Lorenzo Oliva

Smoking habits and recurrence in Crohn's disease

BACKGROUND/AIMS Smoking may be a risk factor for surgical recurrence of Crohns disease. However, other variables associated with recurrence could be confounding factors for smoking. The aim of this study was to evaluate the role of smoking as an independent predictor of clinical, surgical, and endoscopic recurrence. METHODS In a series of 182 patients who underwent surgery for Crohns disease, a multivariate analysis was performed that included all of the significant variables associated with recurrence: sex, age at diagnosis, time between onset of symptoms and surgery, site of disease, indication for surgery, extent of disease, extraintestinal manifestation, and smoking habit. RESULTS Independent predictors of clinical recurrence by the Cox proportional hazard model were smoking (hazard ratio, 1.46; 95% confidence interval [CI], 1.1-1.8), extraintestinal manifestations (hazard ratio, 1.61; 95% CI, 1.0-2.5), and extent of disease (hazard ratio, 1.57; 95% CI, 1.0-2.4). Smoking was the only significant predictor of surgical recurrence (hazard ratio, 2.0; 95% CI, 1.2-2.3). For endoscopic recurrence, logistic regression showed that smoking (odds ratio, 2.2; 95% CI, 1.2-3.8) and extent of disease (odds ratio, 2.6; 95% CI, 1.0-6.7) were predictive factors of recurrence. CONCLUSIONS Smoking is an independent risk factor for clinical, surgical, and endoscopic recurrence in Crohns disease.

Prevalence of Cytomegalovirus Infection in Severe Refractory Ulcerative and Crohn's Colitis

Abstract OBJECTIVES Cytomegalovirus infection has been reported as a cause of refractory inflammatory bowel disease, but no data are available on its prevalence in severe colitis. The aim of this study was to evaluate the prevalence and outcome of cytomegalovirus infection in a consecutive series of patients with severe steroid refractory colitis admitted to our department from 1997 to 1999. METHODS: Among 62 patients with severe colitis, 55 with ulcerative colitis and seven with Crohn’s disease, 19 (30%) were resistant to intravenous steroids and bowel rest. In all of them, rectal biopsies were examined for cytomegalovirus (the flexible proctoscopy being performed without air insufflation and limited to the first 10 cm). Buffy coat preparation on leukocytes was also performed to detect systemic infection. If cytomegalovirus was not detected, cyclosporine was started. RESULTS: In seven (five with ulcerative colitis and two with Crohn’s disease) out of 19 (36%) patients with refractory disease, cytomegalovirus was diagnosed in the rectal specimens as well as by buffy coat preparation. Five patients went into remission after antiviral treatment (three with ganciclovir and two with foscarnet). One patient did not respond and was operated on. In one patient, cytomegalovirus was found in the surgical specimen. CONCLUSIONS: Cytomegalovirus infection is a frequent cause of severe refractory colitis. Rectal biopsy should always be performed in severe steroid-resistant colitis.

Mortality and Causes of Death in Celiac Disease in a Mediterranean Area

No data on mortality in celiac disease arecurrently available in southern Europe. Our aim was toevaluate mortality and the cause of death in adultceliac disease in a Mediterranean area. In all, 228adults with celiac disease were histologicallydiagnosed in our department from 1980 to 1997. Fullinformation on their state of health was obtained in 216of 228 patients. A tabulation of patient-years at risk was constructed in terms of age at diagnosisand the interval from diagnosis. Standardized mortalityratio was calculated by dividing the number of observeddeaths by the number of expected deaths. Twelve deaths were observed, whereas 3.12 deaths wereexpected (SMR = 3.8; 95% CI 2-7). The increasedmortality was mainly observed within four years fromdiagnosis (8 observed; 1.4 expected) (SMR = 5.8; 95% CI 2.5-11.5). Twelve tumors were observed (sixlymphomas). In conclusion, mortality from adult celiacdisease in our geographical area is increased comparedwith the general population, and this increased risk seems due to non-Hodgkinslymphoma.

Intestinal permeability and genetic determinants in patients, first-degree relatives, and controls in a high-incidence area of Crohn's disease in Southern Italy.

OBJECTIVE:A defect of gastrointestinal barrier function is considered to represent an important step in the pathogenesis of Crohns disease (CD) but the mechanisms leading to an increased intestinal permeability (IP) are poorly understood. Since IP is influenced by pro-inflammatory mediators, it seems likely that a genetically determined abnormal immune response may lead to a loss of barrier function.METHODS:In a geographic area in Southern Italy with high incidence of CD we investigated IP (lactulose/mannitol testing) together with the three main mutations of the NOD2/CARD15 and the D299G polymorphism of the toll-like receptor (TLR)-4 gene in 23 families of CD patients (patients and first-degree relatives).RESULTS:Forty-eight percent of CD patients and 40% of their healthy relatives were found to have an abnormal IP compared to 5% of an appropriate control population (p < 0.0001). IP, however, was not associated with the L1007finsC mutation of the NOD2/CARD15 or the D299G variant of the TLR-4 gene. Allele frequency of the only L1007finsC mutation of CARD15 was significantly increased in patients (8.7%, p < 0.003) and in relatives (8.3%, p < 0.024) compared with controls (2.4%), whereas the D299G variant of the TLR-4 gene was found to be increased only in relatives (8.3%, p < 0.022), but not in patients (4.3%) compared with the control population (1.7%).CONCLUSIONS:There was no association between IP and genetic markers. Our findings showed a very high proportion of healthy first-degree relatives to bare alterations suggested to constitute determinants of CD. Mutations of NOD2/CARD15 or TLR-4, however, do not lead to permeability defects emphasizing the importance of additional environmental and/or genetic factors for pathogenesis.

Familial occurrence of inflammatory bowel disease in celiac disease

BACKGROUND The authors have previously reported a possible increased risk of the familial occurrence of Crohns disease in patients with celiac disease. AIM The aim of the current study was to evaluate in a case-control study the familial occurrence of inflammatory bowel disease (IBD) in first-degree relatives of patients with celiac disease. METHODS One hundred eleven consecutive patients with biopsy-proven celiac disease were interviewed to ascertain whether IBD was present in first-degree relatives. The number of relatives, their ages, and possible IBD status were collected in a questionnaire. When a diagnosis of familial IBD was reported, the diagnosis was checked in the hospital records. Two hundred twenty-two controls matched for age and sex (111 from the general population and 111 from orthopedic wards) were also interviewed regarding the possible occurrence of IBD in first-degree relatives. The chi2 test was used to evaluate the difference in proportion of familial occurrence of IBD among individuals with celiac disease and controls. RESULTS Among 600 first-degree relatives of patients with celiac disease, 10 cases of IBD were identified among first-degree relatives (7 cases of ulcerative colitis and 3 cases of Crohns disease), whereas only 1 case of IBD was identified among the 1,196 first-degree relatives of control patients (p < 0.01). When ulcerative colitis and Crohns disease were analyzed separately, only the prevalence of ulcerative colitis was statistically significant (p </= 0.02). CONCLUSIONS This case-control study shows that there is a significantly increased prevalence of familial ulcerative colitis in patients with celiac disease. There was no significant increase in the prevalence of Crohns disease in patients with celiac disease. The possible role of this association is discussed.

Epidemiology of crohn's disease in Sicily: A hospital incidence study from 1987 to 1989

An epidemiologic study of Crohns disease was carried out in the Province of Palermo, Italy, between 1987 and 1989. The incidence of first hospitalization was prospectively evaluated in this period. A total of 103 patients (59 males, 44 females) were diagnosed. The standardized annual incidence was 2.7/100,000. The incidence was quite constant during the 3 years of the study (1987: 2.9/100,000; 1988: 2.4/100,000; 1989: 2.99/100,000).Incidence rates were slightly higher in men than in women. The disease had a bimodal age distribution in female (with peaks at age 20–29 and 60–69) and males (with peaks at age 30–39, 40–49). No cases were observed at age 0–9. The incidence of Crohns disease in southern Italy is comparable to that reported in northern Europe.

The Role of CARD15 Mutations and Smoking in the Course of Crohn's Disease in a Mediterranean Area

AIM:To evaluate the role of CARD15 mutations and smoking in the main events of Crohns disease (CD).PATIENTS AND METHODS:A total of 182 patients with CD were included in a prospective study in order to evaluate the role of CARD15 mutations and smoking in the main outcomes of disease course: first operation and surgical recurrence. The following variables were evaluated in a univariable and multivariable analysis: age, sex, site of disease, pattern, smoking habit, extraintestinal manifestations, duration of disease, and CARD15 mutation. The Kaplan–Meier method for survival curves and Cox model for multivariable analysis were, respectively, used.RESULTS:A total of 110 patients were operated on and 32 were reoperated on. The 7-yr cumulative free rate of surgery was 42% (95% CI 34–51%). At multivariate analysis only stricturing and penetrating pattern were predictors of surgery (HR 1.7, 95% CI 1–2.8; HR 3.2, CI 1.8–5.5, respectively). The 7-yr cumulative free rate of reoperation was 75% (95% CI 0.52–0.88). At multivariable analysis in the model with any CARD15 mutation, only smoking habit at diagnosis (HR 3.6, 95% CI 1.4–9.1) was predictive of surgical recurrence. When single mutations were considered in the model smoking (HR 4.2, 95% CI 1.8–10.1) and L1007fs mutation (HR 2.9, 95% CI 1.1–7.3) were predictive of reoperation.CONCLUSIONS:In CD, smoking predicts recurrence after surgery. The role of CARD15 mutations in the clinical course of CD remains undefined.

Incidence of Crohn’s disease and CARD15 mutation in a small township in Sicily

Background: The incidence of Crohn’s disease (CD) has been shown to be lower in Southern than in Northern Europe. Data on the frequency of the NOD2/CARD15 mutations for Mediterranean area are very scant.Aim: To determine the incidence of CD from 1979 to 2002 in a township in Sicily together with the allele frequency of NOD2/CARD15 mutations in patients, family members and controls, and to determine the allele frequency of these mutations in sporadic CD from other areas of Sicily in comparison with a control population.Methods: Casteltermini is a small town close to Agrigento (Sicily) with a population of 9,130 inhabitants. All the diagnoses of inflammatory bowel disease (IBD) made from 1979 to 2002 were obtained through the local health authority. NOD2/CARD15 mutations were studied in 23 out of the 29 patients with CD in Casteltermini, in 60 family members and in 64 controls. NOD2/CARD15 was also studied in 80 sporadic cases of CD disease among Sicilians outside Casteltermini and 118 healthy controls.Results: From 1979 to 2002, 29 patients with CD and 13 patients with ulcerative colitis (UC) were registered. The 6-year mean incidence of CD ranged from 8.0 to 17 new cases for every 100,000 inhabitants, whereas the mean incidence of UC ranged from five new cases to 7.8 for every 100,000 inhabitants. The allele frequencies of NOD2/CARD15 mutations (L1007finsC, G908R, R702W) were 8.7, 4.3 and 8.7%, respectively, in CD cases; 5.0, 4.2 and 3.1% in family members; 1.6, 2.3 and 3.1% in controls. In sporadic Sicilian CD patients outside Casteltermini the allele frequency was 7.5, 8.1, 6.2% whereas in control population it was 3.3, 1.6, 1.6%.Conclusions: A high incidence of CD compared with UC was observed in this small town in Southern Italy. The frequency of NOD2/CARD15 mutations in CD is similar to other Caucasian population studied so far.

Relationship between site of disease and familial occurrence in Crohn's disease

Concordance in the extent of disease among thefamily members of patients with Crohns disease has notbeen widely investigated. Furthermore, the relationshipbetween the site of the disease and familial occurrence has never been studied. Our aim wasto evaluate the familial occurrence of Crohns diseasein the various sites. Nine hundred thirty-four patientswith Crohns disease, observed consecutively in two gastrointestinal departments, wereinvestigated to determine first-degree familialincidence (in both Crohns disease and ulcerativecolitis). Whenever two or more members were attendingthe same clinic, only one was regarded as a propositus.The analysis, therefore, was carried out on 882patients. The exact site of the disease was determinedin all patients either at diagnosis or during thefollow-up by colonoscopy and by small bowel enema. Therate of concordance in the extent of disease andfamilial occurrence in the various sites was evaluatedand the difference was calculated by chi-square test. Sixty-one propositi were identified among allthe patients. Forty-nine had familial occurrence for thesame disease (concordant patients), whereas 12 had atleast one relative with ulcerative colitis (discordant patients). In 44 propositi with only onerelative affected, the rates of concordance in theextent of the disease were 84, 68, 18, and 0%respectively, for the ileum, the ileum-right colon, theileum-total colon, and the colon. The number of propositiin the various sites was as follows: 4 of 162 (2.4%)patients with the disease located in the colon, 1 of 9(11%) with the jejunum site, 24 of 380 (6.3%) with the ileum site, 16 of 165 (9.7%) with the ileumand right colon site, and 16 of 164 (9.7%) with theileum and total colon site. The chi-square values ofpropositi distribution among other sites and the colon was, respectively, as follows: jejunum,2.2 (N.S.); ileum, 3.4 (P = 0.06); ileum and rightcolon, 7.4 (P = 0.006); and ileum and total colon, 7.4(P = 0.006). This study shows a pronounced concordancein the site of the disease for family members withCrohns disease and suggests that familial occurrence inCrohns disease is less frequent when the disease islocated in the colon rather than elsewhere.

Familial aggregation of inflammatory bowel disease in a Mediterranean area.

To evaluate familial aggregation of inflammatory bowel disease (IBD) in the Mediterranean area and to estimate the disease risk in first degree relatives. 427 patients with IBD were consecutively interviewed in order to obtain a complete pedigree of first degree relatives. Sufficient information was obtained in 98% of 2,685 family members. The prevalence ratio of IBD in family members was estimated and compared to the prevalence ratio of IBD in general population; the ratio was then standardized by age since the prevalence of the disease is age-dependent. The lifetime risk was assessed by the Kaplan Meier method. Thirty index cases (7%) had at least one affected first degree relative. As compared with the general population, first degree relatives of the 427 patients with IBD had a 4.38-fold increase in the age corrected risk of having the same disease. The Kaplan-Meier curve showed a higher risk at 25 years of age for offsprings (3%) than for parents (1%) and siblings (1%) whereas the crude ratio showed a higher risk for siblings (1.9%) compared to parents (0.8%) and offsprings (1%). In the Mediterranean area, the familial prevalence of IBD is higher than in the general population and comparable to North European rates.