Piergiorgio Duca

Accuracy of Ultrasonography, Spiral CT, Magnetic Resonance, and Alpha-Fetoprotein in Diagnosing Hepatocellular Carcinoma: A Systematic Review

BACKGROUND AND AIM:In patients with chronic liver disease, the accuracy of ultrasound scan (US), spiral computed tomography (CT), magnetic resonance imaging (MRI), and alpha-fetoprotein (AFP) in diagnosing hepatocellular carcinoma (HCC) has never been systematically assessed, and present systematic review was aimed at this issue.METHODS:Pertinent cross-sectional studies having as a reference standard pathological examinations of the explanted liver or resected segment(s), biopsies of focal lesion(s), and/or a period of follow-up, were identified using MEDLINE, EMBASE, Cochrane Library, and CancerLit. Pooled sensitivity, specificity, and likelihood ratios (LR) were calculated using the random effect model. Summary receiver operating characteristic (SROC) curve and predefined subgroup analyses were made when indicated.RESULTS:The pooled estimates of the 14 US studies were 60% (95% CI 44–76) for sensitivity, 97% (95% CI 95–98) for specificity, 18 (95% CI 8–37) for LR+, and 0.5 (95% CI 0.4–0.6) for LR−; for the 10 CT studies sensitivity was 68% (95% CI 55–80), specificity 93% (95% CI 89–96), LR+ 6 (95% CI 3–12),and LR− 0.4 (95% CI 0.3–0.6); for the nine MRI studies sensitivity was 81% (95% CI 70–91), specificity 85% (95%CI 77–93), LR+ 3.9 (95%CI 2–7), and LR− 0.3 (95% CI 0.2–0.5). The sensitivity and specificity of AFP varied widely, and this could not be entirely attributed to the threshold effect of the different cutoff levels used.CONCLUSIONS:US is highly specific but insufficiently sensitive to detect HCC in many cirrhotics or to support an effective surveillance program. The operative characteristics of CT are comparable, whereas MRI is more sensitive. High-quality prospective studies are needed to define the actual diagnostic role of AFP.

Mucosal Healing Predicts Late Outcomes After the First Course of Corticosteroids for Newly Diagnosed Ulcerative Colitis

BACKGROUND & AIMS It is uncertain whether mucosal healing after the first course of corticosteroids therapy predicts outcome in patients with ulcerative colitis (UC). We evaluated whether early clinical and endoscopic responses to this therapy are associated with late outcomes in UC. METHODS Patients with newly diagnosed UC who were prescribed corticosteroid therapy (n = 157) were followed up for 5 years. They were evaluated using clinical (Powel-Tuck [PT]) and endoscopic (Baron) indexes after 3 and 6 months, then every 6 months. Outcomes at month 3 (early response) were used to identify patients with complete (group A: PT, 0-1; Baron, 0), partial (group B: PT, 0-1; Baron, 1-3), or no response (group C: persistence of clinical and endoscopic activity). The association between early and late outcomes was assessed. RESULTS After 5 years, there were significant differences between complete and partial responders in the rates of hospitalization (25% in group A vs 48.7% in group B; P = .0152; odds ratio [OR], 2.85; 95% confidence interval [CI], 1.21-6.72), immunosuppression therapy (5% in group A vs 25.6% in group B; P = .0030; OR, 6.55; 95% CI, 1.67-25.67), colectomy (3.3% in group A vs 18.0% in group B; P = .0265; OR, 6.34; 95% CI, 1.24-32.37), and their combination (26.7% in group A vs 48.7% in group B; P = .0249; OR, 2.61; 95% CI, 1.12-6.11). After multivariate analysis, lack of mucosal healing was the only factor associated with negative outcomes at 5 years (immunosuppressors: hazard risk [HR], 10.581; 95% CI, 2.193-51.039; P = .0033; hospitalization: HR, 3.634; 95% CI, 1.556-8.485; P = .0029; colectomy: HR, 8.397; 95% CI, 1.278-55.186; P = .0268). CONCLUSIONS No mucosal healing after corticosteroid therapy is associated with a more aggressive disease course.

Maintenance Treatment With Azathioprine in Ulcerative Colitis: Outcome and Predictive Factors After Drug Withdrawal

OBJECTIVES:Whether the duration of maintenance treatment with azathioprine (AZA) affects the outcome of ulcerative colitis (UC) is unclear. We investigated clinical outcomes and any predictive factors after withdrawal of AZA in UC.METHODS:In this multicenter observational retrospective study, 127 Italian UC patients, who were in steroid-free remission at the time of withdrawal of AZA, were followed-up for a median of 55 months or until relapse. The frequency of clinical relapse or colectomy after AZA withdrawal was analyzed according to demographic, clinical, and endoscopic variables.RESULTS:After drug withdrawal, a third of the patients relapsed within 12 months, half within 2 years and two-thirds within 5 years. After multivariable analysis, predictors of relapse after drug withdrawal were lack of sustained remission during AZA maintenance (hazard ratio, HR 2.350, confidence interval, CI 95% 1.434–3.852; P=0.001), extensive colitis (HR 1.793, CI 95% 1.064–3.023, P=0.028 vs. left-sided colitis; HR 2.024, CI 95% 1.103–3.717, P=0.023 vs. distal colitis), and treatment duration, with short treatments (3–6 months) more disadvantaged than >48-month treatments (HR 2.783, CI 95% 1.267–6.114, P=0.008). Concomitant aminosalicylates were the only predictors of sustained remission during AZA therapy (P=0.009). The overall colectomy rate was 10%. Predictors of colectomy were drug-related toxicity as the cause of AZA withdrawal (P=0.041), no post-AZA drug therapy (P=0.031), and treatment duration (P<0.0005).CONCLUSIONS:Discontinuation of AZA while UC is in remission is associated with a high relapse rate. Disease extent, lack of sustained remission during AZA, and discontinuation due to toxicity could stratify relapse risk. Concomitant aminosalicylates were advantageous. Prospective randomized controlled trials are needed to confirm whether treatment duration is inversely associated with outcome.

Prevalence of Helicobacter pylori Infection and Related Upper Gastrointestinal Lesions in Patients with Inflammatory Bowel Diseases: A Cross-Sectional Study with Matching

BACKGROUND Although a reduced prevalence of Helicobacter pylori infection has been observed in inflammatory bowel disease (IBD) patients, the clinical significance of H. pylori infection in this setting remains unknown. The aim of this study was, therefore, to evaluate the prevalence of H. pylori infection in a large series of IBD patients and the frequency of gastroduodenal lesions in those who agreed to undergo upper GI endoscopy. METHODS Two hundred and sixteen consecutive IBD patients (123 with Crohns disease (CD) and 93 with ulcerative colitis (UC)) had their anti-H. pylori IgG titres measured. Two hundred and sixteen blood donors matched for age, sex, place of birth in Italy, and socioeconomic status served as controls. All patients were offered the possibility of undergoing endoscopy with antral and corpus biopsies regardless of their H. pylori status. RESULTS The overall seroprevalence of H. pylori infection was 48% in IBD patients versus 59% in the control group (P < 0.05), with a significantly lower frequency in CD versus UC patients (41% versus 56%). After adjustment for age, education, and socioeconomic status CD remained associated with a significantly lower risk of H. pylori infection. Previous therapy with sulphasalazine but not with 5-aminosalicylic acid or with steroids/immunosuppressants was associated with a reduced risk of H. pylori infection both in CD and UC patients. One hundred and eighty-nine patients (110 with CD and 79 with UC) underwent endoscopy; the prevalence of peptic ulcer was similar in both groups (5.5% in CD and 5.1% in UC patients); however, 11 more CD patients had gastroduodenal ulcers that were interpreted as CD-related; 7 of these patients had never had foregut symptoms. Two CD patients had granulomatous gastritis at histology, and another 16 patients with CD had H. pylori-negative gastritis. CONCLUSIONS IBD patients have a reduced prevalence of H. pylori infection as compared with matched healthy controls; this appears mostly attributable to a reduced frequency of H. pylori colonization in CD patients. Previous use of sulphasalazine is associated with a reduced risk of infection both in CD and UC patients. Of CD patients 10% have a gastroduodenal localization of their disease, which is often asymptomatic. Of CD patients 15% also have H. pylori-negative gastritis at histology.

Pathological findings in the central nervous system of AIDS patients on assumed antiretroviral therapeutic regimens: retrospective study of 1597 autopsies

Objective: To evaluate the prevalence of HIV-related central nervous system (CNS) lesions (HIV-encephalitis and/or HIV-leukoencephalopathy: HIV-E/L) with and without concomitant opportunistic diseases in a large autopsy series, and to correlate it with the changes in antiretroviral treatment that have occurred since the beginning of the epidemic. Methods: We reviewed 1597 consecutive autopsies of HIV-positive patients performed between 1984 and 2000, and divided into four time periods on the basis of the therapeutic regimens available: 1984–1987, no therapy; 1988–1994, monotherapy (zidovudine); 1995–1996, dual combination therapy with nucleoside reverse transcriptase inhibitors (NRTI); and 1997–2000, triple combination therapy including two NRTI and at least one protease inhibitor or non-NRTI. The data concerning the treatment actually received were collected only for the patients who died during the last period. The χ2-test was used to assess the significance of the differences in prevalence. Results: The CNS of 1210 patients (76%) was affected by opportunistic diseases, HIV-related lesions or both. The prevalence of HIV-related lesions in the four periods was respectively 54%, 32%, 18% and 15%; this reduction was statistically significant (P < 0.000001). During the last period, however, differences in HIV-E/L between treated and untreated patients were not statistically significant, although there were fewer than expected cases among the treated patients (six instead of eight) and more than expected among the untreated patients (10 instead of eight). Conclusions: These neuropathological data from a large autopsy series confirm clinical observations concerning the efficacy of antiretroviral treatment in reducing the frequency of HIV-related CNS lesions in AIDS patients.

Reproducibility of histologic classification of gastric cancer.

A panel review of histologic specimens was carried out as part of a multi-centre case-control study of gastric cancer (GC) and diet. Comparisons of diagnoses of 100 GCs by six pathologists revealed agreement in histologic classification for about 70-80% of the cancers. Concordance was somewhat higher when using the Lauren rather than the Ming or World Health Organization classification systems. Histologic types from reading biopsy tissue agreed with those derived from surgical specimens for 65-75% of the 100 tumours. Intra-observer agreement in histologic classification, assessed by repeat readings up to 3 years apart by one pathologist, was 95%. The findings indicate that, although overall concordance was good, it is important to standardise diagnoses in multi-centre epidemiologic studies of GC by histologic type.

Priorities for emergency department syncope research

STUDY OBJECTIVES There is limited evidence to guide the emergency department (ED) evaluation and management of syncope. The First International Workshop on Syncope Risk Stratification in the Emergency Department identified key research questions and methodological standards essential to advancing the science of ED-based syncope research. METHODS We recruited a multinational panel of syncope experts. A preconference survey identified research priorities, which were refined during and after the conference through an iterative review process. RESULTS There were 31 participants from 7 countries who represented 10 clinical and methodological specialties. High-priority research recommendations were organized around a conceptual model of ED decisionmaking for syncope, and they address definition, cohort selection, risk stratification, and management. CONCLUSION We convened a multispecialty group of syncope experts to identify the most pressing knowledge gaps and defined a high-priority research agenda to improve the care of patients with syncope in the ED.

Lopinavir/ritonavir treatment in HIV antiretroviral-experienced patients: evaluation of risk factors for liver enzyme elevation

To evaluate the risk factors for lopinavir/ritonavir (LPV/r)‐related liver enzyme elevation (LEE) in HIV antiretroviral‐experienced patients.

Genotyping of Pneumocystis jiroveci pneumonia in Italian AIDS patients. Clinical outcome is influenced by dihydropteroate synthase and not by internal transcribed spacer genotype.

Background:Two Pneumocystis jiroveci independent genomic regions, internal transcribed spacer (ITS) 1 and ITS2, and dihydropteroate synthase (DHPS) gene have been used for typing a cohort of HIV-infected Italian patients with P. jiroveci pneumonia (PcP). Methods:Bronchoalveolar lavage samples isolated from 207 HIV-infected adults were ITS and DHPS genotyped by DNA sequencing and by restriction fragment length polymorphism analysis, respectively. Mutant DHPS samples were cloned and ITS typed. Data on severity, treatment, and outcome of PcP were obtained by chart review. Results:High diversity with 46 different ITS genotypes was observed. At the DHPS locus, 9.1% of samples analyzed were found to be mutated. A correlation was observed between DHPS mutants and greater severity of PcP, as defined by higher lactate dehydrogenase (P = 0.015) and need for intubation (P = 0.002), and worse outcomes, as defined by failure of sulfa treatment (P = 0.04), death, and/or relapse of PcP (P = 0.008). There was a significant difference in ITS genotype patterns between DHPS wild-type and mutants (P = 0.028). Conclusions:The present data suggest the absence of a correlation between P. jiroveci ITS types and specific clinical characteristics. DHPS mutations correlate with possible failure of anti-P. jiroveci sulfa therapy, and a trend of association is shown between DHPS mutations and some clinical PcP features.

A pneumatic dilation strategy in achalasia: prospective outcome and effects on oesophageal motor function in the long term

Aliment Pharmacol Ther 31, 658–665