Imerio Angriman

Oxidative DNA damage in the mucosa of ulcerative colitis increases with disease duration and dysplasia.

BackgroundChronic inflammation may contribute to cancer risk through the accumulation of specific products as a result of DNA damage. The role of free radical mediated oxidative DNA damage during inflammation was determined in patients with ulcerative colitis by measuring 8-hydroxydeoxyguanosine (8-OHdG). MethodsPatients with ulcerative colitis were compared according to age, gender, duration and extent of disease, endoscopic and histologic activity, presence or absence of dysplasia/cancer, and biochemical parameters of inflammation. Patients with sporadic colon cancer and irritable bowel syndrome served as controls. Levels of 8-OHdG were assessed by high pressure liquid chromatography with electrochemical detection (mean number of adducts/105 dG residues). ResultsPatients with ulcerative colitis and dysplasia had significantly higher mucosal 8-OHdG concentrations (P = 0.011). 8-OHdG concentrations were significantly higher in older patients (P = 0.010), patients with long-standing disease (P = 0.015), active endoscopic (P = 0.006) or histologic disease (P = 0.003). Covariance analysis showed significant effect of dysplasia on 8-OHdG levels: values higher than 100 adducts/ 105 dG. had a diagnostic value of 80.9% (SE 6.2%). ConclusionsOxidative DNA damage accumulates with the duration of the disease in ulcerative colitis reaching maximal increase if dysplastic lesions are found with possible implications for mutagenic and carcinogenic progression.

A systematic review on the clinical diagnosis of gastrointestinal stromal tumors

The aim of this work was to assess the prevalence of symptoms of gastrointestinal stromal tumors (GISTs) and the diagnostic yield of clinical procedures for its diagnosis.

Health-related quality of life after restorative proctocolectomy for ulcerative colitis: Long-term results

Restorative proctocolectomy (RPC) is the favorite operation for ulcerative colitis, but it may influence health-related quality of life (HRQL). Our aims were to determine the long-term HRQL of patients and its modifications after a 5-year follow-up and to identify any risk factor for a worse outcome. We enrolled 36 patients submitted to RPC (mean followup 8.4 ± 4.7 years), 36 ulcerative colitis (UC) patients, and 36 healthy subjects. We used a previously validated questionnaire that explored bowel symptoms, systemic symptoms, emotional function, and social function. A series of 17 patients had completed the same questionnaire 5 years earlier. Clinical and surgical factors were investigated. Statistical analysis was performed with Student’s t-test, Wilcoxon matched-pairs test, and Fisher’s exact test. The scores of the RPC patients were significantly better than those of moderate or severe UC patients, similar to those with remission/ mild UC, and higher than those of the controls. The scores of patients interviewed 5 years earlier did not change in the present study, except for patients during the first postoperative year, in whom the scores were now significantly better. The analysis of RPC patients in subgroups showed that the use of drugs, high stool frequency, pouchitis, pelvic complications, and younger age at UC diagnosis worsened the HRQL outcome. We concluded that RPC patients, after a long-term follow-up, had an HRQL similar to that of the remission/mild UC patients. Recently operated patients improved their quality of life mainly because of improved emotional function, and patients who had been operated on for a longer time maintained their HRQL. HRQL is influenced by drugs, stool frequency, pouchitis, postoperative pelvic complications, and age at diagnosis.RésuméLa coloprotectomie restauratrice (CPR) est l’intervention préférée dans la rectocolite ulcéro-hémorragique (RCUH), mais elle peut avoir un retentissement sur la qualité de vie (QV). Nos objectifs ont été de déterminer la QV des patients à long terme ainsi que leurs modifications après un suivi de 5 ans et d’identifier les facteurs de risque pour une évolution non favorable. Nous avons analysé les résultats concernant 36 patients ayant eu une CPR (suivi moyen: 8.4 ± 4.7 ans) pour avecRCUH 36 patients avec RCUH et 36 patients de contrôle. Nous avons utilisé un questionnaire validé antérieurement qui explore les symptômes intestinaux, les symptômes systémiques, les fonctions émotionnelle et sociale. Dix-sept patients avaient complété ce même questionnaire cinq ans plus tôt. On a également examiné les facteurs cliniques et chirurgicaux. L’analyse statistique a été réalisée par le test t de Student, de Wilcoxon pour les données appariées et le test exact de Fisher. Les patients CPR ont obtenu des scores significativement plus élevés que les patients présentant une RCUH modérée ou sévère, similaires à ceux présentant une RCUH en rémissionpeu sévère et plus élevés que les patients de contrôle. Les scores des patients interviewés cinq ans plus tôt n’ont pas changé sauf pour la première année postopératoire pendant laquelle il était significativement meilleur. L’analyse des sous-groupes de patients RCUH a montré que l’utilisation des medicaments, une fréquence élevée de l’évacuation, la pouchite, les complications pelviennes et un âge peu élevé au moment de l’intervention ou diagnostic a aggravé l’évolution de la QV. En conclusion, les patients ayant du eu une CPR au long cours jouissent d’une QV similaire à celle des patients en rémission ou avec une RCUH peu sévère. Les patients opérés récemment voient leur QV améliorée principalement en raison de leur fonction émotionnelle alors que les patients opérés il y a plus long temps gardent leur QV. La QV est influencée par l’utilisation des medicaments, la fréquence des selles, la pouchite, les complications postopératoires et l’âge au moment du diagnostic.ResumenLa proctocolectomía restaurativa (PCR) es el tipo de cirurgia en el tratamiento de la colitis ulcerativa, pero puede afectar la calidad de vida al comparla con el buen estado de salud (CVCS). Nuestro propósito fue determinar la CVCS a largo plazo y sus cambios después de S años de seguimiento, identificando factores de riesgo de empeoramiento. Se incorporaron 36 pacientes sometidos a PCR (promedio de seguimiento: 8.4 ± 4.7 años) 36 por colitis ulcerativa (CU), y 36 pacientes sanos. Se utilizó un cuestionario previamente validado para identificar síntomas intestinales, síntomas sistémicos, estado emocional y cualidad de vida en el ambito social. Diecisiete pacientes habían respondido el mismo cuestionario 5 años antes. Factores clínicos y quirúrgicos fueron investigados. Se hizo el análisis estadístico mediante la prueba de Student y las pruebas de apareamiento de Wilcoxon y de exactitud de Fischer. Los pacientes con PCR registraron valores significativamente mejores que los de los pacientes con colitis ulcerativa moderada o severa, una tasa similar a remisión de CU leve y más alta que la de los controles. Los valores de los pacientes entrevistados 5 años antes no mostraron cambio, y sólo aquellos en el primer año postoperatorio registraron ahora mejores valores. El análisis de los subgrupos de pacientes con PCR puso en evidencia que el requerimiento de drogas, la alta frecuencia en la defecatión, la “bolsitis” (pouchitis) las complicaciones pélvicas y la edad más joven en el momento del diagnóstico, desmejoraban la CVCS. En conclusión, los pacientes sometidos a PCR en el seguimiento a largo plazo logran una CVCS similar a la de aquellos con remisión de CU leve. Los pacientes recientemente operados mejoraron su calidad de vida principalmente por causa de un mejor estado emocional, en tanto que los operados con más anterioridad mantienen su CVCS. La CVCS se ve influenciada por el requerimiento de la droga, la frecuencia en la defecatión, la “bolsitis,” las complicaciones pélvicas postoperatorias y la edad en el momento del diagnóstico.

Surgical predictors of recurrence of Crohn’s disease after ileocolonic resection

Background/aimsAnastomotic recurrence after bowel resection is a major problem in Crohn’s disease (CD) surgery. The aims of this retrospective study are to assess the role of anastomotic configuration, the type of suture and the type of surgical approach (laparoscopy-assisted vs laparotomy) in CD recurrence. Secondary end points were to identify any possible predictor that would help the selection of patients for medical prophylaxis.Materials and methodsIn this retrospective study, we enrolled 141 consecutive patients who had undergone ileocolonic resection for CD. Univariate actuarial analysis was performed according to demographic, clinical and surgical predictors. Variables that resulted to be significant at the univariate analysis were included in two multivariate Cox proportional hazards models that analyzed symptomatic and surgical recurrence, respectively.ResultsIn the long-term, handsewn side-to-side anastomosis reported a significantly lower surgical recurrence rate than stapled end-to-side (p < 0.05). At multivariate analysis, anastomosis type, surgical and intestinal complications (p < 0.01) and age at CD onset (p < 0.05) resulted to be significant predictors for re-operation for CD recurrence. Multivariate analysis showed that surgical complication was also a significant predictor of symptomatic recurrence.ConclusionsSide-to-side anastomosis configuration seems to delay re-operation and can be assumed as the standard configuration in ileocolonic anastomosis in CD. Post-operative complications and young age at disease onset might be a signal of aggressive CD that may warrant prophylactic pharmacological therapy.

PDCD4/miR-21 dysregulation in inflammatory bowel disease-associated carcinogenesis

Inflammatory bowel diseases (IBDs; both ulcerative colitis [UC] and Crohn’s colitis [CC]) are well-established predisposing pathological conditions for colorectal cancer (CRC) development. In IBDs, both the endoscopy and the histology assessment of CRC precursors (i.e., dysplasia, also defined as intraepithelial neoplasia) are associated with low interobserver consistency, and no reliable dysplasia-specific biomarker is available. The programmed cell death 4 (PDCD4) tumor suppressor gene is involved in sporadic colorectal oncogenesis, but scanty information is available on its involvement in IBD-associated colorectal oncogenesis. One hundred twenty tissue samples representative of active and inactive IBD and of flat dysplasia were obtained from 30 cases of UC and 30 of CC who undergone colectomy. Twenty additional biopsy samples obtained from patients with irritable bowel syndrome acted as normal controls. PDCD4 expression was assessed by immunohistochemistry; the expression of miR-21 (a major PDCD4 regulator) was investigated by quantitative real-time PCR and in situ hybridization in different series of a hundred samples. Tissue specimens from both controls and inactive IBD consistently featured strong PDCD4 nuclear immunostain; conversely, lower PDCD4 nuclear expression was featured by both active IBD and IBD-associated dysplastic lesions. Significant PDCD4 down-regulation distinguished IBD-associated dysplasia (p < 0.001) versus active IBD. In both active IBD and dysplasia, PDCD4 down-regulation was significantly associated with miR-21 up-regulation. PDCD4 nuclear down-regulation (which parallels miR-21 up-regulation) is involved in the molecular pathway of IBD-associated carcinogenesis. PDCD4 nuclear expression may be usefully applied as ancillary maker in the histological assessment of IBD-associated dysplastic lesions.

Follow-Up of Exocrine Pancreatic Function in Type-1 Diabetes mellitus

In a previous study, mild to moderate exocrine pancreatic insufficiency, as measured by the secretin-pancreozymin test, was found in 23 (43%) of 53 patients with type-1 diabetes mellitus. Of these 53 patients, 20 (7 of whom initially had an abnormal secretin-pancreozymin test) were available for a follow-up examination 11 years later. Of the 7 patients with abnormal exocrine pancreatic function at the first test, 5 remained abnormal and 2 became normal, whereas of the 13 patients with initially normal pancreatic function the test result remained normal in 11 patients and became abnormal in 2. In these 2 groups the test result did not differ significantly between both tests. However, exocrine pancreatic function had returned to normal or had become abnormal in 2 patients, respectively, at the second test. In the 3 patients with exocrine pancreatic insufficiency at the first and second tests, the lipase level had not fallen below 10% or less than the normal level at which steatorrhea occurs and therapy is required. There was no significant correlation between the duration of the diabetes and the test results for both time points of investigation. The data suggest that mild to moderate exocrine pancreatic insufficiency found in type-1 diabetes is due to an early event in the course of the diabetes and does not progress. Therefore, this finding is of minor clinical importance and expensive pancreatic enzyme substitution will not be required.

A systematic review on advancement flaps for rectovaginal fistula in Crohn’s disease: transrectal vs transvaginal approach

Aim  Despite advances in the treatment of Crohn’s disease (CD), the treatment of rectovaginal (RV) fistula remains challenging. Transrectal (RAF) and transvaginal advancement flaps (VAF) represent two possible alternative surgical approaches to this problem. The study aims to review and compare the results of these approaches for RV fistula in CD.

Gastrointestinal stromal tumors: Report of an audit and review of the literature

Gastrointestinal stromal tumors (GISTs), tumors characterized by c-KIT mutations, are the most frequent mesenchymal tumors of the digestive tract. The stomach is the most commonly involved site. Localization, size and mitotic rate are reliable predictors of survival and the two milestones of GISTs treatment are surgery and imatinib. This article is aimed to report the data of an audit, carried out on the morphological and clinical aspects of the disease and to review the present knowledge on GISTs. A total of 172 patients with GISTs (M : F=1 : 1; mean age 65 years) were recruited. The stomach was the most frequently involved site. In 50% of the cases the tumor was smaller than 5 cm, whereas major symptoms were observed in 43% of the cases. Predictors of progressive disease were present only in a small percentage of cases but the disease was in the metastatic phase in over 25% of the cases at diagnosis. Familial aggregation was rare but a consistent share of the patients (21%) had other synchronous or metachronous cancers. The most frequent mutations were in-frame deletions and point mutations of c-KIT exon 11. This report confirms in part the available data on GIST in a consecutive series of patients recruited in Italy and shows that only large collaborative multicenter studies provide data sound enough to enable making reasonable clinical and therapeutic choices, and suggests that, as a measure of secondary prevention, a diagnostic definition should be obtained in all submucosal lesions of the GI tract and that GIST patients should be screened for second tumors.

Inflammatory colonic carcinogenesis: A review on pathogenesis and immunosurveillance mechanisms in ulcerative colitis

Ulcerative colitis (UC) is characterized by repeated flare-ups of inflammation that can lead to oncogenic insults to the colonic epithelial. UC-associated carcinogenesis presents a different sequence of tumorigenic events compared to those that contribute to the development of sporadic colorectal cancer. In fact, in UC, the early events are represented by oxidative DNA damage and DNA methylation that can produce an inhibition of oncosuppressor genes, mutation of p53, aneuploidy, and microsatellite instability. Hypermethylation of tumor suppressor and DNA mismatch repair gene promoter regions is an epigenetic mechanism of gene silencing that contribute to tumorigenesis and may represent the first step in inflammatory carcinogenesis. Moreover, p53 is frequently mutated in the early stages of UC-associated cancer. Aneuploidy is an independent risk factor for forthcoming carcinogenesis in UC. Epithelial cell-T-cell cross-talk mediated by CD80 is a key factor in controlling the progression from low to high grade dysplasia in UC-associated carcinogenesis.

Plasma lipids and inflammation in active inflammatory bowel diseases

Background  Ulcerative colitis (UC) and Crohn’s disease (CD) can cause metabolic and inflammatory alterations.