Noninvasive molecular analysis of Helicobacter pylori : Is it time for tailored first-line therapy?

The main problem of Helicobacter pylori(H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction(PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin susceptibility have shown an overall high sensitivity and specificity when compared with culture or PCR on gastric biopsies. On these bases, two commercial tests are now available although they have shown some controversial findings. A novel PCR method showed a full concordance between tissue and stool results in a preliminary experience. In conclusion, despite poor validation, there is increasing evidence of a potential availability of noninvasive investigations able to detect H. pylori resistances to antibiotics. These kinds of analysis are currently at a very early phase of development and caution should be paid about their clinical application. Only further studies aimed to evaluate their sensitivity and specificity will afford novel data for solid considerations. Nevertheless, noninvasive molecular tests may improve patient compliance, time/cost of infection management and therapeutic outcome. Moreover, the potential risk of a future increase of resistance to quadruple regimens as a consequence of their use on large scale and incomplete patient adherence could be avoided.

phytoestrogens/insoluble fibers and colonic estrogen receptor β: randomized, double-blind, placebo-controlled study

AIM:To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS:A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS:No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69vs 37.708 ± 5.31,P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13,P = 0.04), mRNA (2.278 ± 1.19vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67,P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06vs 0.532 ± 0.11,P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION:The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.

Unexpected me diastinal mass in a liver transplanted patient

To the Editor:The risk of de novo cancer increases by 2 to 7-fold after liver transplantation[1].The most common de novo cancers are both solid(non-melanoma skin cancers,colorectal carcinoma,genito-urinary and head-neck cancer)[2,3]as well as hematologic malignancies,in particular the so-called post-transplant lymphoproliferative disorder[4].

Indications and outcomes of endoscopic resection for nonpedunculated colorectal lesions:A narrative review

In the last years,endoscopic techniques gained a crucial role in the treatment of colorectal flat lesions.At the same time,the importance of a reliable assessment of such lesions to predict the malignancy and the depth of invasion of the colonic wall emerged.The current unsolved dilemma about the endoscopic excision techniques concerns the necessity of a reliable submucosal invasive cancer assessment system that can stratify the risk of the post-procedural need for surgery.Accordingly,this narrative literature review aims to compare the available diagnostic strategies in predicting malignancy and to give a guide about the best techniques to employ.We performed a literature search using electronic databases(MEDLINE/PubMed,EMBASE,and Cochrane Library).We collected all articles about endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)registering the outcomes.Moreover,we analyzed all meta-analyses comparing EMR vs ESD outcomes for colorectal sessile or nonpolypoid lesions of any size,preoperatively estimated as non-invasive.Seven meta-analysis studies,mainly Eastern,were included in the analysis comparing 124 studies and overall 22954 patients who underwent EMR and ESD procedures.Of these,eighty-two were retrospective,twenty-four perspective,nine casecontrol,and six cohorts,while three were randomized clinical trials.A total of 18118 EMR and 10379 ESD were completed for a whole of 28497 colorectal sessile or non-polypoid lesions>5-10 mm in size.In conclusion,it is crucial to enhance the preoperative diagnostic workup,especially in deciding the most suitable endoscopic method for radical resection of flat colorectal lesions at risk of underlying malignancy.Additionally,the ESD necessitates further improvement because of the excessively time-consuming as well as the intraprocedural technical hindrances and related complications.We found a higher rate of en bloc resections and R0 for ESD than EMR for non-pedunculated colorectal lesions.Nevertheless,despite the lower local recurrence rates,ESD had greater perforation rates and needed lengthier procedural times.The prevailing risk for additional surgery in ESD rather than EMR for complications or oncologic reasons is still uncertain.