Digestive and Liver Disease - Articles in Press

Colonic metastasis from a primary adenocarcinoma of the lung presenting with acute abdominal pain - Corrected Proof

Paolo Pozzato, Angela Salerno, Alessandra Cancellieri, Maurizio Ventrucci — 2012-01-31

A 62-year-old man presented with acute abdominal pain due to intestinal subobstruction. He had previously been treated by radiotherapy for pulmonary adenocarcinoma. The patient underwent a colonoscopy revealing an ulcerated polypoid lesion, 3cm in diameter, in the left flexure (Fig. 1). Histology revealed adenocarcinoma which, at immunohistochemistry, was positive for thyroid transcription factor-1 (TTF-1) [A] and cytokeratin 7 (CK-7) [B], and negative for caudal-related homeobox transcription factor 2 (CDX-2) [C], sinaptofisin and cytokeratin 20 (CK-20) [D] (Fig. 2). Accordingly, the lesion was interpreted as metastatic from the lung. The patient was referred to the Oncology Unit for additional chemotherapy.

Screening for liver fibrosis by using FibroScan® and FibroTest in patients with diabetes - Corrected Proof

2012-01-30

Abstract: Background: Patients with diabetes are at risk for nonalcoholic fatty liver disease leading to cirrhosis. Existing guidelines do not advocate screening for liver related complications amongst persons with diabetes.Aim: The aim of this prospective study was to identify patients with severe liver fibrosis amongst patients hospitalized for their diabetes, using non-invasive methods, and to evaluate factors associated with severe fibrosis.Methods: Consecutive patients with type 1 or 2 diabetes had clinical, biological parameters and liver fibrosis evaluation. Severe fibrosis was predicted when FibroTest was >0.59 or liver stiffness >8.7kPa.Results: A total of 277 patients were evaluated (type 1 diabetes 52%). The prevalence of severe fibrosis was 15.5%. By univariate analysis, factors associated with severe fibrosis were age, type 2 diabetes, body mass index, metabolic syndrome, previous cardiovascular events, no retinopathy, past history of foot ulcer, and elevated alanine aminotransferase. By multivariate analysis, factors associated with severe fibrosis were age >50 years, type 2 diabetes, no retinopathy, and past history of foot ulcer.Conclusion: This study showed an elevated prevalence of severe fibrosis in hospitalized diabetic patients, especially patients aged 50 years or older with type 2 diabetes, or with a past history of foot ulcer.

Mycobacterium avium paratuberculosis in Italy: Commensal or emerging human pathogen? - Corrected Proof

2012-01-30

Abstract: Background: Specific bacterial infections or alterations of the gut microbiota likely trigger immuno-pathological phenomena associated with Crohn's disease and ulcerative colitis. Mycobacterium avium subspecies paratuberculosis is a candidate etiological agent of Crohn's disease. Definitive causal connection between Mycobacterium avium subspecies paratuberculosis infection and Crohn's disease has not been demonstrated.Aims: To determine the circulation of Mycobacterium avium subspecies paratuberculosis in Crohn's disease patients and water supplies in an Italian region where this bacterium is endemic in cattle farms.Methods: Mycobacterium avium subspecies paratuberculosis screening was performed on biopsies from human patients, and from water samples, using two different PCR procedures.Results: In hospitals where multiple specimens were obtained from different sites in the intestine, the prevalence of Mycobacterium avium subspecies paratuberculosis infection was 82.1% and 40% respectively in Crohn's disease and ulcerative colitis patients; in another hospital, where single specimens were obtained from patients, the bacterium was not detected. Control subjects also harboured Mycobacterium avium subspecies paratuberculosis, but at a lower prevalence. Tap water samples collected in the study area contained Mycobacterium avium subspecies paratuberculosis DNA.Discussion: The results of screenings for Mycobacterium avium subspecies paratuberculosis in humans are deeply influenced by both the number and location of the collected biopsies. There is a wide circulation of the organism in the study area, considering the prevalence in humans and its presence in drinking water.

An unusual case of dysphagia - Corrected Proof

Stefano Francesco Crinò, Roberta Marino, Elisabetta Buscarini, Piera Leoni — 2012-01-27

A 50-year-old homosexual man presented progressive dysphagia, odynophagia, heartburn and weight loss of 5kg within 2 months. The pain was directly related to the intake of solid food, resulting in a bolus feeling. He reported no chronic heartburn or previous history of caustic ingestion. Physical examination revealed pain in the upper abdominal quadrant without abdominal masses. Laboratory investigations indicated a normal full blood count and tumour markers. A CT scan showed a focal thickening of the wall of the distal oesophagus.

Bone mass in women with celiac disease: Role of exercise and gluten-free diet - Corrected Proof

2012-01-27

Abstract: Background and aim: Celiac patients report fatigue and reduced social activities, which may decrease physical activity. This study investigated the physical activity, fatigue and bone mineral density in celiac women at diagnosis and during diet.Materials and methods: The first group (n=48) had the bone mineral density measured at diagnosis and after 2 years of a gluten-free diet; in the second group (n=47) bone mineral density was measured at diagnosis and after 5 years of a gluten-free diet. Both groups completed a physical activity questionnaire and visual analogue scale for the perception of fatigue at diagnosis and follow-up. Data about smoking habits, alcohol use, presence of gastrointestinal symptoms, drug therapy and body mass index were also collected.Results: At diagnosis, the two groups were similar for all considered variables. At follow-up, the mean body mass index and physical activity questionnaire's score were similar to baseline. The bone density increased in both groups, whilst the physical activity questionnaire and visual analogue scale remained unchanged.Conclusion: The improvement in bone density following a gluten-free diet was significant after 2 years; physical activity is frequently low and plays a minor role in determining the changes in bone mineral density.

“PancPro” as a tool for selecting families eligible for pancreatic cancer screening: An Italian study of incident cases - Corrected Proof

2012-01-27

Abstract: Background: PancPRO is a computer program that estimates the risk of pancreatic cancer for asymptomatic individuals based on a genetic model of susceptibility and the familial incidence of cancer.Aim: To evaluate the distribution of the familial risk in a series of incident cases of pancreatic adenocarcinoma.Materials and methods: The lifetime risk of pancreatic cancer was calculated by PancPro for a hypothetical 40-year-old son of 570 consecutive probands with pancreatic cancer.Results: The 570 risk values were included between 1% and 13%. The distribution was bimodal, with the antimode located at risk=7.5%. Considering a 10-fold risk over the general population as a threshold for including a subject in a surveillance program, 19 families (3.3%) would be selected, totalling 92 first-degree relatives with age >40 years.Conclusions: PancPro is a valid instrument to rank families based on risk of pancreatic cancer.

Can we shorten the small-bowel capsule reading time with the “Quick-view” image detection system? - Corrected Proof

2012-01-27

Abstract: Background: The mean small-bowel capsule reading time is about 60min, and shortening this reading time is a major aim.Aim: To evaluate the efficiency of the “Quick-view” detection algorithm.Methods: Multicentre prospective comparative study. One hundred and six small bowel capsule films from 12 centres reviewed in Quick-view mode by 12 experienced readers. Reading time, image relevance, and comparison of Quick-view reading results to results of initial reading. Review of discordant result by 3 experts.Results: The mean reading time in Quick-view mode was of 11.6min (2–27). Concordant negative results were obtained in 41 cases (38.6%) and concordant positive results in 35 cases (33.0%). A discordant result was obtained in 30 (28.3%) cases: 21 false positive cases (initial reading 12 cases, Quick-view reading 9 cases), 14 false negative cases (initial reading 7, Quick-view 7). Four out of 7 lesions missed at Quick-view reading were not present on the Quick-view film (theoretical sensitivity 93.5%).Conclusion: The Quick-view informatic algorithm detected nearly 94% of significant lesions, and Quick-view reading was as efficient as the initial reading and much shorter. These results are to be confirmed by further studies, but suggest an excellent sensitivity for the Quick-view algorithm.

Endoscopic reduction of a volvulus of the sigmoid colon in a pregnant woman - Corrected Proof

Xavier Dray, Lounis Hamzi, Rea Lo Dico, Emmanuel Barranger — 2012-01-25

A 31-year-old woman, gravida 2, para 1, 37 weeks of gestation, was admitted to the emergency room. She complained of vomiting, abdominal pain and constipation for 12h. She had no history of abdominal surgery. Her previous pregnancy had been uncomplicated. Physical examination revealed a distended abdomen and a non-dilated cervix. Foetal monitoring was normal. Laboratory tests were normal. Colonic obstruction was suspected. In the need of a diagnosis of certainty, and because of the advanced term of pregnancy, a CT-scan was performed. It diagnosed a volvulus of the sigmoid colon. Rectosigmoidoscopy confirmed a typical whirl pattern of the sigmoid with no sign of ischaemia. Endoscopic reduction of the volvulus was successfully performed under close foetal monitoring, without any sedation. A multiperforated tube was placed in the descending colon until delivery. Labour was induced 3 days later. The patient delivered a male infant weighing 3540g with an Apgar scores of 10-10-10. The mother and the baby were doing well until the most recent follow-up (at 8 months). Volvulus of the sigmoid colon accounts for almost half of cases of intestinal obstruction complicating pregnancy. It often occurs in the third trimester. It must be diagnosed early to avoid resection of the sigmoid and colostomy in the mother, and to prevent the high risks of maternal and foetal death .

Post-load insulin resistance does not predict virological response to treatment of chronic hepatitis C patients without the metabolic syndrome - Corrected Proof

2012-01-25

Abstract: Background and aim: The role of insulin resistance in predicting virological response to therapy of chronic hepatitis C is debated. We assessed the association between basal (defined as homeostasis model assessment of insulin resistance (HOMA-IR)>2) and post-load insulin resistance (as oral glucose insulin sensitivity index<9.8mg/kg/min) with the rapid and sustained virological responses in chronic hepatitis C.Methods: Observational prospective study of 124 treatment-naïve patients with chronic hepatitis C not fulfilling the metabolic syndrome criteria, adherent to a standard treatment with pegylated interferon alpha plus ribavirin.Results: Insulin resistance was detected in 50% (by HOMA-IR) and 29% (by oral glucose insulin sensitivity index) of patients. Independent predictors of rapid virologic response were hepatitis C virus (HCV) genotype 2 (odds ratio 5.66; 95% confidence interval 1.88–17.01), HCV genotype 3 (odds ratio 5.23; 95% confidence interval 1.84–14.84) and lower basal ferritin levels (odds ratio 0.99; 95% confidence interval 0.993–0.998). Independent predictors of sustained virologic response were HCV genotype 2 (odds ratio 19.54; 95% confidence interval 2.29–166.41) and HCV genotype 3 (odds ratio 3.24; 95% confidence interval 1.10–9.58). Rapid virologic response was by itself predictive of sustained virologic response (odds ratio 40.90; 95% confidence interval 5.37–311.53).Conclusions: Insulin resistance, measured by both static and dynamic methods, does not predict rapid or sustained virologic response in chronic hepatitis C patients without the metabolic syndrome.

Colorectal stenting as a bridge to surgery reduces morbidity and mortality in left-sided malignant obstruction: a predictive risk score-based comparative study - Corrected Proof

2012-01-24

Abstract: Background: The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity model, and its Portsmouth and colorectal modifications are used to predict postoperative mortality and morbidity after colorectal surgery.Aims: To compare stent placement as a bridge to surgery vs. emergency surgical resection in patients with acute left-sided colorectal cancer obstruction using P-POSSUM and CR-POSSUM.Methods: From January 2008 to December 2009, the physiological and operative scores, morbidity and mortality predicted by the P-POSSUM and CR-POSSUM scores were collected in all consecutive patients with LCCO who underwent surgical resection directly (Group A) or after stent placement (Group B).Results: Eighty-six patients were enrolled (Group A-41 and Group B-45). The observed 30-day mortality rate was 9.8% (4/41) in Group A and 2.4% (1/45) in Group B. The 30-day morbidity rate was 61% (25/41) in Group A and 29% (13/45) in Group B. The mean values of P-POSSUM morbidity (A=70.5% vs. B=34.3%; p=0.001), P-POSSUM mortality (A=13.6% vs. B=2.4%; p=0.001) and CR-POSSUM mortality (A=15.1% vs. B=4.9%; p=0.001) were significantly lower in the Group B patients than in the Group A patients.Conclusions: Bridge to surgery strategy reduces the surgical risks in LCCO, and P-POSSUM and CR-POSSUM scores represent a good tool for comparing the two strategies.

Atorvastatin improves disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-α-lowering property - Corrected Proof

2012-01-24

Abstract: Background: We have previously found that atorvastatin decreases liver injury markers in patients with nonalcoholic steatohepatitis. However, how atorvastatin treatment ameliorates the disease activity in nonalcoholic steatohepatitis patients remains unknown.Aims: We examined here which anthropometric, metabolic and inflammatory variables were improved and related with amelioration of disease activity in atorvastatin-treated nonalcoholic steatohepatitis patients.Methods: Forty-two biopsy-proven nonalcoholic steatohepatitis patients with dyslipidemia were enrolled. Patients were treated with atorvastatin (10mg/day) for 12 months.Results: Atorvastatin significantly decreased liver transaminase, γ-glutamyl transpeptidase, low-density lipoprotein-cholesterol, triglycerides, type IV collagen, and tumour necrosis factor-α levels, whilst it increased adiponectin and high-density lipoprotein-cholesterol. Atorvastatin improved nonalcoholic fatty liver disease activity score and increased liver to spleen density ratio. Multiple stepwise regression analysis revealed that γ-glutamyl transpeptidase, tumour necrosis factor-α and liver to spleen density ratio (inversely) were independently associated with nonalcoholic fatty liver disease activity score. Aspartate aminotransferase, low-density lipoprotein-cholesterol and nonalcoholic fatty liver disease activity score were independent determinants of decreased liver to spleen density ratio.Conclusion: The present study suggests that atorvastatin improves the disease activity of nonalcoholic steatohepatitis partly via its tumour necrosis factor-α-lowering property.

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

2012-01-24

Abstract: Background: Often previously overlooked, microscopic colitis, including collagenous colitis and lymphocytic colitis, has now emerged as a common cause of chronic diarrhoea.Aims: To evaluate the prevalence and incidence of microscopic colitis in patients with diarrhoea of unknown aetiology.Methods: 271 consecutive patients who were referred to the General Hospital of Tomelloso from April 2008 to December 2010 for diarrhoea of unknown aetiology underwent a full colonoscopy to obtain biopsy samples to diagnose microscopic colitis on the basis of commonly accepted histological criteria. All patients were classified according to the Roma III criteria for diarrhoea-dominant irritable bowel syndrome.Results: In 234/271 consecutive patients with normal endoscopic appearance we observed 32/234 patients with microscopic colitis (30 lymphocytic colitis and 2 collagenous colitis) with a prevalence of microscopic colitis of 48 cases/100,000 inhabitants (95%CI: 30–65) and mean annual standardised incidence of 18 cases/100,000 inhabitants (95%CI: 16.0–20.0). Analysing only the patients that met the Roma III criteria (84/271), we observed 10.7% microscopic colitis diagnosis, with higher risk in the presence of autoimmune disease, seronegative celiac disease and intake of non-steroidal anti-inflammatory drugs.Conclusions: Microscopic colitis was found in 13.7% of patients with chronic diarrhoea. Microscopic colitis is present in a relevant proportion of symptomatic patients meeting diagnostic criteria for irritable bowel syndrome (10.7%).

Sorafenib for recurrence of hepatocellular carcinoma after liver transplantation - Corrected Proof

2012-01-20

Abstract: Background: Recurrence of hepatocellular carcinoma after orthotopic liver transplantation not amenable to surgical approaches is associated with poor outcome.Aims: Retrospective evaluation of the safety and efficacy of sorafenib in patients with post-transplant hepatocellular carcinoma recurrence.Methods: Patients with post-transplant hepatocellular carcinoma recurrence were treated with sorafenib. Adverse events were assessed using National Cancer Institute Common Toxicity Criteria of AEs version 3.0, tumour response was evaluated according to Response Evaluation Criteria in Solid Tumours.Results: First-line therapy after recurrence was surgery (n=6), radiation therapy (n=1), chemotherapy (n=1), and sorafenib (n=3). Finally, 11 patients were treated with sorafenib. Nine patients (82%) received an additionally targeted therapy with sirolimus as part of their immunosuppressive regimen. Most common grade 3 adverse events included diarrhoea (46%), hand-foot skin reaction (27%), nausea, fatigue, and leucopoenia (all 18%). Sorafenib had to be discontinued in two patients due to adverse events and six additional patients required a dose adjustment. No deterioration of liver graft function occurred. Median time to progression was 4.1months; however, patients were treated with ongoing sorafenib in case of clinical benefit (median 8.9months). Median overall survival after initiation of sorafenib treatment was 20.1months.Conclusion: Sorafenib in combination with immunosuppression including sirolimus may be administered to patients with post-transplant hepatocellular carcinoma recurrence with acceptable toxicity and without deterioration of liver graft function.

Diagnosis, prevention and treatment of postoperative Crohn's disease recurrence - Corrected Proof

2012-01-20

Abstract: Ileocolonoscopy remains the gold standard in diagnosing postoperative recurrence. After excluding stricture, wireless capsule endoscopy seemed accurate in small series, but no validated score is available. Ultrasonography is a non-invasive diagnostic method reducing radiation exposure and emerging as an alternative tool for identifying post-operative recurrence. Computed tomography enteroclysis yields objective morphologic criteria that help differentiate between recurrent disease and fibrostenosis at the anastomotic site, but ionising radiation exposure limits its use. Magnetic resonance imaging may be equally powerful than ileocolonoscopy in diagnosing postoperative recurrence and in predicting the clinical outcome using specific MR-scores. Biomarkers such as faecal calprotectin and faecal lactoferrin showed promising results, but their specificity in the postoperative period will require further investigation. Numerous medications have tested to prevent and/or to treat postoperative recurrence. Efficacy of mesalamine is very low and comparable to placebo in most series. Thiopurines have modest efficacy in the postoperative setting and are associated with a high rate of adverse events leading to drug withdrawal. Antibiotics such as metronidazole or ornidazole may be effective, but toxicity and drug resistance prevent their long-term use. Anti-Tumour Necrosis Factor therapy is the most potent drug class to prevent and to treat postoperative recurrence in Crohn's disease.

Open conformation tissue transglutaminase testing for celiac dietary assessment - Corrected Proof

2012-01-19

Abstract: Objectives: Anti tissue-transglutaminase antibody is the mainstay of celiac disease serologic testing. Whilst it has high sensitivity in patients on an unrestricted diet, sensitivity is poor for evaluation of gluten free diet adherence.Aim: To assess the utility of a novel assay measuring Immunoglobulin-A antibodies to catalytically active open conformation tissue-transglutaminase in assessment of ongoing gluten exposure in celiac disease patients on an alleged gluten free diet.Methods: Through prospective assessment, 147 patients with celiac disease were divided into good and poor adherence. Open and closed (conventional) tissue-transglutaminase titres were measured using standard enzyme linked immunosorbent assay. 50 patients with inflammatory bowel disease served as disease controls.Results: Overall 128 patients had been on gluten free diet for more than six months and 19 were found to be poorly adherent on dietary review. Within this group 13 (68.4%) and 10 (52.6%) patients respectively were positive for the open conformation and conventional assay (p=0.51). Two and one control patients tested positive for closed and open assays respectively.Conclusions: Compared to native assays open conformation tissue-transglutaminase may have higher sensitivity in the poor gluten free diet adherence group and higher specificity in the control population. Larger population studies are warranted to assess whether the open conformation tissue-transglutaminase assay may be superior to the conventional assay.

Non-invasive assessment of hepatic fibrosis in a series of patients with Wilson's Disease - Corrected Proof

Margherita Sini, Orazio Sorbello, Alberto Civolani, Mauro Liggi, Luigi Demelia — 2012-01-19

Abstract: Background/aims: Liver biopsy has always represented the standard of reference in hepatic fibrosis assessment. Recently, blood markers and instrumental methods have been proposed for non-invasive assessment.The aim of this study was to validate transient elastography and other non-invasive tests compared to liver histology in Wilson's Disease.Methods: Liver stiffness in 35 Wilson's Disease patients was evaluated by Fibroscan, serum fibrosis markers (AST-to-platelet-ratio index and FIB-4) and biopsy.Results: Compared to liver histology, the FibroScan values increased proportionally with progression of the histological fibrosis stage. Significant fibrosis could be predicted with a Fibroscan cut-off value of 6.6kPa. Advanced fibrosis could be predicted with a FibroScan cut-off value of 8.4kPa. Serum fibrosis marker values gave good correlation with hepatic stage.Conclusions: A FibroScan value of 6.6kPa was found to be a significant separation limit for differentiating significant fibrosis stages from milder stages and a fibroscan value of 8.4kPa was found to be a significant separation limit for differentiating advanced fibrosis stages from milder stages. FibroScan values are clinically useful for predicting fibrosis stages and helpful in managing chronic therapy in Wilson's Disease patients.

Type 2 diabetes mellitus and chronic hepatitis C: Which is worse? Results of a long-term retrospective cohort study - Corrected Proof

2012-01-16

Abstract: Background: The long-term outcome in patients with chronic hepatitis C and type 2 diabetes mellitus treated with interferon and ribavirin is unclear. We compared incidence of liver-related events and mortality rates between hepatitis C virus-positive patients with or without diabetes mellitus, and the incidence of diabetes-related events between diabetic patients with and without hepatitis C.Methods: Retrospective study of 309 patients with chronic hepatitis C. Incidence of liver-related events, diabetes-related events and mortality rates were assessed over a mean follow-up of 11.02±4.9 years.Results: 50 (16%) chronic hepatitis C patients had diabetes mellitus. Diabetics showed a higher number of diabetes- and liver-related events than non-diabetics (10% vs 1.5%, p=0.006; 18% vs 5.7%, p=0.007, respectively) with a mortality of 14% vs 1.5% (p=0.0003). Baseline cirrhosis (p=0.002) and non-sustained virological response (p=0.01) were independent risk factors for liver events; diabetes mellitus (p=0.01) and hypertension (p=0.0017) were independent factors for diabetes-related events.Conclusions: In patients with chronic hepatitis C, comorbidity with diabetes mellitus was associated with a higher mortality rate and incidence of liver/diabetes-related events. Independent risk factors for liver-related events were the non-response to antiviral therapy and cirrhosis at baseline.

Does cytotechnician training influence the accuracy of EUS-guided fine-needle aspiration of pancreatic masses? - Corrected Proof

2012-01-06

Abstract: Background/aim: The presence of on-site cytopathologists improves the diagnostic yield of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic masses; however, on-site cytopathologists are not available to all endoscopic units. We hypothesized that experienced cytotechnicians can accurately assess whether an on-site pancreatic mass fine needle aspiration specimen is adequate. The aim of this study was to evaluate the effect of formal cytotechnician training on the diagnostic accuracy of EUS-FNA of pancreatic masses.Methods: Single-centre, prospective study. The cytotechnician made an on-site assessment of specimen adequacy with immediate evaluation of smears over a 12-month period (pre-training period) then over another 12-month period (post-training period), with a year's intermediate training when the cytopathologist and the cytotechnician worked together in the room. The gold standard used to establish the final diagnosis was based on a non-equivocal fine needle aspiration biopsy reviewed by the same expert cytopathologist. The main outcome measurements were the cytotechnician diagnostic accuracy before and after the training period.Results: A total of 107 patients were enrolled in the pre-training period. Cytotechnician in-room adequacy was 68.2% (73/107). The diagnostic accuracy was 74.8%. The adequacy for the blind-review pathologist was 93.4% (100/107), significantly higher (p=0.008) than the cytotechnician's results. During the post-training period, 95 EUS-FNA were performed and reviewed. Cytotechnician in-room adequacy was 87.4% (83/95). The diagnostic accuracy was 90.5%. The adequacy for the blinded pathologist was 95.8% (91/95), not significantly different from the cytotechnician (p=0.23).Conclusions: An adequate training period with an expert pathologist significantly improves the cytotechnician skill in terms of judging adequacy and diagnostic accuracy.

Gastric heterotopia in the proximal oesophagus (“inlet patch”): Association with adenocarcinomas arising in Barrett mucosa - Corrected Proof

William L. Neumann, Giovanni M. Luján, Robert M. Genta — 2012-01-05

Abstract: Background: The prevalence of inlet patches and their association with other conditions of the gastrointestinal tract have been studied prospectively in tertiary care facilities; little is known about practice patterns in private outpatient clinics and endoscopy centres.Aims: To assess prevalence, demographic determinants, and associated clinicopathologic features of inlet patches in patients who had oesophagogastroduodenoscopy in outpatient settings throughout the United States.Methods: Retrospective analysis of the clinicopathologic records of 487,229 unique patients who had oesophagogastroduodenoscopy with biopsies between January 2008 and December 2010.Results: There were 870 patients with inlet patches with a prevalence of 0.18%. Significant associations included male gender (OR 1.68), dysphagia (OR 1.34), upper respiratory complaints (OR 2.81), globus (OR 5.39) Barrett oesophagus (OR 1.55), and adenocarcinomas arising in Barrett mucosa (OR 5.64).Conclusions: The prevalence of inlet patches in a tertiary care setting (0.18%) was considerably lower than reported in prospective studies (3.7% on average). Inlet patches were significantly associated with male gender, dysphagia, upper respiratory complaints, globus, Barrett mucosa, and adenocarcinomas arising in Barrett oesophagus. Further studies will be needed to determine if patients with inlet patches and Barrett mucosa benefit from increased surveillance.

Pretreatment serum microRNA-122 is not predictive for treatment response in chronic hepatitis C virus infection - Corrected Proof

2012-01-03

Abstract: Background: MicroRNA-122 is a liver specific microRNA and is elevated in the sera of patients with chronic hepatitis C virus infection. Hepatic microRNA-122 levels have been described to be reduced in patients with non-response to antiviral treatment with pegylated interferon-α and ribavirin.Aim: Assessment of differences in serum microRNA-122 levels in patients with sustained virological response and non-response.Methods: RNA was extracted from pretreatment serum samples and microRNA-122 and microRNA-16 levels were measured by quantitative PCR and compared in patients with sustained virological response and non-response.Results: The levels of microRNA-122 and microRNA-16 in the sera did not differ between patients with sustained virological response and non-response.Conclusion: Serum microRNA-122 is not a suitable marker for treatment response prediction to combination therapy with pegylated interferon-α and ribavirin in patients with chronic hepatitis C virus infection.

Adenovirus-mediated viral interleukin-10 gene transfer prevents concanavalin A-induced liver injury - Corrected Proof

Yan-Chun Zhou, Sui Chen, Jun-Jun Cao, Shao-Ying Chen, Yan-Fei Xie, Qing-Xia Niu — 2012-01-03

Abstract: Background and aim: Liver injury is closely associated with immune inflammation. Lacking immunostimulatory functions, viral interleukin-10 (vIL-10), a cellular IL-10 homologue, has been an attractive molecule for immunomodulatory therapy. We aimed to reveal a protective effect of the gene transfer of an adenoviral vector encoding vIL-10 on liver injury induced by concanavalin A.Methods: C57BL/6J mice were intravenously injected with adenoviral vector encoding vIL-10 before concanavalin A challenge. Liver injury was assessed. Interferon-γ and interleukin-4 levels were measured by ELISA. The activation of splenic and hepatic immune cells was analysed using an MTT assay.Results: Adenoviral vector encoding vIL-10 pretreatment significantly decreased concanavalin A-mediated elevations in serum alanine aminotransaminase and aspartate aminotransaminase activity, and necrotic area in liver tissues. The protective effect of adenoviral vector encoding vIL-10 was attributed to its inhibition of T cell activation, and production of interferon-γ and interleukin-4 by the immune cells. Recombinant mouse IL-10, a high homologous cytokine to vIL-10, effectively downregulated interferon-γ and interleukin-4 release by hepatic mononuclear cells.Conclusion: Adenovirus vector-mediated vIL-10 gene transfer can prevent concanavalin A-induced hepatic injury, minimise pro-inflammatory cytokine release, and inhibit the activation of T lymphocytes.

Surgical and nonsurgical hospitalization rates and charges for patients with ulcerative colitis in Italy: A 10-year cohort study - Corrected Proof

2011-12-26

Abstract: Background: Today we are observing an increasing incidence of ulcerative colitis associated with an improved survival of patients.Aim: To analyse current rates, outcomes, and costs of inpatient care for ulcerative colitis patients of central Italy.Methods: The cohort included 644 ulcerative colitis patients, living in the Lazio region, with diagnosis made or confirmed by the staff of a single tertiary referral centre in Rome (1997–2006). Follow-up data on hospitalization rates, costs, and colectomy rates were collected from the Regional Hospital Information System.Results: Overall hospitalization rates were 3 times higher than those of the region's general population, reflecting excess admissions for digestive or infectious diseases (standardized hospitalizations rates for digestive-tract: 15.9; for infectious diseases: 3.5). The overall cumulative risk for colectomy was 7.5%. On the average, hospitalizations for ulcerative colitis lasted 10 days. The mean reimbursement for a ulcerative colitis-related hospitalization was EUR 5120 (€4609 for nonsurgical admissions, €8655 for surgical hospitalizations).Conclusion: Ulcerative colitis patients are 3 times more likely to be hospitalized than the general population. Colectomy rates in Italian ulcerative colitis patients resemble those of northern Europe, but most hospital admissions are for diagnostic procedures or medical therapy. Hospitalizations are almost twice as long as those reported in the United States although their mean cost is considerably lower.

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis - Corrected Proof

2011-12-26

Abstract: Background: Nonalcoholic fatty liver disease is a chronic metabolic disorder with significant impact on cardiovascular and liver mortality.Aims: In this study, we examined the effects of silibinin on liver and myocardium injury in an experimental model of nonalcoholic fatty liver disease.Methods: A four-week daily dose of silibinin (20mg/kg i.p.) was administrated to db/db mice fed a methionine–choline deficient diet. Hepatic and myocardial histology, oxidative stress and inflammatory cytokines were evaluated.Results: Silibinin administration decreased HOMA-IR, serum ALT and markedly improved hepatic and myocardial damage. Silibinin reduced isoprostanes, 8-deoxyguanosine and nitrites/nitrates in the liver and in the heart of db/db fed the methionine–choline deficient diet, whereas glutathione levels were restored to lean mice levels in both tissues. Consistently, liver mitochondrial respiratory chain activity was significantly impaired in untreated mice and was completely restored in silibinin-treated animals. TNF-α was increased whereas IL-6 was decreased both in the liver and heart of db/db fed methionine–choline deficient diet. Silibinin reversed heart TNF-α and IL-6 expression to control mice levels. Indeed, liver JNK phosphorylation was reduced to control levels in treated animals.Conclusions: This study demonstrates a combined effectiveness of silibinin on improving liver and myocardial injury in experimental nonalcoholic fatty liver disease.

Hepatitis B virus particles preferably induce Kupffer cells to produce TGF-β1 over pro-inflammatory cytokines - Corrected Proof

Hai Li, Huan-Wei Zheng, Hui Chen, Zhi-Zhi Xing, Hong You, Min Cong, Ji-Dong Jia — 2011-12-16

Abstract: Background: Kupffer cells and related cytokines are thought to play a critical role in liver fibrosis; however, the role played by Kupffer cells in hepatitis B virus-related fibrogenesis is unknown.Methods: Primary rat Kupffer cells were cultured with different titres of hepatitis B virus particles and the concentrations of transforming growth factor (TGF)-β1, interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-α in the culture supernatant were measured every 24h for 7 days. The mRNA and protein levels of these cytokines in Kupffer cells were also analysed using quantitative real-time polymerase chain reaction and western blotting, respectively.Results: Kupffer cells maintained normal morphology and function throughout the 7-day exposure to hepatitis B virus. The concentration of TGF-β1 secreted by hepatitis B virus-stimulated Kupffer cells (6logIU/ml hepatitis B virus) increased 5.38- and 7.75-fold by Days 3 and 7, respectively (p<0.01). Western blotting showed that TGF-β1 expression in Kupffer cells exposed to high titres of hepatitis B virus increased 1.80- and 2.42-fold by Days 3 and 7, respectively (p<0.01). In contrast, Kupffer cell expression and secretion of pro-inflammatory cytokines (IL-6, IL-1 and TNF-α) was unchanged throughout the experiment.Conclusion: Hepatitis B virus preferentially stimulates Kupffer cells to produce the pro-fibrogenic/anti-inflammatory cytokine TGF-β1 rather than the pro-inflammatory cytokines IL-6, IL-1 and TNF-α. This may partly explain why overt liver fibrosis still presents in cases of chronic hepatitis B virus infection with minimal (or no) necro-inflammation.

Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: A pilot study - Corrected Proof

2011-12-12

Abstract: Background: Primary biliary cirrhosis and primary sclerosing cholangitis are two cholestatic diseases characterised by hepatic accumulation of bile acids.Aims: This study compares serum bile acid levels in patients with primary biliary cirrhosis and primary sclerosing cholangitis and from age and sex-matched non cholestatic donors.Methods: Seventeen bile acids were quantified using liquid chromatography coupled to tandem mass spectrometry. Serum samples from cholestatic patients were compared with those of non-cholestatic donors.Results: The concentration of total bile acids, taurine and glycine conjugates of primary bile acids was elevated in both patients with primary biliary cirrhosis and primary sclerosing cholangitis when compared to non-cholestatic donors. Samples from primary sclerosing cholangitis patients displayed reduced levels of secondary acids, when compared to non cholestatic and primary biliary cirrhosis sera. The ratio of total glycine versus total taurine conjugates was reduced in patients with primary biliary cirrhosis, but not in primary sclerosing cholangitis.Conclusion: The present study suggests that circulating bile acids are altered differentially in primary biliary cirrhosis and primary sclerosing cholangitis patients.

Urinary copper excretion before and after oral intake of d-penicillamine in parents of patients with Wilson's disease - Corrected Proof

2011-12-12

Abstract: Background: Urinary copper excretion higher than 100μg/24h is useful for diagnosing Wilson's disease. d-Penicillamine challenge test may produce higher levels than 1400μg/24h, allowing for better diagnostic accuracy. This study investigated whether heterozygotes reach this value and compared copper serum levels, ceruloplasmin, and urinary copper excretion before and after administering d-penicillamine to the parents of Wilson's disease patients.Methods: Fifty parents of adult patients were enrolled to obtain copper serum levels and ceruloplasmin along with 24-h urinary copper excretion before and after administering 1g d-penicillamine.Results: Serum ceruloplasmin and copper levels were significantly lower in fathers than in mothers (mean 21.8×27.8mg%; 71.4×88.0μg%; p≤0.001). The mean of basal 24-h urinary copper excretion was higher in fathers (26.2×18.7μg/24h, p=0.01), but did not differ between the genders after d-penicillamine (521.7×525.3, range 31.6–1085.1μg/24h, p=0.8).Conclusions: The mean values of serum copper, ceruloplasmin, and basal urinary copper excretion were different between males and females. The current diagnostic threshold of 24-h urinary copper excretion after d-penicillamine was not reached by heterozygotes. The increased urinary copper excretion after d-penicillamine challenge was much higher than fivefold the upper limit of normal urinary copper excretion in the majority of heterozygotes and should not be taken into account when diagnosing Wilson's disease.

Severe acute autoimmune hepatitis after natalizumab treatment - Corrected Proof

Andrea Lisotti, Francesco Azzaroli, Stefano Brillanti, Giuseppe Mazzella — 2011-12-12

Immunomodulatory treatment for multiple sclerosis (MS) has been described as related to autoimmune hepatitis (AIH) exacerbation . Recently, six cases of drug-induced liver injury (DILI) after treatment with natalizumab were reported . Here we describe a case of a 31-year-old female patient admitted to our Unit for acute liver failure. Three years earlier the patient was diagnosed with MS, treated with systemic steroids and interferon-beta (IFN-β). The patient presented with an aminotransferase flare followed by a spontaneous normalization after withdrawal of IFN-β (). After drugs suspension, neurological symptoms relapsed and marked worsening of brain abnormalities were found at magnetic resonance imaging. The patient underwent complete screening for autoimmune (autoantibodies) and infectious diseases (HIV, HCV, HBV, Tuberculosis); natalizumab infusion was started in May 2009 at a monthly dose of 300mg.

Colon capsule endoscopy may represent an effective tool for colorectal cancer screening: A single-centre series - Corrected Proof

Alessandro Mussetto, Omero Triossi, Stefano Gasperoni, Tino Casetti — 2011-12-12

We read with great interest the recent review by Spada et al. about colon capsule endoscopy (CCE), a new technique that allows visualization of the colon. Authors reviewed the results shown by CCE in clinical studies and suggested that all patients with suspected colonic disease, referred for a diagnostic colonoscopy, are potentially candidates for a CCE examination and that CCE might be used as a filter for therapeutic colonoscopy. The analysis was made for the first generation PillCam colon (Given Imaging Ltd., Israel), even if a substantial improvement of accuracy has been achieved with second generation CCE, confirmed by a recent multicenter study .

Oesophageal motility impairment in type I myotonic dystrophy: Usefulness of high resolution manometry - Corrected Proof

Guillaume Paris, Eric Verin, Anne-Marie Leroi, Guillaume Gourcerol — 2011-12-12

Dysphagia is an almost constant symptom associated with later stages of type-I myotonic dystrophy (MD1), and may cause aspiration and ultimately pneumonia, which has been reported as the most common cause of death in these patients. This is usually attributed to oro-pharyngeal dysmotility with altered pharyngeal peristaltism associated with decreased upper oesophageal sphincter (UES) closing pressure . However, a few reports pointed out the oesophageal motility involvement in these patients . In the present letter, we report two cases of oesophageal motility impairment in MD1 using high resolution manometry (HRM), which has been recently developed to better map oesophageal motility .

Intrahepatic biliary cystadenoma and cystadenocarcinoma: An experience of 30 cases - Corrected Proof

Chu Wang, Ruoyu Miao, Huilin Liu, Xiaojing Du, Liguo Liu, Xin Lu, Haitao Zhao — 2011-12-12

Abstract: Background and objectives: Intrahepatic biliary cystadenoma and biliary cystadenocarcinoma are extremely rare neoplasms of the liver. They share similar radiological characteristics, and the clinicopathological features are poorly defined. We aim to provide an algorithm for preoperative differentiation of the two diseases.Methods: Patients who underwent liver resection between May 2001 and May 2011 at Peking Union Medical College Hospital with biliary cystadenoma (20 cases) and biliary cystadenocarcinoma (10 cases) were reviewed.Results: Significant differences were shown in age (P=0.030), gender (P=0.002) and symptom duration (P=0.012). Most biliary cystadenomas occurred in women ≤60 years old (85%), whilst most biliary cystadenocarcinomas occurred in older males (50%). Shorter symptom duration indicated a higher risk of biliary cystadenocarcinoma. Arterial blood flow and wall/nodule enhancement tended to be more common in biliary cystadenocarcinoma, but the difference was not significant (P=0.348). A score system was developed. The case-by-case validation and leave-one-out cross-validation showed an accuracy of 95.5% and 90.9%, respectively. The discriminative accuracy for cases from another hospital during the same period was 90.9%.Conclusions: Older age, male gender, and shorter symptom duration are associated with higher possibility of biliary cystadenocarcinoma. Location and blood supply by radiology might be instrumental but still need further verification.

Transient Hepatic Parenchymal Enhancement detected at dynamic imaging: A short instruction manual for the clinician - Corrected Proof

Stefano Colagrande, Silvia Pradella, Silvia Lucarini, Fabio Marra — 2011-12-09

Abstract: Basic knowledge in the interpretation of hepatic imaging is essential for the clinical hepatologist. In recent years, the availability of dynamic imaging studies of the liver using computed tomography or magnetic resonance has led to appreciate the importance of early changes in arterial perfusion for the interpretation of hepatic lesions. Transient Hepatic Parenchymal Enhancement (THPE) is defined as a normal area of liver parenchyma that enhances after injection of contrast agent during the arterial phase of perfusion. Appearance of this sign is mostly associated with a reduction in portal perfusion or with inflammation, and appears in different morphologic patterns. THPE should not be considered a radiological artefact, and its interpretation is essential to avoid misclassification of hepatic lesions that may have clinical significance, such as hepatocellular carcinoma or hepatic metastases. In this short review we provide essential information on the causes, pathophysiology and morphology of THPE, and discuss the relevance of these findings in a clinical perspective.

Amebic colitis in Italy after Christmas - Corrected Proof

Guido Basilisco, Romualdo Grande, Stefano Ferrero — 2011-12-07

After spending his Christmas holidays in Egypt, a 54-year-old business man living in Milan was referred to us because of hematochezia in March 2011. Colonoscopy revealed ulcers in the right colon (arrow, ) and the rectum; the mucosa between the ulcers had a normal appearance. Histological examinations of colonic biopsies revealed a normal mucosal architecture with increased number of eosinophils in the submucosa (arrows, a); no parasites were found. However, serum anti-amoeba antibody levels were high, and the parasite was finally found upon direct stool examination and cultured in Robinson's medium. b shows two chromatoidal bodies (arrows) with the elongated shape and blunt, rounded edges typical of a protozoal cyst. Isoenzymatic characterisation identified an Entamoeba histolytica as zymodeme II. The patient was successfully treated with tinidazole 2g for five days followed by paromomycin 1.4g for seven days.

High tissue-transglutaminase antibody level predicts small intestinal villous atrophy in adult patients at high risk of celiac disease - Corrected Proof

2011-11-28

Abstract: Background: Duodenal biopsy may be unnecessary to confirm celiac disease in patients with high tissue-transglutaminase antibody level.Aims: To define a cut-off value of tissue-transglutaminase antibody with high positive likelihood ratio for duodenal atrophy in patients with suspected celiac disease.Methods: We retrospectively identified 945 patients with suspected celiac disease and classified according to the method used for tissue-transglutaminase antibody assay: Group A (n=393, Eu-tTG® Eurospital), Group B (n=263; Eu-tTG® Eurospital) and Group C (n=289; Celikey® Phadia). Duodenal histology was graded according to Marsh. Sensitivity, specificity, and positive likelihood ratio were used to evaluate cut-off points of tissue-transglutaminase antibody as predictor of villous atrophy.Results: 100% specificity and ∞ positive likelihood ratio for duodenal atrophy was observed at a cut-off value of tissue-transglutaminase antibody 5 times higher than the upper limit of normal. CD diagnosis was confirmed by concordance with antiendomysial antibodies, and by reduction of t-TG titre in all patients and improvement of duodenal histology in 80% during gluten-free diet.Conclusions: Tissue-transglutaminase antibody level 5-folds the upper limit of normal is 100% specific for duodenal atrophy and using this cut-off biopsy could by avoided in 1/3 of patients. Diagnostic criteria of celiac disease in adults need revision.

N-glycan based biomarker distinguishing non-alcoholic steatohepatitis from steatosis independently of fibrosis - Corrected Proof

2011-11-28

Abstract: Background: Non-alcoholic fatty liver disease is a spectrum of disorders ranging from steatosis to non-alcoholic steatohepatitis (NASH). Steatosis of the liver is benign, whereas NASH can progress to cirrhosis or even hepatocellular carcinoma. Currently, a liver biopsy is the only validated method to distinct NASH from steatosis.Aim: The objective of this study was to identify a biomarker specific for NASH based on the N-glycosylation of serum proteins.Methods: N-glycosylation patterns were assessed using DNA sequencer-assisted fluorophore-assisted capillary electrophoresis and compared with histology.Results: Initially, a glycomarker (log[NGA2F]/[NA2]) was developed based on the results obtained in 51 obese non-alcoholic patients scheduled for bariatric surgery. Multivariate analysis showed that our glycomarker had the lowest P-value of all biomarkers in distinguishing NASH from steatosis (P=0.069). The glycomarker was validated in a cohort of 224 non-alcoholic fatty liver disease patients. In both pilot and validation study, glycomarker score increased in ascending amount of lobular inflammation (single-factor ANOVA, P≤0.001 and P=0.012, respectively). The N-glycan profile of immunoglobulin G in the NASH population confirmed the significantly increased undergalactosylation present in these patients.Conclusion: Our glycomarker specifically recognises liver inflammation in obese individuals which is the main trigger for the development of steatohepatitis and can differentiate between steatosis and NASH.

Bleeding and thrombosis in cirrhotic patients: What really matters? - Corrected Proof

Domenico Ferro, Francesco Angelico, Stephen H. Caldwell, Francesco Violi — 2011-11-28

Abstract: Bleeding complications, particularly in the gastro-intestinal tract, may complicate the clinical course of liver cirrhosis. Coexistence of abnormal global tests exploring the platelet and clotting systems generated the hypothesis that cirrhotic patients have “coagulopathy” predisposing to bleeding complications. Using more sophisticated laboratory methods this hypothesis has been partly confuted as cirrhotic patients actually disclose an ongoing prothrombotic state in the portal and systemic circulation that could predispose to thrombosis. Recent data of the literature support this hypothesis as portal vein thrombosis and peripheral thrombosis are frequent features of cirrhosis. We reviewed the literature data to assess the prevalence of bleeding and thrombotic complication in cirrhosis and the role of clotting activation in precipitating them. Whilst it appears scarcely relevant the interplay between the so called “coagulopathy” and bleeding, the interplay between clotting activation and thrombosis seems to be relevant but needs more accurate investigation in larger study populations.

Safety and outcome of chemoradiotherapy in elderly patients with rectal cancer: Results from two French tertiary centres - Corrected Proof

2011-11-28

Abstract: Background: The risks of chemoradiotherapy in elderly patients with rectal cancer have not yet been well-characterised.Methods: We retrospectively reviewed the charts of patients with rectal cancer over 70 years old who were treated with chemoradiotherapy in two French university hospitals.Results: A total of 125 patients were evaluated. Mean age was 75.1±4.1 years and ranged from 70 to 90 years. Adverse effects≥grade 2 were observed in 32% of the patients and adverse effects≥grade 3 in 15%. Dose reduction for toxicity was performed in 18% of the patients and chemoradiotherapy discontinuation was necessary in 9%. Postoperative morbidity was 16% with two treatment-related deaths. Two-year survival rate was 84%. No variables had any influence on treatment-related adverse events.Conclusions: In selected elderly patients, chemoradiotherapy is well-tolerated, without any significant increase in adverse events, and the results are similar to those recorded in younger patients.

Computed tomographic enteroclysis with air and virtual enteroscopy: Protocol and feasibility for small bowel evaluation - Corrected Proof

2011-11-28

Abstract: Background and aims: We describe our optimized protocol for computed tomographic enteroclysis using air as the contrast material and report an early assessment of its clinical performance.Methods: Thirty-one examinations of computed tomographic enteroclysis with air were performed in 30 patients in our hospital from September 2008 to September 2010. The volume of injected air and intra-intestinal pressure were monitored in 16 cases. The data were reviewed for ratios of successful whole small bowel depictions out of the total number of examinations for patients without stenosis. Efforts were made to confirm depicted abnormal findings when possible by other imaging techniques, intra-operative findings, histopathological findings, and subsequent history.Results: The injected air volume and final intra-intestinal pressure were 2925±686ml and 24.5±7.1cm H2O in cases without stenosis. In 19 examinations with anterograde air injection for patients without stenosis, whole small bowel depiction was achieved in 16 (84.2%). Computed tomographic enteroclysis with air was useful for detecting strictures (in Crohn's disease, malignant lymphoma, metastatic carcinoma), Meckel's diverticulum, and for excluding other obstructive conditions in ileus.Conclusions: Computed tomographic enteroclysis with air has a potential to enable the exploration of the whole small bowel, thereby providing information of small bowel lesions that complements other techniques.

Propofol, the preferred sedation for screening colonoscopy, is underused. Results of an international survey - Corrected Proof

Andrea Riphaus, Carlos Macias-Gomez, Jacques Devière, Jean-Marc Dumonceau — 2011-11-28

Abstract: Background: The use of propofol during colonoscopy has become more widespread. To increase availability while maintaining quality and decreasing costs, European Guidelines have been issued for non-anesthesiologist administration of propofol (NAAP). We aimed to assess the current use of propofol during screening colonoscopy.Methods: International survey.Results: Eighty-four questionnaires were collected from endoscopists practicing in 29 countries. Practices were most often located in high-volume community hospitals (Italy, Belgium, Spain, Netherlands in half cases). An anesthesiologist was regularly present in the Endoscopy Unit of 69.0% survey respondents. In low-risk (ASA classification, 1–2) patients, propofol, benzodiazepine+opioids and benzodiazepine alone were used in 45%, 31% and 14% of screening colonoscopies, respectively. Propofol was associated with the highest endoscopist satisfaction (score on a 10-point visual analogue scale, 9.2±1.2 vs. 5.5±1.9 and 4.7±2.0 for benzodiazepine+opioids and benzodiazepine alone, respectively; P<0.0001). NAAP was used by 29.9% of respondents in 9 countries and approximately two-thirds of other endoscopists would consider implementing NAAP. Main reasons for not considering NAAP implementation were medico-legal issues and cost.Conclusion: Propofol provides the highest endoscopist satisfaction but it is used in less than half of screening colonoscopies. Propofol is administered by non-anesthesiologists in one-third of settings; its implementation is foreseen by a majority of endoscopists who do not currently use it.

High frequency of fatal haemophagocytic lymphohistiocytosis syndrome in enteropathy-associated T cell lymphoma - Corrected Proof

2011-11-21

Abstract: Introduction: Enteropathy-associated T-cell lymphoma is a rare form of T-cell lymphoma associated with a poor prognosis and the relative ineffectiveness of standard chemotherapy. The occurrence of haemophagocytic lymphohistiocytosis has been reported only once with this entity.Patients and methods: A retrospective study of 15 patients with enteropathy-associated T-cell lymphoma (type 1 in 12), followed-up in our units, since 1985. Two patients died before starting chemotherapy. The remaining 13 patients were treated with standard chemotherapy (n=7) and purine nucleotide analogues (n=6).Results: Median follow-up was 8.7 (1–97) months. Surgery was required in 10 patients (66%) for intestinal complications (n=7) or elective small bowel resection (n=3). Survival probability was 40% and 20% at 1 and 5 years, respectively (Kaplan–Meier method). Survival was not significantly different between the two chemotherapy regimens. However, a slight decrease of febrile neutropenia was observed in the purine nucleotide analogues group (p=0.06). Haemophagocytic lymphohistiocytosis occurred in 6/15 (40%) cases. In these six patients, haemophagocytic lymphohistiocytosis was always fatal within 3 months.Conclusion: Enteropathy-associated T-cell lymphoma is associated with a poor outcome, independently of the chemotherapy regimens administered and frequent occurrence of haemophagocytic lymphohistiocytosis. The latter complication should be considered for urgent rescue therapy.

Chronic rectal ulcer as result of combined mucosal toxicity of NSAID, argon plasma coagulation and radiotherapy - Corrected Proof

Maximilien Barret, Romain Coriat, Sarah Leblanc, Stanislas Chaussade — 2011-11-21

A 71-year-old woman was referred to our institution for hematochezia. She had a medical history of chronic articular pain that was treated by oral on-demand non-steroidal anti-inflammatory drugs (NSAIDs), and T3N1 squamous-cell carcinoma of the anal canal, successfully treated one year before with concomitant chemoradiotherapy. The patient underwent control endoscopy ten months after radiochemotherapy and was found to have a cicatricial ulcer, corresponding with white 1cm ulceration above the pectineal line, amidst telangiectasia (). A first episode of hematochezia in the patient, related to a haemorrhagic radiation proctitis, was treated with argon plasma coagulation (APC). Six weeks later, the patient reported a recurrence of hematochezia, and a 5cm long ulcer of the lower rectum () was observed through a rectosigmoidoscopy. Biopsies showed aspecific granular tissue, and further examinations helped rule out a tumour recurrence. Rectal bleeding ceased after 10 weeks, and complete reepithelialization of the ulcer was observed after 14 months, with no other treatment other than NSAIDs withdrawal.

Jejunal pseudomelanosis - Corrected Proof

Stijn J.B. Van Weyenberg, Nicole C. Van Grieken — 2011-11-11

A 91-year old man with chronic renal failure attributed to longstanding hypertension presented with rectal blood loss and haemodynamic instability. Medications included furosemide and hydrochlorothiazide. Oesophagogastroduodenoscopy was normal and colonoscopy showed fresh blood in the colon and terminal ileum, without a focus being identified. Because of suspected ongoing midgastrointestinal bleeding, per-oral double balloon endoscopy was performed. The jejunum revealed a speckled pattern of brownish hyperpigmentation beginning shortly after the pylorus and extending up to 1.5m in the mid jejunum (Fig. 1). Jejunal biopsy specimens showed brown pigment deposition within the apical part of otherwise normal villi (Fig. 2A, H&E stain). Additional staining showed the pigment was included in macrophages (Fig. 2B, CD68-stain).

Familial intraductal papillary mucinous neoplasms of the pancreas - Corrected Proof

2011-08-08

Abstract: The prevalence of intraductal papillary mucinous neoplasms in patients with a high risk of pancreatic adenocarcinoma was estimated to be 15%. However, a familial form of intraductal papillary mucinous neoplasms was never described.Methods: Three families (8 patients) with intraductal papillary mucinous neoplasms familial forms were described. Diagnosis was made according to radiological criteria and was confirmed by pathological data. Genetic predisposing factors of pancreatic cancer were searched for.Results: Symptoms related to intraductal papillary mucinous neoplasms were recurrent acute pancreatitis (n=3) or fortuitous discovery (n=5). Number of cystic lesions was ≤3 (n=4) or >3 (n=4). Intraductal papillary mucinous neoplasms involved branch ducts (n=7) or both main pancreatic duct and branch duct (n=1). Severe and moderate dysplasia was found on surgical specimens. No genetic alteration was found (BRCA2, p16 or CDKN2A genes).Conclusion: A familial form of intraductal papillary mucinous neoplasms was found in three families. No pancreatic cancer was found in relatives but an attentive survey has to be proposed.

Increased serum chemerin concentration in patients with chronic pancreatitis - Corrected Proof

2011-07-28

Abstract: Background: Chemerin is a potent chemoattractant for chemokine-like receptor 1 expressing cells and is involved in inflammatory and immune processes that play an important role in chronic pancreatitis.Aim: To test the hypothesis that serum chemerin concentration may be affected in chronic pancreatitis patients and that chemerin can influence the course of chronic pancreatitis by increasing profibrotic cytokine production.Methods: Serum concentrations of chemerin and the major cytokines involved in pancreatic fibrosis such as platelet-derived growth factor BB and transforming growth factor β-1 were determined by ELISA in samples from 40 nondiabetic and 28 diabetic male patients with chronic pancreatitis of alcoholic origin and 40 age-matched healthy controls.Results: Serum concentrations of chemerin were increased both in nondiabetic and diabetic chronic pancreatitis patients compared to controls. Moreover, in chronic pancreatitis patients a positive correlation was found between serum chemerin and platelet-derived growth factor BB as well as transforming growth factor β-1 concentrations.Conclusions: The results indicate for the first time that: (a) chronic pancreatitis in humans is associated with an increased serum chemerin concentration and (b) serum chemerin concentration correlates with serum concentrations of the major profibrotic cytokines. Elevated level of chemerin, by stimulating macrophage infiltration of the pancreas, might lead to overproduction of platelet-derived growth factor BB and transforming growth factor β-1 and, consequently, to pancreatic fibrosis.

WITHDRAWN: Rational reformulation of long-acting preparations: the development of a novel formulation of prolonged-release lanreotide - Corrected Proof

S. Wright — 2009-01-07

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.