Mucosal adhesion and anti-inflammatory effects of Lactobacillus rhamnosus GG in the human colonic mucosa: A proof-of-concept study

AIM To investigate the adhesion and anti-inflammatory effects of Lactobacil us rhamnosus GG (LGG) in the colonic mucosa of healthy and ulcerative colitis (UC) patients, both in vivo and ex vivo in an organ culture model.METHODS For the ex vivo experiment, a total of 98 patients (68 UC patients and 30 normal subjects) were included. Endoscopic biopsies were collected and incubated with and without LGG or LGG-conditioned media to evaluate the mucosal adhesion and anti-inflammatory effects [reduction of tumor necrosis factor alpha (TNFα) and interleukin (IL)-17 expression] of the bacteria, and extraction of DNA and RNA for quantification by real-time (RT)-PCR occurred after the incubation. A dose-response study was performed by incubating biopsies at "regular", double and 5 times higher doses of LGG. For the in vivo experiment, a total of 42 patients (20 UC patients and 22 normal controls) were included. Biopsies were taken from the colons of normal subjects who consumed a commercial formulation of LGG for 7 d prior to the colonoscopy,and the adhesion of the bacteria to the colonic mucosa was evaluated by RT-PCR and compared with that of control biopsies from patients who did not consume the formulation. LGG adhesion and TNFα and IL-17 expression were compared between UC patients who consumed a regular or double dose of LGG supplementation prior to colonoscopy.RESULTS In the ex vivo experiment, LGG showed consistent adhesion to the distal and proximal colon in normal subjects and UC patients, with a trend towards higher concentrations in the distal colon, and in UC patients, adhesion was similar in biopsies with active and quiescent inflammation. In addition, bioptic samples from UC patients incubated with LGG conditioned media (CM) showed reduced expression of TNFα and IL-17 compared with the corresponding expression in controls (P < 0.05). Incubation with a double dose of LGG increased mucosal adhesion and the anti-inflammatory effects (P < 0.05). In the in vivo experiment, LGG was detectable only in the colon of patients who consumed the LGG formulation, and bowel cleansing did not affect LGG adhesion. UC patients who consumed the double LGG dose had increased mucosal concentrations of the bacteria and reduced TNFα and IL-17 expression compared with patients who consumed the regular dose (48% and 40% reduction, respectively, P < 0.05).CONCLUSION In an ex vivo organ culture model, LGG showed consistent adhesion and anti-inflammatory effects. Colonization by LGG after consumption for a week was demonstrated in vivo in the human colon. Increasing the administered dose increased the adhesion and effectiveness of the bacteria. For the first time, we demonstrated that LGG effectively adheres to the colonic mucosa and exerts antiinflammatory effects, both ex vivo and in vivo.

Lack of specific association between gastric autoimmunity hallmarks and clinical presentations of atrophic body gastritis

AIM： To investigate the possible relationships between gastric autoimmune phenomena and clinical presentations of this disorder, in consecutive atrophic body gastritis patients. METHODS： A total of 140 atrophic body gastritis patients, diagnosed as consecutive outpatients presenting with macrocytic or iron deficiency anemia, or longstanding dyspepsia underwent gastroscopy with antral and body biopsies, assay of intrinsic factor, parietal cells and Helicobacter pylori （ H pylon） antibodies. Gastritis was assessed according to Sydney System. RESULTS： Parietal cell antibodies were equally distributed in all clinical presentations, whereas the positivity of intrinsic factor antibodies （49/140, 35%） was significantly higher in pernicious anemia patients （49.2%） than in iron deficiency （21.1%） and dyspeptic patients （27.8%）. No specific pattern of autoantibodies was related to the clinical presentations of atrophic body gastritis. A positive correlation was obtained between the body atrophy score and the intrinsic factor antibody levels （r=0.2216, P=0.0085）. Associated autoimmune diseases were present in 25/140 （17.9%） patients, but the prevalence of autoimmune diseases was comparable, irrespective of the clinical presentations. CONCLUSION： The so-called hallmarks of gastric autoimmunity, particularly in intrinsic factor antibody cannot be usefully employed in defining an autoimmune pattern in the clinical presentations of ABG.

Liver biopsy:analysis of results of two specialist teams

AIM:To analyze the safety and the adequacy of a sample of liver biopsies(LB)obtained by gastroenterologist(G)and interventional radiologist(IR)teams.METHODS:Medical records of consecutive patients evaluated at our GI unit from 01/01/2004 to31/12/2010 for whom LB was considered necessary to diagnose and/or stage liver disease,both in the setting of day hospital and regular admission(RA) care,were retrieved and the data entered in a database.Patients were divided into two groups:one undergoing an ultrasonography(US)-assisted procedure by the G team and one undergoing US-guided biopsy by the IR team.For the first group,an intercostal approach(US-assisted) and a Menghini modified type needle 16 G(length 90 mm) were used.The IR team used a subcostal approach(US-guided) and a semiautomatic modified Menghini type needle 18 G(length 150 mm).All the biopsies were evaluated for appropriateness according to the current guidelines.The number of portal tracts present in each biopsy was assessed by a revision performed by a single pathologist unaware of the previous pathology report.Clinical,laboratory and demographic patient characteristics,the adverse events rate and the diagnostic adequacy of LB were analyzed.RESULTS:During the study period,226 patients,126 males(56%) and 100 females(44%),underwent LB:167(74%) were carried out by the G team,whereas 59(26%) by the IR team.LB was mostly performed in a day hospital setting by the G team,while IR completed more procedures on inpatients(P < 0.0001).The groups did not differ in median age,body mass index(BMI),presence of comorbidities and coagulation parameters.Complications occurred in 26 patients(16 G team vs 10 IR team,P = 0.15).Most gross samples obtained were considered suitable for basal histological evaluation,with no difference among the two teams(96.4% G team vs 91.5% IR,P = 0.16).However,the samples obtained by the G team had a higher mean number of portal tracts(G team 9.5 ± 4.8; range 1-29 vs IR team 7.8 ± 4.1; range 1-20)(P = 0.0192) and a longer mean length(G team 22 mm ± 8.8 vs IR team 15 ± 6.5 mm)(P = 0.0001).CONCLUSION:LB can be performed with similar outcomes both by G and IR.Use of larger dimension needles allows obtaining better samples,with a similar rate of adverse events.

Pernicious anemia: New insights from a gastroenterological point of view

Pernicious anemia （PA） is a macrocytic anemia that is caused by vitamin B12 deficiency, as a result of intrinsic factor deficiency. PA is associated with atrophic body gastritis （ABG）, whose diagnosis is based on histological confirmation of gastric body atrophy. Serological markers that suggest oxyntic mucosa damage are increased fasting gastrin and decreased pepsinogen I. Without performing Schilling＇s test, intrinsic factor deficiency may not be proven, and intrinsic factor and parietal cell antibodies are use- ful surrogate markers of PA, with 73% sensitivity and 100% specificity. PA is mainly considered a disease of the elderly, but younger patients represent about 15% of patients. PA patients may seek medical advice due to symptoms related to anemia, such as weak-ness and asthenia. Less commonly, the disease is suspected to be caused by dyspepsia. PA is frequently associated with autoimmune thyroid disease （40%） and other autoimmune disorders, such as diabetes mellitus （10%）, as part of the autoimmune polyen-docrine syndrome. PA is the end-stage of ABG. Long- standing Helicobacter pylori infection probably plays a role in many patients with PA, in whom the active infectious process has been gradually replaced by an autoimmune disease that terminates in a burned-out infection and the irreversible destruction of the gastric body mucosa. Human leucocyte antigen-DR genotypes suggest a role for genetic susceptibility in PA. PA patients should be managed by cobalamin replacement treatment and monitoring for onset of iron deficiency. Moreover, they should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.

Helicobacter pylori infection and drugs malabsorption

Drug absorption represents an important factor affecting the efficacy of oral drug treatment.Gastric secretion and motility seem to be critical for drug absorption.A causal relationship between impaired absorption of orally administered drugs and Helicobacter pylori(H.pylori)infection has been proposed.Associations have been reported between poor bioavailability of l-thyroxine and l-dopa and H.pylori infection.According to the Maastricht Florence Consensus Report on the management of H.pylori infection,H.pylori treatment improves the bioavailability of both these drugs,whereas the direct clinical benefits to patients still await to be established.Less strong seems the association between H.pylori infection and other drugs malabsorption,such as delavirdine and ketoconazole.The exact mechanisms forming the basis of the relationship between H.pylori infection and impaired drugs absorption and/or bioavailability are not fully elucidated.H.pylori infection may trigger a chronic inflammation of the gastric mucosa,and impaired gastric acid secretion often follows.The reduction of acid secretion closely relates with the wideness and the severity of the damage and may affect drug absorption.This minireview focuses on the evidence of H.pylori infection associated with impaired drug absorption.

Helicobacter pylori and functional dyspepsia: An unsolved issue?

Patients with Helicobacter pylori (H. pylori) infection may complain of dyspeptic symptoms without presence of macroscopic lesions on gastroduodenal mucosa. Such a condition is usually recognized as functional dyspepsia, and different pathogenetic mechanisms are involved. The role of H. pylori in these patients is controversial. Several trials assessed the potential role of H. pylori eradication in improving dyspeptic symptoms, and data of some meta-analyses demonstrated that cure of infection is associated with a small (10%), but significant therapeutic gain as compared to placebo. The reason for which dyspeptic symptoms regress in some patients following bacterial eradication, but persist in others remains unclear. Regrettably, trials included in the meta-analyses are somewhat different for study design, definition of symptoms, assessment of symptoms changes, and some may be flawed by potential pitfalls. Consequently, the information could be not consistent. We critically reviewed the main available trials, attempting to address future research in this field

Artifi cial neural networks in the recognition of the presence of thyroid disease in patients with atrophic body gastritis

AIM: To investigate the role of artifi cial neural networks in predicting the presence of thyroid disease in atrophic body gastritis patients. METHODS: A dataset of 29 input variables of 253 atrophic body gastritis patients was applied to artifi cial neural networks (ANNs) using a data optimisation procedure (standard ANNs,T&T-IS protocol,TWIST protocol). The target variable was the presence of thyroid disease. RESULTS: Standard ANNs obtained a mean accuracy of 64.4% with a sensitivity of 69% and a specifi city of 59.8% in recognizing atrophic body gastritis patients with thyroid disease. The optimization procedures (T&T-IS and TWIST protocol) improved the performance of the recognition task yielding a mean accuracy,sensitivity and specifi city of 74.7% and 75.8%,78.8% and 81.8%,and 70.5% and 69.9%,respectively. The increase of sensitivity of the TWIST protocol was statistically signifi cant compared to T&T-IS. CONCLUSION: This study suggests that artificial neural networks may be taken into consideration as a potential clinical decision-support tool for identifying ABG patients at risk for harbouring an unknown thyroid disease and thus requiring diagnostic work-up of their thyroid status.

Pre-endoscopic screening for Helicobacter pylori and celiac disease in young anemic women

AIM： To evaluate the usefulness of pre-endoscopic serological screening for He//cobacter py/or/ （H py/or/} infection and celiac disease in women aged 〈 50 years affected by iron-deficiency anemia （IDA）. METHODS： One hundred and fifteen women aged 〈 50 years with IDA were tested by human recombinant tissue transglutaminase IgA antibodies （tTG） and anti-H pylori IgG antibodies, tTG and H pylori IgG antibody were assessed using an enzyme-linked immunosorbent assay （ELISA）. All women were invited to undergo upper GI endoscopy. During gastroscopy, biopsies were collected from antrum （n = 3）, gastric body （n = 3） and duodenum （n = 4） in all patients, irrespective of test results. The assessment of gastritis was performed according to the Sydney system and celiac disease was classified by Marsh＇s System. RESULTS： 45.2% women were test-positive： 41 patients positive for H pylori antibodies, 9 patients for tTG and 2 patients for both. The gastroscopy compliance rate of test-positive women was significantly increased with respect to those test- negative （65.4% vs 42.8%; Fisher test P = 0.0239）. The serological results were confirmed by gastroscopy in 100% of those with positive H pylori antibodies, in 50% of those with positive tTG and in 81.5% of test- negative patient. Sensitivity and specificity were 84.8% and 100%, respectively for Hpylori infection and, 80% and 92.8% for tTG. Twenty-eight patients had positive H pylori antibodies and in all the patients, an active Hpylori infection was found. In particular, in 23 out of 28 （82%） patients with positive H pylori antibodies, a likely cause of IDA was found because of the active inflammation involving the gastric body. CONCLUSION： Anti-H pylori IgG antibody and tTG IgA antibody testing is able to select women with IDA to submit for gastroscopy to identify H pylori pangastritis and/or celiac disease, likely causes of IDA.

High-fibre diet and Lactobacillus paracasei B21060 in symptomatic uncomplicated diverticular disease

AIM： To investigate in symptomatic uncomplicated di- verticular disease the efficacy of symbiotics associated with a high-fibre diet on abdominal symptoms. METHODS： This study was a multicentre, 6-too ran- domized, controlled, parallel-group intervention with a preceding 4-wk washout period. Consecutive out- patients with symptomatic uncomplicated diverticular disease, aged 40-80 years, evaluated in 4 Gastroenterology Units, were enrolled. Symptomatic uncomplicated diverticular disease patients were randomized to two treatment arms A or B. Treatment A （n = 24 patients） received 1 symbiotic sachet Flortec~ （Lactobacillus paracasei B21060） once daily plus high-fibre diet for 6 mo. Treatment B （n = 21 patients） received high-fibre diet alone for 6 rno. The primary endpoint was regres- sion of abdominal symptoms and change of symptom severity after 3 and 6 mo of treatment. RESULTS： In group A, the proportion of patients with abdominal pain 〈 24 h decreased from 100% at base- line to 35% and 25% after 3 and 6 mo, respectively （P 〈 0.001）. In group B the proportion of patients with this symptom decreased from 90.5% at baseline to 61.9% and 38.1% after 3 and 6 mo, respectively （P = 0.001）. Symptom improvement became statistically sig- nificant at 3 and 6 mo in group A and B, respectively. The proportion of patients with abdominal pain 〉24 h decreased from 60% to 20% then 5% after 3 and 6 too, respectively in group A （P 〈 0.001） and from 33.3% to 9.5% at both 3 and 6 mo in group B （P = 0.03）. In group A the proportion of patients with ab- dominal bloating significantly decreased from 95% to 60% after 3 mo, and remained stable （65%） at 6-mo follow-up （P = 0.005） while in group B, no significant changes in abdominal bloating was observed （P = 0.11）. After 6 mo of treatment, the mean visual analogic scale （VAS） values of both short-lasting abdominal pain （VAS, mean ± SD, group A： 4.6 ± 2.1 vs 2.2 ± 0.8, P = 0.02; group B： 4.6 ± 2.9 vs 2.0 ± 1.9, P = 0.03） and abdom- inal bloating （VAS, mean ± SD, group A： 5.3 ± 2.2 vs 3.0 ± 1.7, P = 0.005; group B： 5.3 ±3.2 vs 2.3 ± 1.9, P = 0.006） decreased in both groups, whilst the VAS values of prolonged abdominal pain decreased in the Flortec group, but remained unchanged in the high-fibre diet group （VAS, mean ± SD, group A： 6.5 ± 1.5 vs 4.5 ± 2.1, P = 0.052; group B： 4.5 ± 3.8 vs 5.5 ± 3.5）. CONCLUSION： A high-fibre diet is effective in relievingabdominal symptoms in symptomatic uncomplicated di- verticular disease. This treatment may be implemented by combining the high-fibre diet with Flortec~.

‘Les liaisons dangereuses’: Hepatitis C, Rituximab and B-cell non-Hodgkin’s lymphomas

Rituximab has provided a revolutionary contribution to the treatment of B-cell non-Hodgkin’s lymphomas (NHL). A high prevalence of hepatitis C virus (HCV) infection has been described in B-cell NHL patients. Cases of liver dysfunction in HCV-positive patients have been reported with Rituximab-containing regimens. In this paper we review the recent data regarding the effects of Rituximab in NHL patients with HCV infection. We also added a section devoted to improving communication between oncohaematologists and hepatologists. Furthermore, we propose a common methodological ground to study hepatic toxicity emerging during chemotherapy.

A case of oesophageal ulcer developed after taking homeopathic pill in a young woman

Oesophageal ulcers occur mainly as a result of gastrooesophageal reflux disease （GERD）. However, pillinduced oesophageal ulcers are a fairly common event. The lesion is mainly due to entrapment of the pill and/ or its chemical composition thereof. This case report describes an oesophageal mucosa ulcer occurred in a healthy 35-year old woman who had no previous history of oesophageal disorders and received homeopathic medication. The present case reveals that pill entrapment can occur even in the oesophagus of healthy young individuals and that oesophageal mucosal ulcer can be triggered by substances generally thought devoid of any potentially mucosal aggressive effect.

Intestinal metaplasia surveillance:Searching for the roadmap

Atrophic gastritis and intestinal metaplasia(IM) of the stomach are common and are associated with an increased risk for gastric cancer.In the absence of guidelines,a pragmatic management has been performed in Western countries in patients with these premalignant conditions.Recently,formal European guidelines have been delivered on this topic.Basically,it has been recommended that patients with extensive atrophic gastritis(AG) and/or extensive IM should be offered endoscopic surveillance every 3 years.On the contrary,no scheduled endoscopic/histological control has been advised for those patients with precancerous conditions confined to the antrum.In this commentary,we highlighted some potential weaknesses in the management formally recommended by the new guidelines.In detail,we discussed that AG and IM patients do not share the same gastric cancer risk,at least in Western countries,deserving a different approach.Some factors significantly associated with gastric cancer risk,such as IM type,first-degree family history of gastric cancer,and smoking habit have not been considered in tailoring the endoscopic follow-up.Finally,some data would suggest that a 3-year follow-up in patients with extensive gastric precancerous conditions could result in an inadequate secondary prevention.

Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma

AIM:To evaluate if indolent B cell-non Hodgkin's lymphoma(B-NHL) and diffuse large B-cell lymphoma(DLBCL) in hepatitis C virus(HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.METHODS:A group of 24 HCV related B-NHL patients(11 indolent,13 DLBCL) in whom the biological and clinical characteristics were described and confronted.Patients with DLBCL were managed with the standard of care of treatment.Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed.The outcomes of the different approaches were compared.RESULTS:Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype.Five of the 9 patients with indolent HCV-relatedB-NHL treated with only antiviral therapy,achieved a complete response of their onco-haematological disease(55%).Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response(54%).CONCLUSION:HCV genotypes and duration of HCV infection differed between B-NHL subtypes.Indolent lymphomas can be managed with antiviral treatment,while DLBCL is not affected by the HCV infection.

New Era: Endoscopic treatment options in obesity–a paradigm shift

The prevalence of obesity continues to rise,and along with it comes a multitude of health-related consequences.The healthcare community has consistently struggled with providing treatment options to obese patients,in part due to the reluctance of patients in pursuing the more effective(yet invasive)surgical approaches such as sleeve gastrectomy and Rou-en-Y gastric bypass.On the other hand,the less invasive approach such as lifestyle/behavioral interventions and pharmacotherapy(Orlistat,Phenteramine,Phentermine/Topiramate,Locaserin,Naltrexon/Buproprion,and Liraglutide)have very limited efficacy,especially in the morbidly obese patients.Despite our best efforts,the epidemic of obesity continues to rise and pose enormous costs on our healthcare system and society.Bariatric endoscopy is an evolving field generated to combat this epidemic through minimally invasive techniques.These procedures can be performed in an ambulatory setting,are potentially reversible,repeatable,and pose less complications than their invasive surgical counterparts.These modalities are designed to alter gut metabolism by means of space occupation,malabsorption,or restriction.In this review we will discuss different bariatric endoscopic options(such as intragastric balloons,endoscopic sleeve gastroplasty,endoscopic aspiration therapies and gastrointestinal bypass sleeves),their advantages and disadvantages,and suggest a new paradigm where providers may start incorporating this modality in their treatment approach for obese patients.

Is colonoscopy sufficient for colorectal cancer surveillance in all HNPCC patients?

A 34-year-old male with hereditary non-polyposis colon cancer with a mutation in hMSH2 line is reported. Despite regular colonoscopic follow-up, he developed cecal cancer involving the extraluminal area. Due to sub-occlusive symptoms, the patient was submitted to further colonoscopy, however with no clear evidence of neoplasia. Thin slice multiplanar reconstruction computed tomography CT scan performed thereafter revealed a transmural mass 2.5 cm in size localized near the cecal valve. Discussion is made on the reliability of colonoscopic examinations as well as the need for further investigations in the follow-up of patients at very high risk of right-sided colon cancer, such as male hMSH2 carrier affected by hereditary non-polyposis colon cancer.

Controversies in the treatment of digestive neuroendocrine tumors

Gastroenteropancreatic neuroendocrine tumors(NETs)have an incidence of 2.39 per 100,000 inhabitants per year,and a prevalence of 35 cases per 100,000 inhabitants;the gap between these rates is due to the relatively long survival time of these tumors,which can be thus considered as chronic oncological diseases.Recently,more therapeutic options have become available,but criteria for defining timing,priority and sequence of different therapeutic options are still debated.This review offers an overview of pancreatic and small bowel NETs,critically underlining the issues that still need to be clarified and some controversial issues on the therapeutic approach for NET patients.