Risk factors for endoscopic severity of diverticular disease of the colon and its outcome: a real-life case-control study.

BACKGROUND: Diverticular disease is an increasing global problem. AIMS: To assess the factors associated with the severity of diverticular disease and its outcome, analyzing a real-life population. METHODS: A cohort of patients, submitted to colonoscopy from 1 January 2012 to 30 April 2018 was revised. The endoscopic severity of diverticular disease was scored according to the Diverticular Inflammation and Complications Assessment (DICA) classification. RESULTS: A cohort of 11 086 patients was identified during the study period, 5635 with diverticulitis and 5451 without diverticulosis. Blood hypertension, diabetes and angiotensin receptor blocker users occurred more frequently in the study group, while the prevalence of colorectal cancer (CRC) was significantly lower. Age >70 years, BMI >30 and blood hypertension were factors independently related to the presence of diverticulosis, while diabetes and CRC were significantly associated with the absence of diverticulosis. Female sex, age, smoke, appendectomy, proton-pump inhibitors and acetyl-salicylic acid use were directly related to the severity of diverticular disease, while CRC and colonic polyp occurrence were inversely related to the severity of diverticular disease, significantly. Female sex, age >70 years and smoke were significantly related to the severity of diverticular disease. CRC and colonic polyps were significantly less in DICA 3 patients. DICA 3 patients were more often symptomatic, at higher risk of hospital admission, longer hospital stay and higher mean costs. CONCLUSIONS: Several factors are associated with the severity of diverticular disease according to the DICA classification. The DICA classification is also predictive of the outcome of the disease in terms of hospital admission, stay and costs.

Long-term efficacy of rifaximin to manage the symptomatic uncomplicated diverticular disease of the colon.

Although rifaximin is currently advised in managing symptomatic uncomplicated diverticular disease (SUDD) of the colon, no long-term data are available. This retrospective study assessed the outcome of a large cohort of patients with SUDD, treated with rifaximin, during an 8-year follow-up. The study group (group A) included 346 patients with SUDD (median age 64 years, IQR 58-69, 62.4% females), treated with rifaximin 800 mg/d for 7 days every month. The control group (group B) included 470 patients with SUDD (median age 65 years, IQR 59-74 years, 60.8% females), taking any other treatment on demand. Two symptoms (left lower abdominal pain and bloating) were assessed by a visual analog scale (VAS), graded from 0=no symptom to 10=the most severe symptom. Daily bowel movements were also reported. Median (IQR) VAS score for pain was 6 (5-7) in group A and 6 (6-7) in group B at baseline (p=0.109); at 8-year follow-up it was 3 (3-4) and 6 (5-7), respectively (p<0.000). Both bloating and daily bowel movements were significantly reduced in group A. Acute diverticulitis occurred in 9 (2.6%) patients in group A and in 21 (4.5%) patients in group B (p=0.155). Surgery occurred in 4 (1.2%) patients in group A and 9 (1.9%) in group B (p=0.432). Disease-related mortality occurred in no patient in group A and 2 (0.4%) patients in group B (p=0.239). No side effects were recorded during the entire study period. Rifaximin is effective to relieve symptoms and reduce the risk of disease-related complications in patients with SUDD.

Digestive disorders and Intestinal microbiota.

In the last decade, a barge body of scientific literature has suggested that specific alterations of the gut microbiota may be associated with ther development and clinical course of several gastrointestinal diseases, including irritable bowel syndrome, inflammatory bowel disease, celiac disease, gastrointestinal cancer and Clostridium difficile infection. These alterations are often referred to as "dysbiosis", a generic term designing reduction of gut microbiota biodiversity and alterations in its composition. Here, we provide a synthetic overview of the key concepts on the relationship between intestinal microbiota and gastrointestinal diseases, focusing on the translation of these concepts into clinical practice.

The impact of intestinal microbiota on bio-medical research: definitions, techniques and physiology of a "new frontier".

In recent years the metagenomics techniques have allowed to study composition and function of the intestinal microbiota. The microbiota is a new frontier of biomedical research to be explored and there is growing evidence of its fundamental health-promoting activity. The present review gives a synthetic overview on the characteristics and the role of the microbiota in the adult with particular reference to physiology, pathophysiology and relationships with the host and the environment.

The role of diet in the prevention and treatment of Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBD) - Crohn's disease (CD) and ulcerative colitis (UC) - are chronic conditions characterised by relapsing inflammation of the gastrointestinal tract. They represent an increasing public health concern and an aetiological enigma due to unknown causal factors. The current knowledge on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to a dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated with IBD, diet plays an important role in modulating the gut microbiome, and, consequently, it could have a therapeutic impact on the disease course. An overabundance of calories and some macronutrients typical of the Western dietetic pattern increase gut inflammation, whereas several micronutrients characteristic of the Mediterranean Diet have the potential to modulate gut inflammation, according to recent evidence. Immunonutrition has emerged as a new concept putting forward the role of vitamins such as vitamins A, C, E, and D, folic acid, beta carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients showed a limited benefit. Further research is required to evaluate the role of individual food compounds and complex nutritional interventions with the potential to decrease inflammation as a means of prevention and management of IBD. The current dietary recommendations for disease prevention and management are scarce and non evidence-based. This review summarizes the current knowledge on the complex interaction between diet, microbiome and immune-modulation in IBD, with particular focus to the role of the Mediterranean Diet as a tool for prevention and treatment of the disease.

Nutrition and lipidomic profile in colorectal cancers.

BACKGROUND: Adherence to a healthy diet has been reported to be essential for the primary prevention of colorectal cancer, through a reduction of tissue inflammation, a low concentration of circulating lipoproteins and lower levels of serum cholesterol. Since an altered expression of the fatty acids pattern has been demonstrated to be a crucial event in colorectal carcinogenesis, lipidomic analysis is considered able to identify early diagnostic and prognostic biomarkers of complex diseases such as colorectal cancer. METHODS: cell membrane fatty acid profile and serum lipoproteins pattern were evaluated by gas chromatography and electrophoresis method respectively. RESULTS: There is a close association between diet and lipidomic profile in colorectal cancer, both in pre-clinical and clinical studies. A modified serum lipoproteins pattern has been demonstrated to be predominant in intestinal tumors. CONCLUSIONS: The study of fatty acids profile in cell membrane and the evaluation of serum lipoproteins subfractions could be useful to have an integrate vision on the interactions between lipids and the pathogenesis of colorectal cancer and to understand the mechanisms of action and the consequences of these interactions on human health status.

Epidemiology and risk factors for diverticular disease.

Diverticulosis of the colon is the most frequent anatomical alteration diagnosed at colonoscopy. The prevalence of the disease is higher in elderly patients over 65 years old, recent studies show an increment also in youngers over 40 years old. Even its large prevalence in the population, its pathophysiology still remain poorly understood. It's widely accepted that diverticula are likely to be the result of complex interactions among genetic factors, alteration of colonic motility, lifestyle conditions such as smoking, obesity, alcohol consumption, fiber and meat intake with diet. Recently many authors considered also alterations in colonic microbiota composition, co-morbidity with diabetes and hypertension and the chronic assumption of certain medications like PPI, ARB and aspirin, as important risk factors for the development of diverticulosis. The aim of this narrative review is to summarise current knowledges on this topic.

Development and usefulness of the new endoscopic classification: DICA.

Colonic Diverticulosis is one of the most common anatomical findings during colonoscopy. This condition has 60% incidence in the population over 60 years old. About 20% of patients will develop Diverticular Disease, and 5% of them will evolve into Diverticulitis. Until the last years there weren't any approaches for the endoscopic classification of this pathology. In 2013, in Florence, the first endoscopic classification was developed: DICA (Diverticular Inflammation and Complication Assessment). The aim of this article is to focus on the process of the development and the validation of the classification by the pool of gastroenterology experts, and, as well, its usefulness during the clinical practice.

Epidemiology and risk factors of pancreatic cancer.

The most frequent pancreatic cancer is pancreatic adenocarcinoma. It has high and early locally and distant invasiveness; this is the reason why it often shows little sign or symptoms in early stage and poor prognosis after the diagnosis, frequently in advanced stage. Although it is possible to detect this tumor in early stage because of its neoplastic precursor (PanINs). Epidemiological data shows that pancreatic cancer is not very common but obvious it is one of the most neoplastic death-cause in the world. The trend of incidence is quite increasing through years, proportionally to the increase of risk factors. About risk factors, it is not easy to detect in all the cases but it is known the role of some of that: there are hereditary risk factors, such as genetic pattern like HBOC, HNPCC, FAP, PJS, FAMMM, HP and CF and environmental ones (modifiable) such as smoke, alcohol consumption, chronic pancreatitis, obesity and diabetes mellitus. This narrative review aims to analyze the epidemiological data of pancreatic cancer and associated risk factors.

Approach to gastroenterological diseases in primary care.

Gastroenterological diseases are a source of morbidity, mortality and costs, and have a high frequency in general practice; for this reason, we have evaluated the current literature regarding the knowledge and management of these disorders by general practitioners, finding little knowledge and adherence to guidelines, highlighting the need for continuous updating in this regard, and greater collaboration between specialists and general practitioners.

Relationship between Helicobacter pylori infection and GERD.

Gastroesophageal reflux disease (GERD) is due to the chronic exposure of the esophageal mucosa to acid secretion from the stomach. Helicobacter pylori (H.p.) infection, is a risk factor for the development of peptic ulcer, atrophic gastritis and gastric cancer, and causes various effects on gastric function. The relationship between GERD and H.pylori infection is still subject of debate. Background and aim: In literature no clear causal relationship has been established between GERD and H. pylori infection, although some papers support the onset of esophagitis in patients in whom the infection has been cured. Aim of this work is to review the most recent literature data about the relationship between reflux disease and H. pylori infection. Methods: Articles reviewed were found through literature searches on PubMed, Google Scholar using keywords such as gastroesophageal reflux disease, Helicobacter pylori, acid-related disorders, GERD and esophagitis.

Diagnosis of GERD in typical and atypical manifestations.

The manifestations of gastroesophageal reflux disease (GERD) have been recently classified into either esophageal or extra-esophageal syndromes. Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD. Endoscopy had a low sensitivity. Recently, the availability of multichannel intraluminal impedance and pH-monitoring (MII-pH) has modified the diagnostic approach towards atypical manifestations of GERD. There is a rising consensus that this technique should be considered as the gold standard for GERD diagnosis. Gastrin 17 (G-17) has been proposed as a non-invasive marker of GERD, due to the negative feedback between acid and the hormone. G17 levels seem able to identify patients with acid and non-acid reflux.

A non-invasive method for the diagnosis of upper GI diseases.

Upper-GI diseases are one of the most relevant issue in primary care. Nowadays they are still responsible for about 100 million ambulatory care visits only in the US. The diagnosis of almost every upper-GI condition is still deputed to invasive tests such as upper gastrointestinal endoscopy, gastroesophageal manometry or radiography. The possibility of analysing serum markers like Pepsinogens I and II, produced by gastric mucosa, in order to assess the functional characteristics of the upper GI tract has spread itself since the 80's especially in the diagnosis of peptic ulcer. The discovery of Helicobacter pylori by Marshall and Warren in 1983 and the scientific consecration of its role in the pathogenesis of gastric cancer and peptic ulcer (crystallized in Peleo Correa's Cascade, 1992), led to an increase importance of non-invasive tests, raising the attention towards the assessment of both immunoglobulins anti-H.p. and Gastrin hormone produced by antral G cells, as an implementation of the panel of gastric markers. This narrative review aims to analyze the huge landscape of non-invasive tests for diagnosis of GI diseases, studying the literature of the recent years.

Non-invasive method for the assessment of gastric acid secretion.

Methods for the measure of gastric acid secretion include invasive and non-invasive tests. The gold-standard to measure the acid output is the collection of gastric after in basal condition (Basal Acid Output, B.A.O.) and after an i.m. injection of pentagastrin (Maximal Acid Output, M.A.O.). However, direct measurement of gastric acid production is out of order in clinical practice, but many GI symptoms are claimed to be related with acid disorders and empirically cured. Hypochlorhydria is associated with precancerous conditions such as chronic atrophic gastritis (CAG). Acid measurement with non-invasive methods (pepsinogens) is supported by international guidelines.

Epidemiology of gastric cancer and risk factors.

Gastric cancer is, still nowadays, an important healthcare problem worldwide. In Italy, it represents the fifth tumour by frequency in both men and women over 70 years old. A crucial point is represented by the percentage of early gastric cancers usually found, which is actually very low, and it carries to a worse morbidity and mortality. The most important focus in this oncological disease, is to perform an effective detection of the most common precancerous lesion linked with this neoplasia, chronic atrophic gastritis, in order to avoid the future outcome of gastric cancer itself.

Clinical manifestations of chronic atrophic gastritis.

Although the actual prevalence of chronic atrophic gastritis is unknown and it is probable that this entity goes largely underdiagnosed, patients in whom diagnosis is established usually present advanced stages of disease. Destruction of parietal cells, either autoimmune-driven or as a consequence of Helicobacter pylori infection, determines reduction or abolition of acid secretion. Hypo/achloridia causes an increase in serum gastrin levels, with an increased risk of the development of neuroendocrine tumors. Microcytic, hypochromic anemia frequently precedes the development of megaloblastic, vitamin B12-associated anemia. Moreover, vitamin B12 deficiency,may cause elevation of homocysteine, with an increase in the cardiovascular risk, and may be associated with neurological manifestations, mainly characterized by spinal cord demyelination and atrophy, with ensuing sensory-motor abnormalities. Gastrointestinal manifestations seem to be associated with non-acid reflux and tend to be non-specific.

From Sidney to OLGA: an overview of atrophic gastritis.

Chronic gastritis is a long-lasting disease that can lead to a loss of appropriate gastric glands. Gastritis, as term, apply to an inflammation of the stomach, histologically proven, sometimes with structural mucosal changes. Worldwide Helicobacter pylori's infection play a pivotal role as the main etiological effector of chronic active gastritis. H. p. is a bacterium with a selective tropism for the gastric mucosa, able to survive in a hostile environment for colonization of organisms other than itself, able to develop strategies for survival and for avoidance of the defence mechanisms, causing inflammatory changes, that vary from asymptomatic mild gastritis to more severe injury such as peptic ulcer as well as premalignant lesions and malignant tumours. The pattern and distribution of gastritis strongly correlate with these sequelae and chronic atrophic gastritis with intestinal metaplasia is now assessed as a precancerous lesion with definite risk of evolution towards intraepithelial lesions of both low and high grade, as expected in the model of the Correa's cascade. In fact, the leading complication of chronic gastritis remains its close correlation with gastric cancer being biologically linked to H. pylori infection, nowadays known as a class I carcinogen. Gastric carcinogenesis is due to environmental factors, as well as to bacterial strain, host responses and gastric mucosal microbiome dysbiosis. Since, individual patients show different gastric cancer risk, it is mandatory to identify patients at risk of developing gastric cancer to offer a targeted search for lesions with a more rapid development of neoplasm liable, in an early phase, to a less destructive treatment. OLGA staging system is the most reliable and powerful system that allow the recognition of patient with a higher risk of developing gastric cancer.

Autoimmune diseases in autoimmune atrophic gastritis.

Autoimmune diseases, characterized by an alteration of the immune system which results in a loss of tolerance to self antigens often coexist in the same patient. Autoimmune atrophic gastritis, characterized by the development of antibodies agains parietal cells and against intrinsic factor, leads to mucosal destruction that affects primarily the corpus and fundus of the stomach. Autoimmune atrophic gastritis is frequently found in association with thyroid disease, including Hashimoto's thyroiditis, and with type 1 diabetes mellitus, Other autoimmune conditions that have been described in association with autoimmune atrophic gastritis are Addison's disease, chronic spontaneous urticaria, myasthenia gravis, vitiligo, and perioral cutaneous autoimmune conditions, especially erosive oral lichen planus. Interestingly, however, celiac disease, another frequent autoimmune condition, seems to play a protective role for autoimmune atrophic gastritis. The elevated prevalence of autoimmune disease clustering should prompt the clinicial to exclude concomitant autoimmune conditions upon diagnosis of any autoimmune disease.

Effectiveness and Safety of Pylera® in Patients Infected by Helicobacter Pylori: A Multicenter, Retrospective, Real Life Study.

BACKGROUND: Our aims were to assess the real life effectiveness and safety of the new bismuth-containing quadruple therapy in a large population of patients infected by Helicobacter pylori. METHODS: Consecutive dyspeptic H. pylori-positive patients were enrolled, both naïve for treatment and already unsuccessfully treated. Patients were treated with Pylera® 3 capsules 4 times/daily plus omeprazole 20 mg or esomeprazole 40 mg 2 times/daily for 10 days. Eradication was confirmed using a urea-breath test (at least 30 days after the end of the treatment). Efficacy and safety were assessed. RESULTS: A total of 349 patients were treated. H. pylori eradication was achieved in 316 (90.5%, 95% CIs 80.8-1.0) patients in the intention-to-treat population, and in 93.5% (95% CIs 83.5-1.0) in the per-protocol population. No difference in the eradication rate was found between naïve and previously treated patients (91.3 vs. 90.0%, p = 0.901). Adverse events occurred in 55 patients (15.8%, 95% CIs 11.9-20.1). Five patients discontinued treatment: 2 patients suffered from severe abdominal pain, one patient from headache, one patient from diarrhea, and one patient from diffuse urticarial rush. CONCLUSIONS: Pylera® achieved a remarkable eradication rate in real life both as first treatment and as a rescue therapy, with a good safety profile.