Humoral Predictors of Malignancy in IPMN: A Review of the Literature.

Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the pancreatic cyst lesions arising from the pancreatic duct system. IPMN is a potential precursor of pancreatic cancer. The transformation of IPMN in pancreatic cancer is progressive and requires the occurrence of low-grade dysplasia, high-grade dysplasia, and ultimately invasive cancer. Jaundice, enhancing mural nodule >5 mm, main pancreatic duct diameter >10 mm, and positive cytology for high-grade dysplasia are considered high-risk stigmata of malignancy. While increased levels of carbohydrate antigen 19-9 (CA 19-9) (>37 U/mL), main pancreatic duct diameter 5-9.9 mm, cyst diameter >40 mm, enhancing mural nodules <5 mm, IPMN-induced acute pancreatitis, new onset of diabetes, cyst grow-rate >5 mm/year are considered worrisome features of malignancy. However, cross-sectional imaging is often inadequate in the prediction of high-grade dysplasia and invasive cancer. Several studies evaluated the role of humoral and intra-cystic biomarkers in the prediction of malignancy in IPMN. Carcinoembryonic antigen (CEA), CA 19-9, intra-cystic CEA, intra-cystic glucose, and cystic fluid cytology are widely used in clinical practice to distinguish between mucinous and non-mucinous cysts and to predict the presence of invasive cancer. Other biomarkers such as cystic fluid DNA sequencing, microRNA (mi-RNA), circulating microvesicles, and liquid biopsy are the new options for the mini-invasive diagnosis of degenerated IPMN. The aim of this study is to review the literature to assess the role of humoral and intracystic biomarkers in the prediction of advanced IPMN with high-grade dysplasia or invasive carcinoma.

First-phase insulin secretion: can its evaluation direct therapeutic approaches?

Our work is aimed at unraveling the role of the first-phase insulin secretion in the natural history of type 2 diabetes mellitus (T2DM) and its interrelationship with insulin resistance and with ß cell function and mass. Starting from pathophysiology, we investigate the impact of impaired secretion on glucose homeostasis and explore postmeal hyperglycemia as the main clinical feature, underlining its relevance in the management of the disease. We also review dietary and pharmacological approaches aimed at improving early secretory defects and restoring residual ß cell function. Furthermore, we discuss possible approaches to detect early secretory defects in clinical practice. By providing a journey through human and animal data, we attempt a unification of the recent evidence in an effort to offer a new outlook on ß cell secretion.

An update on pancreatic regeneration mechanisms: Searching for paths to a cure for type 2 diabetes.

BACKGROUND: Over the last decades, various approaches have been explored to restore sufficient ß-cell mass in diabetic patients. Stem cells are certainly an attractive source of new ß-cells, but an alternative option is to induce the endogenous regeneration of these cells. SCOPE OF REVIEW: Since the exocrine and endocrine pancreatic glands have a common origin and a continuous crosstalk unites the two, we believe that analyzing the mechanisms that induce pancreatic regeneration in different conditions could further advance our knowledge in the field. In this review, we summarize the latest evidence on physiological and pathological conditions associated with the regulation of pancreas regeneration and proliferation, as well as the complex and coordinated signaling cascade mediating cell growth. MAJOR CONCLUSIONS: Unraveling the mechanisms involved in intracellular signaling and regulation of pancreatic cell proliferation and regeneration may inspire future investigations to discover potential strategies to cure diabetes.

Microbiota in Pancreatic Diseases: A Review of the Literature.

The gut microbiota is a critical element in the balance between human health and disease. Its impairment, defined as dysbiosis, is associated with gastroenterological and systemic diseases. Pancreatic secretions are involved in the composition and changes of the gut microbiota, and the gut microbiota may colonize the pancreatic parenchyma and be associated with the occurrence of diseases. The gut microbiota and the pancreas influence each other, resulting in a "gut microbiota-pancreas axis". Moreover, the gut microbiota may be involved in pancreatic diseases, both through direct bacterial colonization and an indirect effect of small molecules and toxins derived from dysbiosis. Pancreatic diseases such as acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer are common gastroenterological diseases associated with high morbidity and mortality. The involvement of the microbiota in pancreatic diseases is increasingly recognized. Therefore, modifying the intestinal bacterial flora could have important therapeutic implications on these pathologies. The aim of this study is to review the literature to evaluate the alterations of the gut microbiota in pancreatic diseases, and the role of the microbiota in the treatment of these diseases.

Treatment of H. pylori infection: a review.

Helicobacter pylori infection has been indicated as the main pathogenic factor in the development of chronic gastritis, peptic ulcer disease, and gastric malignancies. Although the vast majority of infected subjects do not carry but a mild, asymptomatic gastritis, still there are some cases in which the eradication of the infection appears mandatory. This review addresses current anti-Helicobacter regimens and pharmacological resources, and highlights the pros and cons of each of them, according to the most recent and reliable clinical trials. Also, basic recommendations are given, regarding treatment choice in the event of the failure of a first or second line eradicating strategy, and about the implementation of standard regimens with newer antibacterial devices as probiotics.

Can 13C urea breath test predict resistance to therapy in Helicobacter pylori infection?

BACKGROUND/AIMS: Results of 13C urea breath test (UBT), a noninvasive test for detecting active H. pylori infection, have been regarded also numerically for a possible predictive value on bacterial load and entity of mucosal inflammation. In the present study we wished to determine whether there is a particular value of Delta Over Baseline (DOB) result which could predict resistance to anti-H. pylori therapy. METHODOLOGY: 570 subjects from 1376 tested received a standard triple anti-H. pylori regimen. After a minimum of 6 weeks subjects underwent control UBT testing. Correlation of DOB values at diagnostic and control UBT and sensitivity of different DOB levels to predict resistance to therapy were calculated using simple linear correlation and Bayes' theorem, respectively. RESULTS: Modest linear correlation was observed between DOB values (r2=0.28). The value of 13.0 at diagnostic UBT showed a sensitivity of 65.5% to predict and further positivity at control testing. CONCLUSIONS: In our large series, UBT numerical DOB value weakly predicted resistance to first-line anti-H. pylori therapy.

Post-cholecystectomy alkaline reactive gastritis: a randomized trial comparing sucralfate versus rabeprazole or no treatment.

OBJECTIVE: At present there are no well-established pharmacological approaches in the management of post-cholecystectomy alkaline reactive gastritis. The aim of this study was to assess the effect of sucralfate versus rabeprazole or no treatment on dyspeptic symptoms and endoscopic/histological signs in a population of patients with a history of cholecystectomy and evidence of alkaline reactive gastritis. METHODS: Sixty dyspeptic patients fulfilling the following criteria of inclusion took part in this study: (1) a history of cholecystectomy; (2) no use of anti-inflammatory steroidal and non-steroidal drugs, or abuse of alcohol; (3) evidence of abundant gastric bile reflux at endoscopy; (4) endoscopic signs of chronic gastritis; (5) histological signs of chronic gastritis; and (6) absence of Helicobacter pylori infection. Dyspeptic symptoms were evaluated by means of a self-administered validated questionnaire. Patients included in the study were randomly assigned to one of three treatment groups for 3 months: sucralfate, rabeprazole, observation. Patients were re-evaluated at the end of the treatment. RESULTS: Sucralfate and rabeprazole therapies were both able to significantly reduce epigastric pain, heartburn, bloating and halitosis. Endoscopic/histological signs were lower in both treatment groups compared to the observation group. CONCLUSION: Both sucralfate and rabeprazole therapies are effective treatment options in the patients with alkaline gastritis when compared with observation.

Levofloxacin based regimens for the eradication of Helicobacter pylori.

BACKGROUND: A 7 day treatment scheme based on rabeprazole/levofloxacin/amoxycillin or tinidazole achieved an eradication rate over 90%. However, the combination of drugs and duration of treatment for the correct use of levofloxacin in the eradication of are still unclear. OBJECTIVE: To compare the efficacy and tolerability of rabeprazole/levofloxacin based dual therapies given for 5, 7 or 10 days with rabeprazole/levofloxacin/amoxycillin triple therapy for 7 days. METHODS: One hundred and sixty patients with infection documented by the C-urea breath test and histology were included in this prospective, open label study. Subjects were randomized in four groups: (1) levofloxacin (500 mg o.d.), amoxycillin (1 g b.d.) and rabeprazole (20 mg o.d.) for 7 days; (2) levofloxacin (500 mg o.d.) and rabeprazole (20 mg o.d.) for 5 days; (3) levofloxacin (500 mg o.d.) and rabeprazole (20 mg o.d.) for 7 days; and (4) levofloxacin (500 mg o.d.) and rabeprazole (20 mg o.d.) for 10 days. Six weeks after the end of therapy status was checked by using the C-urea breath test. RESULTS: All patients completed the therapeutic regimens. The eradication rate was not significantly modified by treatment duration in the dual therapy schemes (5 days: 20/40, 50%; 7 days: 28/40, 70%; 10 days: 26/40, 65%). The eradication rate of the 1 week levofloxacin based triple therapy was significantly higher than that observed using any dual therapies (36/40). No major adverse effects were observed. CONCLUSIONS: A rabeprazole/levofloxacin dual eradication regimen is simple and well tolerated but does not achieve an acceptable eradication rate when compared to a 1 week rabeprazole/levofloxacin/amoxycillin triple therapy. The eradication rate did not increase with a longer regimen.

Obscure gastrointestinal bleeding as first symptom of eosinophilic jejunitis in a liver transplant recipient: diagnosis and treatment with single balloon enteroscopy.

The small bowel is only partially accessible to traditional endoscopic techniques. The recently introduced push-and-pull enteroscopy technique allows endoscopists to examine the small bowel in its entirety and enables them to take biopsy specimens and administer treatment. We report the case of a liver transplant recipient presenting with obscure gastrointestinal bleeding, whose diagnosis of eosinophilic enteritis was achieved following a single balloon enteroscopy examination. The patient was discharged 3 days after endoscopic treatment. Eosinophilic enteritis is still not a well known disease. The modality of treatment was suggested by our endoscopic experience and not from codified guidelines. The patient's haemoglobin value was normal 12 months after treatment.

Role of probiotics in patients with Helicobacter pylori infection.

Probiotics are defined as live, nonpathogenic microbial feeds or food supplements that exert a positive influence on their host by altering his microbial balance. As shown in several studies, probiotics also possess a direct antimicrobial effect; for this reason, several authors have tested a possible application in patients with Helicobacter pylori infection. In particular, probiotics may compete directly with H. pylori, possibly through the inhibition of adherence, as well as produce metabolites and antimicrobial molecules, properties supported only by animal or in vitro data. Moreover, implementation of standard anti-H. pylori regimens with probiotics can also improve patients' compliance to therapy, reducing the occurrence of antibiotic-related adverse events. The same effect was also reported after using a combination of two different prebiotics such as butyric acid and inulin in patients who underwent H. pylori eradication treatment. Based on current data, even though an effect against H. pylori has been described, probiotics cannot be considered as an alternative to standard anti-H. pylori treatment. Nevertheless, their use in association with standard anti-H. pylori treatment may be advisable, as they are able to improve patient compliance by reducing antibiotic-related adverse events, thus increasing the number of patients completing the eradication therapy.

Levofloxacin-based triple therapy in first-line treatment for Helicobacter pylori eradication.

BACKGROUND: The standard first-line therapies for Helicobacter pylori eradication are based on clarithromycin and amoxicillin or metronidazole. Recent studies suggested levofloxacin as an alternative option for both first-and second-line H. pylori eradication treatment. AIMS: To compare efficacy and tolerability of two different 7-day standard triple therapies versus 7-day levofloxacin-based triple therapy in first-line treatment for H. pylori infection. METHODS: Three hundred consecutive H. pylori positive patients were randomized to receive: clarithromycin, amoxicillin, esomeprazole (Group A: N = 100); clarithromycin, metronidazole, esomeprazole (Group B: N = 100); or clarithromycin, levofloxacin, esomeprazole (Group C: N = 100). H. pylori status was rechecked by (13)C urea breath test 6 wk after the end of therapy. RESULTS: Sixteen out of 300 patients discontinued treatment because of the occurrence of side effects (Group A, 5; Group B, 7; Group C, 4). The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: Group A, 75% and 79%; Group B, 72% and 77.4%; and Group C, 87% and 90.6%. The eradication rate achieved with levofloxacin-based triple therapy was significantly higher than that with standard therapies in either ITT (87%vs 75%, p <0.05; 87%vs 72%, p <0.01;) or PP analysis (90.6%vs 79%, p <0.05; 90.6 vs 77.4, p <0.05). No difference was found between standard triple therapies. The incidence of side effects was similar among groups. CONCLUSIONS: A 7-day levofloxacin-based triple therapy can achieve higher H. pylori eradication rates than standard regimens. These data suggest levofloxacin-based regimens can be the most effective in first-line anti-H. pylori therapy, at least in the Italian population.

Idiopathic chronic urticaria and celiac disease.

Idiopathic chronic urticaria (ICU) is a chronic relapsing cutaneous disease. Some case reports or studies on small series of celiac disease (CD) patients have suggested a possible association between CD and ICU. The aim of this study was to assess the prevalence of CD in a population of adults ICU patients with respect to healthy controls. We consecutively enrolled 80 patients affected by ICU and 264 blood donors as the control population without a history of ICU. Serum anti-transglutaminase IgG and anti-endomysium IgA antibodies were evaluated in all subjects. In the case of positivity to serology, diagnosis was confirmed by duodenal biopsy. One of 80 (1.25%) ICU patients were positive to both anti-transglutaminase and anti-endomysium antibodies. Duodenal biopsy showed partial villous atrophy. One control of 264 (0.38%) had CD. No statistical difference was found in the prevalence of CD between the two groups. ICU patients do not seem to bear a greater risk for CD compared to the general population.

Helicobacter pylori eradication rate and glycemic control in young patients with type 1 diabetes.

OBJECTIVES: Eradication of Helicobacter pylori is more difficult in adult patients with diabetes than in patients with dyspepsia. It has also been suggested that eradication of H. pylori in children with type 1 diabetes mellitus improves their metabolic control. The aim of the current study was to assess the eradication rate of a standard triple therapy and its effects on glycemic control in young patients with type 1 diabetes. METHODS: The authors enrolled 29 type 1 diabetic patients with H. pylori, 29 type 1 diabetic patients without H. pylori, and 29 dyspeptic children with H. pylori. Groups were matched for gender and age and had similar geographical origin and socioeconomic status. H.pylori status was investigated before and 6 weeks after therapy by C-urea breath test. All enrolled patients with H. pylori were prescribed a standard triple therapy for eradicating H. pylori. Glycosylated hemoglobin A and daily insulin requirement were evaluated at enrollment and 6 months later in all patients with diabetes. The prevalence of the most common gastrointestinal symptoms also was investigated by means of a questionnaire in all subjects at enrollment and 6 months later. RESULTS: Eradication of H. pylori was similar in patients with diabetes (24/29) and those with dyspepsia (23/29) (83%v 79%; P = NS). No difference in metabolic control was observed before or after antibiotic treatment in the patients who experienced H. pylori eradication. No difference in glycemic control was observed after 6 months of follow-up. CONCLUSIONS: The eradication rate of H. pylori infection was similar for young patients with type 1 diabetes and those with dyspepsia and did not improve metabolic control in a short-term follow-up.

Association between Klinefelter syndrome and focal nodular hyperplasia.

Focal nodular hyperplasia is a benign lesion of the liver, predominantly affecting women. Its etiology is unknown. Elevated levels of estrogens have been invoked to play a role in the disease. Klinefelter syndrome is the most common sex chromosome disorder, characterized by 47, XXY karyotype, resulting in male hypogonadism and sex hormone imbalance. We present a case of a 25-year-old man affected by Klinefelter syndrome, admitted to our hospital for aspecific dyspeptic symptoms. During admission he underwent: blood test for the liver function and sexual hormonal status, ultrasonography, echo color power Doppler and computerized tomography scan of the liver, and liver biopsy. A hypergonadotropic hypogonadism was present. Imaging of the liver showed an hepatic lesion that liver biopsy confirmed to be a focal nodular hyperplasia. Although the association could be casual, the sex hormone imbalance present in Klinefelter syndrome may suggest a role in the development of this benign liver lesion.

Helicobacter pylori, gastrointestinal symptoms, and metabolic control in young type 1 diabetes mellitus patients.

OBJECTIVE: The role of Helicobacter pylori infection in metabolic control and gastrointestinal symptoms in type 1 diabetes mellitus (DM1) patients has been debated. The aim of this study was to investigate the prevalence of H pylori, of the more cytotoxic Cag-A-positive strains, and the effects of infection on gastrointestinal symptoms and metabolic control in young DM1 patients. Research Design and Methods. H pylori infection was investigated by using the 13C-urea breath test in 121 DM1 patients (65 males, 56 females; mean age: 15 +/- 6 years) and 147 matched controls. In positive patients, an assay for specific immunoglobulin G against Cag-A was performed. Glycosylated hemoglobin A, daily insulin requirement, and duration of illness were established; a questionnaire concerning the presence of dyspeptic symptoms was administered. RESULTS: No difference in H pylori infection rate between patients and controls was observed. Thirty-four (28.1%) of 121 patients and 43 (29.25%) of 147 controls were infected. Twenty-one patients and 24 controls were positive for Cag-A. Glycosylated hemoglobin A, daily insulin requirement, and duration of illness were not affected by infection nor by Cag-A status. Among gastrointestinal symptoms, only halitosis was related to H pylori infection, but this association disappeared after correction for age. Positive patients with halitosis showed a worse glycemic control than uninfected patients with halitosis. CONCLUSIONS: H pylori infection and Cag-A-positive strains do not affect metabolic control in DM1 patients. With regard to gastrointestinal symptoms studied, H pylori infection, when present in participants with halitosis, seems to predict a worse metabolic control than in H pylori-negative patients with halitosis.

Effect of different probiotic preparations on anti-helicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study.

OBJECTIVES: Several studies show that probiotics may prevent side effects during therapy against Helicobacter pylori (H. pylori). Other reports indicate competitive interaction between some probiotics and H. pylori. We compared efficacy of two different probiotics and one probiotic combination with placebo for preventing anti-H. pylori therapy-related side effects and for improving the eradication rate. METHODS: A total of 85 H. pylori positive, asymptomatic patients were randomized in four groups to receive probiotic or placebo both during and for 7 days after a 1-wk triple therapy scheme (rabeprazole 20 mg b.id., clarithromycin 500 mg b.i.d., and tinidazole 500 mg b.i.d.). Group I (n = 21) received Lactobacillus GG; group II (n = 22), Saccharomyces boulardii; group III (n = 21), a combination of Lactobacillus spp. and biphidobacteria; and group IV (n = 21), placebo. Subjects filled in weekly symptom questionnaires for 4 wk. Blinded investigators collected and analyzed data. H. pylori status was rechecked after 5-7 wk. RESULTS: Side effects occurred mainly during the eradication week. None of them caused therapy discontinuation. In all probiotic-supplemented groups, there was a significantly lower incidence of diarrhea and taste disturbance during the eradication week with respect to the placebo group. Overall assessment of tolerability was significantly better in the actively treated patients than in the placebo group. No differences in the incidence of side effects between the probiotic groups were observed. The H. pylori eradication rate was almost identical between the probiotic and placebo groups. CONCLUSIONS: All the probiotics used were superior to placebo for side effect prevention, but were not associated with better compliance with antibiotic therapy. The effect of probiotic supplementation on side effects during anti-H. pylori regimens seemed to be independent of the probiotic species used.