1,721,002 research outputs found

    Perineal and Pelvic Crohn's Disease: modern options for treatment strategies

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    Outline and summary of the thesis The research project is divided in two parts: the first one describes the cytokine network in perineal and pelvic CD and its relation with the intestinal disease and the second one describes complex fistulas in perineal and pelvic Crohn’s disease. In Chapter 1, the systemic cytokine network was analyzed in chronic perianal CD and in other control groups, confirming not only that TNF-alpha plays a major role in perianal CD but also the importance of IL-6 as a systemic mediator for chronic inflammation suggesting a possible role for its monoclonal antibody in this disease. The next step was to evaluate the cytokine profile in the rectal mucosa of perianal CD patients and its relations with the local and systemic inflammatory status; particular attention was paid to its prognostic value in terms of need of surgery in perianal CD (Chapter 2). In the third section of Part 1 (Chapter 3), the in vivo intimate correlation between systemic inflammation mediated either by the innate immune system or T cell-mediated immunity (expressed by cytokine levels) and intestinal inflammation (expressed by lactoferrin levels) in CD patients who had undergone ileo-colonic resection and were in clinical remission was taken into consideration. The second part of the thesis was focused on complex fistulas (comunication to the bladder (or other urologic complications) or to the vagina) in perineal and pelvic CD. First of all, the threshold to suspect urologic complications in CD was assessed in order to plan correct surgical management (Chapter 1). In Chapter 2 the outcome of surgical repair in a consecutive series of RV fistulas in patients with CD over a 13 year period, within a single referral institution was evaluated. Both early and late outcomes were assessed as was the influence of medical therapy, especially the use of anti-TNF agents, in the closure of these fistulas. At this point, in the third section of this part (Chapter 3), a systematic review on advancement flaps for RV fistulas in CD (transrectal vs transvaginal approach) was performed.La malattia perineale e pelvica di Crohn può essere, in alcuni casi, seria ed invalidante, ponendo problematiche sia di ordine diagnostico che terapeutico a gastroenterologi e chirurghi. Attualmente l’anticorpo monoclonale anti-TNF-alpha (??Infliximab) viene utilizzato per il trattamento del morbo di Crohn refrattaria alla terapia medica convenzionale. Tuttavia, nei pazienti affetti da tale patologia, la risposta all’Infliximab non è completa e recenti studi hanno ricordato l’importanza del trattamento chirurgico associato alla terapia medica nel controllo dell’infiammazione intestinale. Lo scopo della tesi è di analizzare il network citochinico coinvolto nelle complicanze perineali e pelviche della malattia di Crohn e di osservare, nell’era delle terapie biologiche, i risultati del trattamento chirurgico di queste complicanze. Il progetto di ricerca è suddiviso in due parti: la prima descrive il network citochinico nella localizzazione perineale e pelvica di Crohn ed i suoi rapporti con la malattia intestinale mentre la seconda si occupa del trattamento delle fistole complesse nel morbo di Crohn. Nel primo capitolo, è stato analizzato il network citochinico sistemico nella malattia perianale di Crohn ed in altri gruppi di controllo: si è confermato non solo il ruolo centrale che gioca il TNF-alpha nella malattia perianale di Crohn ma anche l’importanza dell’IL-6 come mediatore sistemico dell’infiammazione cronica, suggerendo un possibile utilizzo del suo anticorpo monoclonale in questa malattia. Tali risultati ci hanno spinto ad investigare il network citochinico nella mucosa rettale dei pazienti affetti da malattia perianale di Crohn (Capitolo 2). E’ stato dimostrato che i livelli tissutali di IL-6, IL-1beta? e TNF-alpha sono significativamente più elevati nei pazienti con malattia perianale di Crohn rispetto ai controlli, correlando significativamente con gli indici di attività di malattia; inoltre, i livelli tissutali di IL-1beta? e TNF-alpha correlano significativamente con il grado istologico di malattia. Infine, i livelli tissutali di IL-6 e IL-12 sono risultati essere predittivi di recidiva di malattia e della necessità di chirurgia a livello perianale. Nell’ultima sezione della prima parte (Capitolo 3), è stata evidenziata la correlazione significativa tra la lattoferrina fecale e l’asse IL-6-proteina C reattiva in pazienti con malattia di Crohn in fase di quiescenza in seguito ad intervento di resezione ileo-colica. Abbiamo ipotizzato che l’infiammazione intestinale subclinica, espressa dalla lattoferrina fecale, mantenga uno stato di lieve attività dell’infiammazione sistemica mediante la cascata IL-6-proteina C reattiva. Il ruolo di IL-1beta IL-12 TNF-alpha e TGF-beta1 sembra essere più complesso e legato in maniera meno diretta all’infiltrazione neutrofila mucosale. La seconda parte della tesi è focalizzata sul trattamento chirurgico delle fistole complesse (comunicazioni con la vescica e/o uretere o con la vagina) nella malattia perineale e pelvica di Crohn. Nel primo capitolo è stato rilevato che è necessaria una bassa soglia di sospetto di coinvolgimento ureterale e/o vescicale per affrontare tali problematiche in pazienti che saranno sottoposti ad intervento di resezione per la malattia intestinale. In presenza di una massa addominale palpabile in un paziente affetto da malattia di Crohn si consiglia di eseguire sempre un’ecografia o una TC dell’addome per escludere una complicanza urologica che può essere trattata pre-operatoriamente in modo da migliorare sia lo stato generale del paziente che il quadro intra-operatorio. Viene proposto un algoritmo esemplificativo dell’approccio diagnostico e terapeutico di queste complicanze. Nel capitolo 2, sono stati valutati i risultati del trattamento chirurgico in un gruppo di pazienti con fistole retto-vaginali e malattia di Crohn in un lasso di tempo di 13 anni; le pazienti appartengono al centro di riferimento per le malattie infiammatori croniche intestinali dell’ Università di Lovanio, in Belgio. E’ stato osservato che la chiusura della fistola a lungo termine è ottenuta, nella maggior parte delle pazienti, in seguito alla chirurgia; tuttavia, sono spesso necessari ripetuti interventi chirurgici. Pertanto, le pazienti con fistole retto-vaginali nella malattia di Crohn dovrebbero essere sottoposte ad intervento chirurgico in seguito a guarigione tissutale ottenuta con terapie biologiche. Nell’ultimo capitolo di tale parte, è stata eseguita una revisione sistematica della letteratura internazionale sui lembi d’avanzamento per le fistole retto-vaginali nella malattia di Crohn: approccio trans-rettale vs trans-vaginale. Anche se basato su un limitato numero di articoli con basso livello di evidenza clinica, tale studio suggerisce che non ci sono differenze in termini di risultati tra gli approcci tran-srettale e trans-vaginale. Il tasso di recidiva sembra essere minore in seguito all’approccio trans-rettale. Suggeriamo, pertanto, l’utilizzo dell’approccio trans-rettale come primo intervento, in assenza di stenosi anorettale, mentre l’approccio trans-vaginale potrebbe essere vantaggioso in caso di stenosi anorettale o, in seguito a fallimenti dell’approccio trans rettale

    Gastrointestinal stromal tumour (GIST) presenting as a strangulated inguinal hernia with small bowel obstruction

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    Publishing Group. All rights reserved. Gastrointestinal stromal tumours (GISTs) can arise everywhere along the gastrointestinal (GI) tract. Their presentation in unusual locations should always be taken into account. A 74-year-old man referred to the emergency department for small bowel obstruction caused by an incarcerated inguinal hernia. A CT scan showed a mesenchymal tumour originating from the herniated bowel loop and a mass in the ascending colon. Laparoscopic resection of the mass and laparoscopic right hemicolectomy were performed. The histology showed a ruptured GIST arising from the herniated small bowel and a high-grade dysplasia villous adenoma of the right colon. GISTs can present with symptoms spanning from vague abdominal discomfort to surgical urgencies. Strangulated hernia is an extremely rare presentation, with only two cases described in the literature. A safe surgical approach was obtained with laparoscopy, maintaining surgical radicality. The ileal localisation and the pseudocapsule rupture were the main risk factors on prognostic stratification

    Clear cell sarcoma of the ileum: report of a case and review of the literature.

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    bstract Introduction. Clear cell sarcoma of the gastrointestinal tract (CCS-GI) is an extremely rare and aggressive tumor, which often mimics other neoplastic processes. Because of this feature, its real incidence may have been underestimated, especially in the past when genetic tests were less available than nowadays. To date, less then 30 cases have been described in the literature on the GI tract. Case presentation. We report the case of a 69-year-old woman who presented with active rectal bleeding. After a negative colonoscopy, the patient underwent a video-capsule endoscopy. The latter detected an ileal mass that was surgically resected. The microscopic appearance was consistent with a malignant mesenchymal neoplasm; immunohistochemistry was positive for S100 protein, CD56, and INI1. Fluorescence in situ hybridization showed a translocation involving the EWSR1 (Ewing sarcoma 1) gene region. All these findings were consistent with a CCS-GI. Conclusion. Herein we present a case of CCS-GI, discuss its clinical and pathological features, and review the literature on the subject. © The Author(s) 2012

    Prognostic significance of pathological sub-classification of pT3 rectal cancer

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    Purpose: Patients with pT3 rectal cancer represent a heterogeneous prognostic group. A more accurate histological sub-classification of pT status has been suggested as an improvement of the TNM staging system. The aim of the study was to evaluate the prognostic implication of a histopathologic sub-classification of pT3 rectal cancer. Methods: In this retrospective single-center study, pT3 rectal cancer patients who underwent surgery from January 2000 to December 2018 were evaluated. The maximum depth of tumor invasion beyond the muscularis propria was recorded. A ROC curve identified the best prognostic cutoff value to classify patients in two prognostic groups. Survival curves were estimated by the Kaplan-Meier method, and univariate and multivariate analyses with the Cox regression model were used to find independent factors influencing survival. Results: Overall, 203 patients were included. Four millimeters was identified as the best cutoff value: 82 patients showed a depth of invasion < 4 mm (group A) and 121 ≥ 4 mm (group B). Both the estimated 5-year OS and DFS were statistically better in group A than in group B (OS: 83.9% vs 62.2%, p < 0.01; DFS: 78.3% vs 40.6%, p < 0.01). The depth of tumor invasion was an independent risk factor for OS (HR 2.25, 95% CI 1.26-3.99, p = 0.006) and DFS (HR 2.30, 95% CI 1.40-3.78, p = 0.001). Conclusion: Our findings suggest that a sub-classification of pT3 rectal cancer, based on the depth of tumor invasion, should be considered to be introduced in the TNM staging system

    Perianal Crohn's disease: is there something new?

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    Perianal lesions are common in patients with Crohn's disease, and display aggressive behavior in some cases. An accurate diagnosis is necessary for the optimal management of perianal lesions. Treatment of perianal Crohn's disease includes medical and/or surgical options. Recent discoveries in the pathogenesis of this disease have led to advances in medical and surgical therapy with good results. Perianal lesions in Crohn's disease remain a challenging aspect for both gastroenterologists and surgeons and lead to a greatly impaired quality of life for all patients affected by this disease. A multidisciplinary approach is mandatory to obtain the best results

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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