Isolated nonspecific terminal ileitis: prevalence, clinical evolution and correlation with metachronous diagnosis of Crohn's disease: a retrospective study and review of the literature.

Background: The existing literature does not provide adequate guidance on the diagnosis and management of patients with nonspecific terminal ileitis, while data regarding the percentage of patients who ultimately develop Crohn's disease (CD) are scarce. We evaluated the prevalence and natural course of nonspecific terminal ileitis in patients who underwent colonoscopy during a 11-year period. Methods: All patients with endoscopic findings of terminal ileitis and nonspecific histological findings were included. Exclusion criteria were a clinical history of CD or any other disease that can cause terminal ileitis, or a recent history of using drugs implicated in lesions of the terminal ileum. Results: From 5353 colonoscopies, 92 patients with nonspecific terminal ileitis were identified (prevalence: 1.7%). Among these patients, 56 (61%) had available follow up for ≥6 months after the initial endoscopy. Main indications for endoscopy were chronic diarrhea (37.5%), screening endoscopy (23%), and abdominal pain (20%). Sixteen (29%) patients received medical treatment, while recession of symptoms was recorded in 19 of 43 symptomatic patients (44.1%). Twenty-three (41%) of the 56 patients underwent a second endoscopy and 15 (65.2%) cases had persistent endoscopic findings. Eleven (19.6%) of the 56 patients were eventually diagnosed with CD. The probability of CD diagnosis was significantly higher in patients with persistent symptoms (P=0.002) and endoscopic findings at follow up (P=0.038). Conclusions: Nonspecific terminal ileitis generally has a benign clinical course. However, patients with persistent symptoms and endoscopic lesions are at increased risk for subsequent development of CD.

Chronic constipation in Parkinson's disease: clinical features and molecular insights on the intestinal epithelial barrier.

Background: Chronic constipation (CC) is a severe symptom in Parkinson's disease (PD), with an unclear pathogenesis. Abnormalities of the enteric nervous system (ENS) and/or intestinal epithelial barrier (IEB) may be pathophysiologically relevant in PD patients with CC. We investigated possible molecular changes of the IEB in PD/CCs compared with CCs and controls. Methods: Twelve PD/CCs (2 female, age range 51-80 years), 20 CCs (15 female, age range 27-78 years), and 23 controls (11 female, age range 32-74 years) were enrolled. Ten PD/CCs and 10 CCs were functionally characterized by anorectal manometry (AM) and transit time (TT). Colon biopsies were obtained and assessed for gene and protein expression, and localization of IEB tight junction markers claudin-4 (CLDN4), occludin-1 (OCCL-1), and zonula occludens-1 (ZO-1) by RT-qPCR, immunoblot and immunofluorescence labeling. Results: PD/CCs were clustered in 2 functional categories: patients with delayed TT and altered AM (60%), and a second group showing only modifications in AM pattern (40%). Gene expression of CLDN4, OCCL-1 and ZO-1 was higher in PD/CCs than controls (P<0.05). Conversely, PD/CCs showed a trend to decrease (P>0.05) in CLDN4 and OCCL-1 protein levels than controls, whereas ZO-1 protein was comparable. In PD/CCs compared with controls, decreasing tendency of vasoactive intestinal polypeptide mRNA, protein and immunoreactive fiber density were observed, although the difference was not statistically significant. Conclusion: Transit and anorectal dysfunctions in PD/CCs are associated with difference in ZO-1, OCCL-1 and CLDN4 expression, thus supporting the role of an altered IEB as a contributory mechanism to possible neuronal abnormalities.

Anal defecatory function in ulcerative colitis patients after total proctocolectomy and ileal pouch-anal anastomosis: a prospective cohort study.

BACKGROUND: Total proctocolectomy (TPC) followed by ileal pouch-anal anastomosis (IPAA) remains the only viable option whenever different treatment modalities fail in patients with ulcerative colitis (UC). OBJECTIVE: Prospective cohort pre/post study examining the anal defecatory function and competence in UC patients undergoing TPC plus IPAA using high-resolution anorectal manometry (HR-ARM). PATIENTS: Patients undergoing TPC and IPAA were enrolled in the study and subjected to HR-ARM prior to and 6 months after surgery. The anal resting, squeeze and push pressures were recorded, together with the rectal sensation and the rectal balloon expulsion test. The number of bowel movements, symptoms/signs related to fecal incontinence, as well as the IBDQ-32 quality of life questionnaires were documented during both HR-ARM visits. RESULTS: A total of 20 consecutive UC patients were recruited in our study. The mean (SD) number of bowel movements before the TPC plus IPAA was 10.1 (2.8), while the same number after the pouch surgery was 7.7 (3.1) [ P  = 0.01]. Symptoms or signs of fecal incontinence were noted in one of our patients prior to the operation; however, none of our patients reported any such symptoms after the pouch surgery. The median (IQR) IBDQ-32 questionnaire scores before and after surgery were 121.5 (13.5) and 142.5 (16.0) respectively. At the same time, the anorectal function remained intact since both the anal resting and squeeze pressures were not significantly changed. CONCLUSION: UC patients subjected to TPC-IPAA exhibit improved bowel movements and a normal anal defecatory function and competence post-surgery.

Graded pneumatic dilation in subtype I and II achalasia: long-term experience in a single center.

BACKGROUND: The efficacy of pneumatic dilation (PD) in the management of achalasia has yielded variable results. The availability of high-resolution manometry led to the identification of 3 clinically relevant subtypes of achalasia, revealing the poor efficacy of PD in subtype III. Furthermore, PD showed a lower response rate in patients with subtype III compared to laparoscopic Heller myotomy and peroral endoscopic myotomy. This study aimed to investigate the short- and long-term efficacy, safety profile and side effects of PD with a "graded approach" in subtypes I and II achalasia. METHODS: We enrolled 141 patients (male 67, mean age=66±16.26 years) with achalasia (n=27 subtype I, n=74 subtype II and n=40 subtype III) between January 2010 and July 2020 at St. Orsola University Hospital, Bologna, Italy. We analyzed the data of patients with subtypes I and II, who underwent a graded-protocol PD. Short- and long-term clinical efficacy, complications and gastroesophageal reflux disease (GERD) were recorded. RESULTS: One month after graded protocol PD, 100% subtype I and 96.2% subtype II achalasia patients showed clinical remission. The PD procedure was completed without major complications in all patients. In the long-term follow up (median time: 56 months), 95.5% subtype I and 90% subtype II achalasia patients had an Eckardt score ≤3. GERD occurred in 27.7% of all patients. CONCLUSION: A graded-protocol PD applied in the appropriate achalasia subtypes was shown to be a safe and highly effective approach, in both the short- and long-term.

Specific Neuropeptide Expression in Crohn's Disease Ileocolonic Resection Specimens Is Not Associated with Plexitis at the Ileal Margin or Postoperative Recurrence.

BACKGROUND: Myenteric plexitis is considered a risk factor for postoperative recurrence (POR) in Crohn's disease (CD). The primary purpose of this study was to evaluate the association between neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and substance P (SP) expression and plexitis at the proximal resection margin. The secondary aim was to identify risk factors for POR. METHODS: A retrospective, single-center study on CD patients who underwent ileocolonic resection (ICR) between January 2010 and December 2016 was conducted. The presence and severity of plexitis were evaluated by hematoxylin and eosin stain. Mast cells were highlighted by Giemsa stain. Immunohistochemistry was used to identify T lymphocytes and NPY-, VIP-, and SP-ergic neurons. Neuropeptide expression was quantified using image analysis. RESULTS: Seventy-nine patients were included. No association was detected between NPY, VIP, and SP expression and plexitis. Similarly, the number of involved inflammatory cells, T lymphocytes or mast cells was not correlated with neuropeptide expression. Smoking (hazard ratio [HR] 4.07; 95% confidence interval [CI] 2.08-7.94; p < 0.001), moderate (HR 3.68; 95%CI 1.06-12.73; p = 0.040), and severe myenteric plexitis (HR 7.36; 95%CI 1.12-48.30; p = 0.037) were independent risk factors for endoscopic POR, whereas smoking (HR 2.78; 95%CI 1.01-7.67; p = 0.049), severe myenteric plexitis (HR 20.03; 95%CI 1.09-368.28; p = 0.044), and involved ileal margin (HR 3.45; 95%CI 1.33-8.96; p = 0.011) for clinical POR. CONCLUSIONS: Smoking, moderate or severe myenteric plexitis, and involved ileal margin negatively affect POR in CD patients undergoing ICR. Submucosal and myenteric plexitis at the proximal resection margin is not related to the expression of specific neuropeptides.

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. METHODS: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. RESULTS: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.

Leucine-rich alpha-2 glycoprotein 1, high mobility group box 1, matrix metalloproteinase 3 and annexin A1 as biomarkers of ulcerative colitis endoscopic and histological activity.

OBJECTIVE: The LRG, HMGB1, MMP3 and ANXA1 proteins have been implicated in different inflammatory pathways in ulcerative colitis (UC), but their role as specific biomarkers of both endoscopic and histological activity has yet to be elucidated. In the present study, we aimed to evaluate the LRG1, HMGB1, MMP3 and ANXA1 as potential serum biomarkers for UC endoscopic and histological activity. METHODS: This cross-sectional study included UC patients under 5-ASA, and healthy controls (HC) undergoing colonoscopy. Blood and biopsy samples were obtained and endoscopic Mayo sub-score (Ms) was recorded for the UC patients. Intramucosal calprotectin as a marker of histologic activity was evaluated in all biopsy samples and serum LRG1, HMGB1, MMP3 and ANXA1 levels were measured in the blood samples. RESULTS: The HCs ANXA1 level was lower compared to that of the UC group [P = 0.00, area under the curve (AUC) = 0.881] and so was the HCs MMP3 level compared to that of patients (P = 0.00, AUC = 0.835). The HCs ANXA1 levels were also lower compared to these of the independent Ms groups, even to the Ms = 0 (P = 0.00, AUC = 0.913). UC endoscopic activity was associated with MMP3 levels (r = 0.54, P = 0.000) but not with ANXA1, LRG1 and HMGB1 levels CONCLUSION: Serum ANXA1 is a potential diagnostic biomarker of UC and serum MMP3 is a potential biomarker of UC endoscopic and histological activity.

International consensus on the diagnosis and management of dumping syndrome.

Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose.

High prevalence of asymptomatic peptic ulcers diagnosed during screening endoscopy in patients with cirrhosis.

BACKGROUND: Peptic ulcer disease (PUD) is more prevalent in cirrhotics and this may aggravate prognosis. We investigated the prevalence of PUD in cirrhotics and its potential association with Helicobacter pylori (H. pylori) infection, the underlying etiology and severity of liver disease, and other manifestations of portal hypertension (PH). METHODS: We enrolled consecutive asymptomatic cirrhotic patients who underwent screening endoscopy in a tertiary hospital during a 12-month period. We recorded the presence of PUD and the endoscopic findings associated with PH. H. pylori infection was documented through either histology or CLO-test. The diagnosis of cirrhosis was based on elastography, liver biopsy or a combination of clinical, biochemical and imaging data. RESULTS: One hundred patients (M/F: 54/46, mean age: 61±14 years) were included in the analysis. Viral hepatitis (37%) and alcohol (22%) were the most common causes of cirrhosis. Child-Pugh stage was A/B/C: 60/35/5. PUD was found in 19 patients (14 gastric, 5 duodenal). H. pylori infection was diagnosed in 54%. Varices were detected in 59% (39% needed treatment). PH gastropathy was present in 81% (severe in 33%). The presence of PUD was unrelated to the etiology and the severity of liver disease or to other endoscopic manifestations of PH. No correlation was found between PUD and H. pylori infection. CONCLUSIONS: A high prevalence of PUD was observed in our cirrhotic patients, although they were asymptomatic and had no known risk factors of ulcerogenicity. The value of screening endoscopy for the early diagnosis and treatment of PUD in cirrhotics deserves further investigation.

Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline.

ESGE recommends offering stone extraction to all patients with common bile duct stones, symptomatic or not, who are fit enough to tolerate the intervention.Strong recommendation, low quality evidence.ESGE recommends liver function tests and abdominal ultrasonography as the initial diagnostic steps for suspected common bile duct stones. Combining these tests defines the probability of having common bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends endoscopic ultrasonography or magnetic resonance cholangiopancreatography to diagnose common bile duct stones in patients with persistent clinical suspicion but insufficient evidence of stones on abdominal ultrasonography.Strong recommendation, moderate quality evidence.ESGE recommends the following timing for biliary drainage, preferably endoscopic, in patients with acute cholangitis, classified according to the 2018 revision of the Tokyo Guidelines:- severe, as soon as possible and within 12 hours for patients with septic shock- moderate, within 48 - 72 hours- mild, elective.Strong recommendation, low quality evidence.ESGE recommends endoscopic placement of a temporary biliary plastic stent in patients with irretrievable biliary stones that warrant biliary drainage.Strong recommendation, moderate quality of evidence.ESGE recommends limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult common bile duct stones. Strong recommendation, high quality evidence.ESGE recommends the use of cholangioscopy-assisted intraluminal lithotripsy (electrohydraulic or laser) as an effective and safe treatment of difficult bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends performing a laparoscopic cholecystectomy within 2 weeks from ERCP for patients treated for choledocholithiasis to reduce the conversion rate and the risk of recurrent biliary events. Strong recommendation, moderate quality evidence.

Risk factors for gastroesophageal reflux disease and analysis of genetic contributors.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder with an increasing prevalence. GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications. Several risk factors of GERD have been identified and evaluated over the years, including a considerable amount of genetic factors. Multiple mechanisms are involved in the pathogenesis of GERD including: (1) motor abnormalities, such as impaired lower esophageal sphincter (LES) resting tone, transient LES relaxations, impaired esophageal acid clearance and delayed gastric emptying; and (2) anatomical factors, such as hiatal hernia and obesity. Genetic contribution seems to play a major role in GERD and GERD- related disorders development such Barrett's esophagus and esophageal adenocarcinoma. Twin and family studies have revealed an about 31% heritability of the disease. Numerous single-nucleotide polymorphisms in various genes like FOXF1, MHC, CCND1, anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk. GERD, Barrett's esophagus and esophageal adenocarcinoma share several genetic loci. Despite GERD polygenic basis, specific genetic loci such as rs10419226 on chromosome 19, rs2687201 on chromosome 3, rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors. Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.

Long non-coding RNA in pancreatic adenocarcinoma and pancreatic neuroendocrine tumors.

Interest in non-coding regions of DNA has been increasing since the mapping of the human genome revealed that human DNA contains far fewer genes encoding proteins than previously expected. However, analysis of the derivatives of DNA transcription (transcriptomics) revealed that the majority of the genetic material is transcribed into non-coding RNA (ncRNA), indicating that these molecules probably provide the functional diversity and complexity of the physiology of the human body that cannot be attributed to the proteins. Of these ncRNA, long ncRNA (lncRNA) have a length greater than 200 nucleotides and share many common components with the coding messenger RNA (mRNA): They are transcribed by RNA polymerase II, comprised of multiple exons and subjected to normal RNA splicing giving RNA products of several kilobases. Scientific data reveal the regulatory role of lncRNA in the control of gene expression during cell development and homeostasis. However, to date, very few lncRNAs have been characterized in depth, and lncRNAs are thought to have a wide range of functions in cellular and developmental processes. These molecules will have the possibility to be used as biomarkers and contribute to the development of targeted therapies. Concerning pancreatic cancer, there are limited data in the literature that correlate the growth of these tumors with deregulation of various lncRNA. We herein review the literature regarding the role of lncRNA as a diagnostic and prognostic biomarker and possible therapeutic target in the neoplasms of the pancreas, particularly pancreatic adenocarcinoma and pancreatic neuroendocrine tumors.

The contribution of long non-coding RNAs in Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBDs) are multifactorial autoimmune diseases with growing prevalence but the interaction between genetic, environmental and immunologic factors in their development is complex and remains obscure. There is great need to understand their pathogenetic mechanisms and evolve diagnostic and therapeutic tools. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that are known to interfere in gene regulation but their roles and functions have not yet been fully understood. While they are widely investigated in cancers, little is known about their contribution in other diseases. There is growing evidence that lncRNAs play critical role in regulation of immune system and that they interfere in the pathogenetic mechanisms of autoimmune diseases, like IBDs. Recent studies have identified lncRNAs in the proximity of IBD-associated genes and single nucleotide polymorphisms within IBD-associated lncRNAs as well. Furthermore, blood samples and pinch biopsies were also analyzed and a plethora of lncRNAs are found to be deregulated in Crohn's disease (CD), Ulcerative colitis (UC) or both. (Especially in UC samples the lncRNAs INFG-AS1 and BC012900 were found to be significantly up-regulated. Similarly, ANRIL, a lncRNA that nest different disease associated SNPs, is significantly down-regulated in inflamed IBD tissue.) This review aims at recording for the first time recent data about lncRNAs found to be deregulated in IBDs and discussing suggestive pathogenetic mechanisms and future use of lncRNAs as biomarkers.

Intestinal Bacteria Composition and Translocation of Bacteria in Inflammatory Bowel Disease.

BACKGROUND: Live commensal intestinal bacteria are present in the peripheral blood where they can induce inflammation. OBJECTIVE: To evaluate the intestinal bacteria composition and translocation of bacteria in IBD. METHODS: Both blood and tissue biopsy samples were collected from adult patients with active/inactive Crohn's disease (CD), active/inactive ulcerative colitis (UC) and healthy individuals. Most of the patients were newly diagnosed and none of them received antibiotics. Using a reverse transcription-quantitative real-time PCR (RT-qPCR) method, we determined the composition of microbiota. NOD2/CARD15 genotyping was also studied. RESULTS: Total bacterial DNA concentration was increased in tissue and blood samples of IBD patients compared to healthy controls. Furthermore, the active IBD cases had higher total bacterial DNA concentration levels compared to the inactive cases. Three species characterized dysbiosis in IBD, namely an increase of Bacteroides spp in active and inactive IBD samples, and a decrease in Clostridium leptum group (IV), and Faecalibacterium prausnitzi in both active and inactive IBD patients. No significant association between bacterial translocation and NOD2/CARD15 mutations was found. CONCLUSIONS: The composition of the microbiota in IBD patients differs from that of healthy controls. The high rate of bacterial DNA in the blood samples indicates translocation in inflammatory bowel disease.

Association of survivin promoter polymorphisms with inflammatory bowel disease and response to antitumor necrosis factor therapy.

BACKGROUND/AIM: Recent evidence suggests that survivin, a member of the inhibitors of apoptosis family that prevents cell death and regulates cell division is implicated in the pathogenesis of inflammatory bowel disease (IBD). The aim of the study was to identify a possible association between individual genetic variation, IBD susceptibility, and response to infliximab (IFX). MATERIAL AND METHODS: The expression levels of survivin were detected in pathologic areas of fresh tissues and blood samples by real-time reverse transcriptase - polymerase chain reaction (RT-PCR) from IBD patients. Polymorphisms were identified using the polymerase chain reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Clinical and endoscopic response to IFX was evaluated by ileocolonoscopy performed at baseline and after 12-20 weeks of therapy with patients classified as either responders or nonresponders. RESULTS: No significant differences were found between survivin mRNA levels between patients and controls. Significant differences in both allele and genotype frequencies between Crohn's disease (CD) and ulcerative colitis (UC) patients and controls were found in -31C/G polymorphism. No association with IBD development was found for the -625G/C and -241T/C polymorphisms, since those polymorphisms were overrepresented in a healthy population. Additionally no significant association was found between -31C/G polymorphism and the clinical response of CD patients to IFX. CONCLUSIONS: Survivin promoter polymorphism -31C/G might influence the susceptibility to IBD in the Greek population, but not the CD patient's response to anti-TNF drugs.

Optimized sedation improves colonoscopy quality long-term.

Background. Quality monitoring and improvement is prerequisite for efficient colonoscopy. Aim. To assess the effects of increased sedation administration on colonoscopy performance. Materials and Methods. During Era 1 we prospectively measured four colonoscopy quality indicators: sedation administration, colonoscopy completion rate, adenoma detection rate, and early complications rate in three cohorts: cohort A: intention for total colonoscopy cases; cohort B: cohort A excluding bowel obstruction cases; cohort C: CRC screening-surveillance cases within cohort B. We identified deficiencies and implemented our plan to optimize sedation. We prospectively evaluated its effects in both short- (Era 2) and long-term period (Era 3). Results. We identified that sedation administration and colonoscopy completion rates were below recommended standards. After sedation optimization its use rate increased significantly (38.1% to 55.8% to 69.5%) and colonoscopy completion rate increased from 88.3% to 90.6% to 96.4% in cohort B and from 93.2% to 95.3% to 98.3% in cohort C, in Eras 1, 2, and 3, respectively. Adenoma detection rate increased in cohort C (25.9% to 30.6% to 35%) and early complications rate decreased from 3.4% to 1.9% to 0.3%. Most endoscopists increased significantly their completion rate and this was preserved long-term. Conclusion. Increased sedation administration results in long-lasting improvement of colonoscopy quality indicators.

Serum protein profiling of adults and children with Crohn disease.

OBJECTIVES: Crohn disease (CD) and ulcerative colitis (UC), known collectively as inflammatory bowel diseases (IBDs), are chronic immunoinflammatory pathologies of unknown aetiology. Despite the frequent use of biomarkers in medical practice, there is a relative lack of information regarding validated paediatric biomarkers for IBD. Furthermore, biomarkers proved to be efficacious in adults are frequently extrapolated to the paediatric clinical setting without considering that the pathogenesis of many diseases is distinctly different in children. In the present study, proteomics technology was used to monitor differences in protein expression among adult and young patients with CD, identify a panel of candidate protein biomarkers that may be used to improve prognostic-diagnostic accuracy, and advance paediatric medical care. METHODS: Male and female serum samples from 12 adults and 12 children with active CD were subjected to 2-dimensional gel electrophoresis. Following the relative quantitation of protein spots exhibiting a differential expression between the 2 groups by densitometry, the spots were further characterized by matrix-assisted laser desorption tandem time-of-flight mass spectrometer. The results were confirmed by Western blot analysis. RESULTS: Clusterin was found to be significantly overexpressed in adults with CD, whereas ceruloplasmin and apolipoprotein B-100 were found to be significantly overexpressed in children, indicating that the expression of these proteins may be implicated in the onset or progression of CD in these 2 subgroups of patients. CONCLUSIONS: Interestingly, we found a differential expression of several proteins in adults versus paediatric patients with CD. Undoubtedly, future experiments using a larger cohort of patients with CD are needed to evaluate the relevance of our preliminary findings.

Endoscopic treatments for chronic radiation proctitis.

Chronic radiation proctitis is a complication that occurs in patients who receive radiation therapy for pelvic malignancies. The common presentation is with rectal bleeding, but also rectal pain, diarrhea, tenesmus and even passage of mucus can occur. The optimal treatment of bleeding due to radiation proctitis remains unclear. Among various therapeutic options, medical management is generally ineffective and surgical intervention has a high incidence of morbidity. Promising advances have been made in endoscopic therapy, including argon plasma coagulation (APC), formalin application as well as new techniques such as radiofrequency ablation and cryoablation. APC is a safe, highly effective and long-lasting therapy in patients with rectal bleeding associated with radiation proctitis. It has been shown that several sessions of APC reduce the rate of bleeding and therefore the blood transfusion requirements. Moreover, the effect of treatment is long lasting. However, best results are achieved in patients with mild to moderate radiation proctitis, leaving space for alternative treatments for patients with more severe disease. In patients with severe or refractory radiation proctitis intra rectal formalin application is an appropriate treatment option. Radiofrequency ablation and cryoablation have shown efficacy as alternative methods in a limited number of patients with refractory chronic radiation proctitis.

Inflammatory infiltration of metaplastic epithelium and correlation to previous diagnosis of esophagitis and Barrett's length.

OBJECTIVE: The contact of the gastric refluxate with the lower esophagus results in an inflammatory-mediated tissue damage. The role of inflammation both in the development and in the advance of Barrett's esophagus (BE) has not been elucidated. The aim of this study was to assess the inflammatory infiltration in metaplastic Barrett's epithelium and to explore the association of microscopic inflammation to healed esophagitis and Barrett's length. MATERIAL AND METHODS: Inflammatory infiltration was qualitatively evaluated in well-characterized Barrett's specimens. Esophagitis was healed prior to histological sampling. Univariate comparative analysis was performed based on BE length. RESULTS: Ninety-eight patients (78 male, mean age 58.3 ± 13.3 yrs) were retrospectively studied. Thirty-three cases with long segment BE (LSBE) (33.7%) were spotted. Inflammatory infiltration was mild, moderate, and severe in 35 (35.7%), 54 (55.1%), and 9 (9.1%) specimens, respectively. The samples with moderate/severe inflammatory infiltration were obtained from patients who had more frequently been diagnosed with esophagitis (p = 0.025). Hiatal hernia (p = 0.001), esophagitis (p = 0.019), and previous use of anti-secretory drugs (p = 0.005) were more common in LSBE. CONCLUSIONS: Inflammatory infiltration of Barrett's epithelium was largely moderate despite preceding healing of erosions with PPIs. Previous diagnosis of esophagitis correlated to the degree of inflammation. No association of inflammation to Barrett's length was established.

Increased expression of VEGF, COX-2, and Ki-67 in Barrett's esophagus: does the length matter?

BACKGROUND: Barrett's esophagus (BE) is a major complication of gastroesophageal reflux disease due to its neoplastic potential. The length of the metaplastic epithelium has been associated with cancer risk. Angiogenesis, inflammation, and increased cell proliferation are early events in the malignant sequence. Vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and Ki-67 are indirect markers of these complex mechanisms. AIMS: To examine the expression of VEGF, COX-2 and Ki-67 in BE and investigate whether there is an association to Barrett's length. METHODS: Immunohistochemistry for VEGF, COX-2, and Ki-67 was performed in well-characterized Barrett's samples, evaluated using a qualitative scale and compared between long (LSBE) and short (SSBE) segments. RESULTS: The study population consisted of 98 patients (78 men). LSBE and SSBE was diagnosed in 33 (33.7%) and 65 (66.3%) cases, respectively. VEGF was expressed in vascular endothelium of all Barrett's specimens. COX-2 and Ki-67 expression in metaplastic epithelia was strong in 81.6 and 61.2% of the samples, respectively. Ki-67 expression was significantly stronger in LSBE (p = 0.035), whereas VEGF expression was significantly increased in SSBE (p = 0.031). COX-2 expression was not associated with Barrett's length. CONCLUSIONS: VEGF, COX-2, and Ki-67 were overexpressed in the majority of Barrett's samples. The length was inversely associated with VEGF expression and directly associated with Ki-67 expression.