Endoscopic pancreatic sphincterotomy in patients with IPMN-related recurrent pancreatitis: A single center experience.

BACKGROUND: Acute recurrent pancreatitis (ARP) is a rare manifestation of Intraductal Papillary Mucinous Neoplasms (IPMN) of the pancreas; ARP is a relative indication for pancreatic surgery in the setting of IPMN. Endoscopic pancreatic sphincterotomy (EPS) has been described as a minimal invasive treatment to reduce the episodes of ARP secondary to mucus migration in IPMN. METHODS: patients with IPMN-related ARP treated with ESP from January 2004 to December 2020 were retrospectively selected. Clinical and technical data were recorded. A clinical follow-up (minimum 12 months) was performed to assess the number of episodes of AP occurring after EPS. RESULTS: 25 patients were included. The mean follow-up after ESP was 93.4 months (SD± 56.6). The mean number of AP before and after EPS were respectively 3.29 (SD ± 1.04) and 0.51 (SD ± 0.71). A complete response (no further episodes of AP) and a partial response (>50% reduction of AP episodes) were obtained in 64% and 24% of the cases, respectively, with an overall response rate of 88%. One post-EPS bleeding and one minor-papilla stenosis were reported and were endoscopically managed. Two patients underwent pancreatic resection for the occurrence of high-risk stigmata for cancer progression. CONCLUSIONS: EPS is a safe and effective treatment to reduce the number of episodes of AP in selected patients with IPMNs-related ARP. Prospective trials are needed to confirm these data.

Single-balloon push-and-pull enteroscopy system: does it work? A single-center, 3-year experience.

BACKGROUND: The last decade has seen significant advances in the evaluation of the small bowel. Several endoscopic techniques have been developed in recent years: capsule endoscopy (CE), double-balloon enteroscopy (DBE), and, more recently, the single-balloon enteroscopy (SBE). The aim of this study was to evaluate diagnostic and therapeutic impact, safety, and feasibility of the SBE procedure after a 3-year experience. METHODS: A total of 73 SBE procedures were performed from July 2006 to July 2009. The starting insertion route (oral or anal) of SBE was chosen according to the estimated location of the suspected lesions based on the clinical presentation and, in 48 patients, on the findings of CE. A total of 70 patients with obscure gastrointestinal bleeding (31), suspected malabsorption syndrome (12), polyposis syndromes (11), suspected Crohn's disease (9), and suspected gastrointestinal tumors (7) were recruited. RESULTS: The SBE was not carried out in four patients because of technical problems. Multiple angiodysplasias were found and treated in 9 patients; Peutz-Jeghers syndrome, familial adenomatous polyposis (FAP), and multiple polypectomies were carried out in 8 patients; endoscopic tattoos were performed in 2 patients due to the large diameter of the polyps; and multiple biopsies was performed in only one patient. SBE diagnosed Crohn's disease in four patients, malabsorption syndromes in two, lymphangiectasia in two, eosinophilic enteritis in one, melanoma in one, and nonspecific inflammation in eight. A total of seven small-bowel tumors were diagnosed (all were tattooed). In 23/70 patients the exam was negative. No major complications occurred. CONCLUSION: Single-balloon enteroscopy seems to be safe, useful, and highly effective in the diagnosis and therapy of several small-bowel diseases.

13C-methionine breath tests for mitochondrial liver function assessment.

13C-methionine breath test has been proposed as a non-invasive tool for the assessment of human hepatic mithocondrial function. Two methionine breath labeled with 13C in differents point of his molecular structure have been used for breath test analisys. Aim of this study was to compare two differently 13C-labeled methionines in the evaluation of mitochondrial oxidation in basal conditions and after an acute oxidative stress. 15 healthy male subjects (mean age 30.5 +/- 3.1) received [methyl-13C]-methionine dissolved in water. Breath samples were taken at baseline and and 10, 20, 30, 45, 60, 75, 90, 105 and 120 minutes after the ingestion of the labeled substrate. Forthy-eight hours later, subjects underwent the same test 30 minutes after ethanol ingestion (0,3 g/kg of body weight). Seven-day later, subjects underwent breath test using (L-methionine-1-13COOH) as substrate, in basal condition and after ethanol ingestion. At basal condition, the cumulative percentage of 13CO2 recovered in breath during the test period (%cum-dose) was higher using L-methionine-1-13COOH than [methyl-13C]-methionine (10.25 +/- 1.0 vs 4.07 +/- 0.8; p < 0.01). After ethanol ingestion, % cum dose was significantly decreased at 60 and 120 minutes with both methionines (120 min: 10.25 +/- 1.0 vs 5.03% +/- 1.8; < 0.01 and 4.07 +/- 0.8 vs 2.16% +/- 0.9; p < 0.01, respectively). However, %cum-dose during L-methionine-1-13C-breath test was significantly lower than that observed during methyl-13C-methionine breath test (120 minutes: 5.03% +/- 1.8 vs 2.16% +/- 0.9; p < 0.01). In conclusion, breath test based on L-methionine-1-13COOH seems to show a greater reliability when compared to [methyl-13C]-methionine to assess mitochondrial function because a larger amount of labeled carbon that reaches the Krebs' cicle.

A case-control study comparing methylene blue directed biopsies and random biopsies for detecting pre-cancerous lesions in the follow-up of gastric cancer patients.

OBJECTIVES: To compare the accuracy of Methylene Blue (MB) targeted biopsies with random biopsies in detecting intestinal metaplasia and dysplasia in the follow-up of patients after gastrectomy for gastric cancer. METHODS: Thirty patients (21 Billroth II, 9 Billroth 1) for cancer, referred to the Gastroenterology Unit for an elective esophagogastroduodenoscopy (EGD), were enrolled. All endoscopies were performed with a high-resolution videoendoscope with an adjustable image magnification: EG-485ZH (Fujinon, Omiya, Japan). During EGD three random biopsies were taken in the stomach and, after staining with MB, three targeted biopsies were taken from every stained area. RESULTS: In 28 patients traditional endoscopy showed hyperemia of the anastomosis, in 2 patients a lesion. After MB in 6/30 there were stained area (2 lesions seen with traditional endoscopy and 4 blue areas in other patients). As regards histology: 24 patients showed inflammation, while 2 patients with alterations in traditional endoscopy and with MB showed metaplasia and high grade dysplasia. In 4/30 (13.3%) patients MB guided biopsies showed significant lesions (3 intestinal metaplasia, 1 low grade dysplasia) while random biopsies showed only inflammation. CONCLUSIONS: After partial gastrectomy, the mucosa of the residual stomach usually undergoes severe changes, and these lesions are known to be pre-cancerous. The diagnostic accuracy of the MB technique seems to be superior to random biopsies for identification of intestinal metaplasia, dysplasia, and may be helpful in targeting biopsies and early endoscopic treatment.

Diagnostic and therapeutic impact of double-balloon enteroscopy (DBE) in a series of 100 patients with suspected small bowel diseases.

BACKGROUND: Double-balloon enteroscopy is a newly developed endoscopic method allowing non-surgical full-length exploration of the small bowel, biopsies sample and endoscopic treatment of previously inaccessible lesions. AIM: To prospectively assess the diagnostic and therapeutical impact of double-balloon enteroscopy in patients with suspected or documented small bowel disease. PATIENTS AND METHODS: One hundred consecutive patients referring to our centre for suspected small bowel disease underwent double-balloon enteroscopy. Starting insertion route (anal or oral) of double-balloon enteroscopy was chosen according to the estimated location of the suspected lesions basing on the clinical presentation and on the findings, when available, of previous endoscopic or radiological investigations. Major indications for the procedures were acute recurrent or chronic mid-gastrointestinal bleeding (n=71), suspected gastrointestinal tumours (n=10), suspected Crohn's disease (n=6), chronic abdominal pain and/or chronic diarrhoea (n=8), refractory celiac disease (n=5). RESULTS: One hundred and eighteen double-balloon enteroscopy procedures were carried out. Oral and anal route double-balloon enteroscopies were performed in 54 and 28 patients, respectively, while 18 patients underwent a combination of both approaches. Overall diagnostic yield of double-balloon enteroscopy resulted 69%. Most common pathological findings included angiodysplasias (n=39), ulcerations and erosions of various aetiologies (n=21), tumours (n=7) and ileal stenosis in patients with Crohn's disease suspicion (n=2). In the 65% of the patients examined, double-balloon enteroscopy findings influenced the subsequent clinical management (endoscopic, medical or surgical treatment). No major complications related to the procedure occurred. CONCLUSIONS: Our prospective analysis shows that double-balloon enteroscopy is a useful, safe and well-tolerated new method with a high diagnostic and therapeutic impact for the management of suspected or documented small bowel diseases.

Gender affects 13C-ketoisocaproic acid breath test.

BACKGROUND AND AIMS: 13C-Ketoisocaproic Acid Breath Test (13C-Kica-BT) has been proposed to assess mitochondrial function. Aim of this study is to evaluate whether gender affects mithocondrial oxidation by means of 13C-Kica-BT in healthy subjects in basal conditions and after an acute oxidative stress induced by ethanol. METHODOLOGY: 50 healthy volunteers were given 1 mg/kg of 13C-Kica together with 20 mg/kg of L-leucine dissolved in 200 ml of orange juice. Breath samples were taken at baseline, every 5 minutes for 45 minutes and then every 15 minutes until 2 hours. Forty-eight hours later the test was repeated 30 min after ethanol ingestion (0.5 g/kg body weight). 13CO2 enrichment in breath was analyzed by isotope ratio/mass spectrometry. Statistical analysis was performed using the student's t test. RESULTS: At baseline conditions, the percentage of Ketoisocaproic acid in 2 hours was significantly higher in females than in males. Ethanol significantly reduces the oxidation of Ketoisocaproic acid. Conversely, no differences were observed between groups after the ethanol oral load. CONCLUSIONS: Decarboxylation of 13C-Kica was significantly higher in females than in males. Ethanol decreases Kica decarboxylation in particular in women. Further studies remain needed to establish whether sexual hormones could interfere with the metabolism of Kica.

Characterization of gene expression profile in rat Kupffer cells stimulated with IFN-alpha or IFN-gamma.

BACKGROUND AND AIM: Kupffer cells are intrasinusoidal space located macrophages with phagocytic capacity. Interferons are cytokines with antiviral, antiproliferative and immunomodulatory activities which may influence the activity of Kupffer cells. Aim of this study was to evaluate Kupffer cell gene expression after interferon-alpha or interferon-gamma stimulation in order to investigate a link between these cytokines and macrophage activation. METHODS: Rat Kupffer cells were cultured for 24 h and divided into three groups: unstimulated; stimulated with interferon-alpha and stimulated with interferon-gamma. After 8 h stimulation total RNA was extracted and processed according to Affymetrix protocols and hybridised on R34A microarray gene set. Data analyses was performed using Microarray Analysis Suite 5.0 software. Genes showing remarkably different expression in microarray analysis were confirmed by real-time PCR. RESULTS: Nearly 4000 out of the 8800 genes represented in the array were expressed by Kupffer cells. Among these, interferon-alpha up-regulates 91 genes by over two-fold (antiviral, antigen processing and presentation, and tumour suppressor/proapoptotic genes) and down-regulates 72 genes by 50% or more. Interferon-gamma up-regulates 70 genes by over two-fold and down-regulates 78 genes by 50% or more. Most of the genes induced by interferon-alpha are also induced by interferon-gamma. Down-regulated genes include growth factors and genes involved in cell cycle/proliferation. Real-time PCR confirms the results of the array. CONCLUSION: Interferons directly target rat Kupffer cells and are involved in the regulation of a wide variety of genes. Their expression profile shed light onto molecular mechanism of Kupffer cells activation in specific pathways such as antiviral and antitumour processes.

Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis.

BACKGROUND: Aminosalicylates are the mainstay of therapy to prevent relapse of quiescent ulcerative colitis. The rationale for using probiotics is based on the evidence implicating intestinal bacteria in the pathogenesis of this disorder. AIM: To evaluate the efficacy of Lactobacillus GG alone or in combination with mesalazine vs. mesalazine as maintenance treatment in ulcerative colitis. PATIENTS AND METHODS: 187 ulcerative colitis patients with quiescent disease were randomized to receive Lactobacillus GG 18 x 10(9) viable bacteria/day (65 patients), mesalazine 2400 mg/day (60 patients) or Lactobacillus GG + mesalazine (62 patients). Disease activity index, endoscopic and histological scores were determined at 0, 6 and 12 months and in case of relapse. The primary end point was to evaluate sustained remission. RESULTS: Overall analysis showed no difference in relapse rate at 6 (P = 0.44) and 12 months (P = 0.77) among the three treatment groups. However, the treatment with Lactobacillus GG seems to be more effective than standard treatment with mesalazine in prolonging the relapse-free time (P < 0.05). CONCLUSIONS: Lactobacillus GG seems to be effective and safe for maintaining remission in patients with ulcerative colitis, and it could represent a good therapeutic option for preventing relapse in this group of patients.

Accuracy of laryngeal examination during upper gastrointestinal endoscopy for premalignancy screening: prospective study in patients with and without reflux symptoms.

BACKGROUND AND STUDY AIMS: Gastroesophageal reflux disease may be associated with laryngeal damage caused by reflux material. The aim of this study was to investigate the accuracy of laryngeal examinations during routine upper gastrointestinal endoscopy as a method of screening for major laryngeal injury in a series of patients with reflux symptoms. PATIENTS AND METHODS: A total of 100 consecutive patients with reflux symptoms and 100 control individuals underwent upper gastrointestinal endoscopy with standard or high-resolution magnifying video endoscopes. Any laryngeal abnormalities were initially identified by the gastroenterologist before the scope was inserted into the esophagus. All of the examinations were recorded on video and subsequently reevaluated by an otorhinolaryngologist. All of the patients underwent standard laryngoscopy as a reference procedure. RESULTS: All of the patients completed the study. The sensitivity, specificity, negative predictive value, and positive predictive value of the preliminary laryngeal exploration for detecting laryngeal abnormalities (such as laryngitis and vocal leukoplakia) were 90%, 90%, 92%, and 89%, respectively. High-resolution magnifying endoscopy had a higher sensitivity and specificity than standard endoscopy for detecting laryngeal pathology. Two patients were found to have laryngeal leukoplakia. CONCLUSIONS: This study shows that preliminary diagnosis of laryngeal disorders can be accurately carried out by the gastroenterologist when patients are undergoing upper endoscopy for reflux symptoms. This approach could also be helpful for the timely diagnosis of major reflux-related laryngeal disease.

Improvement of mitochondrial function evaluated by ketoisocaproic acid breath test in patients with HCV infection undergoing albumin dialysis.

BACKGROUND AND AIM: Oxidative injury occurs as a direct result of hepatitis C virus (HCV) core protein expression both in vitro and in vivo, and may be due to a direct effect on mitochondria. The ketoisocaproic acid (KICA) breath test is a simple, reliable, and noninvasive test to evaluate hepatic mitochondrial function. Albumin dialysis (MARS) is an effective bridge treatment for patients with acute failure superimposed on chronic liver disease. The aim of our study was to evaluate the improvement of mitochondrial function measured by KICA in patients undergoing MARS for acute-on-chronic HCV liver failure. MATERIALS AND METHODS: Five patients with HCV chronic infection undergoing MARS treatment for acute decompensation were enrolled. Before and after each MARS treatment, patients underwent blood testing for the main hematochemical parameters as well as for mitochondrial function by the KICA breath test and the arterial ketone bodies ratio (AKBR). RESULTS: MARS treatment effectively decreased the serum level of total bilirubin, bile acids, urea, and ammonium. Moreover, MARS treatment produced an increase in AKBR and in the cumulative percentage of (13)CO(2) recovered in exhaled air 2 hours after KICA ingestion. CONCLUSION: Liver mitochondrial function appears to be beneficially affected by MARS treatment.

Moxifloxacin-based strategies for first-line treatment of Helicobacter pylori infection.

BACKGROUND: Standard anti-Helicobacter pylori therapy may not achieve a satisfactory eradication rate. Fluoroquinolones, such as moxifloxacin, are safe and promising agents for H. pylori eradication. AIM: To compare the efficacy of two 1-week moxifloxacin-based H. pylori eradication regimens with two standard treatments. METHODS: Three hundred and twenty H. pylori-positive subjects were randomized into four groups to receive: moxifloxacin, amoxicillin, esomeprazole (Group MAE); moxifloxacin, tinidazole and esomeprazole (Group MTE); standard triple therapies with clarithromycin, amoxicillin and esomeprazole (Group CAE) or tinidazole (Group CTE) for 7 days. H. pylori status was re-assessed 6 weeks after the end of therapy by 13C urea breath test. RESULTS: Three hundred and twenty patients completed the efficacy analysis per protocol; H. pylori eradication rate in group MTE was 90% (72 of 80) and 92% (72 of 78), in group MAE was 88% (70 of 80) and 89%, (70 of 79) in Group CAE was 73% (58 of 80) and 78% (58 of 74), and in Group CTE was 75% (60 of 80) and 79% (60 of 76), respectively, in intention-to-treat and in per protocol analyses. Eradication rates of moxifloxacin-based triple therapies were significantly higher than that observed using standard triple schemes. The incidence of side effects was significantly lower in moxifloxacin groups than in control groups. CONCLUSIONS: Seven-day moxifloxacin-based triple therapies provide optimal eradication rates with a good compliance when compared with the standard triple therapy schemes.

Helicobacter pylori infection and ischaemic heart disease: an overview of the general literature.

In the last years, a considerable number of studies have been performed on the correlation between Helicobacter pylori infection and ischaemic heart disease. The reason is the supposed role of some chronic infections in the genesis and development of vessel wall injury and atheromatous plaque, as already reported for Chlamydia pneumoniae and herpes viruses. While this association may be theoretically conceivable, it still remains debated from a practical point of view. Epidemiological and animal studies as well as some eradicating trials gave conflicting results, while studies investigating the specific molecular mimicry mechanisms induced by H. pylori strongly support the association. Moreover, none of the studies performed so far did take into account the effect of the genetic susceptibility to develop ischaemic heart disease or to respond to H. pylori infection. In particular, while the exposure to some known risk factor for atherosclerosis should lead to develop ischaemic heart disease, no condition or exposure, either individual or in combination, completely explains the occurrence and the progression of the disease, as many patients develop ischaemic heart disease in the absence of any risk factor. Based on these concepts, can we state that H. pylori infection may cause the same effect in patients with ischaemic heart disease as in healthy subjects? Further studies are needed in order to clarify this issue.

Bacillus clausii therapy to reduce side-effects of anti-Helicobacter pylori treatment: randomized, double-blind, placebo controlled trial.

BACKGROUND: Helicobacter pylori eradication fails in about 10% of patients, particularly because of the occurrence of resistance to antibiotics and side-effects. During anti-H. pylori therapy, probiotics have been successfully used to reduce the incidence of side-effects. AIM: To evaluate the effect of Bacillus clausii, a probiotic, on incidence (primary variable) and severity of antibiotic-associated side-effects during anti-H. pylori therapy. METHODS: One hundred and twenty H. pylori-positive patients were randomly screened to receive: (i) a standard 7 days triple therapy with rabeprazole 20 mg b.d., clarithromycin 500 mg b.d. and amoxicillin 1 g b.d. and B. clausii t.d.s. (each preparation containing 2 x 10(9) spores) for 14 days starting from the first day of treatment. (ii) The same 7 days triple therapy and placebo t.d.s. for 14 days starting from the first day of treatment. Side-effects were assessed using a validated questionnaire and were recorded for 4 weeks from the start of therapy. RESULTS: The incidences of nausea, diarrhoea and epigastric pain in patients treated with B. clausii were significantly lower than in placebo group, in both PP and ITT analysis. Equally, intensity of nausea and diarrhoea in patients treated with B. clausii was significantly lower than in placebo group. There were no differences in adherence to treatment and H. pylori eradication rates between groups. Conclusion : In symptom-free, H. pylori-positive subjects B. clausii bacteriotherapy reduces the incidence of the most common side-effects related to anti-H. pylori antibiotic therapy compared with placebo.

13C-breath tests in the study of microsomal liver function.

Conventional liver tests can be used to estimate a mixture of injury and function but none of these may be regarded as a reliable marker either to quantify functional hepatic reserve or to reflect life-threatening complications of acute and chronic liver diseases. To overcome this limit, many dynamic tests have been developed in order to evaluate the "hepatic functional mass". Among these tests we can include breath tests with 13C-labeled substrates undergoing different metabolic pathways. As concerning the evaluation of microsomal function, two main categories of breath tests have been developed based on the limiting step in the different substrates metabolism. The first group include aminopyrine, caffeine and diazepam, all substrates with a metabolism independent from hepatic blood flow and dependent almost exclusively from the enzymatic activity of different cytochromes P450. The other group is composed of substrates with flow dependent metabolism like methacetin, phenacetin, erythromycin. The aim of this review is to describe the clinical applications of microsomal liver breath tests in different hepatic diseases.

13C-breath tests in the study of mitochondrial liver function.

Breath tests for "dynamic" liver function evaluation have been proposed several years ago. A variety of carbon-labelled breath tests for the assessment of mitochondrial, microsomal and cytosolic liver function have been described with the aim to increase data on liver disease staging, prognosis, and response to therapy. In the last years a great interest is developed about the use of breath test for liver mitochondrial function evaluation since it results impaired in a wide range of liver diseases either of genetic or acquired origin. In these cases mitochondrial oxidative metabolism of some substrates, as far as recovery of the hepatic energy state after a metabolic insult, results impaired because of the disfunction of the electron transport chain and/or ATP synthesis. Ketoisocaproic acid and methionine are the best studied carbon-labelled substrates for the investigation of mitochondrial functional damages related to structural alterations that occur in many liver diseases. Although these tests are simple, cost-effective and safe, to date there is still not general approval for their usefulness in clinical settings since they should fulfill several requirements to overcome the drawbacks of traditional quantitative tests. On the other hand, this field is relatively young and further studies are needed in order to assess the suitable substrate for the evaluation of the complex mitochondrial metabolism both in healthy subjects and in patients with liver disease.

High efficacy of 1-week doxycycline- and amoxicillin-based quadruple regimen in a culture-guided, third-line treatment approach for Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori infection may persist after both first- and second-line current treatments. AIM: To assess the efficacy of a third-line, culture-guided treatment approach for the eradication of H. pylori. METHODS: Patterns of resistance were analysed in H. pylori isolates from 94 consecutive patients in whom H. pylori infection had persisted after two eradication attempts. Using the epsilometer test, susceptibility analysis was performed for amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin. Patients were then treated with a culture-guided, third-line regimen: 89 patients with a 1-week quadruple regimen including omeprazole, bismuth, doxycycline and amoxicillin, and five patients with a 1-week triple regimen containing omeprazole, amoxicillin and levofloxacin or clarithromycin. RESULTS: Ninety-four subjects (100%) were resistant to metronidazole, 89 (95%) to clarithromycin, 29 (31%) to levofloxacin and five (5%) to tetracycline. No resistance to amoxicillin was found in any patient. Overall, H. pylori eradication was obtained in 90% of subjects. The quadruple regimen was effective in 81 patients (92% by per protocol and 91% by intention-to-treat analysis). Four patients (80%, both per protocol and intention-to-treat analysis) were H. pylori-negative after the triple regimen. CONCLUSIONS: A culture-guided, third-line therapeutic approach is effective for the eradication of H. pylori. Furthermore, the 1-week doxycycline- and amoxicillin-based quadruple regimen is a good third-line 'rescue' treatment option.