Novel applications of biomaterials in the management of parastomal hernia and anal fistula

MD (res)The aim of this thesis was to explore novel applications for both traditional and contemporary biomaterials in the management of parastomal hernia and anal fistula. Parastomal hernias can be prevented or repaired using synthetic mesh; however, reported complications include infection, fibrosis and potential bowel erosion. The prophylactic role of a cross-linked collagen implant was assessed in terms of safety, feasibility and potential efficacy. Additionally, the human host response to this implant was evaluated. There were no complications related to infection or the implant‟s proximity to the bowel. The implant had excellent biocompatibility and resistance to degradation in most patients, and although fibrovascular in-growth and ECM deposition were limited, it seems to have excellent potential for soft tissue reinforcement and, more specifically, prevention of parastomal hernias. Anal fistulas are in the main successfully treated by surgical fistulotomy, however damage to the anal sphincter complex and subsequent incontinence have led to the development of other techniques which aim to either lessen or avoid such disturbance. One strategy involves the traditional cutting seton, and a modification of this technique, the „snug‟ silastic seton was assessed. In the short-medium term, this modification was demonstrated to be an effective addition to the fistula surgeon‟s armamentarium, although minor incontinence remained a concern. Other approaches employing contemporary biomaterials, fibrin glue and porcine intestinal submucosa, are aimed at tissue repair, rather than minimizing destruction. Their success rates however are highly variable. A pilot study aiming to assess the safety and potential efficacy of an 4 alternative biomaterial, cross-linked collagen in two different physical formats, was presented. In the short-medium term, both formats were shown to be safe, and equally effective. The results justify continued research into the use of biologically derived materials to heal anal fistulas. In conclusion, although disparate pathologies were addressed, both they and the thesis are unified by demonstrating that an understanding of the specific disease pathology, wound healing, and the host response to materials (synthetic and biological) are central to their successful management

Fibrin Sealant: The Only Approved Hemostat, Sealant, and Adhesive—a Laboratory and Clinical Perspective

Background.Fibrin sealant became the first modern era material approved as a hemostat in the United States in 1998. It is the only agent presently approved as a hemostat, sealant, and adhesive by the Food and Drug Administration (FDA). The product is now supplied as patches in addition to the original liquid formulations. Both laboratory and clinical uses of fibrin sealant continue to grow. The new literature on this material also continues to proliferate rapidly (approximately 200 papers/year).Methods.An overview of current fibrin sealant products and their approved uses and a comprehensive PubMed based review of the recent literature (February 2012, through March 2013) on the laboratory and clinical use of fibrin sealant are provided. Product information is organized into sections based on a classification system for commercially available materials. Publications are presented in sections based on both laboratory research and clinical topics are listed in order of decreasing frequency.Results.Fibrin sealant remains useful hemostat, sealant, and adhesive. New formulations and applications continue to be developed.Conclusions.This agent remains clinically important with the recent introduction of new commercially available products. Fibrin sealant has multiple new uses that should result in further improvements in patient care.</jats:p

Minimal Ιnvasive Surgery in Benign Anorectal Diseases, a systematic review

ΕΙΣΑΓΩΓΗ: Η καλύτερη κατανόηση της ανατομίας του πρωκτικού σωλήνα και του κατώτερου τριτημορίου του ορθού τις τελευταίες δεκαετίες και η τεχνολογική εξέλιξη οδήγησε στην ανάπτυξη ελάχιστα επεμβατικών τεχνικών για την αντιμετώπιση καλοήθων παθήσεων του ορθοπρωκτικού σωλήνα. ΣΚΟΠΟΣ: Να μελετηθούν στην υπάρχουσα βιβλιογραφία οι τεχνικές αυτές και να εκτιμηθεί η δυναμική τους να αντικαταστήσουν καθιερωμένες επεμβατικές τεχνικές στο μέλλον ΥΛΙΚΑ ΚΑΙ ΜΕΘΟΔΟΣ: Έγινε συστηματική ανασκόπηση της υπάρχουσας βιβλιογραφίας σε τρεις βάσεις δεδομένων, χρησιμοποιώντας στα παράθυρα αναζήτησης, τους καθιερωμένους ιατρικούς όρους αιμορροΐδες, περιεδρικό συρίγγιο, και ακράτεια κοπράνων. Μελέτες που συμπεριλήφθηκαν στην έρευνα ήταν αυτές που μελετούσαν τις ελάχιστα επεμβατικές τεχνικές που εφαρμόζονται στην θεραπεία των παθήσεων του ορθοπρωκτικού σωλήνα και αυτές που συγκρίνουν τις τεχνικές αυτές με τις καθιερωμένες επεμβάσεις. ΑΠΟΤΕΛΕΣΜΑΤΑ: Ογδόντα έξι μελέτες συμπεριλήφθηκαν στην συστηματική ανασκόπηση. Η ερμηνεία των αποτελεσμάτων ήταν δύσκολη καθώς πολλές από αυτές ήταν αναδρομικές και είχαν μεγάλη ετερογένεια στον τρόπο επιλογής των ασθενών και στον τρόπο που εφαρμοζόταν η κάθε τεχνική. Αντικρουόμενα συμπεράσματα προέκυψαν ακόμα και για τις ίδιες τεχνικές όταν αυτές συγκρίνονταν μεταξύ τους ως προς τα πρώιμα και όψιμα αποτελέσματα τους. Παγκοσμίως, η χρήση των μεθόδων αυτών αυξάνεται λόγω του ελάχιστα επεμβατικού τους χαρακτήρα αλλά η υπεροχή τους έναντι των παραδοσιακών τεχνικών δεν προκύπτει από την βιβλιογραφία. Οι αναφορές που γίνονται στην χρήση τους ως επικουρικές επεμβάσεις στην υπάρχουσα χειρουργική θεραπεία χρήζουν μεγαλύτερης έρευνας καθώς υπάρχει μεγάλη ετερογένεια στις μικτές αυτές τεχνικές από κέντρο σε κέντρο και δεν υπάρχουν μελέτες που να συγκρίνουν τα αποτελέσματα με αυτά των επιμέρους τεχνικών όταν αυτές εφαρμοστούν ως μονοθεραπεία. ΣΥΜΠΕΡΑΣΜΑΤΑ: Σε επιλεγμένα περιστατικά η εφαρμογή των ελάχιστα επεμβατικών τεχνικών μπορεί να έχει παρόμοια αποτελέσματα με την κλασσική χειρουργική. Οι παλαιότερες τεχνικές δεν φαίνεται να απειλούνται ακόμα από τις νέες. Ωστόσο η συνεχιζόμενη τεχνολογική εξέλιξη μπορεί να οδηγήσει και σε περαιτέρω βελτίωση των τεχνικών αυτών στο μέλλον.INTRODUCTION: Over the last two decades understanding of the anatomy of the anal sphincter and the lower third of the rectum, combined with the development of new equipment has lead to new minimally invasive techniques as a part of the treatment armamentarium of benign anorectal diseases. OBJECTIVE: The aim of this review was to examine the current literature about minimally invasive techniques in the treatment of benign anorectal diseases, specifically in regard to their potential to replace traditional operations. MATERIALS AND METHODS: A systematic search through the electronic databases Medline, Pubmed and Cohrane Library was conducted by using the MeSH terms hemorrhoids, fistula in ano and faecal incontinence. Studies were included if they examined the role of minimally invasive techniques in the treatment of the above medical conditions. Studies were also included if they compared these techniques with the conventional and established surgical treatment. RESULTS: Eighty six studies were included after excluding the duplicate records. The comparison between series was difficult because many were retrospective with a variety of application of the new surgical approaches and with different patient selection criteria. The heterogeneity of the published trials has lead even in conflicting results at the highest level of evidence regarding the efficacy of some of the techniques in short and long term follow up studies. The use of these techniques due to their minimal invasive nature is increasing worldwide but their superiority compared to the conventional treatment has not been proven yet. Their use as a complimentary treatment to the traditional treatment is also reported in some case series but the combined technique is not standardized and there are not randomised controlled trials to compare the reported improved results to the results of these techniques separately. CONCLUSION: Performing a minimal invasive operation in selected cases may improve the overall results but the replacement of the conventional techniques has not been proven yet. Further research is required to assess their role as complimentary treatment to the established more invasive techniques

The use of fibrin sealant during non-emergency surgery : a systematic review of the evidence of benefits and harms

Background Fibrin sealants are used in different types of surgery to prevent the accumulation of post-operative fluid (seroma) or blood (haematoma) or to arrest haemorrhage (bleeding). However, there is uncertainty around the benefits and harms of fibrin sealant use. Objectives To systematically review the evidence on the benefits and harms of fibrin sealants in non-emergency surgery in adults. Data sources Electronic databases [MEDLINE, EMBASE and The Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and the Cochrane Central Register of Controlled Trials)] were searched from inception to May 2015. The websites of regulatory bodies (the Medicines and Healthcare products Regulatory Agency, the European Medicines Agency and the Food and Drug Administration) were also searched to identify evidence of harms. Review methods This review included randomised controlled trials (RCTs) and observational studies using any type of fibrin sealant compared with standard care in non-emergency surgery in adults. The primary outcome was risk of developing seroma and haematoma. Only RCTs were used to inform clinical effectiveness and both RCTs and observational studies were used for the assessment of harms related to the use of fibrin sealant. Two reviewers independently screened all titles and abstracts to identify potentially relevant studies. Data extraction was undertaken by one reviewer and validated by a second. The quality of included studies was assessed independently by two reviewers using the Cochrane Collaboration risk-of-bias tool for RCTs and the Centre for Reviews and Dissemination guidance for adverse events for observational studies. A fixed-effects model was used for meta-analysis. Results We included 186 RCTs and eight observational studies across 14 surgical specialties and five reports from the regulatory bodies. Most RCTs were judged to be at an unclear risk of bias. Adverse events were inappropriately reported in observational studies. Meta-analysis across non-emergency surgical specialties did not show a statistically significant difference in the risk of seroma for fibrin sealants versus standard care in 32 RCTs analysed [n = 3472, odds ratio (OR) 0.84, 95% confidence interval (CI) 0.68 to 1.04; p = 0.13; I2 = 12.7%], but a statistically significant benefit was found on haematoma development in 24 RCTs (n = 2403, OR 0.62, 95% CI 0.44 to 0.86; p = 0.01; I2 = 0%). Adverse events related to fibrin sealant use were reported in 10 RCTs and eight observational studies across surgical specialties, and 22 RCTs explicitly stated that there were no adverse events. One RCT reported a single death but no other study reported mortality or any serious adverse events. Five regulatory body reports noted death from air emboli associated with fibrin sprays. Limitations It was not possible to provide a detailed evaluation of individual RCTs in their specific contexts because of the limited resources that were available for this research. In addition, the number of RCTs that were identified made it impractical to conduct independent data extraction by two reviewers in the time available. Conclusions The effectiveness of fibrin sealants does not appear to vary according to surgical procedures with regard to reducing the risk of seroma or haematoma. Surgeons should note the potential risk of gas embolism if spray application of fibrin sealants is used and not to exceed the recommended pressure and spraying distance. Future research should be carried out in surgery specialties for which only limited data were found, including neurological, gynaecological, oral and maxillofacial, urology, colorectal and orthopaedics surgery (for any outcome); breast surgery and upper gastrointestinal (development of haematoma); and cardiothoracic heart or lung surgery (reoperation rates). In addition, studies need to use adequate sample sizes, to blind participants and outcome assessors, and to follow reporting guidelines.Publisher PDFPeer reviewe

Съвременно лечение на аналните фистули

Аналната фистула е състояние, което е описано практически от началото на медицинската история. Хипократ около 430 г. пр.н.е. описва това заболяване и прилага лигатурен метод за неговото лечение, който се използва с известна модификация и днес. При избора на метод за лечение от основно значение е предоперативното определяне на типа фистула. Фистулите най-често се подразделят на четири различни категории, базирани на отношението им спрямо вътрешния и външния анален сфинктер. Резултатите от хирургичната интервенция при перианални фистули могат да варират в широки граници при различните хирурзи. Те зависят от сложността на фистулата. Често лошите резултати от предприетото лечение не се съобщават. Обикновено има реципрочна корелация между рецидиви и фекална инконтиненция. Доклади с нисък процент рецидиви обикновено са свързани с висок процент на инконтиненция и обратно. Въпреки това е изключително трудно да се сравняват резултатите от тези проучвания поради липсата на стандартизиран подход. Много проучвания, обхващащи голям брой пациенти, имат неадекватно проследяване. Тъй като много автори не дефинират инконтиненцията, читателят често не е запознат с това, дали проблемът е постоянен или временен, дали инконтиненцията е на твърди или течни фекални маси или само на газове. Липсата на стандартна международна класификация прави невъзможно правилната комуникация между различните хирурзи. Като резултат от това не е възможно да се сравнят резултатите от проучванията на различните автори. Много доклади съобщават само сложни фистули, докато в други са включени и голям брой прости. Това поне отчасти обяснява огромните разлики в резултатите на различни автори. Друг проблем е проследяването на пациентите. Докладите, обхващащи голям брой пациенти, по-често имат добра информация от проследяването на пациентите. Периодът на проследяване също е от значение. Често при по-краткотрайно проследяване не се наблюдават рецидиви и усложнения. Хирургичната техника на хирурга също е от значение, както и старанието при проследяването и контролните прегледи на пациентите. Най-много хирурзи са изгубили репутацията си поради последиците от операции на фистули, отколкото след всяка друга оперативна процедура. В САЩ инконтиненцията дори след правилно проведената операция за анална фистула е една от най-честите причини за това, пациентът да съди своя лекар. Хирургът, който има късмет да е първоначалния оператор, е с най-добър шанс да излекува пациента и да ограничи усложненията и инконтиненцията

Tratamiento de las fístulas perianales complejas con una fibrina rica en plaquetas. Estudio piloto

L'únic tractament per a la fístula perianal complexa és la cirurgia. Existeixen dos grups de tractament: les tècniques que seccionen esfínter anal que presenten una elevada eficàcia però que comporten incontinència fecal i les tècniques preservadores de l'esfínter que aconsegueixen uns resultats baixos però no alteren la continència anal. En aquest últim grup existeix una nou sellant biològic (Vivostat®) que aporta diferències amb les anteriorment comercialitzades: és un sellant autòleg i es pot afegir un gel de plaquetes que aportaria varis dels factors que afavoririen la cicatrització. Proposem un estudi per valorar l'eficàcia d'aquest sellant biològic.El único tratamiento para la fístula perianal compleja es la cirugía. Existen dos grupos de tratamiento: las técnicas que seccionan esfínter anal que presentan una elevada eficacia pero que comportan incontinencia fecal y las técnicas preservadoras del esfínter que consiguen unos resultados bajos pero no alteran la continencia anal. En este último grupo existe una nueva cola biológica (Vivostat®) que aporta diferencias con las anteriormente comercializadas: es una cola autóloga y se puede añadir un gel de plaquetas que aportaría varios de los factores que favorecerían la cicatrización. Proponemos un estudio para valorar la eficacia de este sellante biológico

Clinical and experimental studies in idiopathic and Crohn's-related anal fistula

The factors leading to the creation and persistence of anal fistula in Crohn’s disease are poorly understood. As with luminal Crohn’s disease genetic, microbiological and immunological factors are implicated but the immunological and microbiological composition of Crohn’s and idiopathic anal fistulae have been obscure. My data demonstrate a lack of clinically relevant organisms within fistula tracts, a luminally driven immune response and subtle differences in this response between Crohn’s and idiopathic fistulae which may provide the basis for diagnostic tests, interventions and further research. Surgical treatment of anal fistula is characterised by a compromise between risk of recurrence and impairment of continence. In complex, recurrent and multiply operated anal fistulae, fistulotomy can still provide a high success rate with low additional risk of impairment of continence. Rectovaginal fistulae are also difficult to manage both surgically and medically. In the infliximab era, successful healing of Crohn’s RVF remains disappointingly rare. Surgery for RVF requires a variety of approaches but remains a valuable tool in the treatment of both Crohn’s and non-Crohn’s tracts. Medical treatment of Crohn’s anal fistulae with combination thiopurine and anti-TNFα agents has demonstrated good short term results. Clinical and radiological data to 3 years follow up demonstrate that around a third of patients maintain healing on infliximab, radiological healing lags behind clinical remission by around a year, and cessation may lead to recurrence in spite of a healed tract on MRI. A treatment for anal fistula with high success and low risk of impairment of continence in complex anal fistulae eludes colorectal surgeons and gastroenterologists. A treatment combining the best aspects of current fistula management with novel elements prompted by improved aetiological understanding must be the goal for fistula surgeons and is the inspiration behind this thesis