Pre-treatment sarcopenic assessments as a prognostic factor for gynaecology cancer outcomes: systematic review and meta-analysis.

INTRODUCTION: Gynaecology cancers, including ovarian (OC), endometrial (EC), and cervical (CC), are prevalent with high mortality. Sarcopenia is found in 38.7% of cancer patients, adversely affecting prognosis. Computed tomography (CT) is performed routinely in oncology, yet CT assessments of sarcopenia are not commonly used to measure prognosis. This systematic review and meta-analysis aimed to evaluate the prognostic potential of pre-treatment sarcopenia assessments on overall survival (OS) and progression free survival (PFS) in gynaecology cancer. METHODOLOGY: Four electronic databases were systematically searched from 2000 to May 2020 in English: Ovid Medline, EMBASE, Web of Science, and CINAHL plus. Titles and abstracts were screened, eligible full-texts were reviewed, and data from included studies was extracted. Meta-analyses were conducted on homogenous survival data, heterogenous data were narratively reported. RESULTS: The initial search yielded 767 results; 27 studies were included in the systematic review (n = 4286), all published between 2015 and 2020. Meta-analysis of unadjusted results revealed a negative effect of pre-treatment sarcopenia on OS in OC (HR: 1.40, 1.20-1.64, p < 0.0001) (n = 10), EC (HR: 1.42, 0.97-2.10, p = 0.07) (n = 4) and CC (HR: 1.10, 0.93-1.31, p = 0.28) (n = 5), and a negative effect on PFS in OC (HR: 1.28, 1.11-1.46, p = 0.0005) (n = 8), EC (HR: 1.51, 1.03-2.20, p = 0.03) (n = 2) and CC (HR: 1.14, 0.85-1.53, p = 0.37) (n = 2). Longitudinal analysis indicated negative effects of muscle loss on survival. Overall, there was a high risk of bias. CONCLUSION: Pre-treatment sarcopenia negatively affected survival in gynaecology cancers. Incorporating such assessments into cancer management may be beneficial. Heterogeneity in sarcopenia assessments makes data interpretation challenging. Further research in prospective studies is required.

Early treatment with ursodeoxycholic acid for cholestasis in children on parenteral nutrition because of primary intestinal failure.

BACKGROUND: There is conflicting evidence as to whether ursodeoxycholic acid (UDCA) reduces the incidence of parenteral nutrition-associated cholestasis. AIM: To investigate the efficacy of UDCA on parenteral nutrition-associated cholestasis in children with intestinal failure due to short bowel syndrome or to other causes. METHODS: Children with cholestasis received 30 mg/kg/day UDCA. Improvement or normalization of parenteral nutrition-associated cholestasis was evaluated at 6 months of therapy and at the last follow-up. In a subgroup of children, serum UDCA levels were measured while receiving UDCA and after 4 weeks withdrawal. RESULTS: Twelve children were treated with UDCA. Full remission or partial improvement of parenteral nutrition-associated cholestasis occurred in 11 of 12 children. In three of four children, withdrawal of UDCA was associated with a rebound rise of cholestasis. Only one of 12 treated children showed no improvement and in this patient, in contrast to four other patients, plasma levels of UDCA did not increase during treatment. CONCLUSIONS: Ursodeoxycholic acid was effective in controlling parenteral nutrition-associated cholestasis. The efficacy of UDCA also in children with short bowel is related to intestinal absorption.

Medical strategies for weight loss in the overweight and obese patient.

In recent years, obesity has become a major public health problem in Western countries. The World Health Organization has defined obesity as a global epidemic of the third millennium. Treatment options for weight management include dietary intervention, physical activity, behavior modification, pharmacotherapy and surgery. However, the complexity of this chronic condition necessitates a coordinated multidisciplinary team-approach to the care of obese patients who fail weight control. The long-term duration of the treatment and the necessity of monitoring compliance and effectiveness should be considered. The objective of this article was to review the major controlled randomized clinical trials dealing with the different medical strategies for weight loss and its maintenance in overweight and obese patients.

Effects of Lactobacillus GG on genes expression pattern in small bowel mucosa.

BACKGROUND AND AIMS: Probiotics have been used for cure and prevention of several clinical conditions. However, further insights into the mechanism of action are needed to understand the rationale of their use. The aim of this study was to investigate the influence of Lactobacillus GG on the genetic expression patterns in the small bowel mucosa. METHODS: Six male patients (38+/-5 years) with endoscopically proven oesophagitis were enrolled. All patients were treated for 1 month with esomeprazole and randomised to receive Lactobacillus GG or placebo. After 1 month of treatment, upper endoscopy was repeated. Biopsies of the duodenal mucosa were taken prior to and after the treatment, and the genes expression patterns were assessed using GeneChip Human U133A array. Genes with significant expression changes were selected and analysed to identify specific cellular pathways modified by Lactobacillus GG. To support the array data, 10 target genes were studied using Syber-Green PCR. RESULTS: Microarray analysis showed that Lactobacillus GG administration determined the up- and down-regulation of 334 and 92 genes, respectively. Real-time PCR confirmed the reliability of the analysis. Lactobacillus GG mainly affected the expression of genes involved in immune response and inflammation (TGF-beta and TNF family members, cytokines, nitric oxide synthase 1, defensin alpha 1), apoptosis, cell growth and cell differentiation (cyclins and caspases, oncogenes), cell-cell signalling (ICAMs and integrins), cell adhesion (cadherins), signal transcription and transduction. CONCLUSIONS: These data indicate that administration of Lactobacillus GG is associated with a complex genetic response of the duodenal mucosa, reflected by the up- and down-regulation of several genes involved in specific cellular pathways.

Meta-analysis: the effect of probiotic administration on antibiotic-associated diarrhoea.

BACKGROUND: Antibiotic-associated diarrhoea can be attributed in part to imbalances in intestinal microflora. Therefore, probiotic preparations are used to prevent this diarrhoea. However, although several trials have been conducted, no conclusive evidence has been found of the efficacy of different preparations, e.g. Lactobacillus spp. and Saccharomyces spp. AIM: To conduct a meta-analysis of the data in the literature on the efficacy of probiotics in the prevention of antibiotic-associated diarrhoea. METHODS: A literature search was performed of electronic databases, Abstract Books and single paper references. Data were also obtained from the authors. Only placebo-controlled studies were included in the search. The Mantel-Haenszel test was used to estimate the relative risk for single studies and an overall combined relative risk, each study being submitted to the Mantel-Haenszel test for homogeneity. RESULTS: Twenty-two studies matched the inclusion criteria. Only seven studies (881 patients) were homogeneous. The combined relative risk was 0.3966 (95% confidence interval, 0.27-0.57). CONCLUSIONS: The results suggest a strong benefit of probiotic administration on antibiotic-associated diarrhoea, but further data are needed. The evidence for beneficial effects is still not definitive. Published studies are flawed by the lack of a placebo design and by peculiar population features.

Meta-analysis: the relationship between Helicobacter pylori infection and gastro-oesophageal reflux disease.

BACKGROUND: The relationship between Helicobacter pylori infection and its treatment and gastro-oesophageal reflux disease (GERD) is controversial. AIMS: To establish if H. pylori infection is associated with the presence of GERD and if anti-H. pylori treatment leads to de novo GERD or rebound/exacerbation of GERD. METHODS: A search of MEDLINE and EMBASE databases was made. Pooled odds ratios (OR) were calculated for de novo GERD and rebound/exacerbated GERD after anti-H. pylori therapy in case-control studies and in therapeutic trials. RESULTS: Fourteen case-control studies and 10 clinical trials were included. Among case-control studies, pooled OR for the association between H. pylori negative status and GERD was 1.34 [95% confidence interval (CI) 1.15-1.55]. Among therapeutic trials, pooled OR for the association anti-H. pylori therapy - GERD was 2.54 (95% CI 1.92-3.37). The OR for de novo GERD was 3.25 (95% CI 2.09-5.33), and for rebound/exacerbated GERD was 2.39 (95% CI 1.75-3.34). Associations were higher among Asian studies than among North American and European studies. CONCLUSIONS: This meta-analysis shows significant association between absence of H. pylori infection and GERD symptoms, and a positive association between anti-H. pylori therapy and occurrence of both de novo and rebound/exacerbated GERD. The significance of these associations appears to have been inflated by the effect of single trials and by geographical variations.

Mono, dual and triple moxifloxacin-based therapies for Helicobacter pylori eradication.

BACKGROUND: Moxifloxacin is a broad spectrum fluoroquinolone with single daily administration, currently used, above all, for respiratory tract infections. AIM: To compare the efficacy of different 1-week moxifloxacin-based Helicobacter pylori eradication regimens. METHODS: One hundred and twenty H. pylori-positive subjects were randomized to receive moxifloxacin (400 mg/day), moxifloxacin (400 mg/day) and lansoprazole (30 mg/day) or moxifloxacin (400 mg/day), lansoprazole (30 mg/day) and clarithromycin (500 mg b.d.). H. pylori status was reassessed 6 weeks after the end of therapy, and both intention-to-treat and per protocol analyses were performed. RESULTS: One hundred and nineteen of the 120 patients completed the study. H. pylori eradication was achieved in 22.5% of patients treated with moxifloxacin, in 33.3% of subjects treated with moxifloxacin and lansoprazole and in 90% of patients treated with moxifloxacin, clarithromycin and lansoprazole. CONCLUSIONS: Mono and dual moxifloxacin-based therapies are not acceptable for H. pylori eradication; conversely, moxifloxacin-based triple therapy may be considered as a new, effective, first-line therapy option.

Levofloxacin-based triple therapy vs. quadruple therapy in second-line Helicobacter pylori treatment: a randomized trial.

BACKGROUND: Levofloxacin has been shown to be effective in Helicobacter pylori eradication. Two 10-day levofloxacin-based triple therapies were compared with standard 7- and 14-day quadruple regimens in second-line treatment. METHODS: Two hundred and eighty consecutive patients who failed to respond to standard triple therapy (clarithromycin, amoxicillin, rabeprazole) were randomly assigned to four groups: (1) levofloxacin 500 mg o.d., amoxicillin 1 g b.d., rabeprazole 20 mg b.d. for 10 days (LAR, n = 70); (2) levofloxacin 500 mg o.d., tinidazole 500 mg b.d., rabeprazole 20 mg b.d. for 10 days (LTR, n = 70); (3) tetracycline 500 mg q.d.s., metronidazole 500 mg t.d.s., bismuth salt 120 mg q.d.s., rabeprazole 20 mg b.d. for 7 days (7TMBR, n = 70); and (4) for 14 days (14TMBR, n = 70). Helicobacter pylori status and side-effects were assessed 6 weeks after treatment. RESULTS: The eradication rate was 94% in the LAR group and 90% in the LTR group in both intention-to-treat and per protocol analyses. Helicobacter pylori eradication was achieved in 63 and 69% of the 7TMBR group and in 69 and 80% of the 14TMBR group in intention-to-treat and per protocol analysis, respectively. Side-effects were significantly lower in the LAR and LTR groups than in the 14TMBR group. CONCLUSION: Ten-day levofloxacin-based therapies are better than standard quadruple regimens as second-line option for H. pylori eradication.

Probiotics in antibiotic-associated diarrhoea.

Antibiotic-associated diarrhoea is a common event. In some cases, it could represent a life-threatening event. Clostridium difficile colitis is a further distinct complication of antibiotic administration. Treatment options for antibiotic-associated diarrhoea and Clostridium difficile colitis include supplementation with several types of probiotics, as overviewed in this paper. Three randomised, double-blind, controlled clinical trials show a therapeutic effect of Saccharomyces boulardii in antibiotic-associated diarrhoea. The efficacy of Lactobacillus acidophilus and bulgaricus has also been ascertained in two double-blind controlled studies. Other studies focusing on Lactobacillus as a new preventive agent for antibiotic-associated diarrhoea are not double-blind. Among these, a positive effect of Lactobacillus rhamnosus GG, Bifidobacterium longum and Enterococcus faecium SF68 has been reported. Effectiveness of probiotics in antibiotic-associated diarrhoea has, therefore, a consistent scientific rationale, however few studies have performed an assessment of bacterial recovery in stools, and this approach may be helpful in deciding a more rigorous dose standardisation.

Probiotics and Helicobacter pylori eradication.

The need for new strategies for Helicobacter pylori eradication, alternative or complementary to antibiotic therapy, has recently claimed the attention of many investigators. Pre-clinical studies have shown the inhibition of Helicobacter pylori growth by Lactobacilli and the anti-Helicobacter pylori action of Lactobacillus salivarius, Lactobacillus acidophilus and Lactobacillus casei subspecies rhamnosus strains, possibly due to the production of lactic acid or to the secretion of an autolysin. Clinical studies have demonstrated a persistent reduction in delta over baseline values at the 13C urea breath test independently of omeprazole administration with Lactobacillus acidophilus La1, the eradication in 6 out of 14 patients with Lactobacillus acidophilus alone, positive results in patients in which a standard Helicobacter pylori triple therapy was randomly supplemented with Lactobacillus acidophilus.

Second-line levofloxacin-based triple schemes for Helicobacter pylori eradication.

BACKGROUND: The recommended second-line therapy for Helicobacter pylori (H. pylori) eradication is a quadruple regimen that fails in up to 30% of patients. Several recent studies suggest levofloxacin-based triple therapies as an alternative rescue treatment. However, dosage and length of levofloxacin-based regimens have not been established. AIM: To compare the efficacy and tolerability of four second-line levofloxacin-based schemes for H. pylori eradication. METHODS: One hundred and sixty patients (aged 18-70 years, 72 male patients) who were H. pylori positive after standard triple therapies were randomised to receive esomeprazole 20mg b.d. and amoxicillin 1g b.d. plus levofloxacin 500 mg o.d., for 7 or 10 days (Groups A and B) or levofloxacin 500 mg b.d. for 7 days or 10 days (Groups C and D). H. pylori status was assessed by 13-C Urea Breath Test or rapid urease test, before and 6 weeks after therapy. Incidence of side effects was evaluated by a questionnaire. RESULTS: No dropouts were observed. Eradication of H. pylori infection was successful in: 65% of patients in Group A; 90% in Group B; 70% in Group C; 85% in Group D. Based upon duration of treatment, eradication rates were: 67.5% in 7 days groups and 87.5% in 10 days groups (p=0.004). Dosage of levofloxacin did not affect the eradication rates (77.5% both in the once daily and twice daily groups). Mild adverse events were reported overall in 16% of patients (22.5% in 7 days groups; 27.5% in 10 days groups; p=0.58; 12% in the once daily group; 32.5% in the twice daily group; p=0.04). CONCLUSIONS: 10 days levofloxacin-based second-line regimens were effective in curing H. pylori infection in more than 85% of patients with a lower incidence of adverse effects in levofloxacin single-dosage scheme. The 10 days levofloxacin-based regimens were more effective than 7 days course of treatment showing that duration of therapy is the crucial factor affecting eradication rate.

Probiotics and small bowel mucosa: Molecular aspects of their interactions.

Probiotics are described as "friendly bacteria" that could improve the intestine defense by interacting with the resident microflora. There is a large body of evidence suggesting that consumption of functional food containing probiotics exerts positive effects on human health. Several clinical trials have highlighted the efficiency of probiotics in the prevention and treatment of different gastrointestinal disorders including the prevention of antibiotic associated diarrhea, the remission in patients with inflammatory bowel disease, beneficial effects against Helicobacter pylori infection, positive effects in patients affected by allergies and atopic diseases. The clinical benefits of probiotics use are mainly attributed to their antimicrobial substances production and their positive interactions with the enterocytes to reinforce the intestinal epithelial barrier. Moreover, there is evidence suggesting that probiotics stimulate both specific and non-specific host immune responses. Recently, have been published some experiments performed with the DNA microarray technology which provided a global gene screening of the complex bacteria-host interplay. Nevertheless, the molecular mechanisms by which probiotics enhance the intestinal host defense are still not completely elucidated. Here, we review the experiments and clinical studies to date on the complex mechanisms regulating the communication between probiotics and their hosts.

Push-and-pull enteroscopy in the small bowel using the double-balloon technique: results of a prospective European multicenter study.

BACKGROUND AND STUDY AIMS: The aim of this study was to evaluate the feasibility, safety, and clinical impact of push-and-pull enteroscopy (PPE) in patients with suspected or documented small-bowel diseases, in a prospective multicenter trial in three European medical centers. PATIENTS AND METHODS: A total of 100 patients (mean age 56 +/- 16 years; range 13 - 90) were included at the three institutions between July and November 2004. The leading symptoms were: acute recurrent or chronic gastrointestinal bleeding (n = 64), polyposis syndrome (n = 8), chronic abdominal pain (n = 7), chronic diarrhea (n = 7), and others (n = 14). RESULTS: No major PPE-associated complications such as perforation, bleeding, or relevant injury to the small-bowel tissue or mesentery were encountered. Minor complications occurred in 12 %. The mean time required to carry out the procedure from the oral and anal approaches was 75 +/- 19 min (32 - 150 min). The average insertion depths into the small bowel were 200 +/- 70 cm per PPE session (220 +/- 90 cm with the oral approach and 130 +/- 80 cm with the anal approach). The average radiation exposure (including diagnostic and therapeutic interventions) was 2.1 +/- 2.4 min and 155 +/- 159 dGy/cm2. PPE was fully diagnostic in 72 % of cases. The majority of the patients (34 %) were suffering from angiodysplasias; ulcerations and erosions of various etiologies were seen in 16 %, and polyps and tumors in 13 %. The PPE findings played a role in the subsequent treatment in 62 % of the patients. Endoscopic treatments, including argon plasma coagulation, polypectomy, dilation, and foreign-body extraction, were carried out in 42 %. Medical treatment was given in 12 %, and patients were referred for surgery in 8 % of cases. CONCLUSIONS: This prospective analysis shows that PPE is safe and has a high diagnostic and therapeutic yield in patients with suspected or known small-bowel disease.

Helicobacter pylori treatment: a role for probiotics?

Many new therapeutic strategies are studied to improve Helicobacter pylori eradication rate. Probiotics are live microorganisms which, upon administration, may interact with the human microflora and positively affect the health status. The use of probiotics in the field of H. pylori infection has been proposed for improving eradication rate and tolerability and for compliance of multiple antibiotic regimens used for the infection. Results from laboratory studies and from clinical trials seem to confirm the expectancies, but there is lack of standardization in terms of type of probiotic strain used, dosage and timing of supplementation. Before further ongoing trials and future studies will clarify these points, probiotics could remain a useful adjunct to standard anti-H. pylori therapies, but cannot take the place of other validated options.

Helicobacter pylori CagA-positive strains affect oxygen free radicals generation by gastric mucosa.

BACKGROUND: Helicobacter pylori plays a key role in production of reactive oxygen metabolites (ROMs). However, the importance of virulent CagA-positive H. pylori strains remains to be determined. The aim of this study was to assess ROMs production in gastric biopsies of patients infected by H. pylori. Results were correlated to CagA status and acute inflammatory infiltration. METHODS: Patients undergoing gastroscopy were enrolled. H. pylori infection was assessed by histology and 13C urea breath test. CagA status was assessed through serology. ROMs were assayed in gastric biopsies by luminol-enhanced chemiluminescence (CLS). Gastric mucosal inflammation was histologically graded and neutrophils were individually counted. Macroscopical damage was scored according to a modified Lanza score. RESULTS: 40 out of 60 patients evaluated were H. pylori (HP) positive. Of the 40 infected patients, 24 were CagA-positive. CLS emission was significantly higher in HP-CagA-positive patients than in HP-CagA-negatives and uninfected. ROMs production showed a significant correlation to neutrophil infiltrate in all groups. CONCLUSIONS: Gastric mucosa of patients infected by HP-CagA-positive strains is characterized by a higher generation of ROMs and by greater neutrophil counts than that observed in HP-CagA-negative subjects. Since ROMs production is associated with DNA oxidative damage, a long-term stimulation by these strains might be relevant in the pathogenesis of gastric malignancies. Assessment of CagA status might be useful to discriminate patients in which H. pylori eradication is advisable.

Helicobacter pylori infection affects eosinophilic cationic protein in the gastric juice of patients with idiopathic chronic urticaria.

BACKGROUND: Helicobacter pylori, the main cause of gastritis and peptic ulcer, has been associated with idiopathic chronic urticaria (ICU), an immunological skin disorder of unknown origin. Eosinophilic cationic protein (ECP) is a cytotoxic molecule secreted by the activated eosinophils involved in the pathogenesis of ICU. We assessed serum/gastric juice ECP levels and gastric mucosal eosinophil infiltration in ICU patients infected or not with H. pylori and evaluated the modification after bacterium eradication. METHODS: 33 patients with ICU and 25 dyspeptic controls underwent upper gastrointestinal endoscopy for histological evaluation and assessment of H. pylori infection. One-week triple therapy was given to H. pylori-positive patients. Serum and gastric juice ECP levels, eosinophil infiltration from gastric mucosal sections and urticaria symptoms were evaluated in all patients at enrollment and 8 weeks after eradication. RESULTS: 19 of 33 (57%) ICU patients and 16 of 25 (64%) controls were found to be infected with H. pylori. Serum ECP was significantly higher in ICU patients compared to controls, regardless of infectious status. Gastric juice ECP and gastric eosinophil infiltration were significantly higher in infected ICU patients when compared both to uninfected ICU patients and controls. H. pylori eradication determined a significant decrease in gastric juice ECP and gastric eosinophil infiltration only in ICU patients. Moreover, a total or partial remission of urticaria symptoms was observed only in ICU patients in whom the bacterium was eradicated. CONCLUSIONS: Although H. pylori infection affects gastric juice ECP and eosinophil infiltration of ICU patients, the role of the bacterium in the pathogenesis of this skin disorder still remains uncertain.