Prevalence of Colonic Diverticulosis in Patients Affected by Ulcerative Colitis: A Prospective Study.

BACKGROUND: Diverticulosis of the colon is an acquired condition that results from herniation of the mucosa and submucosa through defects in the muscular layer. The true prevalence of colonic diverticulosis is difficult to measure because most individuals are asymptomatic. In particularly, in literature, there are few studies about the prevalence of colonic diverticulosis in patients affected by ulcerative colitis (UC). GOALS: To investigate the prevalence of colonic diverticulosis in UC and in adult patients referred in a single center. STUDY: Consecutive patients, referred to our institution to undergo a colonoscopy for colorectal cancer screening and/or for UC assessment, between January 1, 2014 and December 31, 2014, were studied. RESULTS: Six hundred five consecutive patients were studied: 438 (72.4%) due to colorectal cancer screening (group A) and 167 (27.6%) for UC assessment (group B). Prevalence of colonic diverticulosis was higher in group A than group B (27.8% vs. 10.8%, P<0.0001). Female gender in patients with colonic diverticulosis was higher in group A than group B (55.7% vs. 22.2%, P=0.0106). Sigma and left colon was mainly involved in group A than group B (97.6% vs. 66.7%, P=0.0001), whereas in group B the right colon was mainly involved in group B versus group A (22.2% vs. 0.8%, P=0.0009). CONCLUSIONS: Prevalence of colonic diverticulosis was significantly lower in patients with UC than in control group. UC may, therefore, be a protective factor for colonic diverticulosis occurrence.

A randomized trial comparing 4.8 vs. 2.4 g/day of oral mesalazine for maintenance of remission in ulcerative colitis.

BACKGROUND: Mesalazine is used as maintenance therapy in ulcerative colitis but the optimal dosage is still controversial. AIM: To compare the remission-maintenance efficacy and tolerability of two daily doses of oral mesalazine (4.8 g and 2.4 g) in patients with ulcerative colitis with frequent relapses in a randomized controlled trial. METHODS: 112 ulcerative colitis patients in remission were enrolled and randomly allocated to treatment for 1 year with oral mesalazine at a daily dose of 4.8 g (n=56, Group A) or 2.4 g (n=56, Group B). RESULTS: At the end of the 12 months, intention to treat analysis revealed persistent remission in 42 (75%) in Group A and 36 (64.2%) in Group B (p=0.3). The higher daily dose (4.8 g) proved to be significantly more effective for maintaining remission in patients under 40 years of age (90.5% Group A vs. 50% Group B; Fisher's exact test, p=0.0095) and in those with extensive disease (90.9% Group A vs. 46.7% Group B; Fisher's exact test, p=0.0064). CONCLUSIONS: In ulcerative colitis patients younger than 40 years and/or with extensive disease, a daily dose of 4.8 g oral mesalazine results in increased rates and duration of remission compared to 2.4 g.

Extraintestinal manifestations in a large series of Italian inflammatory bowel disease patients.

AIM: To investigate prevalence, type and time of onset of extraintestinal manifestations (EIMs) in a series of Italian inflammatory bowel disease (IBD) patients. METHODS: Data of 811 IBD consecutive patients, first referred to our Centre from 2000 to 2011, were retrospectively evaluated. RESULTS: Eight hundred and eleven IBD patients (437 M, 374 F) were studied: 595 ulcerative colitis (UC) (73.4%) and 216 Crohn's disease (CD) (26.6%). Among these, 329 (40.6%) showed EIMs: 210 UC (35.3%) and 119 CD (55.1%) (P < 0.0001). Considering the time of the diagnosis of IBD, 37 EIMs (11.2%) were developed before, 229 (69.6%) after and 63 (19.2%) were simultaneous. The type of EIM were as follows: 240 musculoskeletal (29.6%), in 72 CD patients and in 168 UC (P < 0.0001); 47 mucocutaneous (5.8%), in 26 CD and in 21 UC (P = 0.0049); 26 ocular (3.2%), in 16 CD and in 10 UC (CD 7.4% vs UC 1.7%, P = 0.0093); 6 hepatobiliary (0.8%); 10 endocrinological (1.2%). In particular, with regards to the involvement of the musculoskeletal system, arthritis Type 1 was found in 41 CD (19%) and in 61 UC (10.2%) (P = 0.0012) and Type 2 in 25 CD (11.6%) and in 100 UC (16.8%) (P = 0.0012). CONCLUSION: Mucocutaneous manifestations, arthritis Type 1 and uveitis were significantly more frequent in CD than UC. The complications of the musculoskeletal system were the mostly observed ones, often with symptoms more severe than intestinal ones, confirming the need for close cooperation with rheumatologists.

Biological therapy for dermatological manifestations of inflammatory bowel disease.

Ulcerative colitis and Crohn's disease are the two forms of inflammatory bowel disease (IBD). The advent of biological drugs has significantly changed the management of these conditions. Skin manifestations are not uncommon in IBD. Among the reactive lesions (immune-mediated extraintestinal manifestations), erythema nodosum (EN) and pyoderma gangrenosum (PG) are the two major cutaneous ills associated with IBD, while psoriasis is the dermatological comorbidity disease observed more often. In particular, in the last few years, anti-tumor necrosis factor (TNF)-α agents have been successfully used to treat psoriasis, especially these kinds of lesions that may occur during the treatment with biological therapies. The entity of the paradoxical manifestations has been relatively under reported as most lesions are limited and a causal relationship with the treatment is often poorly understood. The reason for this apparent side-effect of the therapy still remains unclear. Although side effects may occur, their clinical benefits are undoubted. This article reviews the therapeutic effects of the two most widely used anti-TNF-α molecules, infliximab (a fusion protein dimer of the human TNF-α receptor) and adalimumab (a fully human monoclonal antibody to TNF-α), for the treatment of the major cutaneous manifestations associated with IBD (EN, PG and psoriasis).

Evaluation of fatty acid synthase expression in oesophageal mucosa of patients with oesophagitis, Barrett's oesophagus and adenocarcinoma.

BACKGROUND AND AIM: To evaluate the expression of fatty acid synthase (FAS) in the oesophagitis-Barrett's oesophagus-oesophageal adenocarcinoma sequence compared with p53 and Ki67 expressions, retained for a long time reliable markers of oesophageal cells biological behaviour. METHODS: In Barrett's oesophagus, oesophagitis and oesophageal adenocarcinoma patients, biopsies were taken from pathologic sites of the mucosa for histological and immuno-histochemical detection of FAS, p53 and Ki67. FAS expression was positive, when a strong granular cytoplasmic staining was observed in oesophageal cells. Ki67 and p53 was defined positive, when nuclear staining was clearly detected at 10x magnification. RESULTS: A mild expression of FAS was found in 39% of patients with oesophagitis. The amount of FAS expression increased up to 70% in Barrett's oesophagus while this was present in all patients with oesophageal adenocarcinoma (p = 0.0001). In Barrett's oesophagus, p53 was mildly or intensely expressed in 77% and in 15% of cases, respectively, and mildly or intensely expressed in 33% and 67% of patients with oesophageal adenocarcinoma, respectively, (p = 0.0001). Ki67 was mildly expressed in 17% of oesophagitis cases and was absent in the majority of cases. In Barrett's oesophagus, a mild Ki67 expression was present in 46% of cases, and in oesophageal adenocarcinoma it was present prevalently in intense form (67%; p = 0.0001). CONCLUSIONS: The over-expression of p53, Ki67 and FAS in otherwise similar morphological groups may be useful to stratify patients into selected prognostic subgroups in order to achieve better clinical approaches.

Morphologically and immunohistochemically undifferentiated gastric neoplasia in a patient with multiple metastatic malignant melanomas: a case report.

INTRODUCTION: Malignant melanoma is a neoplasia which frequently involves the gastrointestinal tract (GIT). GIT metastases are difficult to diagnose because they often recur many years after treatment of the primary cutaneous lesion and also manifest clinically at an advanced stage of the neoplasia. Furthermore, GIT metastases can appear in various morphological forms, and therefore immunohistochemistry is often useful in distinguishing between a malignant melanoma and other malignancies. CASE PRESENTATION: We report the case of a 60-year-old man with a multiple metastatic melanoma who underwent an upper endoscopy to clarify the possible involvement of the gastric wall with a mass localized in the upper abdomen involving the pancreas and various lymph nodes, which was previously described with computed tomography. Clinically, the patient reported a progressive loss of appetite, nausea and vomiting. The upper endoscopy and histological examination revealed a gastric location of an undifferentiated neoplasm with an absence of immunohistochemical characteristics referable to the skin malignant melanoma that was removed previously. CONCLUSION: The present case report shows the difficulty in diagnosing a metastatic melanoma in the GIT and therefore, it seems worthwhile to consider metastatic malignant melanoma in the differential diagnosis of undifferentiated neoplasia.

Role of desmoplasia in recurrence of stage II colorectal cancer within five years after surgery and therapeutic implication.

BACKGROUND: Colorectal cancer (CRC) metastasis is enhanced in patients with venous embolization increasing the risk of recurrence and therefore mortality rate. Several evidences indicate that stage II patients have an abrupt recurrence within five years from surgery. This fact, led us to investigate the role played by different histological variables on CRC invasiveness. AIM: To demonstrate if quantitative and qualitative desmoplastic response and lymphocytic infiltration are prognostic factor involved in the recurrence of CRC within five years from surgery, considering possible clinical and therapeutical implications. METHODS: Thirty-four patients with CRC underwent colectomy and the UICC-TNM classification was applied for disease staging. Histological variables were semi-quantitatively evaluated. Qualitative evaluation of desmoplasia was obtained with the hematoxillin-eosin method. RESULTS: Survival rate arose 88% at stage II, at five years of follow-up, and the 12% not treated with adjuvant chemotherapy developed metastasis. Desmoplasia is strongly associated with venous neoplastic invasiveness (OR: 21.93; 95%CI: 1.012-475.26, p = 0.02), and therefore, with mortality rate (OR: 14.33; 95%CI: 0.67-304, p = 0.04). Moreover, mortality rate was significantly higher in patients with immature desmoplasia compare to mature stromal tissue (OR: 15.61, 95%CI: 0.69-343.38, p = 0.04). CONCLUSIONS: These observations should prompt a future evaluation of desmoplasia to extent more suitably the use of adjuvant chemotherapy in II stage patients. Further clinical trials are needed to determine if these findings will be able to reduce mortality rate, in stage II CRC patients.

Hematological malignancies in chronic inflammatory bowel diseases: report of five cases and review of the literature.

Several forms of primary and secondary hematological malignancies were rarely observed during the clinical course of inflammatory bowel diseases (IBD). Patients needing a prolonged treatment with immunosuppressants, such as azathioprine or methotrexate, with familiarity and genetic predisposition seem to be at a higher risk of leukemia. On the other hand, asthenia, thickness, and fever may be the symptoms of the onset of each kind of hematological malignancy. The finding of anemia, alteration of leukocyte count and large undetermined cells may suggest increased probability of abnormal proliferation of a single white blood cell line. In this report, the occurrence of hematological malignancies is described in five patients affected by IBD (three with ulcerative colitis and two with Crohn's disease) attending our Gastroenterology Unit.

2-week triple therapy for Helicobacter pylori infection is better than 1-week in clinical practice: a large prospective single-center randomized study.

BACKGROUND: Proton pump inhibitor (PPI)-based triple therapies are considered the standard regimens for Helicobacter pylori eradication, but the optimal duration of these regimens is still controversial. The aim of this study was to compare the efficacy of 1-week versus 2-week triple therapies in H. pylori-positive patients. MATERIALS AND METHODS: A total of 486 consecutive H. pylori-positive patients were randomized to receive omeprazole, 20 mg b.i.d., clarithromycin 500 mg b.i.d., and either amoxicillin 1 g b.i.d. or metronidazole 500 mg b.i.d. for 1 or 2 weeks. Upper gastrointestinal endoscopy and histology were performed at entry and 2 months after the end of therapy. H. pylori status was defined according to histology and urea breath test. RESULTS: At intention-to-treat analysis, 2-week therapy with omeprazole, amoxicillin, and clarithromycin achieved a significantly higher eradication rate than 1- or 2-week regimens with metronidazole (70% versus 52%, p = .003, versus 56%, p < .01) and the same therapy for 1-week (70% versus 57%, p = .05). At per-protocol analysis, 2-week therapy with omeprazole, amoxicillin, and clarithromycin showed a significantly higher eradication rate than 1-week of amoxicillin and metronidazole (77% versus 62%; p = .03) but no difference with 1-week same regimen (66%) or 2-week metronidazole and clarithromycin regimen (72%). Compliance and tolerability were good for all regimens. CONCLUSIONS: Two-week therapies, independently of antibiotic combination, lead to a significant increase of H. pylori eradication rate compared to 1-week therapies, with same compliance and tolerability, even if, taking account of low-eradication rates, one must question whether the triple therapy should still be used.

Colorectal motor and sensitivity features in patients affected by ulcerative proctitis with constipation: a radiological and manometric controlled study.

BACKGROUND AND AIM: Constipation may be present in ulcerative proctitis (UP), but its pathogenesis has not yet been evaluated. The aim of this article is to investigate functional and morphologic features of the anorectal region in patients with UP and constipation. MATERIALS AND METHODS: Eleven patients with quiescent clinical, endoscopic, and histological UP and constipation and 10 patients with functional constipation (FC) underwent radiologic evaluation of intestinal transit time, anorectal manometry, and defecography. Transit time was measured with radiograms at 72 h after ingestion of radiopaque markers. Manometry was carried out using a continuous perfused catheter and a balloon inflated with increasing volumes of air. Defecography was performed after the injection of a barium-sulfate solution in the rectum, with the registration of videotapes during straining, squeezing, and evacuation. RESULTS: Manometry showed in UP significantly lower values of rectal compliance than those in FC (3.10 and 5 mL/mmHg, respectively) (P = 0.03). Rectal sensitivity threshold was increased but without significant differences in UP and FC (30 and 50 mL air, respectively). At defecography, the median value of rectosacral space was increased in UP in comparison with FC (1.30 vs 0.8; P = 0.002). Lateral rectal diameter in UP was lower than in FC (6 and 8.8 cm, respectively; P = 0.016). Nonsymptomatic rectocele, mucosal prolapse, descending perineum, and abdominopelvic dyssynergy were equally present in UP and FC. The majority of UP patients showed a prolonged intestinal transit time similar to FC patients, and, more frequently, they showed low transit in the left colon in comparison with the right colon in comparison with FC patients. CONCLUSIONS: This study suggests that constipation in UP may be correlated with rectal fibrosis, which reduces the transit of stools from the left colon. The concomitance of asymptomatic anorectal organic or functional alteration may contribute to worsen constipation.

Mesenteric adenitis caused by Yersinia pseudotubercolosis in a patient subsequently diagnosed with Crohn's disease of the terminal ileum.

Although the association between inflammatory bowel disease and gastrointestinal infections has been suggested, the mechanisms involved in the pathogenesis of Crohn's disease (CD) are still undetermined. We report the case of a man, who presented with mesenteric adenitis initially due to a Yersinia pseudotubercolosis infection, who was later diagnosed with Crohn's disease. This case is in keeping with recent evidence in the literature which suggests that CD is a disease linked to abnormal immune responses to enteric bacteria in genetically susceptible individuals.

Overexpression of fatty acid synthase in ulcerative colitis.

Fatty acid synthase is an enzyme that catalyzes the synthesis of long-chain fatty acids. The enzyme expression is minimal in adult tissues and very high in many cancers. Ulcerative colitis is a chronic inflammatory bowel disease that, when long-standing, is associated with an increased risk of colon cancer. The aim of the present study was to establish whether fatty acid synthase levels in the mucosa without dysplasia of patients with long-standing ulcerative colitis were higher than in control subjects. Three groups of patients were selected: 30 with active ulcerative colitis, 30 with ulcerative colitis in remission, and 30 undergoing colonoscopy for colorectal cancer screening, as healthy control subjects. Fatty acid synthase expression was evaluated with immunohistochemical procedures. The enzyme was detected in all patients with active colitis, in most patients with quiescent disease, in both pathologic and normal mucosa, but in only 3 healthy control subjects. Our results suggest that extension of ulcerative colitis is greater than that revealed by common diagnostic techniques.

Skeletal muscle disorders associated with inflammatory bowel diseases: occurrence of myositis in a patient with ulcerative colitis and Hashimoto's thyroiditis--case report and review of the literature.

Ulcerative colitis (UC) and Crohn's disease are inflammatory bowel diseases often associated with extra-intestinal manifestations. Of these, neutrophilic dermatoses and arthropathies are the more frequently observed, while the occurrence of striated muscle disorders, namely, myositis, has been very rarely diagnosed in these kinds of patients. The coexistence of immuno-mediated diseases in patients with inflammatory bowel diseases and myositis suggests a common aetiopathogenetic mechanism underlying these conditions. The present report refers to a rare case of a 51-year-old female with UC and Hashimoto's thyroiditis who developed myositis.

Anti-tissue transglutaminase antibodies in inflammatory bowel disease: new evidence.

Anti-tissue transglutaminase, previously held to be identical to anti-endomysial antibodies in celiac sprue, has been reported in inflammatory bowel disease patients. To investigate these data further, we evaluated serum and intestinal anti-tissue transglutaminase in inflammatory bowel disease patients, with respect to the Crohn's disease activity index and the integrated disease activity index. Study population comprised: 49 patients with Crohn's disease and 29 patients with ulcerative colitis; 45 patients with celiac sprue and 85 autoimmune patients as disease controls; and 58 volunteers as healthy controls. Immunoglobulin A (IgA) anti-recombinant human tissue transglutaminase and anti-endomysial antibody detection in sera and fecal supernatants were performed. Adsorption of positive sera with recombinant human tissue transglutaminase were also performed. Marked increased anti-tissue transglutaminase concentrations were found in celiac sprue, while low-positive values were also found in Crohn's disease and ulcerative colitis. Anti-endomysial antibodies were detectable only in celiac sprue. Antigen adsorption resulted in a significant reduction of the anti-tissue transglutaminase either in celiac sprue or inflammatory bowel disease sera. A significant correlation between anti-tissue transglutaminase and Crohn's disease activity index or integrated disease activity index scores was found. Anti-tissue transglutaminase was also detectable in fecal supernatants from inflammatory bowel disease patients. Data highlight that both circulating and intestinal anti-tissue transglutaminases are detectable in inflammatory bowel disease, and that they are related to disease activity. These features underline that, in addition to anti-tissue transglutaminase, an anti-endomysial antibody test is necessary in the diagnostic work-up of celiac sprue, especially in patients with known inflammatory bowel disease.

Oral mesalazine (5-ASA) treatment may protect against proximal extension of mucosal inflammation in ulcerative proctitis.

OBJECTIVES: Studies aimed at establishing which characteristics of patients with ulcerative proctitis could be predictive of the extension of inflammation have failed to provide conclusive results. The aim of the study was to evaluate the prognostic role of clinical and therapeutic parameters in patients with proctitis. PATIENTS AND METHODS: Case records of 138 patients with ulcerative proctitis were retrospectively evaluated. The following parameters were considered: gender; age at onset of disease; smoking habits; histologic severity of disease at onset; mean number of clinical relapses of disease per year; mean duration of oral and topical mesalazine treatment; and number of topical corticosteroid treatments per year. RESULTS: Twenty-eight patients were excluded from the analysis for different reasons. During follow-up, inflammation spread proximally in 33 of 110 patients (30%). Patients with extended proctitis showed a significantly higher number of relapses and a shorter duration of oral mesalazine treatment than patients with nonprogressive proctitis (p < 0.001 for both). The multivariate analysis also found that the mean duration of topical mesalazine treatment was longer in patients with extended proctitis. CONCLUSIONS: Ulcerative proctitis patients with more frequent relapses who need a longer duration of topical therapy are at higher risk of extension of the disease, while a more prolonged oral mesalazine treatment period protects against the proximal spread of rectal inflammation.

Oxidative damage of the gastric mucosa in Helicobacter pylori positive chronic atrophic and nonatrophic gastritis, before and after eradication.

BACKGROUND: Helicobacter pylori is the main cause of gastritis and a primary carcinogen. The aim of this study was to assess oxidative damage in mucosal compartments of gastric mucosa in H. pylori positive and negative atrophic and nonatrophic gastritis. MATERIALS AND METHODS: Five groups of 10 patients each were identified according to H. pylori positive or negative chronic atrophic (Hp-CAG and CAG, respectively) and nonatrophic gastritis (Hp-CG and CG, respectively), and H. pylori negative normal mucosa (controls). Oxidative damage was evaluated by nitrotyrosine immunohistochemistry in the whole mucosa and in each compartment at baseline and at 2 and 12 months after eradication. Types of intestinal metaplasia were classified by histochemistry. RESULTS: Total nitrotyrosine levels appeared significantly higher in H. pylori positive than in negative patients, and in Hp-CAG than in Hp-CG (p <.001); no differences were found between H. pylori negative gastritis and normal mucosa. Nitrotyrosine were found in foveolae and intestinal metaplasia only in Hp-CAG. At 12 months after H. pylori eradication, total nitrotyrosine levels showed a trend toward a decrease in Hp-CG and decreased significantly in Hp-CAG (p =.002), disappearing from the foveolae (p =.002), but remaining unchanged in intestinal metaplasia. Type I and II of intestinal metaplasia were present with the same prevalence in Hp-CAG and CAG, and did not change after H. pylori eradication. CONCLUSIONS: Oxidative damage of the gastric mucosa increases from Hp-CG to Hp-CAG, involving the foveolae and intestinal metaplasia. H. pylori eradication induces a complete healing of foveolae but not of intestinal metaplasia, reducing the overall oxidative damage in the mucosa.