Evaluation of the intraepithelial papillary capillary loops in benign and malignant oral lesions by in vivo Virtual Chromoendoscopic Magnification: a preliminary study.

This preliminary study aims to establish the Virtual Chromoendoscopic Magnification (VCM) feasibility to visualize and distinguish the Intraepithelial Papillary Capillary Loops (IPCL) patterns of benign oral pathologies from malignant ones. Thirty-one consecutive subjects affected by oral lesions/pathologies underwent white light examination and VCM imaging by the Narrow Band Imaging System (Olympus Medical Systems Corp., Tokyo, Japan). A class system of four IPCL types corresponding to progressive vessel disarray was adopted. IPCL type IV were considered criterion of “malignancy”. A histopathological exam completed the diagnosis: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. IPCL patterns of benign oral entities ranged from types I to III. IPCL type IV was associated with malignancy in 4 out of 6 cases. Sensitivity, specificity, PPV, and NPV were 100%, 93%, 67% and 100%, respectively. This study preliminarily describes IPCL patterns of different oral mucosal diseases and confirms the association between IPCL IV and oral cancer.

A think tank of the Italian Society of Colorectal Surgery (SICCR) on the surgical treatment of inflammatory bowel disease using the Delphi method: ulcerative colitis.

The majority of patients suffering from ulcerative colitis (UC) are managed successfully with medical treatment, but a relevant number of them will still need surgery at some point in their life. Medical treatments and surgical techniques have changed dramatically in recent years, and available guidelines from relevant societies are rapidly evolving, providing UC experts with updated and valid practical recommendations. However, some aspects of the management of UC patients are still debated, and the application of guidelines in clinical practice may be suboptimal. The Italian Society of Colorectal Surgery (SICCR) sponsored the think tank in order to identify critical aspects of the surgical management of UC in Italy. The present paper reports the results of a think tank of Italian colorectal surgeons concerning surgery for UC and was not developed as an alternative to authoritative guidelines currently available. Members of the SICCR voted on several items proposed by the writing committee, based on evidence from the literature. The results are presented, focusing on points to be implemented. UC management relies on evaluations that need to be individualized, but points of major disagreement reported in this paper should be considered in order to develop strategies to improve the quality of the evidence and the application of guidelines in a clinical setting.

A think tank of the Italian society of colorectal surgery (SICCR) on the surgical treatment of inflammatory bowel disease using the Delphi method: Crohn's disease.

The management of Crohn's disease (CD) requires extensive expertise. Many treatment options are available, and surgery still plays a crucial role. In recent years, many medical societies have provided surgeons and gastroenterologists dealing with CD with authoritative guidelines. However, a certain degree of variation can be observed in these papers, and application of guidelines in clinical practice should be improved. The Italian society of colorectal surgery (SICCR) promoted the project reported here, which consists of a think tank of Italian colorectal surgeons to address the surgical aspects of CD management. Members of the society were invited to express their opinions on several items proposed by the writing committee, based on evidence available in the literature. The results are presented, focusing on relevant points. The present paper is not an alternative to available guidelines; rather, it offers a snapshot of the attitudes of SICCR surgeons about the surgical treatment of CD. The management of CD is, by necessity, patient-tailored, and it is based on clinical data and surgeon's preference, but the committee was able to identify some points of major disagreement and suggested strategies to improve quality of available data and acceptance of guidelines.

Helicobacter pylori infection but not small intestinal bacterial overgrowth may play a pathogenic role in rosacea.

BACKGROUND AND AIMS: Recent studies suggest a potential relationship between rosacea and Helicobacter pylori (H. pylori) infection or small intestinal bacterial overgrowth (SIBO), but there is no firm evidence of an association between rosacea and H. pylori infection or SIBO. We performed a prospective study to assess the prevalence of H. pylori infection and/or SIBO in patients with rosacea and evaluated the effect of H. pylori or SIBO eradication on rosacea. METHODS: We enrolled 90 patients with rosacea from January 2012 to January 2013 and a control group consisting of 90 patients referred to us because of mapping of nevi during the same period. We used the (13)C Urea Breath Test and H. pylori stool antigen (HpSA) test to assess H. pylori infection and the glucose breath test to assess SIBO. Patients infected by H. pylori were treated with clarithromycin-containing sequential therapy. Patients positive for SIBO were treated with rifaximin. RESULTS: We found that 44/90 (48.9%) patients with rosacea and 24/90 (26.7%) control subjects were infected with H. pylori (p = 0.003). Moreover, 9/90 (10%) patients with rosacea and 7/90 (7.8%) subjects in the control group had SIBO (p = 0.6). Within 10 weeks from the end of antibiotic therapy, the skin lesions of rosacea disappeared or decreased markedly in 35/36 (97.2%) patients after eradication of H. pylori and in 3/8 (37.5%) patients who did not eradicate the infection (p < 0.0001). Rosacea skin lesions decreased markedly in 6/7 (85.7%) after eradication of SIBO whereas of the two patients who did not eradicate SIBO, one (50%) showed an improvement in rosacea (p = 0.284). CONCLUSIONS: Prevalence of H. pylori infection was significantly higher in patients with rosacea than control group, whereas SIBO prevalence was comparable between the two groups. Eradication of H. pylori infection led to a significant improvement of skin symptoms in rosacea patients.

The course of inflammatory bowel disease during pregnancy and postpartum: a prospective European ECCO-EpiCom Study of 209 pregnant women.

BACKGROUND: The impact of pregnancy on the course of IBD is still controversial. AIM: To investigate the impact of pregnancy on IBD and to search for factors with potential impact on remission. METHODS: Pregnant IBD women from 12 European countries were enrolled between January 2003 and December 2006 and compared at conception (1:1) with nonpregnant IBD women. Data on disease course were prospectively collected at each trimester during pregnancy and in the postpartum (6 months) using a standardised questionnaire. RESULTS: A total of 209 pregnant IBD women were included: 92 with Crohn's disease (CD; median age 31 years, range 17-40) and 117 with ulcerative colitis (UC; median age 32 years, range 19-42). No statistically significant difference in disease course during pregnancy and postpartum was observed between pregnant and nonpregnant CD women. Longer disease duration in CD and immunosuppressive therapy were found to be risk factors for activity during pregnancy. Pregnant UC women were more likely than nonpregnant UC women to relapse both during pregnancy (RR 2.19; 95% CI: 1.25-3.97, 0.004) and postpartum (RR 6.22; 95% CI: 2.05-79.3, P = 0.0004). During pregnancy, relapse was mainly observed in the first (RR 8.80; 95% CI 2.05-79.3, P < 0.0004) and the second trimester (RR 2.84, 95% CI 1.2-7.45, P = 0.0098). CONCLUSIONS: Pregnant women with Crohn's disease had a similar disease course both during pregnancy and after delivery as the nonpregnant women. In contrast, pregnant women with ulcerative colitis were at higher risk of relapse during pregnancy and in the postpartum than nonpregnant ulcerative colitis women.

Effect of immunosuppressive therapy on patients with inflammatory bowel diseases and hepatitis B or C virus infection.

Viral hepatitis reactivation has been widely reported in patients undergoing immunosuppressive therapy; however, few data are available about the risk of HBV and HCV reactivation in patients with inflammatory bowel disease, receiving immunosuppressive drugs. The aim of our study was to assess the prevalence of HBV and HCV infection in a consecutive series of patients with inflammatory bowel disease and to value the effects of immunosuppressive therapy during the course of the infection. Retrospective observational multicenter study included all consecutive patients with inflammatory bowel disease who have attended seven Italian tertiary referral hospitals in the last decade. A total of 5096 patients were consecutively included: 2485 Crohn's disease and 2611 Ulcerative Colitis. 30.5% and 29.7% of the patients were investigated for HBV and HCV infection. A total of 30 HBsAg positive, 17 isolated anti-HBc and 60 anti-HCV-positive patients were identified. In all, 20 patients with HBV or HCV infection received immunosuppressive therapy (six HBsAg+; four isolated anti-HBc+ and 10 anti-HCV+). One of six patients showed HBsAg+ and one of four isolated anti-HBc+ experienced reactivation of hepatitis. Two of six HBsAg patients received prophylactic therapy with lamivudine. Only one of 10 anti-HCV+ patients showed mild increase in viral load and ALT elevation. Screening procedures for HBV and HCV infection at diagnosis have been underused in patients with inflammatory bowel disease. We confirm the role of immunosuppressive therapy in HBV reactivation, but the impact on clinical course seems to be less relevant than previous reported.

Pregnancy outcome in inflammatory bowel disease: prospective European case-control ECCO-EpiCom study, 2003-2006.

BACKGROUND: Inflammatory bowel disease (IBD) frequently affects women during their reproductive years. Pregnancy outcome in women with IBD is well described, particularly in retrospective studies. AIM: To evaluate the pregnancy outcome in patients with IBD in a prospective European multicentre case-control study. METHODS: Inflammatory bowel disease pregnant women from 12 European countries were enrolled between January 2003 and December 2006 and matched (1:1) to non-IBD pregnant controls by age at conception and number of previous pregnancies. Data on pregnancy and newborn outcome, disease activity and therapy were prospectively collected every third month using a standard questionnaire. Logistic regression analysis with odds ratio was used for statistical analyses. P value<0.05 was considered significant. RESULTS: A total of 332 pregnant women with IBD were included: 145 with Crohn's disease (CD) and 187 with ulcerative colitis (UC). Median age (range) at conception was 31 years (15-40) in CD and 31 (19-42) in UC patients. No statistically significant differences in frequency of abortions, preterm deliveries, caesarean sections, congenital abnormalities and birth weight were observed comparing CD and UC women with their non-IBD controls. In CD, older age was associated with congenital abnormalities and preterm delivery; smoking increased the risk of preterm delivery. For UC, older age and active disease were associated with low birth weight; while older age and combination therapy were risk factors for preterm delivery. CONCLUSION: In this prospective case-control study, women with either Crohn's disease or ulcerative colitis have a similar pregnancy outcome when compared with a population of non-inflammatory bowel disease pregnant women.

Infliximab in drug-naïve patients with failed ileorectal anastomosis for Crohn's disease: a new chance for sparing the rectum?

The aim of this intervention study is to determine whether long-term infliximab therapy can decrease the proctectomy rate in patients with failed total colectomy and ileorectal anastomosis (IRA) for Crohn's disease (CD). Twelve patients (5 females) - with a median age of 36.6 years (range 18-56 years), previously treated with IRA (5 in our institution and 7 referred) for colorectal and perianal CD (median Crohn's Disease Activity Index 334.5, range 220-426), with rectal disease recurrence requiring proctectomy, no responders to conventional therapy but infliximab-naïve - were treated with infliximab infusions (Remicade™ 5 mg/kg at 0, 2, 6 weeks and then every 8 weeks) to avoid proctectomy. The main outcome measures consisted of IRA preservation and bowel function at study end. Mortality and major adverse reactions have not been observed. At the time of the median follow-up (57.4 months, range 36-92), the rectum was preserved in 10 patients (83.3%). One patient underwent proctectomy 6 weeks after the beginning of the treatment for unresponsiveness to drugs and another after 26 weeks for rectal stenosis. Anorectal function (maximum tolerated volume: 239 ± 43 vs. 294 ± 36 ml) and quality of life (Inflammatory Bowel Disease Questionnaire score 89.2 ± 20.6 vs. 173.8 ± 31.9) improved, and the Wexner Continence score (4.4 ± 2.4 vs. 1.7 ± 1.0) and daily defecations (5.2 ± 1.03 vs. 2.7 ± 1.05) decreased in 10 patients. Our results, although preliminary, are encouraging and seem to justify a less aggressive approach in patients with rectal and perianal recurrence after IRA for CD.

[Non-alcoholic hepatic steatosis: the role of policosanols in associated hyperlipidemia]. / La steatosi epatica non alcolica: il ruolo dei policosanoli nelle iperlipemie associate.

AIM: The purpose of this study was to evaluate the efficacy of policosanols in the treatment of associated hyperlipidemia in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: We conducted a retrospective study on 52 patients with NAFLD. Pretreatment patients' data (total cholesterol, LDL cholesterol, triglycerides, ALT, and AST) were collected and analyzed. Furthermore, based on weight and height, we calculated the Body Mass Index (BMI) and, based on blood glucose and insulin levels, we estimated the Human Omeostatic Assesment Index (HOMA). After that, all patients were treated with a policosanols' supplement (Frilipid®) and a hypocaloric balanced diet, and then followed over time with quarterly inspections. We collected and analyzed data on three subsequent quarterly monitoring during treatment. RESULTS: The collected and analyzed data showed a significant reduction in total cholesterol, LDL cholesterol and HOMA index (P<0.002). It was also found a trend not statistically significant for a marked reduction in ALT, AST, triglycerides, and BMI. CONCLUSION: The use of policosanols is shown effective in the treatment of associated hyperlipidemia and insulin resistance in patients with fatty liver disease.

Breath test for differential diagnosis between small intestinal bacterial overgrowth and irritable bowel disease: an observation on non-absorbable antibiotics.

AIM: To estimate the prevalence of small intestine bacterial overgrowth (SIBO) among patients with an earlier diagnosis of irritable bowel disease (IBS) in our geographical area, and to collect information on the use of locally acting non-absorbable antibiotics in the management of SIBO. METHODS: A non-interventional study was conducted in 73 consecutive patients with a symptom-based diagnosis. RESULTS: When the patients underwent a "breath test", 33 (45.2%) showed the presence of a SIBO. After treatment with rifaximin 1,200 mg/d for seven days in 32 patients, 19 (59.4%) showed a negative "breath test" one week later as well as a significant reduction of symptoms, thus confirming the relationship between SIBO and many of the symptoms claimed by patients. In the other 13 patients, "breath test" remained positive, and a further cycle of treatment with ciprofloxacin 500 mg/d was given for 7 additional days, resulting in a negative "breath test" in one patient only. CONCLUSION: (1) about half of the patients with a symptomatic diagnosis of IBS have actually SIBO, which is responsible for most of the symptoms attributed to IBS; (2) only a "breath test" with lactulose (or with glucose in subjects with an intolerance to lactose) can provide a differential diagnosis between IBS and SIBO, with almost identical symptoms; and (3) the use of non-absorbable antibiotics may be useful to reduce the degree of SIBO and related symptoms; it must be accompanied, however, by the correction of the wrong alimentary habits underlying SIBO.

Infliximab in severe ulcerative colitis: short-term results of different infusion regimens and long-term follow-up.

BACKGROUND: Severe ulcerative colitis is a life-threatening disorder, despite i.v. glucocorticoids treatment. Infliximab has been proposed as a safe rescue therapy. AIM: To evaluate short- and long-term effectiveness and safety of infliximab in severe refractory ulcerative colitis. METHODS: Eighty-three patients with severe ulcerative colitis (i.v. glucocorticoids treatment-refractory) were treated with infliximab in 10 Italian Gastroenterology Units. Patients underwent one or more infusions according to the choice of treating physicians. Short-term outcome was colectomy/death 2 months after the first infusion. Long-term outcome was survival free from colectomy. Safety data were recorded. RESULTS: Twelve patients (15%) underwent colectomy within 2 months. One died of Legionella pneumophila infection 12 days after infliximab. Early colectomy rates were higher in patients receiving one infusion (9/26), compared with those receiving two/more infusions (3/57, P = 0.001, OR = 9.53). Seventy patients who survived colectomy and did not experience any fatal complications were followed-up for a median time of 23 months; 58 patients avoided colectomy during the follow-up. Forty-two patients were maintained on immunosuppressive drugs. No clinical features were associated with outcomes. CONCLUSIONS: Infliximab is an effective and relatively safe therapy to avoid colectomy and maintain long-term remission for patients with severe refractory ulcerative colitis. In the short term, two or more infusions seem to be more effective than one single infusion.

Increased risk of breast cancer in first-degree relatives of Crohn's disease patients. An IG-IBD study.

BACKGROUND: Increased rates of colorectal cancer have been reported in patients with ulcerative colitis as well as with Crohn's colitis. This risk could be the result of shared genetic susceptibility and could be co-inherited rather than being just secondary to a long-standing, extensive mucosal inflammation. AIM: To assess the prevalence of all malignancies in first-degree relatives of Crohn's disease patients in order to establish whether any association exists. PATIENTS AND METHODS: A total of 632 outpatients with a diagnosis of Crohn's disease and 632 control subjects were recruited. Information concerning the presence of malignancies was collected in 3,292 first-degree relatives of Crohn's disease patients and in 3,303 first-degree relatives of controls. RESULTS: Two hundred and fourteen (6.5%) subjects were found to be affected by malignancy in the first-degree relatives of Crohn's disease patients and 180 (5.5%) in the first-degree relatives of controls. Forty-seven (7.4%) of Crohn's disease patients had a first-degree relative with IBD, but none of them had cancer. The frequency of extra-intestinal malignancies was higher in first-degree relatives of Crohn's disease patients than in those of controls (p=0.011). Frequency of breast cancer in female relatives of Crohn's disease patients, mainly in mothers, was two-fold higher than that in controls (0.91% versus 0.42%; odds ratio=2.16; 95% confidence interval=1.14-4.08; p=0.015). The presence of breast cancer showed no association with any specific phenotype of disease in Crohn's patients. CONCLUSIONS: These results did not corroborate the hypothesis about a common genetic susceptibility between Crohn's disease and colorectal cancer. An unexpected finding was the more frequent occurrence of extra-digestive malignancies. The prevalence of breast cancer in first-degree relatives of Crohn's disease patients, in particular the mothers, was more than double than in those of controls. This association, if confirmed, would suggest that there may exist common genetic and/or environmental factors for Crohn's disease and breast cancer.

Infliximab and newly diagnosed neoplasia in Crohn's disease: a multicentre matched pair study.

BACKGROUND AND AIMS: The widespread use of anti-tumour necrosis factor alpha antibody (Infliximab) in Crohn's disease (CD) raises concerns about a possible cancer risk in the long term. In a matched pair study, we assessed whether Infliximab is associated with an increased risk of neoplasia. METHODS: In a multicentre matched pair study, 404 CD patients treated with Infliximab (CD-IFX) were matched with 404 CD patients who had never received Infliximab (CD-C). Cases and controls were matched for sex, age (+/-5 years), site of CD, age at diagnosis (+/-5 years), immunosuppressant use, and follow up. New diagnoses of neoplasia from April 1999 to October 2004 were recorded. RESULTS: Among the 404 CD-IFX, neoplasia was diagnosed in nine patients (2.22%) while among the 404 CD-C, seven patients developed neoplasia (1.73%) (odds ratio 1.33 (95% confidence interval 0.46-3.84); p=0.40). The survival curve adjusted for patient year of follow up showed no differences between CD-IFX and CD-C (p=0.90; log rank test). In the CD-IFX group, there was one cholangiocarcinoma, three breast cancers, one skin cancer, one leukaemia, one laryngeal cancer, and two anal carcinomas. Among the 7/404 (1.73%) CD-C, there were three intestinal adenocarcinomas (two caecum, one rectum), one basalioma, one spinalioma, one non-Hodgkin's lymphoma, and one breast cancer. Age at diagnosis of neoplasia did not differ between groups (CD-IFX v CD-C: median 50 (range 40-70 years) v 45 (27-72); p=0.50). CONCLUSION: In our multicentre matched pair study, the frequency of a new diagnosis of neoplasia in CD patients treated with Infliximab was comparable with CD patients who had never received Infliximab.

Different phenotypes in Muir-Torre syndrome: clinical and biomolecular characterization in two Italian families.

The Muir-Torre syndrome (MTS) is an autosomal dominant genodermatosis characterized by the presence of sebaceous gland tumours, with or without keratoacanthomas, associated with visceral malignancies. We describe and characterize two families in which the ample phenotypic variability of MTS was evident. After clinical evaluation, the skin and visceral tumours of one member of a family with 'classic' MTS and one member of a family with a 'peculiar' MTS phenotype without sebaceous lesions, but with only multiple keratoacanthomas, were analysed for microsatellite instability (MSI) and by immunohistochemistry. Tumours of both individuals showed MSI, with a concomitant lack of MSH2 immunostaining in all evaluated skin and visceral lesions; moreover, in the proband of family 2 a constitutional mutation (C-->T substitution leading to a stop codon) in the MSH2 gene was identified. We conclude that the diagnosis of MTS, which is mainly clinical, should take into account an ample phenotypic variability, which includes both cases with typical cancer aggregation in families and cases characterized by the association of visceral malignancies with multiple keratoacanthomas (without sebaceous lesions), without an apparent family history of cancer.

Infliximab in the treatment of Crohn's disease: predictors of response in an Italian multicentric open study.

BACKGROUND: Almost 20% of patients with active Crohn's disease are refractory to conventional therapy. Infliximab is a treatment of proven efficacy in this group of patients and it is not clear which variables predict a good response. AIMS.: To evaluate the role of infliximab looking at the predictors of response in a large series of patients with Crohn's disease. PATIENTS AND METHODS: Five hundred and seventy-three patients with luminal refractory Crohn's disease (Crohn's Disease Activity Index (CDAI)>220-400) (312 patients) or with fistulising disease (190 patients) or both of them (71 patients) were treated with a dose of 5 mg/kg in 12 Italian referral centres. The primary endpoints of the study were clinical response and clinical remission for luminal refractory and fistulising disease. We evaluated at univariable and multivariable analysis the following variables: number of infusions, sex, age at diagnosis, smoking habit, site of disease, previous surgery, extraintestinal manifestations and concomitant therapies, and type of fistulas. RESULTS: Patients with luminal refractory disease: 322 patients (84.1%) had a clinical response and 228 (59.5%) reached clinical remission. Patients with fistulising disease: 187 patients (72%) had a reduction of 50% of the number of fistulas and in 107 (41%) a total closure of fistulas was observed. For luminal disease, single infusion (OR 0.49, 95% CI 0.28-0.86) and previous surgery (OR 0.53, 95% CI 0.30-0.93) predicted a worse response for fistulising disease. Other fistulas responded worse than perianal fistulas (OR 0.57, 95% CI 0.303-1.097). CONCLUSION: In Crohn's disease infliximab is effective in luminal refractory and in fistulising disease. A single infusion and previous surgery predicted a worse response in luminal disease whereas perianal fistulas predicted a better response than other type of fistulas.