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Antonio Francavilla

Publications and source records attributed to Antonio Francavilla.

14 recordsLinked to original sources
PubMed2026

Fecal immunochemical tests from population-based colorectal cancer screening programs support prospective microbiome cohorts.

BACKGROUND: Large, prospective cohorts are needed to research the gut microbiome's role in colorectal cancer (CRC) risk. We evaluated the gut microbiome leveraging residual fecal immunochemical tests (FIT) from a CRC screening program in Turin, Italy, and conducted one of the largest population-based case-control studies across the adenoma-carcinoma sequence to date. METHODS: We extracted DNA from residual FIT stool, used whole-genome shotgun sequencing, and included those with CRC (N = 44), advanced adenomas (N = 269), early adenomas (N = 134), and FIT-negative controls (N = 478). Alpha diversity, beta diversity, and species, gene, and pathway relative abundances were estimated. Multivariable logistic regression models were used to estimate associations of these metrics with colorectal neoplasms. RESULTS: Alpha diversity was mostly inversely associated with colorectal neoplasms, particularly early adenomas (OR: 0.45, 95% CI: 0.25-0.80; P = 0.01). Presence of oral pathogens, including Parvimonas micra, was associated with higher odds of CRC. Furthermore, Escherichia coli and Bacteroides fragilis were strongly associated with higher odds of all colorectal neoplasms. Several genes and pathways were associated with colorectal neoplasms. CONCLUSIONS: Our findings align with smaller studies of the gut microbiome and colorectal neoplasms, supporting that CRC screening programs provide opportunities to prospectively study the gut microbiome's association with cancer risk in large populations.

Humans↗
PubMed2006

Functional modification of CD11c+ liver dendritic cells during liver regeneration after partial hepatectomy in mice.

Local immunosuppression within the liver and sex steroid changes, in both blood and tissue during liver regeneration, are well-recognized events. Dendritic cells (DC) play pivotal roles in the induction and regulation of immune responses. Their numbers are expanded markedly in vivo by fms-like tyrosine kinase 3 ligand (Flt3L) administration, without modification of their maturation state. Recent evidence suggests that estrogen can modulate DC function and promote a Th2-type immune response. Few data are available concerning the role of DC in liver regeneration. After 75% partial hepatectomy (PH) in male C57BL/6 mice, CD11c+ liver (L)DC increased significantly within 6 hours and maintained an immature phenotype. Numbers returned to pre-hepatectomy levels by 24 hours. The expanded LDC population showed increased IL-10 and reduced IFN-gamma gene transcription. Using these DC compared with control LDC as T cell stimulators in 72-hour mixed leukocyte cultures, IL-10 production was enhanced and IFN-gamma production reduced. LDC isolated 6 hours after 75% PH exhibited enhanced estrogen receptor (ER) expression, concomitant with increased serum estrogen levels. By contrast, spleen (S)DC isolated before and after PH showed no significant changes in their function (maturation state, T cell stimulatory activity, cytokine production, and ER expression). Increased liver regeneration (more than 50%) was observed 48 hours after 40% PH in the Flt3L-pretreated compared with the PBS group. In conclusion, interstitial LDC may play a key role in local immune regulation during liver regeneration, possibly linking estrogen-mediated immune modulation and hepatocyte proliferation.

Animals↗
PubMed2006

Sliding gastric hiatal hernia diagnosis by transabdominal ultrasonography: an easy, reliable and non-invasive procedure.

OBJECTIVE: Data in the literature suggest the possibility of using ultrasonography to diagnose sliding gastric hiatal hernia. The aim of this study was to confirm the diagnostic accuracy of transabdominal ultrasonography for the diagnosis of sliding gastric hiatal hernia, using endoscopy as the reference test. The latter procedure was used since it also recognizes the presence of esophagitis and/or varices, two pathological conditions that could per se influence ultrasonographic evaluation, based on measurement of the esophageal diameter. MATERIAL AND METHODS: A total of 180 consecutive patients, admitted to our hospital for endoscopy, were examined. Of these, 12 patients were not included in the final study. After fasting, the remaining 168 patients were first evaluated by ultrasonography and later by endoscopy. Esophageal diameter was measured by ultrasonography at the level of the diaphragmatic hiatus. RESULTS: Using a diameter > or = 18 mm as the sensitivity threshold, 29 patients potentially affected by hiatal hernia were identified by ultrasonography. Upper endoscopy examination confirmed the presence of hiatal hernia in 24 of these patients and documented 4 additional hernias in the group of patients with a transdiaphragmatic esophageal diameter <18 mm (positive and negative predictive values were 82.7% and 97%, respectively). Analysis of the distribution of esophageal varices and esophagitis in all 168 excluded the possibility that these pathological conditions could influence the esophageal diameter. CONCLUSIONS: Ultrasonography represents a simple and well-tolerated diagnostic approach in sliding gastric hiatal hernia. The good diagnostic accuracy suggests its potential use in clinical and epidemiological settings.

Adolescent↗
PubMed2006

Differential immunohistochemical expression of syndecan-1 and tumor necrosis factor alpha in colonic mucosa of patients with Crohn's disease.

Tumor necrosis factor alpha (TNFalpha) in intestinal mucosa plays a key role in the inflammation characterizing Crohn's disease (CD). Moreover, adhesion molecule syndecan-1 mediates the maintenance of mucosal integrity and supports tissue repair. Therefore, our aim in this study was to correlate simultaneous expression of TNFalpha and syndecan-1 in patients affected by CD. Biopsies from 10 patients with CD of large bowel and 10 subjects with irritable bowel syndrome (controls) were studied by immunohistochemical detection of both TNFalpha and syndecan-1 on successive serial sections. Overall labeling index (OLI) was indicated by the percentage of positive stromal (i.e., nonepithelial) cells/1000 counted in randomized fields, whereas selected labeling index (SLI) was represented by the simultaneous evaluation of both molecules in a same single selected field of each specimen. TNFalpha and syndecan-1 OLI were significantly higher in CD compared with controls, while SLI showed an inverse relationship between the molecules in CD which was not observed in controls. Epithelial syndecan-1 cytoplasmatic staining of superficial epithelium was associated with loss of basolateral staining in the crypts and high stromal TNFalpha in CD. In conclusion, TNFalpha and syndecan-1 expression is increased in the intestinal mucosa of patients with CD. However, the expression of the two molecules is inversely related when a single field is considered, these data supporting the possibility of a downregulation exerted by TNFalpha.

Adult↗
PubMed2005

Improved efficacy of 10-Day sequential treatment for Helicobacter pylori eradication in children: a randomized trial.

BACKGROUND & AIMS: The currently recommended first-line eradication treatment of Helicobacter pylori in children is usually successful in about 75%. Recently, in adults, a novel 10-day sequential treatment has achieved an eradication rate of 95%. The aim of the study was to assess the H pylori eradication rate of the sequential treatment regimen compared with conventional triple therapy in children. METHODS: Seventy-eight consecutive children with H pylori infection were randomized to receive either sequential treatment (omeprazole plus amoxicillin for 5 days, followed by omeprazole plus clarithromycin plus tinidazole for another 5 days) (n = 38; 15 boys [39.5%]; median age, 11.0 years [range, 3.3-16 years]) or triple therapy (omeprazole, amoxicillin, and metronidazole) for 1 week (n = 37; 15 boys [40.5%]; median age, 9.9 years [range, 4.3-16 years]). H pylori infection was based on 2 out of 3 positive tests results: 13C-urea breath test, rapid urease test, and histologic analysis. Eradication was assessed by 13C-urea breath test 8 weeks after therapy. RESULTS: Seventy-four patients completed the study. H pylori eradication was achieved in 36 children receiving sequential treatment (97.3%; 95% confidence interval, 86.2-99.5) and 28 children receiving triple therapy (75.7%; 95% confidence interval, 59.8-86.7) (P < .02). Compliance with therapy was good (>95%) in all. CONCLUSIONS: Our study shows, for the first time in children, that 10-day sequential treatment achieves a higher eradication rate than standard triple therapy, which is consistent with the results of adult studies.

Adult↗
PubMed2005

A new oral delivery system for 5-ASA: preliminary clinical findings for MMx.

BACKGROUND: Multi-matrix (MMx), a new delivery system for mesalazine, seems to release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left-sided disease and (2) to gain additional insights as to how the therapy would compare with topical 5-ASA. METHODS: Patients received either 1.2 g of 5-ASA MMx three times per day plus placebo enema or 4 g of 5-ASA enema plus placebo tablets for 8 weeks. The primary endpoint was clinical remission (clinical activity index < or =4) at 8 weeks. Secondary endpoints were endoscopic and histologic remissions. RESULTS: Seventy-nine patients were enrolled. Clinical remission rates at 4 and 8 weeks were 57.5% and 60.0% for patients treated with MMx and 68.4% and 50.0% for patients randomized to 5-ASA enemas, respectively (95% confidence interval for the difference at 8 weeks, -12 to +32). Endoscopic remission was achieved by 45.0% of patients on 5-ASA MMx and by 36.8% of those on enema, whereas 15.0% and 8% of patients, respectively, showed histologic remission. Compliance was 97.0% for oral and 87.5% for topical therapy. In the enema group, compliance was 88.0% for the patients in remission and 65.5% for those with active disease. CONCLUSIONS: Preliminary studies suggest that similar rates for induction of remission can be expected from 5-ASA enemas and MMx for patients with left-sided ulcerative colitis.

Administration, Oral↗
PubMed2005

Helicobacter pylori status and symptom assessment two years after eradication in pediatric patients from a high prevalence area.

OBJECTIVES: To establish the rate of Helicobacter pylori reinfection in children from an H. pylori high prevalence area, possible clinical features predictive of reinfection and the usefulness of re-treatment. METHODS: 65 consecutive children attending the authors' department between 1998 and 2000 who had proven successful H. pylori eradication were enrolled; 52 took part. Patients and family members were invited to undergo C-urea breath testing and to complete a simple questionnaire regarding symptoms and socioeconomic status. Patients with H. pylori reinfection were offered treatment; eradication was assessed by C-urea breath test 8 weeks after completion of treatment. RESULTS: Of 52 children, 15 (28.8%) were H. pylori positive. Variables predictive of reinfection were age at primary infection and presence of an infected sibling. Although reinfected children were more frequently symptomatic than non-reinfected patients, no specific symptom was associated with reinfection. Of the nine re-treated patients who returned 8 weeks after completing therapy, the bacterium was eradicated in five (56%). CONCLUSIONS: The 12.8% per year reinfection rate in childhood at 2 years that we observed should prompt a re-evaluation of H. pylori status even after a successful eradication. Living in an H. pylori high prevalence area increases the annual risk of reinfection by approximately fourfold over the annual risk in H. pylori low prevalence areas.

Adolescent↗
PubMed2004

Ursodeoxycholate further increases bile-duct cell proliferative response induced by partial bile-duct ligation in rats.

BACKGROUND: Bile salts (BSs) stimulate cholangiocyte proliferation in vitro and in vivo in normal rats. In this study, we evaluated the effects of BS-enriched diets on cholangiocyte proliferative activity already triggered by partial bile-duct ligation (pBDL), a surgical model that induces mild cholestatic conditions, focusing our attention on ursodeoxycholate (UDC). METHODS: Animals (n=45) were fed either a standard diet, or a 0.2% deoxycholate- or 0.2% UDC-enriched diet for 4 weeks. Then, in each group, ten animals underwent pBDL and five underwent sham operation. Serum and biliary BS levels, serum cholestasis and cytolysis indexes, as well as liver conventional histology, apoptosis and proliferative activity were evaluated 48 h after the operation. RESULTS: Animals that underwent pBDL showed sustained proliferative response compared with sham-operated rats. BS-enriched diets did not influence cholangiocyte proliferation in sham-operated rats. However, significantly increased proliferation was observed in pBDL rats fed a UDC-enriched diet. The evaluation of humoral and histological parameters excluded the possibility that the increased proliferation induced by UDC-enriched diet could be related to concomitant liver cell damage. CONCLUSION: A UDC-enriched diet is able to amplify the magnitude of the cholangiocyte hyperplastic process, which occurs by a stimulatory mechanism after partial bile-duct ligation.

Administration, Oral↗
PubMed2003

Influence of ursodeoxycholate-enriched diet on liver tumor growth in HBV transgenic mice.

Hepatitis B virus (HBV) transgenic mice (official designation, Tg [Alb-1 HBV] Bri 44) invariably develop macroscopically evident tumors within the 20th month of life. Sustained proliferative activity seems to play an important role in the development of these lesions. We previously showed that ursodeoxycholate (UDC) stimulates hepatocyte proliferation in various experimental settings. Herein, we tested the assumption that biological factors able to further increase liver cell proliferation, such as UDC, could accelerate tumor development in this animal model. For this study, 22 eight-week-old male transgenic mice were divided into 2 groups; 11 animals received a standard diet, and 11 received a UDC-enriched diet. The 2 groups were further divided into 2 subgroups of 5 and 6 animals each and were sacrificed at 3 and 15 months of age, respectively. These different times were chosen to exclude diet-related toxicity (in 3-month-old mice) and evaluate tumor growth (in 15-month-old mice). In addition, hepatocyte proliferation was assessed in all animals. In 3-month-old mice receiving UDC, cholestatic and cytolytic indices as well as liver histology were comparable to those in controls. At 15 months, all UDC-treated mice showed large multinodular tumors whereas only 33% of controls developed smaller uninodular neoplasms. Hepatocyte proliferation was increased in all animals receiving UDC compared with controls. In conclusion, the increase in serum UDC (undetectable in mice fed a standard diet), in the absence of any toxic effect on the liver, suggests the involvement of this bile salt in the stimulation of hepatocyte proliferation and tumor growth.

Adenoma, Liver Cell↗
PubMed2002

Depletion of mitochondrial DNA in the skeletal muscle of two cirrhotic patients with severe asthenia.

Qualitative and quantitative alterations of mitochondrial DNA (mtDNA) in the skeletal muscle from two patients with cirrhosis and severe asthenia have been studied. The 4977 bp (mtDNA(4977)) and the 7436 bp (mtDNA(7436)) mtDNA deletions, as well as other mtDNA deletions, revealed by long extension PCR (LX-PCR), were found in the two patients, whereas the 10,422 bp (mtDNA(10,422)) mtDNA deletion was absent. Altogether, the qualitative alterations of mtDNA in cirrhotic patients with severe asthenia were comparable to those of age-matched healthy individuals. The mtDNA content, on the contrary, was substantially decreased in both patients with respect to control. Such mtDNA depletion might be explained by an increased, disease-related, oxidative damage to mtDNA, which probably affects the replication of the mitochondrial genome as already suggested in other oxidative stress-associated diseases.

Asthenia↗
PubMedDate not supplied

A new semiquantitative method of quantifying Helicobacter pylori in antigen stools.

Stool antigen test for Helicobacter pylori, a noninvasive assay, is emerging as a strong competitor to urea breath test (UBT). Nevertheless, although the UBT delta value is a semiquantitative indicator of H. pylori intragastric load, until now the H. pylori stool antigen test has been used only as a qualitative investigation. We report here the results of a study performed with the aim of obtaining a semiquantitative measurement of bacterial amount in stools. We studied 15 patients with dyspepsia using H. pylori positivity at histology, the rapid urease test, UBT, and the H. pylori stool antigen test. The result of this last test was expressed by a numerical value we obtained by applying the principle of "standard points" to the absorbance units at spectrophotometric reading. This measurement was previously validated by testing probe sampling of H. pylori stool antigen with known pure and stool-mixed bacterial amounts. A numerical result for H. pylori stool antigen was correlated to UBT delta for each patient using Pearson's r test. Finally, a Student t test was performed to investigate possible differences in UBT and H. pylori stool antigen test values between anti-CagA-positive and -negative patients. We obtained a curve of saturation with both known amount of pure and stool-mixed bacteria. Pearson's r test showed a significant correlation between UBT delta value and H. pylori stool antigen measurement (r = 0.77; p < 0.001). Urea breath test delta and H. pylori stool antigen test values were significantly higher in anti-CagA-positive patients. Our data suggest that a numerical estimation of H. pylori stool antigen may be feasible. This evaluation, similarly to UBT delta, may represent a semiquantitative determination of bacterial intragastric load.

Adult↗
PubMedDate not supplied

Gene expression analysis in HBV transgenic mouse liver: a model to study early events related to hepatocarcinogenesis.

Hepatitis B virus (HBV) is one of the major etiological factors responsible for the development of hepatocellular carcinoma (HCC). We used a transgenic mouse, containing HBV sequences, as a model system to unravel the molecular mechanisms of hepatocarcinogenesis induced by HBV. We chose this animal model because it consistently develops liver cancer after intermediate steps that mimic the natural history of HBV infection in humans. In this study, we focus our attention on the early events leading to liver cancer. We compared the gene expression profile of 3-month-old transgenic mice with that of 3-month-old wild-type (wt) animals. In the transgenic mouse, microarray data analysis showed a total of 45 significantly differentially expressed genes, 25 highly expressed (fold change > or =2; P = 0.0025), and 20 downregulated (fold change < or =0.5; P = 0.0025). These genes belong to several different functional categories such as the regulation of immunological response, transcription, intracellular calcium ion mobilization, regulation of cell cycle and proliferation, NF-kappab signal transduction cascades, and apoptosis. In particular, the upregulation of the antiapoptotic gene NuprI and the downregulation of the proapoptotic gene Bnip3 were found. This observation was supported by an in vitro apoptosis assay that showed downregulation of apoptosis in hepatocytes of HBV transgenic mouse compared with wt mice treated with staurosporine. In conclusion, our experimental approach allowed identification of new genes modulated by HBV and showed that the apoptotic process was deregulated in transgenic mouse hepatocytes. These data shed light on one possible mechanism by which HBV induces hepatocarcinogenesis.

Animals↗
PubMedDate not supplied

Transcatheter arterial chemoembolization (TACE) in treatment of hepatocellular carcinoma.

BACKGROUND/AIMS: Substantial differences about the efficacy of transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma are reported in literature. This probably depends on the fact that in each single study, different patient selection criteria, type of epidemiological approach, end points adopted and kind of technical approach were used. This study aims to evaluate the efficacy of segmental transcatheter arterial chemoembolization in amelioring patient survival and to determine which patients might really benefit from this treatment. METHODOLOGY: To achieve our goals 193 consecutive patients (110 treated and 83 untreated) were studied. They were selected in the same period of time and matched as far as their demographic and clinical characteristics. RESULTS: Our results demonstrate that both in treated and control patients, Child class, alpha-fetoprotein and tumor diameter significantly influenced survival, resulting important prognostic factors. Transcatheter arterial chemoembolization significantly ameliorated survival in treated patients compared to controls (p < 0.0001). CONCLUSIONS: Transcatheter arterial chemoembolization significantly ameliorates survival in patients with hepatocellular carcinoma. However, the presence of large tumors producing high alpha-fetoprotein levels in patients with advanced Child class should discourage treatment.

Adult↗