A. D'Arienzo

Cigarette smoking and appendectomy are risk factors for extraintestinal manifestations in ulcerative colitis.

OBJECTIVE:Two common factors, cigarette smoking and appendectomy, have been found to play a role in ulcerative colitis (UC). Data on their role in the development of extraintestinal manifestations (EIM) are scarce.METHODS:The relationship between cigarette smoking, appendectomy, and EIM was examined in a prospective study involving 535 (M/F = 319/216) consecutive UC patients followed up for 18 yr. We considered the major EIM: seronegative spondyloarthropathy, pyoderma gangrenosum/erythema nodosum, acute anterior uveitis, and primary sclerosing cholangitis. We excluded patients with a history of EIM or those colectomized before study entry, ex-smokers, and those who started to smoke during the course of UC.RESULTS:In UC patients, seronegative spondyloarthropathy and dermatologic complications were found increased in smokers (p< 0.0001; p= 0.001) or in subjects with appendectomy (p= 0.0003; p= 0.02), while acute anterior uveitis and primary sclerosing cholangitis did not differ. The Kaplan-Meier analysis showed 18-yr rates for EIM of 71% in smokers and 45% in nonsmokers (log-rank test, p= 0.0001), and of 85% in patients with appendectomy and 48% in those without (p= 0.0001). Cox proportional-hazard model showed that cigarette smoking and appendectomy are independent factors promoting EIM. In smokers with appendectomy the adjusted hazard ratio (3.197, 95% CI 1.529–6.684) was higher than in patients with appendectomy alone (2.617, 95% CI 1.542–4.442) or smoking alone (1.947, 95% CI 1.317–2.879).CONCLUSIONS:In UC patients, appendectomy and cigarette smoking are prognostic factors for the development of EIM. The unfavorable effect of cigarette smoking on EIM is additive to that of appendectomy.

Interactions between metabolic disorders (diabetes, gallstones, and dyslipidaemial and the progression of chronic hepatitis C virus infection to cirrhosis and hepatocellular carcinoma. A cross-sectional multicentre survey

BACKGROUND Diabetes, gallstones and dyslipidaemia are widespread, metabolically related, disorders that can affect the liver, often in a clinically silent fashion. AIM To investigate whether the presence of these disorders may worsen chronic viral disease by inducing additional liver damage, revealed by variations in serum increases of aminotransferase, alkaline phosphatase and gamma-glutamyl-transpeptidase activities. PATIENTS AND METHODS This retrospective, cross-sectional study involved 1,195 patients with chronic hepatitis C virus infection: 47.2% chronic hepatitis, 45.2% cirrhosis, and 7.6% hepatocellular carcinoma. 14.9% of patients had enzymatic cholestasis, defined as combined increase of alkaline phosphatase and gamma-glutamyl-transpeptidase. A Log-linear statistical model was applied to the following variables: stages of liver disease, diabetes, cholelithiasis, hypertriglyceridaemia, hypercholesterolaemia, and enzymatic cholestasis. RESULTS Log-linear analysis, applied to categorical variables, revealed, for the first time, a three-way interaction between the stages of chronic liver disease, diabetes, and enzymatic cholestasis. Two-way interactions demonstrated that liver disease stages correlated directly to the prevalence of cholelithiasis and inversely to hypercholesterolaemia. Irrespective of the liver disease stage, hypertriglyceridaemia correlated to hypercholesterolaemia. CONCLUSIONS This study discloses a synergistic liver damaging effect of diabetes and hepatitis C virus. The three-way interaction obtained by our analysis suggests that diabetes is a risk factor for the progression of viral liver disease and that it contributes to disease evolution, at least in part, by induction of cholestasis.

Magnetic resonance imaging with ferumoxil, a negative superparamagnetic oral contrast agent, in the evaluation of ulcerative colitis.

OBJECTIVE:The introduction of new oral contrast agents that enhance image quality has increased the importance of magnetic resonance imaging (MRI) in the management of ulcerative colitis. The aim of our study was to investigate the usefulness of a new negative superparamagnetic oral contrast (ferumoxil) alone or in association with gadolinium i.v. in the assessment of the disease.METHODS:Twenty-eight patients with clinically active ulcerative colitis and 10 control subjects entered the study. In each patient a clinical, endoscopic, histological, and MRI evaluation was performed. In particular, in 14 patients affected by ulcerative colitis (group A) and in five controls, magnetic resonance images were acquired 1 h after the oral administration of 900 ml of ferumoxil, while the remaining 14 patients (group B) and five controls were submitted to double-contrast MRI (ferumoxil and gadolinium). In both groups, wall thickness, length of affected bowel segments, and, in group B, also percent contrast enhancement were calculated.RESULTS:The comparison of endoscopic and MRI extent of disease was statistically significant. Wall thickness and, in group B, also percent contrast enhancement were significantly correlated with clinical and endoscopic activities. In each group wall thickness was significantly different in the activity phases of the disease.CONCLUSIONS:MRI with negative superparamagnetic oral contrast is comparable to endoscopy in the assessment of ulcerative colitis. The double-contrast imaging does not provide more information than single oral contrast, so we concluded that the latter is preferable in the follow-up of the disease and in patients unable or with a poor compliance to undergo endoscopy.

Colonoscopic removal of a polypoid arteriovenous malformation.

A 53-year-old male presenting with a 3-month history of intermittent mild rectal bleeding was found, on double contrast barium enema, to have a large polyp on a long stalk in the sigmoid colon. Large bowel endoscopy confirmed the presence of a 2 cm pedunculated polyp which was removed using a diathermic snare, with slight bleeding following the procedure that did not require endoscopic haemostasis. Only after histologic examination was the polyp shown to be a colonic arteriovenous malformation. Endoscopically, arteriovenous malformations generally appear as flat or elevated bright red lesions. A pedunculated polypoid appearance is extremely uncommon. In this case, no gastrointestinal bleeding or polypoid recurrence was observed during the 12 months of clinical and endoscopic follow-up.

Preventive and Therapeutic Effects of Lactobacillus Paracasei B21060–Based Synbiotic Treatment on Gut Inflammation and Barrier Integrity in Colitic Mice

BACKGROUND Although gut microbiota perturbation is recognized as a main contributing factor to the pathogenesis of inflammatory bowel disease, synbiotic therapies, as prevention or treatment, have remained overlooked. OBJECTIVE To verify whether Lactobacillus paracasei B21060-based synbiotic therapy could prevent or repair colon damage in a mouse model of colitis, we performed treatments before and after colitis induction. METHODS The experimental study lasted 19 d. Experimental colitis was induced in BALB/c mice by giving them dextran sodium sulfate (DSS, 2.5%) in drinking water (days 7-12) followed by DSS-free water (days 13-19) (DSS group). L. paracasei B21060 (2.5 × 10(7) bacteria/10 g body weight) was orally administered 7 d before DSS [synbiotic as preventive treatment (P-SYN) group] or 2 d after DSS [synbiotic as therapeutic treatment (T-SYN) group] until day 19. Another group was not treated with DSS or synbiotic and was given tap water (control group), for a total of 4 groups. RESULTS Compared with the DSS group, both synbiotic-treated groups had significantly less pronounced weight loss and colon damage. Consistently, mRNA levels of chemokine (C-C motif) ligand 5 in the colon were reduced in both P-SYN and T-SYN mice compared with the DSS group (51%, P < 0.05 and 72%, P < 0.001, respectively). In the P-SYN and T-SYN groups, neutrophil elastase transcription was also reduced (51%, P < 0.01 and 59%, P < 0.001, respectively). Accordingly, oxidative/nitrosative stress was lower in P-SYN and T-SYN mice than in the DSS group. In P-SYN and T-SYN mice, colonic gene expression of tumor necrosis factor (47%, P < 0.01 and 61%, P < 0.001, respectively) and prostaglandin-endoperoxide synthase 2 (45%, P < 0.01 and 35%, P < 0.05, respectively) was lower, whereas interleukin 10 mRNA was doubled compared with the DSS group (both P < 0.5). Remarkably, epithelial barrier integrity (zonulin and occludin) and gut protection (β-defensin and mucin expression) were completely restored in P-SYN and T-SYN mice. CONCLUSIONS Our data highlight the beneficial effects of this synbiotic formulation in acutely colitic mice, suggesting that it may have therapeutic and possibly preventive efficacy in human colitis.

The prognostic value, in active ulcerative colitis, of an increased intensity of colonic perivisceral fat signal on magnetic resonance imaging with ferumoxil

OBJECTIVE:In active ulcerative colitis (UC), magnetic resonance imaging (MRI) with ferumoxil, a superparamagnetic oral contrast agent, accurately evaluates, in our experience, the increased wall thickness and frequently shows a stronger perivisceral fat signal intensity (PFSI). The aim of our study was to evaluate the clinical significance of these MRI findings in active UC.METHODS:Twenty-four consecutive patients affected by moderate pancolitis were enrolled. At entry, each patient underwent MRI with ferumoxil to evaluate wall thickness and PFSI. Two groups of patients were individuated: group A (increased PFSI) and group B (normal PFSI). After obtaining remission, the number of relapses and, at each flare-up, the clinical activity index (CAI) were evaluated in all patients in a 2-yr follow-up period. The mean CAI was calculated at the end of the follow-up in each patient. Where there was colectomy, a complete histological examination of the colon was performed.RESULTS:PFSI was increased in 16 patients (group A) and was normal in the remainder (group B). There was a significant difference of wall thickness, number of relapses/yr, and mean CAI between the two groups of patients. No difference was observed with regard the duration of disease. Six patients of group A and no patient of group B underwent colectomy. The histological evaluation showed an increased thickness of the entire colonic wall with significant changes of the perivisceral fat structures.CONCLUSIONS:An increased PFSI on MRI identifies a group of UC patients with an increased wall thickness, significantly higher than that observed in patients with normal PFSI and seems to be related to a poor prognosis.

Per-rectal portal scintigraphy with technetium-99m pertechnetate for the early diagnosis of cirrhosis in patients with chronic hepatitis

We evaluated the role of per-rectal portal scintigraphy with 99m-technetium pertechnetate (99m-Tc test) for early diagnosis of cirrhosis. Forty patients with biochemical evidence of chronic liver disease were studied. Laparobiopsy documented chronic active hepatitis (CAH) without cirrhosis in 22 of the patients and CAH with cirrhosis (CAHc) in 18 patients. Clinical or laboratory findings could not differentiate between CAH and CAHc. Twelve healthy volunteers served as controls. The results, expressed as shunt index (SI), i.e., the ratio between heart radioactivity and the sum of heart and liver radioactivity in the first 30 s of observation, were: controls 5.66 +/- 1.66, CAH 15.27 +/- 2.83 and CAHc 24.88 +/- 3.95. A significant difference between the mean SI values in the three groups studied (F = 142.71, p less than 0.0001) was observed. At values less than 17, our test showed a predictivity of 100% for cirrhosis exclusion, while at values higher than 19 the predictive positive value for a diagnosis of cirrhosis was 100%. Invasive diagnostic procedures should be performed only in patients with SI values between 17-19.

An evaluation of urinaryd-glucaric acid excretion during acute hepatitis in man

The excretion of urinaryd-glucaric acid (d-GA), one of the final metabolites of glucuronic acid was determined in 49 patients with acute hepatitis. A 3.7-fold increase ofd-GA was found at an early stage of the disease (37.13 μmol/24hr±3.08se vs 9.91 μmol/24hr±1.18se in normal controls), when serum transaminases and bilirubin were very high (SGOT 589 I.U.±41se; SGPT 954 I.U.±61se; serum bilirubin 8.41 mg/100 ml±0.76se). A lower but significantly elevatedd-GA excretion was also found in the recovery phase of hepatitis at a time when both serum transaminases and bilirubin were considerably reduced (SGOT 89 I.U.±14se; SGPT 185 I.U.±30se; serum bilirubin 1.05 mg/100 ml±0.20se). Urinary glucuronides and free glucuronic acid, measured as total glucuronic acid, were also significantly increased in early hepatitis (1164 mg/24hr±54se vs 782 mg/24hr±84se in normal subjects), but no correlation was found withd-GA excretion. A short treatment with phenobarbital which led to a 3-fold increase ofd-glucaric acid in 12 normal subjects did not cause any further change in the patients with early acute hepatitis. While the mechanism of the urinaryd-GA increase in hepatitis still remains underfined, the findings of this study support the conclusion that its increase may not reflect an induction of liver microsomal enzymes.