on local availability and expertise. Gastrojejunostomy is a safe method of direct biliary access with a relative low risk of postoperative gastrojejunal stricture (3/11 patients in a recent study) . It could be addressed to patients with a long afferent limb, when repeated biliary access is needed or when BE is not available.

Lymphocytic duodenosis: Aetiology and long-term response to specific treatment - Corrected Proof

2012-04-12

Abstract: Background: The clinical significance of lymphocytic duodenosis remains unclear.Aim: To prospectively assess the aetiology of lymphocytic duodenosis and the patterns of clinical presentation.Methods: Ninety consecutive patients with lymphocytic duodenosis and clinical symptoms of the coeliac disease spectrum were prospectively included. All subjects underwent serological testing and HLA genotyping for coeliac disease, assessment of Helicobacter pylori infection, and parasite stool examination. Intake of non-steroidal anti-inflammatory drugs was also recorded. The final aetiology of lymphocytic duodenosis was evaluated on the basis of the long-term response to specific therapy.Results: More than one initial potential aetiology was observed in 44% of patients. The final diagnosis was gluten-sensitive enteropathy alone or associated with Helicobacter pylori infection in 43.3%, Helicobacter pylori infection (without gluten-sensitive enteropathy) in 24.4%, non-steroidal anti-inflammatory drugs intake in 5.5%, autoimmune disease in 3.3%, and parasitic infection in 2.2%. Among first degree relatives and patients with chronic diarrhoea, the most common final diagnosis was gluten-sensitive enteropathy. In contrast, in the group presenting with chronic dyspepsia the most common diagnosis was Helicobacter pylori infection (‘Diarrhoea’ vs ‘Dyspepsia’ groups, p=0.008).Conclusions: Lymphocytic duodenosis is often associated with more than one potential initial aetiology. Clinical presentation may be useful to decide the initial therapeutic approach with these patients.

Risk factors and outcome of acute severe lower gastrointestinal bleeding in Crohn's disease - Corrected Proof

2012-04-12

Abstract: Background: Acute severe lower gastrointestinal bleeding in Crohn's disease is uncommon, but is a diagnostic and therapeutic challenge. We aimed to identify risk factors for acute lower gastrointestinal bleeding in patients with Crohn's disease and assess the cumulative probability of rebleeding in relation to therapeutic modality.Methods: We retrospectively reviewed the medical records of 70 Crohn's patients (4.0%) with acute severe lower gastrointestinal bleeding and compared these with matched 140 Crohn's patients without bleeding.Results: The cumulative probability of bleeding after diagnosis of Crohn's disease was 1.7%, 3.6%, 6.5%, and 10.3% after 1, 5, 10, and 20 years respectively. At presentation, the median haemoglobin concentration was 8.4g/dL (range, 4.7–11.6g/dL). Use of azathioprine/6-mercaptopurine decreased the risk of lower gastrointestinal bleeding (OR: 0.525, 95% CI: 0.304–0.906, p=0.021). Bleeding recurred in 29 patients (41.4%) after a median time of 3.2 months (range, 15 days–94.7 months). One out of eleven patients treated with infliximab rebled. The cumulative probability of rebleeding tended to be lower in patients treated with infliximab than in those receiving other treatments (p=0.076).Conclusions: Azathioprine/6-mercaptopurine may reduce the risk of acute severe lower gastrointestinal bleeding. The rebleeding is common, but infliximab may decrease rebleeding.

Glaucoma and Helicobacter pylori: Eyes wide shut? - Corrected Proof

2012-04-12

Helicobacter pylori infection is worldwide spread disease with a definite morbidity and mortality . Besides different gastroduodenal diseases, this infection has been significantly associated with both idiopathic thrombocypenic purpora and idiopathic iron deficiency anaemia . Moreover, a possible pathogenetic role of H. pylori has been hypothesised also in different extra-digestive disorders, including glaucoma. This is a serious ocular disease characterised by a progressive optic neuropathy mainly due to a raised intraocular pressure (IOP) . Unfortunately, the causes of primary open-angle glaucoma (POAG) – the most common form of glaucoma – are still unclear. There are millions of people with glaucoma worldwide, and such a disease is the second most common cause of blindness . Therefore, any new finding which potentially unravels its aetiology is welcoming. In the last decade, H. pylori infection has been claimed as a factor causing POAG, and an interesting review focused on such a field has been recently published . Basically, the main conclusion was that, because of the coexistence of both positive and negative data on the correlation between the two diseases, further studies are needed . We agree that further investigations are needed, especially when considering that the available data come from studies with potential drawbacks. In detail, here we discuss data on: (1) infection prevalence; (2) pathogenetic mechanisms; and (3) clinical relevance.

Imidazolium salt attenuates thioacetamide-induced liver fibrosis in mice by modulating inflammation and oxidative stress - Corrected Proof

Nur-Afidah Mohamed Suhaimi, Lang Zhuo — 2012-04-09

Abstract: Background and aim: Oxidative stress contributes to liver fibrosis through the activation of hepatic stellate cells. In a cell-based screening study, a class of imidazolium salts demonstrates anti-fibrogenic properties. Little is known on imidazolium salt mechanistic effects. We investigated the anti-fibrogenic effect of one of the imidazolium salts, 1,3-bisbenzylimidazoliumbromide (DBZIM), in a chronic mouse model of liver fibrosis and evaluated the mechanism of this treatment.Methods: Liver fibrosis was induced in mice by oral feeding of thioacetamide for 16 weeks. DBZIM was administered weekly, starting on the first day or 12 weeks from the day of thioacetamide administration. Hepatic function, histology and oxidative stress were examined. Expression of key inflammatory molecules and the molecular mechanism of DBZIM were assessed in hepatic stellate cells.Results: DBZIM decreased the fibrogenic response in thioacetamide-mice as measured by collagen deposition and α-smooth muscle actin expression (P<0.01). DBZIM improved liver function and reduced both oxidative damage and inflammation (P<0.01). Most importantly, our findings report the discovery that astrocyte elevated gene-1, involved in tumour progression, was up-regulated in thioacetamide-mice and DBZIM modulated astrocyte elevated gene-1 and NF-κB expression.Conclusion: These findings indicate DBZIM is a potent therapeutic agent for the treatment of liver fibrosis.

Cognitive performance is impaired in coeliac patients on gluten free diet: A case–control study in patients older than 65 years of age - Corrected Proof

2012-04-09

Abstract: Introduction: Retrospective studies and case reports suggest an association between coeliac disease and impaired cognitive function.Aim: To evaluate functional and cognitive performances in coeliac disease vs. control patients older than 65 years.Method: Eighteen coeliac disease patients (75±4 years, group A) on gluten free diet since 5.5±3 years and 18 age-sex matched controls (76±4 years, group B) were studied using a battery of neuropsychological tests. Results of functional and cognitive tests are expressed as “row scores” and as “equivalent scores” by relating “raw scores” to reference rank categories.Results: Barthel Index of functional performance was similar in the 2 groups. “Raw score” was significantly lower in coeliac disease than controls for Mini Mental Test Examination (p=0.02), Trail Making Test (p=0.001), Semantic Fluency (p=0.03), Digit Symbol Test (p=0.007), Ideo-motor apraxia (p<0.001) and Bucco-facial apraxia (p<0.002). “Equivalent score” was also lower in coeliac disease than controls for Semantic memory (p<0.01) and for Ideo-motor apraxia (p=0.007).Conclusion: Cognitive performance is worse in elderly coeliac disease than control patients, despite prolonged gluten avoidance in coeliacs. Awareness on the increasing phenomenon of late-onset coeliac disease is important to minimize diagnostic delay and prolonged exposure to gluten that may adversely and irreversibly affect cognitive function.

Functional aspects of distal oesophageal spasm: The role of onset velocity and contraction amplitude on bolus transit - Corrected Proof

2012-04-05

Abstract: Background: Distal oesophageal spasm is a rare and under-investigated motility abnormality. Recent studies indicate effective bolus transit in varying percentages of distal oesophageal spasm patients.Aim: Explore functional aspects including contraction onset velocity and contraction amplitude cut-off values for simultaneous contractions to predict complete bolus transit.Methods: We re-examined data from 107 impedance-manometry recordings with a diagnosis of distal oesophageal spasm. Receiver operating characteristic analysis was conducted, regarding effects of onset velocity on bolus transit taking into account distal oesophageal amplitude and correcting for intra-individual repeated measures.Results: Mean area under the receiver operating characteristic curve for saline and viscous swallows were 0.84±0.05 and 0.84±0.04, respectively. Velocity criteria of >30cm/s when distal oesophageal amplitude>100mmHg and 8cm/s when distal oesophageal amplitude<100mmHg for saline and 32cm/s when distal oesophageal amplitude>100mmHg and >7cm/s when distal oesophageal amplitude<100mmHg for viscous had a sensitivity of 75% and specificity of 80% to identify complete bolus transit. Using these criteria, final diagnosis changed in 44.9% of patients. Abnormal bolus transit was observed in 50.9% of newly diagnosed distal oesophageal spasm patients versus 7.5% of patients classified as normal. Distal oesophageal spasm patients with distal oesophageal amplitude>100mmHg suffered twice as often from chest pain than those with distal oesophageal amplitude<100mmHg.Conclusion: The proposed velocity cut-offs for diagnosing distal oesophageal spasm improve the ability to identify patients with spasm and abnormal bolus transit.

Comment to “Unusual evolution of ciprofloxacin-induced hepatitis revealing a possible link with IgG4-associated autoimmune hepatitis” - Corrected Proof

Cumali Efe — 2012-04-05

Recently, Anty et al. reported a case of that developed IgG4-associated autoimmune hepatitis (AIH) after ciprofloxacin intake. This entity is very rare, and to date only a few cases have been reported. Firstly, the author attempts to investigate IgG4-associated autoimmune hepatitis in this patient whilst she had definitive AIH according to revised scoring system was questionable . As it is stated in the study, low serum IgG levels should not be a reason for further evaluation because in a recent study serum IgG levels were within the normal range in 31% of AIH patients. Secondly, it would have been an advantage to know duration of therapy in this patient as drug induced-AIH and drug induced liver injury with AIH features have been described in clinical practice . In this group of patients, 3–6 months of steroid therapy is sufficient to sustain remission and patients usually do not require further therapy . However, if relapses occur after discontinuation of steroids, it is more reasonable to consider the patient as having true AIH or IgG4-associated AIH that was unmasked by ciprofloxacin. Thirdly, at least currently, it is neither cost-effective nor good time management to measure serum IgG4 levels or perform immunohistochemical pathologic examination in patients who present with unexplained acute or sub-acute hepatitis, while IgG4-associated AIH is very rare clinical entity. Finally, I applaud the authors on drawing attention to one of the differential diagnosis in patients presented with features of AIH.

Prevalence and clinical relevance of enteropathy associated with systemic autoimmune diseases - Corrected Proof

2012-04-02

Abstract: Objective: To assess whether systemic autoimmune diseases are a risk group for coeliac disease and if there is a systemic autoimmune diseases-associated enteropathy.Methods: 183 patients with systemic autoimmune diseases were included. Duodenal biopsy was carried out on patients with positive coeliac genetics (HLA-DQ2-DQ8) and/or serology and/or symptoms of the coeliac disease spectrum. When enteropathy was found, causes, including gluten sensitivity, were investigated and categorized according to a sequentially applied treatment. Results were analysed with Chi-square or Fisher exact tests.Results: The prevalence of coeliac disease with atrophy was 0.55% (1 of 183 patients). Thirty-eight of the 109 patients (34.8%) who underwent duodenal biopsy had lymphocytic enteropathy (8 infectious, 5 due to gluten sensitive enteropathy, 5 HLA-DQ2/DQ8 who did not accept gluten-free diet and 20 of unknown aetiology). Lymphocytic enteropathy was unrelated to disease activity or immunosuppressants. HLA-DQ2 was more frequent in connective tissue disease (41.5%) compared with systemic vasculitis and autoinflammatory diseases (17.9%) (p=0.02), whereas a lower percentage of lymphocytic enteropathy was observed in the former (20.2% vs. 41.6%). Lymphocytic enteropathy was clinically irrelevant in cases with no definite aetiology.Discussion: One third of systemic autoimmune diseases patients had enteropathy of uncertain clinical meaning in the majority of cases, which was rarely due to gluten sensitive enteropathy.

MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in gastric cancer - Corrected Proof

2012-03-30

Abstract: Background: A thorough understanding of gastric cancer at the molecular level is urgently needed. One prominent oncogenic microRNA, miR-21, was previously reported to be upregulated in gastric cancer.Methods: We performed an unbiased search for downstream messenger RNA targets of miR-21, based on miR-21 dysregulation, by using human tissue specimens and the MKN28 human gastric carcinoma cell line. Molecular techniques include microRNA microarrays, cDNA microarrays, qRT-PCR for miR and mRNA expression, transfection of MKN28 with miR-21 inhibitor or Serpini1 followed by Western blotting, cell cycle analysis by flow cytometry and luciferase reporter assay.Results: This search identified Serpini1 as a putative miR-21 target. Luciferase assays demonstrated direct interaction between miR-21 and Serpini1 3′UTR. miR-21 and Serpini1 expression levels were inversely correlated in a subgroup of gastric cancers, suggesting a regulatory mechanism that included both of these molecules. Furthermore, Serpini1 induced growth retardation of MKN28 and induced vigorous G1/S arrest suggesting its potential tumour-suppressive function in the stomach.Conclusion: Taken together, these data suggest that in a subgroup of gastric cancers, miR-21 is upregulated, inducing downregulation of Serpini1, which in turn releases the G1–S transition checkpoint, with the end result being increased tumour growth.

Ischemic biliary injury following extra-corporeal membrane oxygenation (ECMO) - Corrected Proof

Ali Akbar, Todd H. Baron — 2012-03-30

Extra-corporeal membrane oxygenation (ECMO) is occasionally used in adults with acute lung failure. We report an association between ischemic biliary duct injury (IBDI) and ECMO, successfully treated endoscopically.

Gossypiboma - Corrected Proof

Yu-Chih Liu, Chih-Ming Huang — 2012-03-30

A 93-year-old man visited our hospital due to low-grade fever for one day. On examinations, his vital signs were stable except a temperature of 38.3°C. Physical examination revealed diffuse abdominal tenderness without rebound tenderness. A laboratory evaluation was unremarkable except for elevated levels of white blood cell count and C-reactive protein. A lesion with heterogeneous radiodensity was noted in the right upper abdomen on chest radiography (Fig. A, arrowheads) with a radiopaque shadow band (Fig. A, asterisk). Computed tomography of abdomen disclosed a gossypiboma (Fig. B, arrowheads) containing gas and band (Fig. B, asterisk) located in subphrenic area. Tracing back his history, the patient had undergone open cholecystectomy three years prior to this event. We surgically removed the left-behind sponge (Figs. C and D) and debrided the subphrenic area. His recovery was uneventful and was transferred to chronic care centre.

Phase II study of sirolimus in treatment-naive patients with advanced hepatocellular carcinoma - Corrected Proof

2012-03-29

Abstract: Background: Rapalogs are emerging as promising targeted anticancer drugs. Activation of the PI3K/Akt/mTOR pathway has been observed in 15–50% of hepatocellular carcinomas.Methods: In this phase II study, patients with advanced hepatocellular carcinoma and underlying cirrhosis received sirolimus (20mg/week for 1 month then 30mg/week). Tumour response was assessed every 8 weeks. The primary endpoint was the objective tumour response rate according to the Response Evaluation Criteria in Solid Tumours criteria. Secondary endpoints included the objective response according to the modified Response Evaluation Criteria in Solid Tumours criteria, safety, and pharmacokinetic parameters.Results: Twenty-five patients received sirolimus for a median of 20.6 weeks. Two patients had an objective response (8%, 95CI: 0.98–26.03), including one complete response, and 8 patients had stable disease. There were 2 cases of grade 5 toxicity (infections) and 5 cases of grade 3 toxicity. The main grade 1/2 toxicity was mild transient fatigue (76%). Median time to radiological progression and overall survival were 15.3 weeks (range: 8.2–173.9) and 26.4 weeks (range: 8.2–173.9) respectively. Use of the modified Response Evaluation Criteria in Solid Tumours criteria did not identify any further responders.Conclusion: These data suggest that first-line sirolimus shows antitumoural efficacy in advanced hepatocellular carcinoma. Larger trials with Child A patients are needed.

Comment to “Precut sphincterotomy, repeated cannulation and post-ERCP pancreatitis in patients with bile duct stone disease” - Corrected Proof

Paolo Cantù, Federica Villa, Stefania Baroni, Sergio Brunati — 2012-03-29

We read with interest the paper by Testoni et al. reporting retrospective data concerning the use of needle-knife precut and post-endoscopic retrograde cholangio-pancreatography (ERCP) pancreatitis in the field of choledocholithiasis. On the basis of the large amount of data (2004 ERCPs) analyzed, the authors suggest that early performance of needle-knife precut did not increase the overall rate of pancreatitis in difficult cannulation and should be preferred after 9 cannulation attempts over persisting with standard technique. Moreover data on the occurrence of pancreatitis split into high vs standard risk patients are also convincing in favour of early (<10 attempts) precut (7.7% early vs 28.6% late precut) despite the absence of significant statistical difference. In the case of pancreatitis after precut many factors could play a role, i.e. experience of the endoscopist, selection of cases, timing and technique used. Recently consistent data in favour of early precut to reduce the rate of pancreatitis have been shown in a meta-analysis by Cennamo et al. . However, whether endoscopist experience is a major determinant in precut timing has not been proved. In the paper by Testoni et al. including ERCPs performed by four experienced endoscopists, the overall rate of early precut was 6% (121/2004 ERCPs) or 40% of elegible cases (121/301, including 180 difficult cannulations), as shown in Table 2. Because of its retrospective design, this study does not add data on the role of endoscopist experience on precut timing. Considering technical aspects of precut, access to the biliary tree in difficult cases was performed by Testoni and co-workers by freehand cut starting 5-mm above the papillary orifice and directed upward, i.e. fistulotomy. To our knowledge one only prospective randomized study compared the rate of pancreatitis after fistulotomy or after traditional precut technique starting from the papillary orifice. In accordance to these limited data we are convinced that fistulotomy as described by Testoni et al. is the more rational “second attempt” in difficult cannulation. In these cases an S-shape instead of a J-shape anatomy of the intraduodenal portion of the choledocus is often present. When traditional cannulation fails fistulotomy represents the appropriate technique leading to access to the superficial portion of the S-shaped choledocus maintaining a safe distance from the papillary orifice, thus limiting oedema, the major determinant for post-ERCP pancreatitis. In our medium-volume endoscopy unit, from January 2009 to October 2011, after 9 unsuccessful cannulation attempts, fistulotomy was needed in 13 patients (8.2% overall, 19.4% in high risks patients) evaluated for suspected choledocholitiasis, with an overall success rate of 85% (failures in two patients with Billroth II gastrectomy). Taking into account the limited prospective data, no pancreatitis occurred in our series of patients undergoing fistulotomy vs 4.1% of mild-moderate pancreatitis in patients undergoing traditional cannulation (p=ns). Moreover, excluding patients with acute biliary pancreatitis, mean serum amylase levels 24h post-ERCP were similar between groups: 247 UI, traditional cannulation vs 147 UI, fistulotomy (p=0.3), underlining that thermal injury of the papillary orifice did not occur after fistulotomy. These data are in line with those by Testoni et al. Waiting for large randomized studies aiming to explore the advantages of early precut, the retrospective data presented by Testoni et al. reinforced our policy to continue in a two-step technique (traditional cannulation followed by fistulotomy). The role of the systematical use of early fistulotomy in difficult cannulation should be considered. The impact of this policy on the expected increase in the use of fistulotomy should be evaluated in prospective multicenter studies.

Endoscopic ultrasound image of hydatid membranes in the common bile duct - Corrected Proof

Francesco Azzolini, Lorenzo Camellini, Guido Menozzi, Romano Sassatelli — 2012-03-29

A 25-year-old Caucasian male was admitted to our Department for abdominal pain, fever, jaundice and cholestasis. Transabdominal ultrasonography showed a cyst in the left lobe of the liver, minimal ascites, dilatation of the main biliary duct and biliary sludge in the gallbladder.

Bowel preparation with polyethylene glycol electrolyte solution: Optimizing the splitting regimen - Corrected Proof

2012-03-28

Abstract: Aim: Quality of bowel cleansing significantly increases shorter the time between bowel solution intake and endoscopic examination. We tested the efficacy and patient tolerability following a modified polyethylene glycol electrolyte (PEG) splitting regimen.Methods: This was a prospective, single-blind, randomized, study. Patients were assigned to receive either PEG 4L the afternoon before colonoscopy or PEG 3L the day before and 1L 3h before the procedure the day of colonoscopy.Results: The study population consisted of 336 patients, including 168 participants in each study arm. Although the bowel preparation quality was similarly quoted as excellent/good following the split and full regimen (95.2% vs 92.8%; p=0.3), a significant (p<0.0001) shift from good towards an excellent preparation (26.8% vs 68.4%) was observed following the split regimen as compared to the full regimen (55.4% vs 37.5%). The incidence of side-effects did not differ. When patients were asked about a future preparation if needed, 69% and 31% following the split and full regimen, respectively, declared to accept again the same preparation, the difference being statistically significant (p<0.001).Conclusions: Our data found that an excellent bowel cleansing could be frequently achieved by simply modifying the split regimen from the standard PEG 2 plus 2L to 3 plus 1L.

Spirulina improves non-alcoholic steatohepatitis, visceral fat macrophage aggregation, and serum leptin in a mouse model of metabolic syndrome - Corrected Proof

2012-03-26

Abstract: Background: Nutritional approaches are sought to overcome the limits of pioglitazone in metabolic syndrome and non-alcoholic fatty liver disease. Spirulina, a filamentous unicellular alga, reduces serum lipids and blood pressure while exerting antioxidant effects.Aim: To determine whether Spirulina may impact macrophages infiltrating the visceral fat in obesity characterizing our metabolic syndrome mouse model induced by the subcutaneous injection treatment of monosodium glutamate.Methods: Mice were randomized to receive standard food added with 5% Spirulina, 0.02% pioglitazone, or neither. We tested multiple biochemistry and histology (both liver and visceral fat) readouts at 24weeks of age.Results: Data demonstrate that both the Spirulina and the pioglitazone groups had significantly lower serum cholesterol and triglyceride levels and liver non-esterified fatty acid compared to untreated mice. Spirulina and pioglitazone were associated with significantly lower leptin and higher levels, respectively, compared to the control group. At liver histology, non-alcoholic fatty liver disease activity score and lipid peroxide were significantly lower in mice treated with Spirulina.Conclusions: Spirulina reduces dyslipidaemia in our metabolic syndrome model while ameliorating visceral adipose tissue macrophages. Human studies are needed to determine whether this safe supplement could prove beneficial in patients with metabolic syndrome.

Endoscopic ultrasound-fine needle aspiration diagnosis and treatment of a gastric intramural pseudocyst - Corrected Proof

Carmelo Luigiano, Vincenzo Cennamo, Francesco Ferrara, Carlo Fabbri — 2012-03-26

A 66-year-old man presented with a 6-month history of heartburn, vomiting and epigastric pain. Medical history included left hemicolectomy for a perforated diverticulum, alcohol abuse, chronic pancreatitis and an endoscopic diagnosis of gastritis.

Spontaneous hemoperitoneum secondary to a ruptured gastric stromal tumour - Corrected Proof

Ling Chen, Zhonglian Li, Yihong Sun, Xinyu Qin — 2012-03-23

Frank bleeding of gastrointestinal stromal tumour (GIST) is less common and almost always within the gastrointestinal tract, even though these tumours can be very exophytic. Here we report a case of hemoperitoneum secondary to a spontaneously ruptured GIST. In October 2006, a 38-year-old man was referred to us with a 1-day history of progressive upper quadrant abdominal pain. On examination, he had distended abdomen with localized tenderness, reboundness and guarding in the epigastrium. There were no other specific signs and findings elicited. Sonography and computed tomography (Fig. 1) of abdomen showed a soft-tissue mass originated in the stomach wall (white arrow), and ascites (black arrow) within the peritoneum. After the presence of uncoagulated blood was confirmed by an abdominal paracentesis, the patient was taken to the operating theatre. The emergency laparotomy was performed showing about 3l of hemoperitoneum. There was a ruptured mushroom-like neoplasm (8cm×6cm), with active bleeding, arose by a pedicle from the region of greater curvature (Fig. 2). Considering not invaded gastric mucosa macroscopically and no regional lymph nodes enlarged, single resection of the neoplasm was performed and the small crevasse of the seromuscular wall was sutured. Histopathology showed gastric stromal tumour with the number of mitoses less than 5/50 high-power fields. In December 2011, at last follow-up, our patient was well with no further recurrences.

Nuclear factor-κB predicts outcome in locally advanced rectal cancer patients receiving neoadjuvant radio-chemotherapy - Corrected Proof

2012-03-23

Abstract: Background: NF-κB expression has been shown to be responsible for resistance to antineoplastic agents.Aims: The aim of our study was to investigate the importance of NF-κB expression as prognostic factor in locally advanced rectal cancer patients receiving neoadjuvant radiochemotherapy.Methods: We retrospectively analysed the immunoreactivity for NF-κB in patients with locally advanced rectal cancer who underwent neoadjuvant treatment (chemotherapy and/or radiotherapy) in our Institution between March 2003 and June 2006.Results: Seventy-four consecutive patients were enrolled into this study. Immunohistochemistry analysis for NF-κB was performed both in biopsies and in primary tumour samples. NF-κB was considered positive when at least 1% of the tumour cells showed nuclear positivity. A significant correlation between a positive NF-κB nuclear expression, both in biopsies and in tumour samples, and a worse overall survival was observed.Moreover, median time to progression was significantly shorter in the NF-κB-positive subgroup of patients.Conclusion: Globally, our findings seem to suggest that NF-κB could represent an important parameter able to predict the outcome in patients receiving neoadjuvant treatment for rectal cancer. It also could be useful in order to select patients to receive adjuvant chemotherapy, intensifying the adjuvant therapy and, in the next future, obviating the use of drugs involving NF-κB system in their mechanism of action in NF-κB-positive patients.

Vinyl chloride exposure and cirrhosis: A systematic review and meta-analysis - Corrected Proof

Elisa Frullanti, Carlo La Vecchia, Paolo Boffetta, Carlo Zocchetti — 2012-03-23

Abstract: Background: It has been proposed that vinyl chloride exposure is associated with increased risk of death from cirrhosis, although epidemiologic evidence is limited.Methods: We analyzed the risk of death from cirrhosis by occupational vinyl chloride exposure by conducting a meta-analysis on seven available studies, including more than 40,000 workers exposed to vinyl chloride mostly in North America and Europe, with a total of 203 deaths from cirrhosis.Results: All epidemiological studies on vinyl chloride exposure and risk of death from cirrhosis resulted in an overall relative risk of 0.73 (95% confidence interval 0.61–0.87). Thus, the epidemiologic evidence does not suggest an excess mortality from cirrhosis in vinyl chloride-exposed workers; this is consistent with histopathological observations in livers of angiosarcoma patients and of vinyl chloride-exposed rodents revealing no signs of cirrhosis.Conclusion: Overall, our findings indicate the absence of increased risk of death from cirrhosis in vinyl chloride-exposed workers.

Pancreatic heterotopia at the gastroesophageal junction - Corrected Proof

Ali Choukair, Lara Younan, Ala I. Sharara — 2012-03-23

A 44 year old female presented with mild epigastric pain of few months duration. Esophagogastroduodenoscopy showed subtle flat polypoid tissue at the gastric cardia with a mosaic pattern on narrow band imaging (Fig. 1). Biopsies revealed pancreatic heterotopia with nests of acinar tissue located at the base of the mucosal glands with abundant eosinophilic and granular cytoplasm in the apical and middle portions and basophilic in the basal area (Fig. 2). Pancreatic heterotopias (PH), defined as pancreatic tissue lacking anatomical and vascular communication with the normal pancreas, can occur anywhere in the gastrointestinal tract (most commonly stomach followed by small bowel) but its biological significance remains uncertain. The prevalence of PH at the gastroesophageal junction (GEJ) ranges from 18 to 32%. These lesions are usually clinically silent. A malignant change is extremely rare. This entity has been commonly referred to as pancreatic acinar metaplasia since it was thought to be associated with chronic inflammation . However, in a prospective study, no association with chronic gastritis was identified and patients with PH were significantly younger than those without PH raising the possibility of a congenital origin. PH found exclusively above the GEJ is associated with female gender, the presence of Helicobacter pylori while PH below the GEJ is inversely associated with female gender without association with H. pylori or reflux symptoms.

Massive liver polycystic disease in a kidney transplanted patient - Corrected Proof

Pasquale Esposito, Francesca Bosio, Teresa Rampino, Antonio Dal Canton — 2012-03-23

A 57-year-old woman was admitted for nausea, vomiting and abdominal pain. She had an adult dominant polycystic kidney disease (ADPKD), associated with multiple liver cysts with normal hepatic function. The kidneys had been removed ten years earlier, when she underwent kidney transplantation. At admission renal function was normal, but severe liver injury was proven by new-onset ascites, increased bilirubin level (2.1mg/dl), reduced albumin concentration (2.6g/dl) and prolonged prothrombin international normalised ratio (INR 1.7). The patient reported she had been involved in a road accident two weeks earlier. Magnetic resonance imaging (MRI) showed massive polycystic liver disease (PCLD) (Fig. 1, Panel A, star indicates the transplanted kidney) with haemorrhagic cysts, probably due to the recent trauma (Fig. 1, Panel B, arrows).

Antiviral therapy and fibrosis progression in patients with mild–moderate hepatitis C recurrence after liver transplantation. A randomized controlled study - Corrected Proof

2012-03-19

Abstract: Backgrounds/aims: We evaluated the effect of antiviral therapy on fibrosis progression in patients with histological features of mild/moderate HCV disease recurrence defined by a Grading score≥4 and Staging score up to 3 (Ishak) at 1 year after liver transplantation.Methods: Seventy-three consecutive patients with mild/moderate recurrence were randomized either to no treatment or to receive Pegilated-Interferon-alfa-2b and ribavirin for 52 weeks. Liver biopsies obtained at baseline (1 year after transplantation) and 2 years afterwards were evaluated for assessment of disease progression, defined as worsening of at least 2 staging points or progression to stage 4 or higher.Results: As for these two major histological end points there were no statistically significant differences between the 2 groups (36.1% vs. 50%, p=0.34 and 36.1% vs. 38.9%, p=1). Fifteen treated patients (41%) achieved a sustained virological response which was associated with a reduced risk of fibrosis worsening for both endpoints when compared to viremic patients (p=0.04).Conclusions: Although antiviral-therapy was beneficial in preventing fibrosis progression in patients achieving a sustained virological response, the majority of the overall population of our patients with mild–moderate disease recurrence could not benefit from antiviral therapy either because they either could not be treated or did not respond to treatment (EudraCT number: 2005-005760).

Faecal occult blood test and iron deficiency anaemia - Corrected Proof

Alberto Piperno — 2012-03-07

I read with interest the article by Cilona et al. discussing the role of faecal occult blood test (FOBT) in predicting bleeding lesions in upper and lower gastrointestinal (GI) tract in patients with iron deficiency anaemia (IDA). This is a controversial point that needs some considerations. An ideal faecal occult blood test (FOBT) for the evaluation of iron deficiency would reliably detect bleeding from all anatomic sites. However, most published observations on the performance of FOBTs have focused on colorectal cancer (CRC) screening. Conclusions from these data on detection of CRC cannot directly be extrapolated to the application of FOBTs in patients with IDA because the occult blood loss is as often, if not more often, located in the upper GI tract than in the lower intestinal tract. Three types of FOBTs are commercially available, and each targets a different component of the haemoglobin molecule, which may or may not remain stable intraluminally. Previous studies showed that HemoQuant test which measures both heme and heme-derived porphyrin, detects occult upper GI tract blood loss significantly more frequently than the guaiac-type or immunochemical tests (I-FOBT) . This is because I-FOBT targets antigenic sequences on the globin chains of haemoglobin which may be completely destroyed in proximal gut by the abundant peptidases. Accordingly, Levy et al. showed that I-FOBT positivity was not correlated with the finding of likely-to-bleed upper GI lesions at oesophago-gastro-duodenoscopy (EGD). Cilona et al. showed that a positive I-FOBT was an independent predictor of potential bleeding in either upper GI tract or colon. However, among the 63 patients with lesions, 25 (39.7%) had negative I-FOBT, including 3 of 12 (25%) patients with cancer and 5 of 10 (50%) patients with colon polyps. The percentage of false negative was higher in patients with lesions in the upper GI tract than in those with at least one lesion in the colon (17 out of 39 (58.6%) and 8 out of 24 (33.3%), respectively) although the difference does not reach statistical significance (Fisher's exact test: p=0.44). Thus, the main question is whether performing FOBTs to screen IDA patients for endoscopic evaluation is useful. A negative FOBT might generate the erroneous belief that no bleeding causes are present (including tumour or pre-cancerous lesions) and lead to delayed endoscopy and application of timely and appropriate medical or surgical treatments. It was shown that FOBT does not play a pivotal role in predicting the presence of cancer in patients with IDA and the recently revised British Society of Gastroenterology guidelines for the management of IDA specifies that FOBT is of no benefit in the investigation of IDA, being insensitive and non-specific . EGD and colonoscopy should be routinely considered in all postmenopausal female and all adult male patients where IDA has been confirmed unless there is a history of significant overt non-GI blood loss. In menstruating women with IDA the indication to perform EGD and colonoscopy is limited to specific conditions. It has been suggested that serial FOBT may be indicated as a triage for GI tract blood loss in children, premenstrual women, and the very elderly before endoscopy is undertaken. At the best of my knowledge, reliable studies evaluating advantages and disadvantages of such policy are not available and the study of Cilona et al. does not clarify this issue. In conclusion, despite its low sensitivity and specificity, FOBT remain the most reliable screening test able to significantly reduce mortality for CRC. By contrast, its usefulness in screening patients with IDA is unproved and can lead to risky reassurance of patients and physicians.

Long term efficacy of gastric electrical stimulation in intractable nausea and vomiting - Corrected Proof

2012-03-05

Abstract: Background: Although the efficacy of gastric electrical stimulation has been reported in short-term studies, there is a lack of data on the long-term improvement of nausea and vomiting by gastric electrical stimulation in patients with delayed or normal gastric emptying.Methods: Thirty-one patients were implanted at our centre for severe and chronic nausea and/or vomiting medically refractory. Patients were evaluated at baseline, 6 months then 5 years after implantation (mean follow-up 80±4 months) using a symptomatic and quality of life scores.Key results: Amongst the 31 patients, 4 were lost to follow-up, 6 explanted due to lack of improvement, and 1 patient died. Out of the 20 patients evaluated over 5 years, the quality of life score showed 27% improvement (p<0.01), including nausea (62%; p<0.01), vomiting (111%; p=0.03), satiety (158%; p<0.01), bloating (67%; p<0.01) and epigastric pain (43%; p=0.03). Over 5 years, 15/20 patients reported a 50% improvement with a global satisfaction rated at 64±6%. Therefore, 15/27 patients (56%) were improved by gastric electrical stimulation over 5 years in intention to treat. Improvement of nausea 6 months after implantation was predictive of 5-year success of gastric electrical stimulation (p=0.04). Finally, patients with delayed gastric emptying or with normal gastric emptying rate before surgery were similarly improved over 5 years (60% versus 50% respectively).Conclusion: Gastric electrical stimulation is safe and effective in the long term in patients with medically refractory nausea and vomiting, with an efficacy over 50% beyond 5 years in intention to treat. Gastric emptying measured before implantation did not influence the response rate over 5 years.