Polidocanol injection decreases the bleeding rate after colon polypectomy: a propensity score analysis.

BACKGROUND: EMR is the standard of care for the resection of large polyps. OBJECTIVE: To compare the efficacy and safety profile of submucosal polidocanol injection with epinephrine-saline solution injection for colon polypectomy with a diathermic snare. DESIGN: After 1-to-1 propensity score caliper matching, comparison of submucosal epinephrine injection was performed with polidocanol injection. SETTING: Endoscopic suite at the University of Foggia between 2005 and 2014. PATIENTS: Of 711 patients who underwent endoscopic resection of colon sessile polyps 20 mm or larger, 612 were analyzed after matching. INTERVENTIONS: Submucosal epinephrine injection in 306 patients and polidocanol injection in 306 patients. MAIN OUTCOME MEASUREMENTS: Univariate and multivariate logistic regression models aimed at identifying independent predictors of postpolypectomy bleeding (PPB). RESULTS: The 2 groups presented similar baseline clinical parameters and lesion characteristics. All patients had a single polyp 20 mm or larger; the median size was 32 mm (interquartile range [IQR], 25-38) in the polidocanol group and 32 (IQR, 24-38) in the epinephrine group (P=.7). Polidocanol was more effective in preventing both immediate and delayed PPB (P<.001 and P=.003, respectively), and its efficacy was confirmed in almost all of the subgroups, regardless of polyp size and histology. Postprocedure perforation was observed in 2 patients (0.3%), both in the epinephrine group (P=.49). The 2 groups did not differ in the number of snare resections of lesions or the procedure duration (P=.24 and .6, respectively). LIMITATIONS: Absence of randomization. CONCLUSION: The submucosal injection of polidocanol for colon EMR is effective and significantly lowers the PPB rate.

Altered molecular pattern of mucosal healing in Crohn's disease fibrotic stenosis.

AIM: To investigate tumor necrosis factor-α (TNF-α), syndecan 1 and basic fibroblast growth factor (bFGF) balance in Crohn's disease (CD) strictures. METHODS: Our study was performed on 24 surgical specimens of CD fibrotic stenosis. Ten histological normal surgical samples were retrieved for both the large and small bowel from patients with benign conditions and healthy tissue represented control collection. Sex and age in controls did not differ from CD group. Three endoscopic biopsy specimens taken after informed consent in subjects with normal colon were also used as negative controls. TNF-α, syndecan 1 and bFGF were detected by both reverse transcriptase reverse transcriptase polymerase chain reaction after mRNA extraction (results expressed as fold-change) and immunohistochemistry. RESULTS: TNF-α did not show any significant difference between CD and control specimens (1.54 ± 1.19; P > 0.05). Very high levels of bFGF were observed in CD (11.76 ± 4.65; P < 0.001) unlike syndecan 1 which showed a moderate increase (5.53 ± 2.18; P < 0.005). analysis of variance (ANOVA) plus Student-Neumann-Keuls showed: bFGF > syndecan 1 > TNF-α = control. Immunoreactivity for bFGF was observed in epithelial, stromal, endothelial cells and even in the muscular layer, whilst in normal tissue it was almost unexpressed. Syndecan 1 and TNF-α staining was confined to mucosal epithelial and stromal cells, while in controls syndecan 1 was found in its normal site, i.e., basolateral area of the crypts and TNF-α very poorly expressed. CONCLUSION: Fibrotic stenosis of CD may be the final result of an irreversible transformation of different cells into fibrogenic phenotype no longer inhibited by post-transcriptional regulation.

Probiotic multistrain treatment may eradicate Helicobacter pylori from the stomach of dyspeptics: a placebo-controlled pilot study.

UNLABELLED: Probiotics survive in gastric environment competing with H. pylori. We studied probiotic "multistrain" administration in dyspeptics with H. pylori (placebo-controlled study). Forty patients with H. pylori (urea breath test - UBT - and IgG) were treated for 10 days with a mixture of 8 species of probiotics. Control group represented by 40 positive subjects received placebo. A second UBT and H. pylori stool antigen (HpSA) detection were performed after 1 month. Patients who remained infected were treated with triple therapy undergoing another UBT after 30 days. A second line therapy was administered in remaining positive patients. STATISTICS: Fisher's exact probability and Student's t tests. Thirteen out of 40 patients using probiotics became negative, while controls remained positive, irrespectively of the initial UBT delta value. No difference in the eradication rates between the two groups was found (68%-71%). After second line therapy two patients remained positive. An adequate supplementation with probiotics might eradicate H. pylori.

The use of human albumin for the treatment of ascites in patients with liver cirrhosis: item of safety, facts, controversies and perspectives.

Albumin constitutes approximately one half of the proteins in the plasma and plays a pivotal role in modulating the distribution of fluid between body compartments. Hence it is commonly employed in cirrhotic patients in association with diuretics for the treatment of ascites. Nevertheless, its usefulness is controversial in this condition and well-stated only in some circumstances. The item of safety of the drug appears to be convincing due to the accurate cautions in the course of its preparation. Side effects are described in literature only as sporadic events. Indeed, albumin administration is effective to prevent the circulatory dysfunctions after large-volume paracentesis and renal failure and after Spontaneous Bacterial Peritonitis (SBP). Finally albumin represents, associated with vasoconstrictors, the therapeutic gold standard for the hepatorenal-syndrome (HRS). Physiopathological bases of the therapeutic use of albumin in hepatic cirrhosis consist in both hypoalbuminemia and portal hypertension consequences. In fact, cirrhotic patient with ascites, in spite of hydrosaline retention, shows an effective hypovolemia with peripheral arterial vasodilatation and increase in heart rate. Therefore the effectiveness of albumin administration in the treatment of ascites is due to its plasma volume expander property as well as its efficacy in restoring plasmatic oncotic pressure. Trials are in progress in order to define the effectiveness of the prolonged home-administration of human albumin in the treatment and prevention of ascites. Finally, it has been recently demonstrated that the binding, transport and detoxification capacities of human albumin are severely reduced in cirrhotics and this impairment correlates with the degree of liver failure. Therefore, the next challenge will be to determine whether the alterations of non-oncotic properties of albumin are able to forecast mortality in cirrhotics with ascites and exogenous albumin chronic administration will be effective in predicting and preventing such alterations.

Infliximab therapy downregulation of basic fibroblast growth factor/syndecan 1 link: a possible molecular pathway of mucosal healing in ulcerative colitis.

BACKGROUND: It is known that syndecan 1 in inflammatory bowel diseases is able to migrate from epithelial basolateral site to the stromal area and apical surface of epithelium with a consequent activation and modulation of basic fibroblast growth factor (bFGF), and this process sustains mucosal healing of ulcers. On the other hand, tumour necrosis factor (TNF) α mucosal levels are directly related to the entity of the damage in these disorders. Aim of the study A 'post-hoc' retrospective study was performed to estimate mucosal TNF α in rectal biopsies of subjects with ulcerative colitis (UC) before and after effective infliximab therapy and its relationship with syndecan 1, bFGF and endoscopic mucosal healing. MATERIAL AND METHODS: Paraffin-embedded rectal samples from 12 patients with UC responders to infliximab were analysed for TNF α, syndecan 1 and bFGF before and 6 months after therapy using a real-time reverse transcriptase polymersase chain reaction. Additionally, syndecan 1 location was evaluated by immunohistochemistry. Samples from 12 subjects with irritable bowel symptoms without endoscopic/histological abnormalities represented the control group. Mucosal healing induced by the treatment was defined by an endoscopic Mayo subscore changing from 2-3 to 0. ANOVA plus Student-Newman-Keuls was used for statistical analysis. RESULTS: The authors found that in the active disease, an increase in TNF α (p<0.001) is accompanied by raised levels of both syndecan 1 (p<0.005) and bFGF (p<0.005) compared with the control group. Infliximab-induced TNF α decrease to levels similar to controls is associated with both endoscopic mucosal healing and adhesion molecule/growth factor significant reduction. Additionally, syndecan 1 location, which is predominant in the stromal cells and apical epithelium in the active disorder, is quite exclusively located at the basolateral epithelial area in both healed mucosa and controls. CONCLUSIONS: Balanced interaction among TNF α inhibition by infliximab, syndecan 1 migration, bFGF repair modulation and final adhesion molecule reversal to its normal location might represent a suitable molecular pathway of endoscopic mucosal healing in UC.

From chronic liver disorders to hepatocellular carcinoma: Molecular and genetic pathways.

Hepatocarcinogenesis is a process attributed to progressive genomic changes that alter the hepatocellular phenotype producing cellular intermediates that evolve into hepatocellular carcinoma (HCC). During the preneoplastic phase, the liver is often the site of chronic hepatitis and/or cirrhosis, and these conditions induce liver regeneration with accelerated hepatocyte cycling in an organ that is otherwise proliferatively at rest. Hepatocyte regeneration is accelerated by upregulation of mitogenic pathways involving molecular and genetic mechanisms. Hepatic growth factors, inhibitors and triggers may also play a role. This process leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that have telomerase re-expression, microsatellite instability, and occasionally structural aberrations in genes and chromosomes. Development of dysplastic hepatocytes in foci and nodules and the emergence of HCC are associated with the accumulation of irreversible structural alterations in genes and chromosomes even if the genomic basis of the malignant phenotype is largely heterogeneous. Therefore, a malignant hepatocyte phenotype may be produced by changes in genes acting through different regulatory pathways, thus producing several molecular variants of HCC. On these bases, a key point for future research will be to determine whether the deletions are specific, due to particular loci in the minimally deleted regions of affected chromosome arms, or whether they are non-specific with loss of large portions of chromosomes or entire chromosome arms leading to passive deletion of loci. The final aim is the possibility of identifying a step where carcinogenetic processes could be terminated.

Worldwide H. pylori antibiotic resistance: a systematic review.

BACKGROUND AND AIMS: Prevalence of H. pylori antibiotic resistance is increasing worldwide, and it is the main factor affecting efficacy of current therapeutic regimens. Our aim was to review recent data on H. pylori resistance towards antibiotics in different countries. METHODS: A systematic review of studies concerning primary H. pylori antibiotic resistance published through January 2006 to December 2009 was performed. Data were analyzed according to geographic area, age, sex, and gastroduodenal pathology. RESULTS: The overall H. pylori antibiotic resistance rates were 17.2% (95% CI: 16.5-17.9%) for clarithromycin, 26.7% (95% CI: 25.2-28.1%) for metronidazole, 11.2% (95% CI: 9.6-12.7%) for amoxycillin, 16.2% (95% CI: 14.4-18%) for levofloxacin, 5.9% (95% CI: 4.7-7.1%) for tetracycline, 1.4% (95% CI: 0.81-9%) for rifabutin and 9.6% (95% CI: 8.5-10.7%) for multiple antibiotics. Prevalence rate of clarithromycin, metronidazole, and levofloxacin resistance significantly increased from Europe to Asia, America and Africa. Tetracycline resistance is low (<3%) in all countries, but Africa (43.9%). Prevalence of clarithromycin resistance was higher in non-ulcer dyspepsia patients, whilst metronidazole resistance was higher in peptic ulcer patients. Both resistances were significantly higher in female than in male patients. Data regarding amoxicillin resistance are highly conflicting. CONCLUSION: The worldwide H. pylori antibiotic resistance towards different antibiotics has increased. Such a phenomenon may affect therapeutic management in different countries.

Helicobacter pylori antibiotic resistance and [13C]urea breath test values.

A correlation between delta over baseline (DOB) values of the [(13)C]urea breath test (UBT) and Helicobacter pylori clarithromycin resistance has been reported, suggesting a possible predictive role of UBT in therapeutic outcome. However, available data are limited and conflicting. This study aimed to clarify this issue, assessing the possible relationship between H. pylori resistance towards different antibiotics (clarithromycin, metronidazole and levofloxacin) and UBT values. The data showed similar DOB values between susceptible and resistant strains for clarithromycin (46.9+/-32.3 vs 45.7+/-30.6; P=0.8), metronidazole (46.4+/-29.6 vs 47.4+/-37.9; P=0.8), and levofloxacin (45.0+/-30.2 vs 54.2+/-38.4; P=0.08). Likewise, comparable DOB values were observed between susceptible and multidrug-resistant strains (45.4+/-29.6 vs 54.8+/-44.8; P=0.1). In conclusion, our data failed to find a significant correlation between UBT values and H. pylori antibiotic resistance.

Advanced adenocarcinoma of terminal ileum: an unusual neoplasm revealed by an unusual diagnostic tool.

BACKGROUND AND AIM: Terminal ileum adenocarcinoma is a rare tumour. Its incidence or prevalence among the other sites of gastro-intestinal tract is unknown, since it has been only sporadically described. Since contrast enhanced ultrasonography has been recently used to study bowel alterations in the course of neoplastic or inflammatory disorders, we report here a case of a rare tumour (terminal ileum poorly differentiated adenocarcinoma) in which the investigation played a pivotal role to obtain a defined diagnosis. MATERIALS AND METHODS (CASE REPORT): Here we report the case of a 62 year old male patient. Due to intestinal occlusive symptoms and body weight decrease of about 8 Kg, he performed an abdominal computed tomography, intestinal magnetic resonance with double contrast medium, colonoscopy and contrast enhanced ultrasonography using a second generation medium. RESULTS: In our case the peculiar aspect is that no arterial enhancement was observed and the finding remained unchanged for about 2.48 minutes as well as after a further administration of 1.5 ml of contrast medium. This aspect was not suggestive of an active inflammation such as Crohn's disease, where a marked contrast medium enhancement should be expected. CONCLUSIONS: At present it is too speculative to emphasize contrast enhanced ultrasonography as usefulness tool in the diagnosis of terminal ileum tumors. Nevertheless, our preliminary experience strongly encourages the diffusion of the method.

Metabolic syndrome and gastro-esophageal reflux: A link towards a growing interest in developed countries.

The aim of this Editorial is to describe the growing possibility of a link between gastro-esophageal reflux disease (GERD) and metabolic syndrome on the light of recent epidemiological and pathophysiological evidence. The state of the art of GERD is described, based on recent definitions, pathophysiological evidence, epidemiology in developed countries, clinical subtypes together with a diagnostic approach specifically focussed on the appropriateness of endoscopy. Metabolic syndrome is accurately defined and the pivotal role of insulin resistance is emphasized. The strong relationship between GERD and metabolic syndrome has been pathophysiologically analyzed, taking into account the role of obesity, mechanical factors and metabolic changes. Data collected by our group regarding eating habits and GERD are briefly summarized at the end of a pathophysiological analysis. The literature on the subject strongly supports the possibility that lifestyle and eating habits may be involved in both GERD and metabolic syndrome in developed countries.

Phenotypic and genotypic Helicobacter pylori clarithromycin resistance and therapeutic outcome: benefits and limits.

INTRODUCTION: Primary clarithromycin resistance is increasing worldwide, and it has been regarded as the main factor reducing the efficacy of Helicobacter pylori therapy. However, the clinical consequence of either phenotypic or genotypic resistance still remains unclear. This study aimed to evaluate: (i) the concordance between phenotypic (culture) and genotypic (real-time PCR) tests in assessing primary clarithromycin resistance; and (ii) the role of both in therapeutic outcome. METHODS: A post hoc subgroup study was selected from a double-blind, placebo-controlled trial, enrolling 146 patients with dyspepsia or peptic ulcers never previously treated. Real-time PCR and Etest on bacterial culture for assessing clarithromycin resistance were performed. [(13)C]urea breath test (UBT), histology and rapid urease tests at entry and UBT after 4-8 weeks were used to assess infection and eradication. All patients received a 10 day therapy. RESULTS: Prevalence of clarithromycin phenotypic resistance was significantly lower as compared with genotypic resistance (18.4% versus 37.6%, P < 0.001). A concordance between the two methods was present in 71.2% of cases. A significant difference in the eradication rate was seen between clarithromycin-susceptible and -resistant strains, when assessed with either Etest (92.4% versus 55.5%, P < 0.001) or a PCR-based method (94.5% versus 70.9%; P < 0.001). Of note, the eradication rate showed the lowest value (30.7%) when phenotypic bacterial resistance was genetically linked to the A2143G point mutation. CONCLUSIONS: This study showed that: (i) there is a relevant discordance between the two methods; and (ii) phenotypic clarithromycin resistance markedly reduces H. pylori eradication when it is linked to a specific point mutation.

The source of Helicobacter pylori infection in the neonatal period.

AIMS: To investigate the transmission of Helicobacter pylori in the perinatal period. METHODS: H. pylori status of 180 women was preliminarily screened by serology and stool antigen test (SAT) within the fourth day after delivery and a positive value was confirmed by (13)C-urea breath test. Infants were analyzed by SAT at 1, 6, 12 and 18 months of age. H. pylori status was also investigated in the medical and paramedical staff of the Neonatology Unit. RESULTS: H. pylori infection was found in 34.4% of the women. At the 1(st) month of age, 5 out of 172 newborns (2.9%) were H. pylori positive by SAT. Three out of the five positive infants were born to H. pylori non-infected mothers. Formula feeding (P=0.02) and admission in intermediate-risk neonatal unit (P=0.01) were significantly related to a positive H. pylori result. Medical and paramedical staff of the neonatology unit was found H. pylori positive in 34.8% of cases. All five H. pylori positive children spontaneously cleared the infection. CONCLUSIONS: Perinatal H. pylori SAT positive status is low in our area, and it may be found both in infants from infected or non-infected mothers. Formula feeding and admission in intermediate-risk neonatal unit appear to be related with H. pylori infection.

Helicobacter pylori vacA arrangement and related diseases: a retrospective study over a period of 15 years.

Peptic ulcer disease incidence is decreasing. Both s1m1 and s1m2 vacA gene combinations of Helicobacter pylori have been associated with the development of major gastroduodenal diseases. This study assessed whether H. pylori vacA gene arrangement changed over 15 years in a Southern Italy area. H. pylori-positive patients observed in January-June 1989 and January-June 2005 were selected. Histological specimens were retrieved to extract DNA for vacA arrangement characterization (mid-m and peptide signal-s regions) by using the polymerase chain reaction. Fifty-nine patients in the first period and 56 matched patients in the second period were evaluated. A correlation between s1 presence and intestinal metaplasia at histology was found. Overall, the s1m1 combination increased (P < 0.01) and s2m2 decreased (P < 0.001) during the study period. In detail, s1m1 (P < 0.05) and s1m2 (P < 0.01) increased, and s2m2 decreased (P < 0.001) in dyspeptic patients, while only s1m1 increased (P < 0.01) in peptic ulcer patients. Finally, few cases of s2m1 combination in both series were found. Our results show some unexpected aspects that require confirmation. In detail, the increased prevalence of potential more virulent H. pylori strains contrasts with peptic ulcer incidence reduction.

Tumour necrosis factor alpha in segmental colitis associated with diverticula.

The pathogenesis of segmental colitis associated with diverticula (SCAD) is unclear, but tumour necrosis factor alpha (TNF-alpha) has been shown to play a pivotal role in the pathogenesis of inflammatory bowel diseases. The aim of this study was to assess TNF-alpha levels in patients with SCAD. In a post hoc analysis of a prospective multicenter study, tissue samples from 13 patients diagnosed with SCAD were subjected to histological analyses. The severity of the inflammation was assessed by means of a histological score and histomorphometry (number of inflammatory cells/mm2). Immunohistochemical staining with an antibody against TNF-alpha was performed on all biopsies and the degree of staining expressed as the percentage of positive stromal cells/1000 counted (TNF-alpha score). Matched patients with irritable bowel syndrome (IBS) were used as controls. Over-expression of TNF-alpha was found in all SCAD patients (38.6 +/- 10.4%), and it was associated with a high histological score (2.5 +/- 0.5) and neutrophil cell count (16.3 +/- 3/mm2). These values were distinctly higher than those found in the IBS controls. Our data suggest that TNF-alpha activity is involved in SCAD pathogenesis, similarly to what occurs in Crohn's disease and ulcerative colitis.