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The knowledge that 5-aminosalicylic acid (5-ASA) is the active compound of sulphasalazine and that it acts topically has stimulated the use of 5-ASA containing enemas and ocher similar compounds such as olsalazine and 4-aminosalicylic acid (4-ASA). 5-ASA enemas have been shown to be effective in controlling active disease in clinical trials and have also been shown to be of benefit in prevention of relapses. Olsalazine enemas have not demonstrated significantly better results than placebo 4-ASA enemas are effective but the results obtained have differed as to effective dose

5-Aminosalicylic acid (5-ASA) enemas constitute a first-line therapy for patients with mild to moderate attacks of ulcerative colitis. To date, based on the results of different studies, 5-ASA enemas appear to be satisfactory in at least two-thirds of patients treated. Beclomethasone is one of the new corticosteroids which appear to have minimal systemic effects. The authors have assessed the efficacy of a four week course of 3 mg beclomethasone enemas compared to 2 g 5-ASA enemas in patients with ulcerative colitis. Preliminary analysis would suggest that both therapies are effective in more than 50% of cases.

Forty patients with active hemorrhoidal disease were entered into this double-blind trial, 20 of whom were randomized to treatment with 5-aminosalicylic acid (5-ASA) (500 mg) suppositories. Clinical and sigmoidoscopic assessment was carried out before the start of the trial and after two weeks of treatment. At the end of the study, 5-ASA suppositories showed results superior to those of placebo for all parameters evaluated (P

Barium enema and colonoscopy are contraindicated in severe attacks of ulcerative colitis because of the possibility of toxic megacolon and perforation. The authors have assessed abdominal ultrasound in 38 patients with severe ulcerative colitis. Ultrasound revealed bowel wall thicknesses ranging from 3.9 to 9.2 mm (mean 7.7) extending the whole length of the colon, to the transverse colon, and to the descending colon, respectively, in 18, 10 and eight patients. The degree of bowel thickening was related to the severity of inflammation based on clinical, sigmoidoscopic and histological evaluation. In two patients, ultrasound showed a thin bowel wall distended without motility, suggesting the diagnosis of toxic megacolon (confirmed radiologically). An excellent correlation (95%) was found between ultrasound and technetium-99 scanning. Ultrasound might be a reasonable first investigation in the assessment of patients with severe ulcerative colitis.

Background: The management of individuals with familial adenomatous polyposis (FAP) includes invasive prophylactic surgery and intensive endoscopic surveillance to reduce their risk of colorectal cancer. FAP patients frequently ask for dietary recommendations to alleviate bowel disturbances after prophylactic colectomy, and to prevent the formation and growth of new adenomas. We have enriched the multidisciplinary outpatient clinic for FAP with nutritional support. This paper presents the results of the first six months of this nutritional activity., Methods: Sixty-eight individuals with FAP, >18 years of age, who underwent a prophylactic total colectomy, entered in this observational study. At the baseline visit, participants underwent anthropometric measurements, answered the Mediterranean Diet Adherence Screener (MEDAS), the Faecal Incontinence Quality of Life (FIQL) questionnaire, and reported the number of their diarrhoeal discharges per day. They received dietary recommendations including specific information about the inflammatory food to reduce (red/processed meat, sugar, sweets), and the Mediterranean food to increase (vegetables, fruits, whole grain cereal in cream and legumes' hummus)., Results: After six months, participants repeated the same baseline measurements. Fifty-three individuals with FAP completed the six-month follow-up. The before-after analysis showed significant improvements in patients' body composition measurements and MEDAS score. Participants significantly reduced the number of diarrhoeal discharges per day. FIQL results showed improvements in lifestyle, behaviour, and depression scores., Conclusions: These results suggest that targeted low-inflammatory Mediterranean dietary recommendations are effective in improving anthropometric parameters, diet quality, and various aspects of quality of life related to bowel function in individuals with FAP., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Individuals with Familial Adenomatous Polyposis (FAP) or APC -associated polyposis, an autosomal dominant inherited condition, develop multiple adenomatous polyps and have an increased colorectal cancer (CRC) risk. A change in diet can help reduce cancer risk, and several dietary components have an antitumor effect. We aimed to evaluate the potential of the anti-inflammatory and anticancer substances quercetin (QER), epigallocatechin gallate (EGG) and fisetin (FIS) in decreasing the risk of CRC by reducing the growth of polyps in an organoid model., Methods: Patient-derived organoid (PDO) lines were generated from polyps obtained from patients with FAP undergoing prophylactic colectomy. PDOs were treated with QER, EGG, or FIS to determine their effect on cell growth. Changes in caspase 3/7 activity and expression of inflammation and apoptosis mediators were assessed by luminescent and colorimetric assays., Results: Three PDO lines with different inactivating pathogenic variants in the APC gene were developed using a combinatorial approach. FIS was the most active of the three substances tested, presenting the lowest IC50 in all PDO lines (range: 42.6-9.2 uM). The IC50 was defined as the concentration required to halve the number of cells after 72 hours. All molecules tested induced apoptosis through activation of caspases 3/7., Conclusions: QER, EGG, and FIS can be easily taken from foods or dietary supplements, show toxicity on PDOs derived from adenomatous polyps, while they are known to be harmless on normal cells. Diets enriched with these substances could be potential supplemental treatments to reduce the risk of CRC in individuals with FAP., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Despite advancements in therapeutic strategies, the development of drug resistance and metastasis remains a serious concern for the efficacy of chemotherapy against colorectal cancer (CRC). We have previously demonstrated that low expression of ribosomal protein uL3 positively correlates with chemoresistance in CRC patients. Here, we demonstrated that the loss of uL3 increased the metastatic capacity of CRC cells in chick embryos. Metabolomic analysis revealed large perturbations in amino acid and glutathione metabolism in resistant uL3-silenced CRC cells, indicating that uL3 silencing dramatically triggered redox metabolic reprogramming. RNA-Seq data revealed a notable dysregulation of 108 genes related to ferroptosis in CRC patients. Solute Carrier Family 7 Member 11 (SLC7A11) is one of the most dysregulated genes; its mRNA stability is negatively regulated by uL3, and its expression is inversely correlated with uL3 levels. Inhibition of SLC7A11 with erastin impaired resistant uL3-silenced CRC cell survival by inducing ferroptosis. Of interest, the combined treatment erastin plus uL3 enhanced the chemotherapeutic sensitivity of uL3-silenced CRC cells to erastin. The antimetastatic potential of the combined strategy was evaluated in chick embryos. Overall, our study sheds light on uL3-mediated chemoresistance and provides evidence of a novel therapeutic approach, erastin plus uL3, to induce ferroptosis, establishing individualized therapy by examining p53, uL3 and SLC7A11 profiles in tumors.

Colorectal cancer (CRC) often involves wild-type p53 inactivation by MDM2 and MDM4 overexpression, promoting tumor progression and resistance to 5-fluoruracil (5-FU). Disrupting the MDM2/4 heterodimer can proficiently reactivate p53, sensitizing cancer cells to 5-FU. Herein, we developed 16 peptides based on Pep3 ( 1 ), the only known peptide acting through this mechanism. The new peptides, notably 3 and 9 , showed lower IC 50 values than 1 . When incorporated into tumor-targeted biodegradable nanoparticles, these exhibited cytotoxicity against three different CRC cell lines. Notably, NPs/ 9 caused a significant increase in p53 levels associated with a strong increment of its main downstream target p21 inducing apoptosis. Also, the combined treatment of 9 with 5-FU caused the activation of nucleolar stress and a synergic apoptotic effect. Hence, the co-delivery of MDM2/4 heterodimer disruptors with 5-FU through nanoparticles might be a promising strategy to overcome drug resistance in CRC.

Lynch Syndrome is an autosomal dominant cancer predisposition syndrome caused by germline pathogenic variants or epimutation in one of the DNA mismatch repair genes. De novo pathogenic variants in mismatch repair genes have been described as a rare event in Lynch Syndrome (1-5%), although the prevalence of de novo pathogenic variants in Lynch Syndrome is probably underestimated. The de novo pathogenic variant was identified in a 26-year-old woman diagnosed with an adenocarcinoma of the caecum with mismatch repair protein deficiency at immunohistochemistry and a synchronous neuroendocrine tumor of the appendix with normal expression of mismatch repair proteins. DNA testing revealed deletion of exon 6 of the MLH1 gene. It appeared to be a de novo event, as the deletion was not detected in the patient's parents. The presence of a mosaicism in the patient was excluded and haplotype analysis demonstrated the paternal origin of the chromosome harboring the deletion. The de novo deletion probably originated either from a very early postzygotic or a single prezygotic mutational event, or from a gonadal mosaicism. In conclusion, the identification of de novo pathogenic variants is crucial to allow proper genetic counseling and appropriate management of the patient's family., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Total colectomy with ileorectal anastomosis (TC/IRA) is one of the prophylactic surgical options in patients with familial adenomatous polyposis (FAP). This study investigated the effectiveness of superior rectal artery (SRA) preservation during TC/IRA in reducing anastomotic leakage (AL)., Methods: This retrospective study was based on prospectively collected data (01/2000 - 12/2022) at the National Cancer Institute, Milan, Italy. FAP patients undergoing TC/IRA were enrolled. A 1:1  propensity score matching (PSM) was performed. Associations between SRA preservation and complications were investigated using univariate and multivariate analysis., Results: The study population included 211 patients undergoing TC/IRA (Sex: 106 Male, 105 Female; Age: median 30 yrs, IQR: 20-48 yrs), 82 with SRA preservation (SRA group) and 129 without SRA preservation (controls). After PSM, 75 patients were considered for each group. SRA preservation was associated with fewer complications (OR 0.331, 95% CI 0.116; 0.942) in univariate logistic regression analysis. AL events were significantly fewer in the SRA group than in the control group (0 vs 12, p = 0.028). The SRA group had fewer overall surgical complication and pelvic sepsis rates (p = 0.020 and p = 0.028, respectively). Median operative time was significantly longer in the SRA group (340 min vs 240 min, p<0.001), and median hospital stay was significantly shorter (6 vs 7 days, p=0.017). Twenty-seven patients in the SRA group experienced intraoperative anastomotic bleeding, which was controlled endoscopically. Superimposable results were obtained analyzing the whole patient cohort., Conclusions: SRA preservation can be considered an advantage in this patient population, despite adding a further technical step during surgery and thereby prolonging the operative time. Intraoperative endoscopic checking of possible anastomotic bleeding sites is recommended., (© 2023. Springer Nature Switzerland AG.)

Purpose: Colorectal adenomatous polyposis is characterized by the onset of tens to thousands of adenomas in the colorectal epithelium and, if not treated, leads to a lifetime increased risk of developing colorectal cancer compared to the general population. Thus, prophylactic surgery is recommended. This study aims to investigate the quality of life of colorectal adenomatous polyposis patients following prophylactic surgery and indirectly compares these findings with those of healthy adults of the normative sample., Methods: All patients who underwent prophylactic surgery for polyposis and were in follow-up at the hereditary digestive tract tumors outpatient department of our institute were eligible for the study. The Short Form-36 questionnaire and 21 ad hoc items were used at the time of clinical evaluation., Results: A total of 102 patients were enrolled. For the SF-36 domains, mean values ranged from 64.18 for vitality to 88.49 for physical functioning, with the highest variability for role-physical limitations; the minimum value of functioning was reached for role-physical limitations, role-emotional limitations, and social functioning. The maximum value of functioning was reached for role-emotional limitations (73.96%) and role-physical limitations (60.42%). In total, 48.96% and 90.63% of patients reported no fecal or urinary incontinence episodes, respectively; 69.79% of patients did not have problems in work/school resumption or the personal sexual sphere., Conclusion: Quality of life following prophylactic surgery for these patients seems to be good when indirectly compared to HP-normative samples'. Young adult patients appear to quickly manage and adapt to changes in bowel functioning. A minority of patients may experience social and sexual issues., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Despite recent therapeutic advancements, resistance to 5-fluorouracil (5-FU) remains a major obstacle to the successful treatment of this disease. We have previously identified the ribosomal protein uL3 as a key player in the cell response to 5-FU, and loss of uL3 is associated with 5-FU chemoresistance. Natural products, like carotenoids, have shown the ability to enhance cancer cell response to drugs and may provide a safer choice to defeat chemoresistance in cancer. Transcriptome analysis of a cohort of 594 colorectal patients revealed a correlation between uL3 expression and both progression-free survival and response to treatment. RNA-Seq data from uL3-silenced CRC cells demonstrated that a low uL3 transcriptional state was associated with an increased expression of specific ATP-binding cassette ( ABC ) genes. Using two-dimensional (2D) and three-dimensional (3D) models of 5-FU-resistant CRC cells stably silenced for uL3, we investigated the effect of a novel therapeutic strategy by combining β-carotene and 5-FU using nanoparticles (NPs) as a drug delivery system. Our results indicated that the combined treatment might overcome 5-FU chemoresistance, inducing cell cycle arrest in the G2/M phase and apoptosis. Furthermore, the combined treatment significantly reduced the expression levels of analyzed ABC genes. In conclusion, our findings suggest that β-carotene combined with 5-FU may be a more effective therapeutic approach for treating CRC cells with low levels of uL3.

We carefully read the comment by Serrano et al. [...].

Background: The balance between quality of life and colorectal cancer risk in familial adenomatous polyposis (FAP) patients is of primary importance. A cut-off of less than 30 polyps under 1 cm of diameter in the rectum has been used as an indication for performing ileo-rectal anastomosis (IRA) in terms of lower rectal cancer risk. This study aimed to assess clinical and surgical features of FAP patients who developed cancer of the rectal stump., Methods: This retrospective study included all FAP patients who underwent total colectomy/IRA from 1977 to 2021 and developed subsequent rectal cancer. Patients' features were reported using descriptive statistics by considering the overall case series and within pre-specified classes of age (<20, 20-30, and >30 years) at first surgery., Results: Among the 715 FAP patients, 47 (6.57%, 95% confidence interval: 4.87; 8.65) developed cancer in the rectal stump during follow-up. In total, 57.45% of the population were male and 38.30% were proband. The median interval between surgery and the occurrence of rectal cancer was 13 years. This interval was wider in the youngest group ( p -value: 0.012) than the oldest ones. Twelve patients (25.53%) received an endoscopic or minimally invasive resection. Amongst them, 61.70% were Dukes stage A cancers., Conclusions: There is a definite risk of rectal cancer after total colectomy/IRA; however, the time interval from the index procedure to cancer developing is long. Minimally invasive and endoscopic treatments should be the procedures of choice in patients with early stage cancers.

Objective: In Crohn's disease (CD), the relationship between genetic predisposition and smoking has not been well defined. The aim of this study was to compare the smoking habits at the time of the diagnosis of CD patients having familial occurrence of inflammatory bowel disease (IBD) with those of some control groups., Methods: In a multicenter study, 136 CD patients with a relative with IBD, 272 healthy controls matched for sex and age, 500 CD patients without familial occurrence of IBD, and 84 ulcerative colitis patients (UC) with familial occurrence of IBD were personally interviewed about their smoking habits. In addition, data for 35 healthy siblings of patients with familial CD were collected by interviewing the patients' relatives., Results: The prevalence of smokers was found significantly higher in CD patients with a family history for IBD than in healthy controls and in familial UC patients (OR 2.28 CI 1.5-3.48 and OR 5.81 CI 3.15-10.75, respectively). No significant difference was found either in the percentage of smokers or in the number of cigarettes smoked per day between familial and sporadic CD patients. Among all siblings of CD patients, 72% of affected siblings and 34% of healthy siblings were smokers, concordant with their relatives., Conclusions: In CD patients with familial occurrence of IBD, the percentage of smokers is elevated. It is possible that in a genetically predisposed population, smoking could be an important environmental factor in determining CD or expressing this disease instead of UC.

The rationale for supplementation with n-3 fatty acids to promote the health of the gastrointestinal tract lies in the antiinflammatory effects of these lipid compounds. The first evidence of the importance of dietary intake of n-3 polyunsaturated fatty acids was derived from epidemiologic observations of the low incidence of inflammatory bowel disease in Eskimos. The aim of this paper was to briefly review the literature on the use of n-3 fatty acids in inflammatory bowel disease (ulcerative colitis and Crohn disease), the results of which are controversial. The discrepancies between studies may reside in the different study designs used as well as in the various formulations and dosages used, some of which may lead to a high incidence of side effects. Choosing a formulation that lowers the incidence of side effects, selecting patients carefully, and paying strict attention to experimental design are critical when investigating further the therapeutic potential of these lipids in inflammatory bowel disease.

Purpose: The aim of our study was to compare the efficacy and safety of oral mesalazine with mesalazine suppositories in patients with active ulcerative proctitis., Patients and Methods: A four-week, randomized, single-blind trial was performed in 58 patients with active, histologically confirmed ulcerative proctitis (< or = 15 cm) to evaluate the efficacy and safety of oral 800-mg mesalazine tablets taken three times per day (n = 29) compared with 400 mg of mesalazine suppositories administered three times per day (n = 29). Patients were evaluated at study entry and after two and four weeks. Efficacy evaluations included a disease activity index, which represents a score with four variables: stools frequency, rectal bleeding, mucosal appearance, and physician's assessment of disease severity. Histologic activity was also assessed at study entry and after two and four weeks in accordance with the criteria by Truelove and Richard. Safety assessment included clinical laboratory parameters and adverse event reports., Results: There were no significant differences with regard to baseline comparisons of demographics and severity between the two treatment groups. Improvement in mean disease activity index score was significantly greater with suppositories compared with oral mesalazine, both at two-week and four-week visits (mean disease activity index scores at baseline, two, and four weeks: suppositories = 7.7, 2.59, and 1.48; tablets = 7.42, 5.72, and 3.48, respectively (P < 0.001)). The rate of histologic remission was significantly greater with suppositories compared with tablets both at two and four weeks (P < 0.01). There were no significant differences in adverse events or clinical laboratory results between treatment groups., Conclusions: Results of this study indicate that treatment with mesalazine suppositories produces earlier and significantly better results than oral mesalazine in the treatment of active ulcerative proctitis.

Background: Mesalazine suppositories at 500 mg b.d. are a safe and effective treatment for patients with ulcerative proctitis or distal proctosigmoiditis. Recently a mesalazine 1 g suppository (Pentasa) has been developed., Methods: Fifty patients with active ulcerative colitis extending not beyond 20 cm from the anus on sigmoidoscopy, participated in a randomized single-blind study comparing the efficacy, tolerance and acceptance of the new Pentasa mesalazine 1 g suppository, given once daily versus Claversal mesalazine 500 mg suppository b.d., Results: After 2 weeks, clinical remission was observed in 16 of 25 (64%) in the Pentasa group and in 7 of 25 (28%) in the Claversal 500 mg b.d. treated group; sigmoidoscopic remission occurred in 13 of 25 (52%) in the Pentasa group and in six of 25 (24%) in the Claversal group (P < 0.01). After 4 weeks, clinical and sigmoidoscopic remission were observed, respectively, in 84 and 76% of patients treated with Pentasa suppositories, and in 80 and 72% of patients treated with Claversal suppositories 500 mg b.d. (P = N.S.). The patients' evaluation for tolerability and practicality showed that the Pentasa suppository was significantly superior to the Claversal suppository., Conclusions: Pentasa 1 g suppository once daily induces a quicker clinical and sigmoidoscopic remission, and was better tolerated, than the Claversal 500 mg suppository b.d., and it may represent an advance for the topical treatment of distal proctosigmoiditis.

Background: Recent data indicate that 5-aminosalicylic acid (5-ASA) is most effective in preventing relapse of Crohn's disease in patients with a short duration of remission before enrollment., Aim: To evaluate the efficacy of oral 5-ASA treatment, started immediately after achieving steroid-induced remission, in preventing clinical relapses of Crohn's disease., Methods: Patients with active Crohn's disease, achieving remission on steroids, were randomized to oral 5-ASA 3 g/day or placebo, while steroids were tapered over 6 weeks. The trial was terminated after interim analysis showed a slightly higher relapse rate in the 5-ASA group, and the calculated probability of seeing a statistically significant difference by completing the study was minimal., Results: Final analysis included 117 patients (58 taking 5-ASA and 59 taking placebo; follow-up 9.2 +/- 6.5 months). Cumulative relapse rates at 6 and 12 months were 34% and 58% in 5-ASA patients and 31% and 52% in placebo patients, respectively (rate difference +0.095; 95% CI = -0.085 to +0.274). Subgroups analysis showed that 5-ASA was equally ineffective in patients with ileal, colonic or ileocolonic disease., Conclusions: Contrary to previous results, in our study early introduction of treatment with oral 5-ASA did not prevent relapse in Crohn's disease patients treated with steroids to induce remission.

Background: Mucosal inflammation of the ileal pouch (pouchitis) is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. Broad-spectrum antibiotics are the mainstay of treatment, however, 15% of patients with pouchitis have a chronic, treatment-resistant disease., Aim: To determine the safety and efficacy of bismuth carbomer enemas in achieving and maintaining remission in treatment-resistant chronic pouchitis., Methods: Twelve patients with treatment-resistant chronic pouchitis were treated nightly for 45 days with enemas containing elemental bismuth complexed with carbomer. Diagnosis of pouchitis and response to treatment were evaluated with the Pouchitis Disease Activity Index (PDAI), which includes clinical, sigmoidoscopic and histological criteria. Serum bismuth concentrations were determined by atomic absorption., Results: Ten of 12 patients (83%) went into remission, with a significant decrease of mean total PDAI score from 12 (range 9-15) to 6 (4-15) (P < 0.002), and were continued on bismuth carbomer enemas administered every third night for 12 months. Patients were monitored clinically, sigmoidoscopically and histologically every 2 months for evidence of recurrence (increase > or = 2 in the clinical symptom portion of the PDAI). Six of 10 patients (60%) were able to maintain remission throughout the 12-month trial; 4/10 had an exacerbation, two of which occurred soon after discontinuing daily treatment. Serum bismuth levels were negligible in all patients and no side-effects were registered., Conclusions: Our findings suggest that bismuth carbomer enemas are safe and effective in achieving and maintaining remission in patients with treatment-resistant chronic pouchitis.

Background: Antineutrophil cytoplasmic antibodies (ANCAs) from patients with vasculitidis can induce neutrophils to release oxygen radicals in vitro. ANCAs with a perinuclear pattern of immunofluorescence are found in most patients with ulcerative colitis, but several findings are against ANCAs having a pathogenetic role in this disease., Aims: To evaluate the influence of ANCAs associated with ulcerative colitis on the respiratory burst activity of neutrophils., Patients: Serum samples were obtained from 14 patients with ulcerative colitis, seven of whom showed positivity for p-ANCAs, three patients with vasculitidis, two with positivity for p-ANCAs, and one for c-ANCAs, and seven healthy volunteers., Methods: A positive ANCA serology was determined with a standard indirect immunofluorescence assay. Purified immunoglobulins (IgGs) were prepared from serum samples by DEAE-Affigel blue chromatography. Human neutrophils were prepared by dextran-Ficoll-Hypaque separation. Superoxide anion (O2-.) generation was measured by following the superoxide dismutase inhibitable reduction of ferricytochrome., Results: There were no significant differences among samples from ulcerative colitis IgG p-ANCA positive, ulcerative colitis IgG p-ANCA negative patients, and controls on O2-. production, whereas ANCA positive IgG from vasculitidis significantly enhanced O2-. release (p < 0.001)., Conclusions: p-ANCAs associated with ulcerative colitis have no effect on the respiratory burst activity of normal human neutrophils in vitro. These results reinforce the hypotheses that ANCAs are unlikely to contribute to the pathogenesis of ulcerative colitis.

Concordance in the extent of disease among the family members of patients with Crohn's disease has not been widely investigated. Furthermore, the relationship between the site of the disease and familial occurrence has never been studied. Our aim was to evaluate the familial occurrence of Crohn's disease in the various sites. Nine hundred thirty-four patients with Crohn's disease, observed consecutively in two gastrointestinal departments, were investigated to determine first-degree familial incidence (in both Crohn's disease and ulcerative colitis). Whenever two or more members were attending the same clinic, only one was regarded as a propositus. The analysis, therefore, was carried out on 882 patients. The exact site of the disease was determined in all patients either at diagnosis or during the follow-up by colonoscopy and by small bowel enema. The rate of concordance in the extent of disease and familial occurrence in the various sites was evaluated and the difference was calculated by chi-square test. Sixty-one propositi were identified among all the patients. Forty-nine had familial occurrence for the same disease (concordant patients), whereas 12 had at least one relative with ulcerative colitis (discordant patients). In 44 propositi with only one relative affected, the rates of concordance in the extent of the disease were 84, 68, 18, and 0% respectively, for the ileum, the ileum-right colon, the ileum-total colon, and the colon. The number of propositi in 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 ileum and right colon site, and 16 of 164 (9.7%) with the ileum and total colon site. The chi-square values of propositi distribution among other sites and the colon was, respectively, as follows: jejunum, 2.2 (N.S.); ileum, 3.4 (P = 0.06); ileum and right colon, 7.4 (P = 0.006); and ileum and total colon, 7.4 (P = 0.006). This study shows a pronounced concordance in the site of the disease for family members with Crohn's disease and suggests that familial occurrence in Crohn's disease is less frequent when the disease is located in the colon rather than elsewhere.

Aim: To determine the systemic uptake of 5-aminosalicylic acid (5-ASA) and acetyl-5-ASA (Ac-5-ASA) at steady state during treatment with either an azo-bond preparation, olsalazine, or a delayed-release mesalazine., Methods: In an open cross-over trial with randomized sequence, 15 patients with ulcerative colitis in remission were given 7-day courses of olsalazine (Dipentum 1.0 g daily) and of mesalazine (Asacol 1.6 g daily). Plasma and urine were collected on days 6 and 7 of each course and concentrations of 5-ASA and Ac-5-ASA were determined by high-performance liquid chromatography (HPLC)., Results: Mean steady-state plasma concentrations of 5-ASA and Ac-5-ASA were significantly higher after treatment with mesalazine than with olsalazine (P < 0.0001). Total urinary excretion of 5-ASA and Ac-5-ASA as a percentage of the given dose was significantly higher on mesalazine than on olsalazine (P < 0.01). Only two patients experienced, during the first 3 days of treatment with olsalazine, transient watery diarrhoea which resolved spontaneously. No unexpected or major changes in haematology or biochemistry were detected during the study., Conclusion: As 5-ASA acts locally, the lower systemic load provided by olsalazine may increase efficacy and reduce the potential risk of nephrotoxicity during long-term maintenance treatment of ulcerative colitis.