[Show abstract][Hide abstract] ABSTRACT: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by vascular malformations. The genes known to be associated with HHT include ENG (HHT1), ACVRL1 (HHT2) and SMAD4 (JPHT). It has been reported that circulating CD34+ cell subsets repair damaged vessels. To investigate whether mobilization of these cells is present in the peripheral blood (PB) of HTT patients, we analyzed CD34+ cells, CD34+VEGFR-2+ progenitor or mature endothelial cells, and CD34+CD133+VEGFR-2− hematopoietic progenitor cells (HPCs). Cytofluorimetric analysis was performed in 150 HTT patients and 43 healthy subjects (CTRLs). In HTT patients, PB CD34+ cells were significantly increased; the frequency of endothelial cells was higher (P = 0.002), while the frequency of CD34+CD133+VEGFR-2− HPCs was lower (P = 0.00007) than in CTRLs. Results were comparable in patients with ENG or ACVRL1 gene mutation; in patients with ENG mutation, the frequency of the cell subsets inversely correlated with the age of the patients at time of sampling (CD34+), disease duration (CD34+VEGFR-2+), and age at disease onset (CD34+CD133+VEGFR-2−). In conclusion, HHT patients show an increase of circulating endothelial cells and a decrease of HPCs. In patients with ENG mutation, the frequency of CD34+ endothelial cells correlates with specific clinical characteristics suggesting that their active turnover characterizes the initial phase of the disease.
International Journal of Hematology 12/2014; 101(1). DOI:10.1007/s12185-014-1698-4 · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Prevalence of gastroduodenal lesions is changing in the last decades. Prevalence of Helicobacter pylori infection, non-steroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitor (PPI) therapy may be involved in such a phenomenon. We assessed gastroduodenal lesions prevalence in a nationwide study. Materials and methods: Consecutive patients who underwent upper endoscopy for the first time in 24 Italian centres between January 2012 and 31 March 2012 were enrolled. Prevalence of gastric ulcer (GU), duodenal ulcer (DU), gastric erosions (GE), duodenal erosions (DE), gastric polyp (GP), Barrett's oesophagus (BE), and neoplasia was assessed. Results: Overall, 1054 (M/F: 388/666; Mean age: 57.5 +/- 5 years) patients were enrolled. H. pylori infection was detected in 356 (33.9%) patients, 358 (34%) were taking NSAIDs, and 532 (50.5%) PPIs. PPI therapy was associated with a significantly lower H. pylori detection rate (27.8% vs 39.8%; OR: 0.6, 95% CI 0.45-0.77; P < 0.001). GU, DU, GE, DE, GP and BE were detected in 17 (1.6%), 13 (1.2%), 150 (14.2%), 50 (4.7%), 51 (4.8%) and 17 (1.6%), respectively. Moreover, 3 (0.3%) distal gastric cancers were observed. H. pylori infection remained the most prevalent factor for all gastroduodenal lesions, but gastric polyp. One third of patients with GU and GE were taking only NSAIDs therapy. Conclusions: The prevalence of peptic ulcer was very low(<3%), with a similar rate between DU and GU. As many as half patients were on ongoing PPI therapy. Such a therapy could affect both the detection rate of H. pylori infection and the real prevalence of gastroduodenal lesions.
European Journal of Internal Medicine 09/2014; 25(8). DOI:10.1016/j.ejim.2014.08.010 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The burden of gastric precancerous conditions and factors associated with their detection have not been fully investigated in community-based settings. Little is known about adherence to Sydney system for histopathology of gastric biopsies.Objective
We aimed to investigate what really happens in clinical practice with regard to the detection of gastric atrophy and intestinal metaplasia in dyspeptic patients.Methods
We performed a nationwide survey of 979 consecutive patients (50–65 years old) with dyspeptic symptoms, examined at 24 gastrointestinal endoscopy units throughout Italy. Clinical information was collected from questionnaires; a standard bioptic mapping was performed in each unit, biopsies from each patient were analyzed by histopathology performed according to daily clinical practice in each local histopathology center.ResultsSeparate descriptions of antral and corporal biopsies were included in 679 pathology reports (69%), whereas Sydney system was applied in 324 reports (33%). Gastric atrophy without intestinal metaplasia (GA) and gastric atrophy with intestinal metaplasia (GIM) were detected in 322 (33%) patients. The full adherence to Sydney system significantly increased the probability of detecting GIM (OR 9.6, 95% CI 5.5–16.7), GA (OR 1.92, 95% CI 1.07–3.44), and either of the conditions (OR 6.67, 95% CI 4.36–10.19).Conclusions
This nationwide survey showed that in one-third of dyspeptic patients, gastric precancerous conditions are detected. In daily routine practice, only 1/3 of histology reports were worked out adhering to Sydney system showing that international guidelines are poorly observed in clinical practice. This may represent a critical element for surveillance strategies for gastric cancer.
[Show abstract][Hide abstract] ABSTRACT: In 2011 the three major Italian gastroenterological scientific societies (AIGO, the Italian Society of Hospital Gastroenterologists and Endoscopists; SIED, the Italian Society of Endoscopy; SIGE, the Italian Society of Gastroenterology) prepared their official document aimed at analysing medical care for digestive diseases in Italy, on the basis of national and regional data (Health Ministry and Lombardia, Veneto, Emilia-Romagna databases) and to make proposals for planning of care.
Digestive diseases were the first or second cause of hospitalizations in Italy in 1999–2009, with more than 1,500,000 admissions/year; however only 5–9% of these admissions was in specialized Gastroenterology units.
Reported data show a better outcome in Gastroenterology Units than in non-specialized units: shorter average length of stay, in particular for admissions with ICD-9-CM codes proxying for emergency conditions (6.7 days versus 8.4 days); better case mix (higher average diagnosis-related groups weight in Gastroenterology Units: 1 vs 0.97 in Internal Medicine units and 0.76 in Surgery units); lower inappropriateness of admissions (16–25% versus 29–87%); lower in-hospital mortality in urgent admissions (2.2% versus 5.1%); for patients with urgent admissions due to gastrointestinnal haemorrhage, in-hospital mortality was 2.3% in Gastroenterology units versus 4.0% in others. The present document summarizes the scientific societies’ official report, which constitutes the “White paper of Italian Gastroenterology”.
[Show abstract][Hide abstract] ABSTRACT: The scarcity of human and structural resources for specialized gastroenterology care is a problem in many Western countries. Data regarding the resources for Italian Gastroenterology, so far lacking, have been thus searched and evaluated. Based on an agreement protocol between the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO) and the Ministry of Health, national data regarding all Institutions providing gastroenterological care were analysed. Hospital beds in Gastroenterology units are presented by region, regimen of stay and per million inhabitants as of January 2011.
Association of Hospital Gastroenterologists and Endoscopists also performed a survey of gastroenterology units in all Italian regions regarding number of ordinary/day hospital beds and the number of staff gastroenterologists.
The Ministry data showed a total of 174 Gastronterology Units in Italy, a total of 2062 hospital beds for the discipline, for a proportion of 34.2 beds per million inhabitants.
The Association of Hospital Gastroenterologists and Endoscopists survey showed a total of 1425 gastroenterologists in Italy.
These data should represent a key reference for appropriate planning of specialized care for digestive diseases.
[Show abstract][Hide abstract] ABSTRACT: This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to investigate whether pulmonary shunt grade on transthoracic contrast echocardiography (TTCE) predicts the size of pulmonary arteriovenous malformations (PAVMs) on chest computed tomography (CT) and subsequent feasibility for transcatheter embolotherapy.We prospectively included 772 persons with possible or definite hereditary haemorrhagic telangiectasia, who underwent both TTCE and chest CT for screening of PAVMs. A quantitative three-point grading scale was used to classify the pulmonary shunt size on TTCE (grade 1-3). Transcatheter embolotherapy was performed for PAVMs deemed large enough for endovascular closure on chest CT.TTCE documented pulmonary shunting in 510 (66.1%) patients. The positive predictive value of a pulmonary shunt grade 1, 2 and 3 on TTCE for presence of PAVMs on chest CT was 13.4%, 45.3% and 92.5%, respectively (p<0.001). None of the 201 persons with a pulmonary shunt grade 1 on TTCE had PAVMs on chest CT large enough for transcatheter embolotherapy, while 38 (25.3%) and 123 (77.4%) individuals with a pulmonary shunt grade 2 and 3 on TTCE, respectively, underwent endovascular closure of PAVMs.Pulmonary shunt grade on TTCE predicts the size of PAVMs on chest CT and their feasibility for subsequent transcatheter embolotherapy. Chest CT can be safely withheld from all persons with a pulmonary shunt grade 1 on TTCE, as any PAVM found in these subjects will be too small for transcatheter embolotherapy.
European Respiratory Journal 03/2014; 44(1). DOI:10.1183/09031936.00133713 · 7.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Liver transplantation (LT) in patients with hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber, disease is a problematic procedure. In patients with hepatic involvement due to clinically significant arterovenous malformations, there is high risk of intraoperative bleeding and intra- or perioperative complications. Some surgical corrections have been proposed for venous problems, concerning the vena caval anastomosis. A common finding in HHT is arterial enlargement of the celiac trunk and of the common hepatic artery. We report 2 cases of LT in HHT where the arterial anastomosis was successfully performed using the splenic artery of the recipient, which shows less tendency for enlargement than the celiac trunk.
[Show abstract][Hide abstract] ABSTRACT: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia. Mutations in either ENG or ACVRL1 account for around 85% of cases, and 10% are large deletions and duplications. Here we present a large novel deletion in ACVRL1 gene and its molecular characterization in a 3 generation Italian family. We employed short tandem repeats (STRs) analysis, direct sequencing, multiplex ligation-dependant probe amplification (MLPA) analysis, and 'deletion-specific' PCR methods. STRs Analysis at ENG and ACVRL1 loci suggested a positive linkage for ACVRL1. Direct sequencing of this gene did not identify any mutations, while MLPA identified a large deletion. These results were confirmed and exactly characterized with a 'deletion-specific' PCR: the deletion size is 4,594 bp and breakpoints in exon 3 and intron 8 show the presence of short direct repeats of 7 bp [GCCCCAC]. We hypothesize, as causative molecular mechanism, the replication slippage model. Understanding the fine mechanisms associated with genomic rearrangements may indicate the nonrandomness of these events, highlighting hot spots regions. The complete concordance among MLPA, STRs analysis and 'deletion-specific PCR' supports the usefulness of MLPA in HHT molecular analysis.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: A pulmonary right-to-left shunt (RLS) carries the risk of cerebral paradoxical embolization and severe neurological complications. Recognising patients at risk is important to facilitate appropriate management strategies, but a direct relation between pulmonary shunt size and risk of complications remains controversial. OBJECTIVE: This study evaluated the potential relation between pulmonary shunt size on transthoracic contrast echocardiography (TTCE) and prevalence of cerebral manifestations in persons screened for hereditary haemorrhagic telangiectasia (HHT). METHODS: We conducted a two-center, cross-sectional study of all consecutive persons screened for HHT between 2004 and 2011. Pulmonary shunt grading was performed according to contrast opacification of the left ventricle on TTCE (grade 0, no microbubbles; 1, <30 microbubbles; 2, 30-100 microbubbles; 3, >100 microbubbles). Cerebral manifestations were defined as ischemic stroke, transient ischemic attack or brain abscess, diagnosed by a neurologist and confirmed by appropriate imaging techniques. RESULTS: A pulmonary RLS was present in 530 out of 1038 patients (51.1%, mean age 44.3±15.6 years, 58.6% women). The presence of a cerebral manifestation (n=51) differed significantly between pulmonary shunt grades on TTCE; 1.4%, 0.4%, 6.5% and 20.9% for grade 0, 1, 2 and 3 respectively. Pulmonary shunt grade 1 was not associated with an increased prevalence of cerebral manifestations (OR 0.44, 95%CI 0.05-4.13, p=0.47), while pulmonary shunt grade 2 (OR 4.78, 95%CI 1.14-20.0, p=0.03) and grade 3 (OR 10.4, 95%CI 2.4-45.3, p=0.002) were both independent predictors for the prevalence of a cerebral ischemic event or brain abscess. CONCLUSION: Pulmonary RLS grade on TTCE is strongly associated with the prevalence of cerebral complications in patients screened for HHT.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Defensive medicine is becoming more frequent behaviour and has an impact on the economic 'health' of national healthcare systems. AIM: The aim of this study was to clarify the impact of defensive medicine on gastroenterological practices in Lombardy. METHODS: Gastroenterologists attending the Lombardy Annual Gastroenterological Conference received a questionnaire based on multiple choice tests and visual analogue scales. The questionnaire was divided into three parts evaluating the respondent's characteristics, the number of procedures prescribed, and the percentage of those performed with a defensive purpose. RESULTS: Sixty-four of 107 participants (60%) completed the questionnaire, 94% of whom reported practising defensive medicine. The percentage of defensively requested procedures amounted to 18% of all digestive endoscopies, 8.9% of abdominal ultrasonography scans, 4.9% of abdominal computed tomography or magnetic resonance scans, and 12.2% of all consultations. The total number of defensive procedures prescribed per month by the participants was 878, and 31.7% of the performed procedures (n=4897) were reported to defensively based. On the basis of the 2012 regional reimbursement fees, the yearly cost of defensive procedures prescribed and/or performed by all gastroenterologists in Lombardy was estimated to be € 8,637,835. CONCLUSIONS: Our findings indicate that defensive medicine profoundly affects current medical practices among gastroenterologists, and has a considerable economic impact.
[Show abstract][Hide abstract] ABSTRACT: Activin A receptor, type II-like kinase 1 (also called ALK1), is a serine-threonine kinase predominantly expressed on endothelial cells surface. Mutations in its ACVRL1 encoding gene (12q11-14) cause type 2 Hereditary Haemorrhagic Telangiectasia (HHT2), an autosomal dominant multisystem vascular dysplasia. The study of the structural effects of mutations is crucial to understand their pathogenic mechanism. However, while an X-ray structure of ALK1 intracellular domain has recently become available (PDB ID: 3MY0), structure determination of ALK1 ectodomain (ALK1(EC)) has been elusive so far. We here describe the building of a homology model for ALK1(EC), followed by an extensive bioinformatic analysis, based on a set of 38 methods, of the effect of missense mutations at the sequence and structural level. ALK1(EC) potential interaction mode with its ligand BMP9 was then predicted combining modelling and docking data. The calculated model of the ALK1(EC) allowed mapping and a preliminary characterization of HHT2 associated mutations. Major structural changes and loss of stability of the protein were predicted for several mutations, while others were found to interfere mainly with binding to BMP9 or other interactors, like Endoglin (CD105), whose encoding ENG gene (9q34) mutations are known to cause type 1 HHT. This study gives a preliminary insight into the potential structure of ALK1(EC) and into the structural effects of HHT2 associated mutations, which can be useful to predict the potential effect of each single mutation, to devise new biological experiments and to interpret the biological significance of new mutations, private mutations, or non-synonymous polymorphisms.
PLoS ONE 10/2011; 6(10):e26431. DOI:10.1371/journal.pone.0026431 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute biliary pancreatitis (ABP) is a clinical condition that can rapidly evolve into a life-threatening one. Endoscopic retrograde cholangiopancreatography (ERCP) has been considered the standard treatment of ABP for many years, though it entails the risk of morbidity and mortality. Endoscopic ultrasonography (EUS) can reliably diagnose choledocholithiasis avoiding unnecessary ERCP in patients with no stones in the biliary tract.
We undertook a systematic review of the randomized controlled trials and clinical trials comparing EUS and ERCP to evaluate procedure performance, complication rates, clinical course of pancreatitis, and hospital stay according to the treatment given.
A computerized bibliographic search was performed from 1994 to April 2010. Two reviewers assessed the methodological quality of eligible trials and independently extracted data from the included trials.
Seven studies enrolled 545 patients with acute pancreatitis of suspected biliary origin. Only one was a randomized controlled trial. EUS had a lower failure rate than ERCP in all the studies included, avoiding ERCP in 71.2% of cases. No complications were related to EUS, whereas sphincterotomy was associated with bleeding in up to 22% of patients. The procedures did not influence the clinical course of pancreatitis.
A strategy based on EUS before ERCP in patients with ABP may be an effective alternative to diagnostic ERCP.
European journal of gastroenterology & hepatology 05/2011; 23(5):367-74. DOI:10.1097/MEG.0b013e3283460129 · 2.15 Impact Factor