Fecal calprotectin in clinical practice: a noninvasive screening tool for patients with chronic diarrhea.

BACKGROUND: Surrogate markers of colorectal inflammation are increasingly being recognized as important in differentiating organic from functional intestinal disorders. Fecal calprotectin (FC) can be easily measured in the stool, being released by leukocytes in inflammatory conditions. AIM: We evaluated FC as an index of inflammation in consecutive outpatients referred for colonoscopy for chronic, nonbloody diarrhea. METHODS: Stool specimens of 346 outpatients with chronic, nonbloody diarrhea, referred for colonoscopy, were measured for FC levels. The proportion of patients correctly diagnosed with the test and the relationship with endoscopic and histologic findings were measured. RESULTS: Abnormal endoscopic findings were detected in 104 patients (30.1%). Histologic findings included 142 patients (41.0%) with inflammation and 204 (59.0%) without inflammation. Fecal excretion of calprotectin significantly correlated with the finding of inflammation at endoscopy and histology (P<0.0001). When 150 mcg/g of stool was used as the upper reference limit, FC showed 75.4% sensitivity and 88.3% specificity, with 81.7% positive and 83.7% negative predictive values for histologic inflammation. CONCLUSIONS: In outpatients referred for colonoscopy a measurement of FC is accurate to identify those with histologic inflammation. Assay of FC may be a reliable and noninvasive screening tool to identify inflammatory causes of chronic, nonbloody diarrhea.

Fluoroquinolone-induced liver injury: three new cases and a review of the literature.

PURPOSE: Fluoroquinolones are popular and widely used in primary care and hospital settings. Premarketing studies showed a favourable side-effect profile. However, significant morbidity and the need for liver transplantation for acute liver failure have been reported. We reviewed the available data on liver damage linked to fluoroquinolones. METHODS: A systematic search of case reports on the MEDLINE database encompassing the years 2000-2011 was carried out. Additional references were found by a manual search of the retrieved paper. We also describe three new cases of hepatotoxicity attributable to fluoroquinolones seen at our Unit. RESULTS: Thirty-five cases were retrieved from MEDLINE (51.4% male). According to the RUCAM scale, liver injury was classified as hepatocellular (51.4%), cholestatic (28.6%) or mixed (20.0%). Older age (≥ 65 years) was present in 42.8%. The time between initiation of treatment and hepatic injury ranged from 1 to 39 days (median 8 days). According to the RUCAM score, our cases were classified to be "highly probable" or "probable". Only one patient underwent liver biopsy, which showed the features of liver damage linked to drug exposure. Liver enzymes from all patients return to normal range within 4 weeks of withdrawal. Only one patient showed a renal failure, associated with liver injury, with a need for haemodialysis for 3 weeks. CONCLUSIONS: Fluoroquinolones are substantially safe antibiotics. Although fluoroquinolone-related hepatic injury occurs infrequently, its consequences can be severe. Patients should also be cautioned to avoid re-exposure to other members of the fluoroquinolone class.

Clinical features and outcomes of patients with drug-induced autoimmune hepatitis: a retrospective cohort study.

BACKGROUND: Drugs and herbal products can induce autoimmune hepatitis. We assessed frequency and clinical outcomes of patients suffering from drug-induced autoimmune hepatitis. METHODS: All patients with drug-induced liver injury admitted between 2000 and 2011 were retrospectively studied. Diagnoses of drug-induced autoimmune hepatitis and idiopathic autoimmune hepatitis were made according to simplified criteria. After discharge, all patients had regular follow-up and were contacted to update outcomes. RESULTS: Among 10,270 in-hospital patients, 136 (1.3%) were diagnosed with drug-induced liver injury. Among them, 12 (8.8%) were diagnosed as drug-induced autoimmune hepatitis (41.7% males, age range 17-73); 8 (66.7%) were with jaundice at admission. Liver biopsies showed a pattern compatible with drug-induced autoimmune hepatitis, featured by severe portal inflammation and lymphoplasmacytic infiltrate. Drug-induced autoimmune hepatitis group had a shorter duration of drug intake, and higher values of transaminases and gamma globulins. All patients received immunosuppressive therapy with subsequent clinical remission, and five achieved a steroid-free long-term remission. CONCLUSIONS: A diagnosis of drug-induced autoimmune hepatitis was quite rare in our cohort, and clinical pattern was similar to idiopathic autoimmune hepatitis. Severe portal inflammation, prominent portal-plasma cells, rosette formation and severe focal necrosis were significantly more frequent in drug-induced autoimmune hepatitis as compared to drug-induced liver injury.

Treatment of hepatocellular carcinoma: present and future.

Hepatocellular carcinoma is a major health problem. It is the sixth most common cancer worldwide and the third most common cause of cancer-related death. Despite the availability of several treatment opportunities, diagnosis is still made in an advanced phase, limiting application of most therapeutic choices that currently are based on the Barcelona Clinic Cancer Liver Classification and include surgical resection, orthotopic liver transplantation and ablative methods for very early and early disease, arterial chemoembolization for intermediate stages and systemic therapy with sorafenib for advanced hepatocellular carcinoma. Thanks to novel advancements in knowledge of molecular pathogenesis of this tumor, many new systemic agents and locoregional treatments are in different stages of clinical development and they represent an important promise of further improvements in patients' survival.

Survival of patients with hepatocellular carcinoma (HCC) treated by percutaneous radio-frequency ablation (RFA) is affected by complete radiological response.

BACKGROUND: Radio-frequency ablation (RFA) has been employed in the treatment of Barcelona Clinic Liver Cancer (BCLC) early stage hepatocellular carcinoma (HCC) as curative treatments. AIM: To assess the effectiveness and the safety of RFA in patients with early HCC and compensated cirrhosis. METHODS: A cohort of 151 consecutive patients with early stage HCC (122 Child-Pugh class A and 29 class B patients) treated with RFA were enrolled. Clinical, laboratory and radiological follow-up data were collected from the time of first RFA. A single lesion was observed in 113/151 (74.8%), two lesions in 32/151 (21.2%), and three lesions in 6/151 (4%) of patients. RESULTS: The overall survival rates were 94%, 80%, 64%, 49%, and 41% at 12, 24, 36, 48 and 60 months, respectively. Complete response (CR) at 1 month (p<0.0001) and serum albumin levels (p = 0.0004) were the only variables indipendently linked to survival by multivariate Cox model. By multivariate analysis, tumor size (p = 0.01) is the only variable associated with an increased likehood of CR. The proportion of major complications after treatment was 4%. CONCLUSIONS: RFA is safe and effective for managing HCC with cirrhosis, especially for patients with HCC ≤3 cm and higher baseline albumin levels. Complete response after RFA significantly increases survival.

Serology in adults with celiac disease: limited accuracy in patients with mild histological lesions.

Celiac disease (CD) is a gluten-triggered enteropathy, presenting with insidious clinical patterns. It can occasionally be diagnosed in asymptomatic subjects. Our aim was to define the relationship among symptoms at diagnosis, serological markers [tissue transglutaminase antibodies (tTGA), anti-endomysium antibodies (EMA) anti-actin antibodies (AAA)] and degree of mucosal damage. A total of 68 consecutive adult patients with CD were enrolled. Intestinal biopsies were scored according to the Marsh classification modified by Oberhuber: I-II minimal lesions or absent villous atrophy; IIIA partial villous atrophy; IIIB-C total villous atrophy (TVA). HLA-typing was done for all patients. No association between clinical presentation and severity of mucosal damage was found. Presence of EMA or tTGA was significantly associated with more severe mucosal damage (P < 0.001). Of 12 patients, 11 with AAA were also positive for TVA. The severity of mucosal damage is the main factor governing the detectability of serological markers of CD. The sensitivity of serological testing is questionable in patients with minimal lesions.

5-HT1A/1B, 5-HT6, and 5-HT7 serotonergic receptors recruitment in tonic-clonic seizure-induced antinociception: role of dorsal raphe nucleus.

Pharmacological studies have been focused on the involvement of different neural pathways in the organization of antinociception that follows tonic-clonic seizures, including 5-hydroxytryptamine (5-HT)-, norepinephrine-, acetylcholine- and endogenous opioid peptide-mediated mechanisms, giving rise to more in-depth comprehension of this interesting post-ictal antinociceptive phenomenon. The present work investigated the involvement of 5-HT(1A/1B), 5-HT(6), and 5-HT(7) serotonergic receptors through peripheral pretreatment with methiothepin at doses of 0.5, 1.0, 2.0 and 3.0 mg/kg in the organization of the post-ictal antinociception elicited by pharmacologically (with pentylenetetrazole at 64 mg/kg)-induced tonic-clonic seizures. Methiothepin at 1.0 mg/kg blocked the post-ictal antinociception recorded after the end of seizures, whereas doses of 2.0 and 3.0 mg/kg potentiated the post-ictal antinociception. The nociceptive thresholds were kept higher than those of the control group. However, when the same 5-hydroxytryptamine receptors antagonist was microinjected (at 1.0, 3.0 and 5.0 microg/0.2 microL) in the dorsal raphe nucleus, a mesencephalic structure rich in serotonergic neurons and 5-HT receptors, the post-ictal hypo-analgesia was consistently antagonized. The present findings suggest a dual effect of methiothepin, characterized by a disinhibitory effect on the post-ictal antinociception when peripherally administered (possibly due to an antagonism of pre-synaptic 5-HT(1A) serotonergic autoreceptors in the pain endogenous inhibitory system) and an inhibitory effect (possibly due to a DRN post-synaptic 5-HT(1B), 5-HT(6), and 5-HT(7) serotonergic receptors blockade) when centrally administered. The present data also suggest that serotonin-mediated mechanisms of the dorsal raphe nucleus exert a key-role in the modulation of the post-ictal antinociception.