Background and aims: Smoking tobacco has opposite effects on the different forms of inflammatory bowel disease (IBD). It predisposes to the development of Crohn's disease (CD) yet is associated with a reduced incidence of ulcerative colitis (UC). We have studied sib pairs discordant for both smoking and IBD phenotype (UC or CD) to investigate whether smoking determines the type of IBD that develops in individuals with very similar genetic susceptibility. Patients: Smoking habits and disease characteristics were analysed in 242 IBD pedigrees (658 patients). Within this group there were 339 affected sibling pairs of whom 89 were discordant for smoking when diagnosed. Results: Smoking at diagnosis was associated with development of CD (odds ratio (OR) 3.55; 95% confidence limits 2.50-5.02; p<0.001) in all of the familial patients, with increases when analysed for ileocaecal disease, fibrostenosis, and intestinal resection. Smokers were also protected from UC (OR 0.28; 0.2-0.4; p<0.001). Of 89 sibling pairs discordant for smoking at diagnosis, 23 were also discordant for disease type-in 21 of these, CD occurred in the smoker and UC in the non-smoker (OR 10.5; 2.6-92; p<0.0001). Conclusions: Smoking is a strong environmental risk factor for Crohn's disease and increases the likelihood of needing surgery. However, sib pairs who are discordant for both smoking and IBD type almost always show CD in the smoker and UC in the non-smoker, and so in some cases tobacco consumption acts on IBD genetic predisposition to shift the phenotype from UC towards CD. The explanation of part of the apparent "protective" effect of smoking on sporadic UC may be that the form of IBD that develops in a proportion of smokers is not UC but CD.

Background-Genetic anticipation has been proposed to explain observed age diVerences at diagnosis of Crohn's disease in aVected parents and oVspring. Aims-To compare aVected parent-child pairs with Crohn's disease and ulcerative colitis with a control group of non-familial patients with inflammatory bowel disease (IBD) in order to quantify whether ascertainment bias could account for this eVect. Methods-137 aVected parent-child pairs from 96 families and 214 patients with sporadic IBD were studied. Age at onset of symptoms and diagnosis were ascertained by interview and disease confirmed from clinical records. Results-Of the 137 aVected parent-child pairs, 50 had Crohn's disease only, 51 had ulcerative colitis only, and in 36, one had Crohn's disease and the other ulcerative colitis. The median age of parents at diagnosis was 17.5 years older, 16 years older, and 18 years older in the Crohn's disease, ulcerative colitis, and mixed disease families respectively (p<0.001 in each case). These observed age diVerences were compatible with those predicted from the regression lines of years of birth against age at diagnosis for the non-familial IBD patients. No evidence was found for an eVect of parental sex on age at diagnosis or disease extent in oVspring. Conclusions-There was no evidence of genetic anticipation or genomic imprinting of age at diagnosis in this sample of IBD families. Ascertainment bias is responsible for the age diVerences at diagnosis between aVected parents and children. (Gut 1999;44:808-811)

were included (n=109). Demographic, clinical characteristics, treatment and outcomes for these patients were extracted from a hospital-based registry. Outcomes evaluated were the progression-free survival (PFS), OS and toxicities. Results: The baseline profile of patients was: mean (standard deviation) age of 65.9 (9.1) years; 86.1% of males; 54.1% of current smokers; and 82.3% with performance status 0-1. Half of patients were diagnosed with adenocarcinoma, 37.6% with squamous and the rest with other NSCLC types. Two third of patients (66.1%) were diagnosed with stage IV. 75.2% of patients received nivolumab as second line therapy and 21.1% as third line. 93.3% of patients had received platinum-based therapy as first line. The median PFS of nivolumab-treated patients was 3 (2, NR) months with a median treatment duration of 2.9 months. The median OS was not reached. 52 (47.4%) patients experienced one or more toxicity(s) during immunotherapy. The most frequent were pulmonary (13.9%) and gastrointestinal (13.9%) toxicities. No difference was detected in the PFS among patients with different histological type. Conclusions: This study provides useful insights regarding the real-world experience with nivolumab in Greece and the results are consistent with those of other real-world studies and clinical trials.

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