Association of a probiotic to a Helicobacter pylori eradication regimen does not increase efficacy or decreases the adverse effects of the treatment: a prospective, randomized, double-blind, placebo-controlled study

Abstract Background The treatment for the eradication of Helicobacter pylori (H. pylori) is complex; full effectiveness is rarely achieved and it has many adverse effects. In developing countries, increased resistance to antibiotics and its cost make eradication more difficult. Probiotics can reduce adverse effects and improve the infection treatment efficacy. If the first-line therapy fails a second-line treatment using tetracycline, furazolidone and proton-pump inhibitors has been effective and low cost in Brazil; however it implies in a lot of adverse effects. The aim of this study was to minimize the adverse effects and increase the eradication rate applying the association of a probiotic compound to second-line therapy regimen. Methods Patients with peptic ulcer or functional dyspepsia infected by H. pylori were randomized to treatment with the furazolidone, tetracycline and lansoprazole regimen, twice a day for 7 days. In a double-blind study, patients received placebo or a probiotic compound (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Streptococcus faecium) in capsules, twice a day for 30 days. A symptom questionnaire was administered in day zero, after completion of antibiotic therapy, after the probiotic use and eight weeks after the end of the treatment. Upper digestive endoscopy, histological assessment, rapid urease test and breath test were performed before and eight weeks after eradication treatment. Results One hundred and seven patients were enrolled: 21 men with active probiotic and 19 with placebo plus 34 women with active probiotic and 33 with placebo comprising a total of 55 patients with active probiotic and 52 with placebo. Fifty-one patients had peptic ulcer and 56 were diagnosed as functional dyspepsia. The per-protocol eradication rate with active probiotic was 89.8% and with placebo, 85.1% (p = 0.49); per intention to treat, 81.8% and 79.6%, respectively (p = 0.53). The rate of adverse effects at 7 days with the active probiotic was 59.3% and 71.2% with placebo (p = 0.20). At 30 days, it was 44.9% and 60.4%, respectively (p = 0.08). Conclusions The use of this probiotic compound compared to placebo in the proposed regimen in Brazilian patients with peptic ulcer or functional dyspepsia showed no significant difference in efficacy or adverse effects. Trial registration Current Controlled Trials ISRCTN04714018

Accuracy of endoscopic ultrasound-guided fine-needle aspiration in the suspicion of pancreatic metastases

Abstract Background Metastases to the pancreas are rare, and usually mistaken for primary pancreatic cancers. This study aimed to describe the histology results of solid pancreatic tumours obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosis of metastases to the pancreas. Methods In a retrospective review, patients with pancreatic solid tumours and history of previous extrapancreatic cancer underwent EUS-FNA from January/1997 to December/2010. Most patients were followed-up until death and some of them were still alive at the end of the study. The performance of EUS-FNA for diagnosis of pancreatic metastases was analyzed. Symptoms, time frame between primary tumour diagnosis and the finding of metastases, and survival after diagnosis were also analyzed. Results 37 patients underwent EUS-FNA for probable pancreas metastases. Most cases (65%) presented with symptoms, especially upper abdominal pain (46%). Median time between detection of the first tumour and the finding of pancreatic metastases was 36 months. Metastases were confirmed in 32 (1.6%) cases, 30 of them by EUS-FNA, and 2 by surgery. Other 5 cases were non-metastatic. Most metastases were from lymphoma, colon, lung, and kidney. Twelve (32%) patients were submitted to surgery. Median survival after diagnosis of pancreatic metastases was 9 months, with no difference of survival between surgical and non-surgical cases. Sensitivity, specificity, positive and negative predictive values, and accuracy of EUS-FNA with histology analysis of the specimens for diagnosis of pancreatic metastases were, respectively, 93.8%, 60%, 93.8%, 60% and 89%. Conclusion EUS-FNA with histology of the specimens is a sensitive and accurate method for definitive diagnosis of metastatic disease in patients with a previous history of extrapancreatic malignancies.

MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer

Abstract Background MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation. Methods We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines. Results MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. In vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells. Conclusion In conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer.

MYC, FBXW7 and TP53 copy number variation and expression in gastric cancer

BACKGROUND: MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation. METHODS: We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines. RESULTS: MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. In vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells. CONCLUSION: In conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer.

Die Rolle der Autoimmunreaktion gegen das SLA/LP-Molekül bei autoimmuner Hepatitis

In der vorliegenden Arbeit wurde die Rolle des SLA/LP Proteins bei der autoimmunen Hepatits untersucht. Zum einen sollte die Hypothese einer aberranten Expression des SLA/LP Moleküls als Auslöser der Autoimmunreaktion gegen SLA/LP überprüft werden. Hierzu wurde die Expression des SLA/LP Moleküls in Leber und Lymphozyten von Patienten mit verschiedenen hepatischen Erkrankungen und bei gesunden Personen bestimmt. Die quantitativen Expressionsanalysen wurden mittels real-time PCR unter Einsatz SLA/LP-spezifischer Oligonukleotide durchgeführt. Es zeigte sich, dass SLA/LP ubiquitär im Körper exprimiert wird, mit erhöhter Expression im Pankreas. Die Ergebnisse der SLA/LP Expressionsanalysen in peripheren mononukleären Blutzellen und Leberparenchymzellen von Patienten mit einer autoimmunen Hepatitis ergaben keine Hinweise auf eine aberrante Expression des SLA/LPs. Es konnte gezeigt werden, dass SLA/LP im Leberparenchym der Patienten tendenziell eher erhöht exprimiert wird, doch war kein Unterschied zwischen unterschiedlichen hepatischen Erkrankungen nachweisbar. Somit konnte in dieser Arbeit gezeigt werden, dass eine aberrante Expression nicht für die Auslösung der Erkrankung zuständig ist. Zum andern sollte in dieser Arbeit überprüft werden, ob eine Autoimmunreaktion gegen SLA/LP zu einer Entzündung in der Leber führen kann. Hierzu wurden Mäuse unterschiedlicher Stämme mit SLA/LP Protein in komplettem Freunds Adjuvans immunisiert und auf Leberschädigung und Leberentzündung untersucht. Es konnte gezeigt werden, dass SLA/LP-Autoimmunität Leberentzündung und Leberschädigung auslösen kann. Die Auslösung der Hepatitis war aber vom Mausstamm und der Defizienz von Interleukin 10 abhängig. Somit scheint unter bestimmten immunologischen Bedingungen eine Immunreaktion gegen SLA/LP zu einer Leberentzündung und Leberschädigung zu führen.

La ricerca traslazionale in farmacologia gastroenterologica

Il presente studio si concentra sull’analisi degli aspetti traslazionali nella ricerca farmacologica applicata alla Gastroenterologia. La trattazione si articola in due parti: una prima elaborazione teorica, che permette di inquadrare nel contesto della ricerca traslazionale il razionale scientifico ed etico alla base delle attività sperimentali eseguite durante il triennio; una seconda parte, nella quale si riportano i metodi, i risultati e le osservazioni conclusive derivanti dallo studio sperimentale. Nella prima parte vengono analizzate alcune caratteristiche delle procedure, adottate nella ricerca in ambito farmacologico gastrointestinale, che permettono di ottenere un dato verosimile derivabile da modelli diversi rispetto all’organismo umano. Sono inclusi nella trattazione gli aspetti etici dell’utilizzo di alcuni modelli animali di patologie intestinali organiche e funzionali in relazione al loro grado di predittività rispetto alla realtà sperimentale clinica. Nella seconda parte della trattazione, viene presentato uno studio esplorativo tissutale multicentrico sul ruolo del sistema oppioide e cannabinoide nella sindrome dell’intestino irritabile (IBS). Obiettivo dello studio è la valutazione dell’espressione e la localizzazione del recettore oppioide µ (µOR), del suo ligando β endorfina (β-END) e del recettore cannabinoide 2 (CB2) nei pazienti con IBS ad alvo costipato (IBS-C) e diarroico (IBS-D), ed in soggetti sani (HC). I dati ottenuti indicano un’implicazione del sistema oppioide e cannabinoide nella risposta immune alterata riscontrata nei pazienti con IBS ed in particolare nel sottogruppo IBS-C. La presente trattazione suggerisce come la creazione di nuovi sistemi di indagine sempre più validi da un punto di vista traslazionale possa dipendere, almeno in parte, dalla capacità di integrare realtà disciplinari, tecnologie ed esperienze metodologiche diverse nel contesto della ricerca in campo biomedico e farmacologico ed in particolare tramite un mutuo scambio di informazioni tra realtà clinica e ricerca di base

Esophageal Dilation in Eosinophilic Esophagitis: Effectiveness, Safety, and Impact on the Underlying Inflammation

Esophageal dilation often leads to long-lasting relief of dysphagia in eosinophilic esophagitis (EoE). The aim of this study was to define the effectiveness, safety, and patient acceptance of esophageal dilation in EoE. In addition, we examined the influence of dilation on the underlying esophageal inflammation.

Characteristics of Reflux Episodes and Symptom Association in Patients With Erosive Esophagitis and Nonerosive Reflux Disease: Study Using Combined Impedance–pH Off Therapy

We sought to compare reflux and symptom association patterns in patients with nonerosive reflux disease (NERD), erosive esophagitis (EE), and in healthy volunteers (HVs).

NCX-1000, a nitric oxide-releasing derivative of UDCA, does not decrease portal pressure in patients with cirrhosis: results of a randomized, double-blind, dose-escalating study

NCX-1000 (2(acetyloxy) benzoic acid-3(nitrooxymethyl)phenyl ester) is an nitric oxide (NO)-releasing derivative of ursodeoxycholic acid (UDCA), which showed selective vasodilatory effect on intrahepatic circulation in animal models of cirrhosis. This study was aimed at testing the efficacy and tolerability of this compound in patients with cirrhosis and portal hypertension.

Fecal calprotectin correlates more closely with the Simple Endoscopic Score for Crohn's disease (SES-CD) than CRP, blood leukocytes, and the CDAI

Studies evaluating the correlation between the widely used Simple Endoscopic Score for Crohn's disease (SES-CD) and noninvasive markers are scarce. The aim of this study was to evaluate the correlation between the SES-CD and fecal calprotectin, C-reactive protein (CRP), blood leukocytes, and the Crohn's disease activity index (CDAI).

Evidence of a Generalized Defect of Acinar Cell Function in Shwachman-Diamond Syndrome

: Because the acinar cells of the exocrine pancreas in patients with Shwachman-Diamond syndrome (SDS) are severely depleted, we hypothesized that a similar deficiency may be present in acinar cells of the parotid gland.

Is detection of bacterial DNA in ascitic fluid of clinical relevance?

In patients with cirrhosis, bacterial DNA has been found in ascites reflecting bacterial translocation. However, the clinical relevance of this finding is ill-defined especially compared with the standard diagnostics for detection of spontaneous bacterial peritonitis (SBP). Furthermore, other DNA tests have not been sufficiently evaluated.

Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy

The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have increased in the past 20 years. GEP-NETs are heterogeneous tumors, in terms of clinical and biological features, that originate from the pancreas or the intestinal tract. Some GEP-NETs grow very slowly, some grow rapidly and do not cause symptoms, and others cause hormone hypersecretion and associated symptoms. Most GEP-NETs overexpress receptors for somatostatins. Somatostatins inhibit the release of many hormones and other secretory proteins; their effects are mediated by G protein-coupled receptors that are expressed in a tissue-specific manner. Most GEP-NETs overexpress the somatostatin receptor SSTR2; somatostatin analogues are the best therapeutic option for functional neuroendocrine tumors because they reduce hormone-related symptoms and also have antitumor effects. Long-acting formulations of somatostatin analogues stabilize tumor growth over long periods. The development of radioactive analogues for imaging and peptide receptor radiotherapy has improved the management of GEP-NETs. Peptide receptor radiotherapy has significant antitumor effects, increasing overall survival times of patients with tumors that express a high density of SSTRs, particularly SSTR2 and SSTR5. The multi-receptor somatostatin analogue SOM230 (pasireotide) and chimeric molecules that bind SSTR2 and the dopamine receptor D2 are also being developed to treat patients with GEP-NETs. Combinations of radioactive labeled and unlabeled somatostatin analogues and therapeutics that inhibit other signaling pathways, such as mammalian target of rapamycin (mTOR) and vascular endothelial growth factor, might be the most effective therapeutics for GEP-NETs.

Intrapancreatic Accessory Spleen Misdiagnosed as a Nonsecreting Endocrine Tumor: Case Report and Review of the Literature

In a large series of nonselected autopsy investigations an accessory spleen was found in 10-30%. The second most common site is the pancreatic tail (17%). We report a case of intrapancreatic accessory spleen misdiagnosed as a nonsecreting neuroendocrine tumor of the pancreas. Nuclear scintigraphy may provide the definitive diagnosis of an intrapancreatic spleen and therefore prevent patients from unnecessary major surgery.

Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by dense tissue eosinophilia; it is refractory to proton pump inhibitor therapy. EoE affects all age groups but most frequently individuals between 20 and 50 years of age. Topical corticosteroids are effective in pediatric patients with EoE, but no controlled studies of corticosteroids have been reported in adult patients.