Validation of the German Inflammatory Bowel Disease Fatigue (IBD-F) Questionnaire.

INTRODUCTION: Fatigue is a common symptom in patients with inflammatory bowel diseases (IBD). To date, there is no instrument to assess IBD-specific fatigue in German. The aim of this study was to translate the IBD Fatigue (IBD-F) scale and to test its psychometric properties in a German IBD population. METHODS: After completing the translation process, 20 IBD patients participated in a pilot testing phase. For further analyses, 180 IBD patients with fatigue answered the IBD-F (Sections I, II, III) and the IBD Questionnaire (IBDQ-D). Reliability was tested by using Cronbach's alpha and corrected item-total correlation. Exploratory factor analyses (EFA) were carried out. Spearman's correlation was calculated between the IBD-F and IBDQ-D . 78 patients could be included to calculate the test-retest reliability. RESULTS: The German version of the IBD-F shows high face and content validity. Internal consistency was excellent, with a Cronbach's alpha of 0.93-0.98. Corrected item-total correlations ranged from 0.51 to 0.89. The correlation between the IBD-F and the IBDQ-D was statistically significant for Section I (rs=-0.59; p<0.01) and Section II (rs=-0.76; p<0.01) of the IBD-F. The EFA identified one relevant factor for each section. Test-retest reliability was acceptable for Section I (intraclass correlation coefficient (ICC)=0.73) and Section II (ICC=0.84). CONCLUSION: The German version of the IBD-F is a reliable and valid tool to assess fatigue in IBD.

Advanced Pancreatic Ductal Adenocarcinoma: Moving Forward.

Globally, the death rate of pancreatic ductal adenocarcinoma (PDAC) has doubled over 30 years and is likely to further increase, making PDAC a leading cause of cancer-related death in the coming years. PDAC is typically diagnosed at an advanced stage, and modified FOLFIRINOX or nab-paclitaxel and gemcitabine are the mainstay of systemic therapy. For elderly patients with good performance status, low-dose treatment can preserve quality of life without compromising cancer control or survival. Maintenance therapy should be considered in PDAC patients achieving disease control with systemic therapy. In particular, olaparib has demonstrated a progression-free survival benefit of 3.6 months in a subgroup of PDAC patients with germline BRCA1/2 mutations (ca. 10% of all PDAC). Pancreatic enzyme replacement therapy is often omitted in the treatment of patients with PDAC, with possibly deleterious consequences. Small intestinal bacterial overgrowth is highly prevalent in patients with PDAC and should be considered in the diagnostic algorithm of PDAC patients with bloating and diarrhea. Rivaroxaban has been associated with a reduced risk of thrombosis without an increase in major bleeding events, and its use should be considered in every patient with advanced PDAC undergoing systemic therapy.

The BRAF Status May Predict Response to Sorafenib in Gastrointestinal Stromal Tumors Resistant to Imatinib, Sunitinib, and Regorafenib: Case Series and Review of the Literature.

BACKGROUND: Sorafenib has shown efficacy in patients with imatinib-, sunitinib-, and regorafenib-resistant gastrointestinal stromal tumors (GISTs). No biomarker is currently available for predicting response to sorafenib in patients with GIST. METHODS: We herein report 3 patients with imatinib-, sunitinib-, and regorafenib-resistant metastasized GISTs, who were treated with sorafenib. Besides receptor tyrosine kinase KIT and platelet-derived growth factor receptor α, also BRAF was tested for mutations. RESULTS: Sorafenib therapy induced a long-term disease control in 2 out of 3 patients over a period of 49 and 19 months, respectively. Sorafenib-responsive GISTs were BRAF wild-type, whereas the sorafenib-resistant GIST carried a BRAF V600E mutation. CONCLUSION: We confirm sorafenib as an effective therapeutic option in patients with imatinib-, sunitinib-, and regorafenib-resistant GISTs. Larger studies are required to corroborate whether BRAF mutation may predict sorafenib resistance in GISTs.

Helicobacter pylori eradication therapy is not associated with the onset of inflammatory bowel diseases. A case-control study.

BACKGROUND AND AIMS: A negative association between H. pylori and inflammatory bowel disease (IBD) has been previously reported. There were also case reports suggesting a new onset of IBD 6-12 months after H. pylori eradication therapy. In a case-control study we investigated whether previous H. pylori eradication therapy was associated with the risk of developing IBD. METHODS: IBD outpatients with both Crohn´s disease (CD) and ulcerative colitis (UC) were enrolled. Age- and sex-matched blood donors served as controls in a 1:2 fashion. Information on demographics, medical history, previous H. pylori infection and eradication therapy was recorded. Serum samples for H. pylori serology testing (anti-H. pylori-IgG and anti-CagA-IgG) were obtained. Controls that received H. pylori eradication therapy during the 12 months previous to enrollment were excluded. RESULTS: Overall, 127 IBD patients (CD N= 90; UC N=37) and 254 controls were enrolled. The prevalence of H. pylori infection (positive H. pylori serology and/or previous eradication) in IBD patients and controls was 11% and 23%, respectively (OR 0.4, 95% CI 0.21-0.74, p<0.003). Four patients (3%) developed IBD (3 MC and 1 CU) after receiving successful H. pylori eradication (latency 6-12 months). The rate of previous H. pylori eradication therapy in patents who successively developed IBD was lower but not statistically different from that observed in the control group (OR 0.43, 95% CI 0.14-1.29, p=0.16). CONCLUSIONS: In our study previous H. pylori eradication therapy was not associated with the onset of IBD. Whether in a subgroup of patients, H. pylori eradication therapy may trigger a latent IBD, cannot be excluded.

Nutrition in Patients with Gastric Cancer: An Update.

BACKGROUND: Nutritional management of patients with gastric cancer (GC) represents a challenge. SUMMARY: This review provides an overview of the present evidence on nutritional support in patients with GC undergoing surgery as well as in those with advanced disease. KEY MESSAGE: For patients undergoing surgery, the preoperative nutritional condition directly affects postoperative prognosis, overall survival and disease-specific survival. Perioperative nutritional support enriched with immune-stimulating nutrients reduces overall complications and hospital stay but not mortality after major elective gastrointestinal surgery. Early enteral nutrition after surgery improves early and long-term postoperative nutritional status and reduces the length of hospitalization as well. Vitamin B12 and iron deficiency are common metabolic sequelae after gastrectomy and warrant appropriate replacement. In malnourished patients with advanced GC, short-term home complementary parenteral nutrition improves the quality of life, nutritional status and functional status. Total home parenteral nutrition represents the only modality of caloric intake for patients with advanced GC who are unable to take oral or enteral nutrition. PRACTICAL IMPLICATIONS: Early evaluations of nutritional status and nutritional support represent key aspects in the management of GC patients with both operable and advanced disease.

Effect of probiotic or prebiotic supplementation on antibiotic therapy in the small intestinal bacterial overgrowth: a comparative evaluation.

UNLABELLED: Bacterial intestinal overgrowth syndrome (SIBO) treatment is based on antibiotics. Probiotics have been shown to give similar results, whilst no study is available about prebiotics. This study evaluated the addition of probiotics or prebiotics to antibiotics on SIBO symptoms in a 6-month follow-up. We enrolled 40 patients (14 males and 26 females) reporting abdominal compliant without gastrointestinal diseases/alarm symptoms. SIBO was diagnosed by the agreement of lactulose and glucose breath tests. Patients were randomly divided into two groups homogeneous for sex and age: group 1 received Rifaximin 400 mg/day for 7 days/month followed by Lactobacillus casei for 7 days more and group 2 antibiotic followed by short chain fructo-oligosaccharides. All patients recorded a questionnaire for subjective symptom evaluation according to Rome III criteria and Bristol scale for stool characters before the study and after 6 months. STATISTICS: Student's t and Fisher's exact tests. In group 1, a significant improvement was obtained in 5 out of 6 symptoms, whilst in group 2 in 4 out of 6 symptoms (nausea and number of bowel movements failed to improve). Despite we observed a trend of probiotics to be more effective than prebiotics, the difference in the percentage of improved symptoms was not significant (83,3% vs 66.6%; p= 0.57). Our preliminary data show a good outcome with sequential antibioticprobiotic/ prebiotic administration in patients with SIBO.

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

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

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

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

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

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

Mechanisms of Helicobacter pylori antibiotic resistance: An updated appraisal.

Helicobacter pylori (H. pylori) antibiotic resistance is the main factor affecting the efficacy of the current eradicating therapies. The aim of this editorial is to report on the recent information about the mechanisms accounting for the resistance to the different antibiotics currently utilized in H. pylori eradicating treatments. Different mechanisms of resistance to clarithromycin, metronidazole, quinolones, amoxicillin and tetracycline are accurately detailed (point mutations, redox intracellular potential, pump efflux systems, membrane permeability) on the basis of the most recent data available from the literature. The next hope for the future is that by improving the knowledge of resistance mechanisms, the elaboration of rational and efficacious associations for the treatment of the infection will be possible. Another auspicious progress might be the possibility of a cheap, feasible and reliable laboratory test to predict the outcome of a therapeutic scheme.

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

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

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

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